Pharma Super Table

DRUG

MOA and INDICATION

ADVERSE EFFECTS

NOTABLE PROPERTIES

i. Acetylcholine

Muscarinic agonist; activates M1 through M3 receptors in all peripheral tissues. Results to increased secretion, smooth muscle contraction (except in vascular smooth muscles where it causes relaxation) and changes in heart rate

CNS stimulation, miosis, cyclospasm, brochoconstriction, excessive GI and GU smooth musc le contraction, increased secretory activity of sweat gland, airways etc, vasodilation

very short lived DOA: 5-30sec, apidly hydrolyzed by AChE; acts on both M and N receptors

ii.Betanechol

Muscarinic agonist; activates M1 through M3 receptors in all peripheral tissues (same as Ach) ; for Bladder and bowel atony

Cylospasm, diarrhea, urinary urgency, vasodilation, reflex tachycardia, sweating

Results in smooth muscle contraction except in vascular smooth muscles where it causes relaxation; resistant to AChE, orally active, act on M receptors only

iii. Carbachol

Nonselective muscarinic and nicotinic agonist; similar to betanechol; used topically for glaucoma treatment

Cylospasm, diarrhea, urinary urgency, vasodilation, reflex tachycardia, sweating

acts on both M and N receptors, DOA: 30mins-2hrs

Partial muscarinic agonist; used for treatment of Glaucoma, Sjogren's syndrome and Sicca syndrome

Miosis, blurring of vision

good lipid solubility compared to choline esters

i. Nicotine

Agonist at both NN and NM receptos; activates autonomic post ganglionic neurons (both sympathetic and parasympathetic) and skeletal muscle neuromuscular end plates ; for Smoking Cessation

Generalized ganglionic stimulation (hypertension, tachycardia, nausea, vomiting, diarrhea)

Able to enter the CNS and activates NN receptors ; DOA: 1-6h only

ii. Varenicline

Selective partial agonist at nicotinic receptors; used exclusively for smoking cessation

Generalized ganglionic stimulation (hypertension, tachycardia, nausea, vomiting, diarrhea)

longer DOA than nicotine: 12-24h

Binds briefly to active site of acetylcholinesterase (AChE) and prevents access of acetylcholine (Ach); Amplifies all actions of Ach; increases parasympathetic activity and somatic neuromuscular transmission ; for Myasthenia gravis diagnosis (Tensilon test)

Miosis, salivation, nausea, vomiting, diarrhea, bradycardia

parenteral, very short lived DOA: 515min

1. AUTONOMIC DRUGS Cholinomimetics A. Direct Acting Choline Esters

B. Direct Acting Muscarinic Alkaloids i. Pilocarpine

C. Direct Acting Nicotinic Agonists

D. Short Acting Cholinesterase Inhibitor (Alcohol) i. Edrophonium

(Carbamates) i. Neostigmine

Forms covalent bonds with AChE, but is hydrolyzed and released; Longer acting than Edrophonium ; for Myasthenia gravis treatment; reversal of nondepolarizing muscular blockade, Ogilvie syndrome


poor lipid solubility, oral, DOA: 30min-2h

ii. Pyridostigmine

Longer acting effect compared to Neostigmine


poor lipid solubility, oral, DOA: 4-8h

iii. Physostigmine

Natural alkaloid tertiary amine, similar to neostigmine


good lipid solubility: able to enter the CNS, DOA: 4-8h

Similar to neostigmine but with slower release


moderate lipid solubiliy, DOA: 27days

malathion: scabicide, parathion: insecticide


high lipid solubiliy, DOA: 7-30 days

Competitively blocks all muscarinic receptors, antagonizes histamine and serotonin ; for motion sickness, dec. acid secretion in the GIT

Drowsiness, blurring of vision, dry eyes, constipation, dry mouth, urinary retention

known as Hyoscine-N-ButylBromide (Buscopan)

ii. Atropine

Nonselective competitive antagonism at all muscarinic receptors in the CNS and peripheral tissues; causes mydriasis and cycloplegia; mandatory antidote for severe cholinesterase inhibitor poisoning ; Mydriatic, cycloplegic, antidote for organophosphate poisoning (DOC), for bradycardia, hypersalivation and to decrease airway secretion during general anesthesia

Tachycardia, mydriasis, cyloplegia, skin flushing, delirium, hallucinations, urinary retention, constipation

DOC for organophosphate poisoning; notorious for causing hyperthermia

iv. Homatropine

Similar to atropine but with a shorter duration of action (12-24h) ; Mydriatic, cycloplegic in eye examinations Similar to atropine but with a shorter duration of action (3-6h), Mydriatic, cycloplegic in eye examinations Similar to atropine but with the shortest duration of action (15-60min); Mydriatic, cycloplegic in eye examinations

F. Long Acting C holinesterase Inhibitors (Organophosphates) i. Echothiophate ii. Malathion, Parathion Cholinoceptor Blocking Drugs i. Scopolamine

v. Cyclopentolate

vi. Tropicamide

Mydriatic, cycloplegic


shorter DOA among cholineceptor blockers (15-60min)

(Carbamates) i. Neostigmine

Forms covalent bonds with AChE, but is hydrolyzed and released; Longer acting than Edrophonium ; for Myasthenia gravis treatment; reversal of nondepolarizing muscular blockade, Ogilvie syndrome


poor lipid solubility, oral, DOA: 30min-2h

ii. Pyridostigmine

Longer acting effect compared to Neostigmine


poor lipid solubility, oral, DOA: 4-8h

iii. Physostigmine

Natural alkaloid tertiary amine, similar to neostigmine


good lipid solubility: able to enter the CNS, DOA: 4-8h

Similar to neostigmine but with slower release


moderate lipid solubiliy, DOA: 27days

malathion: scabicide, parathion: insecticide


high lipid solubiliy, DOA: 7-30 days

Competitively blocks all muscarinic receptors, antagonizes histamine and serotonin ; for motion sickness, dec. acid secretion in the GIT

Drowsiness, blurring of vision, dry eyes, constipation, dry mouth, urinary retention

known as Hyoscine-N-ButylBromide (Buscopan)

ii. Atropine

Nonselective competitive antagonism at all muscarinic receptors in the CNS and peripheral tissues; causes mydriasis and cycloplegia; mandatory antidote for severe cholinesterase inhibitor poisoning ; Mydriatic, cycloplegic, antidote for organophosphate poisoning (DOC), for bradycardia, hypersalivation and to decrease airway secretion during general anesthesia


DOC for organophosphate poisoning; notorious for causing hyperthermia

iv. Homatropine

Similar to atropine but with a shorter duration of action (12-24h) ; Mydriatic, cycloplegic in eye examinations Similar to atropine but with a shorter duration of action (3-6h), Mydriatic, cycloplegic in eye examinations Similar to atropine but with the shortest duration of action (15-60min); Mydriatic, cycloplegic in eye examinations

F. Long Acting C holinesterase Inhibitors (Organophosphates) i. Echothiophate ii. Malathion, Parathion Cholinoceptor Blocking Drugs i. Scopolamine

v. Cyclopentolate

vi. Tropicamide



shorter DOA among cholineceptor blockers (15-60min)

vii. Ipratropium

Competitive nonselective antagonist at muscarinic receptors ; for BA and COPD

Dry mouth, cough, nasal dryness

not as effective as SABAs but less tachycardia and arrhythmia ; few muscarinic effects outside the lungs

viii. Tiotropium

Similar to Ipratropium but with longer duration of action

Dry mouth, cough, nasal dryness

not as effective as SABAs but less tachycardia and arrhythmia ; few muscarinic effects outside the lungs

ix. Oxybutinin

Nonselective muscarinic antagonist which reduces detrussor smooth muscle tone spasms ; for decreasing urgency in mild cystitis and dec. bladder spasm after urologic surgery


for urinary urgency and incontinence

x. Pralidoxime

Regenerates active acetylcholinesterase; can relieve skeletal muscle and endplate block ; Usual antidote for early stage cholinesterase inhibitor poisoning

muscle weakness

Must be administered before 6-8 hours of organophosphate bond with cholinesterase occurs ; has oxime group which has high affinity for phosphorus

xi. Hexamethonium, Mecamylamine, Trimethaptan

Competitively blocks all Nn nicotinic Ach receptors ; for Hypertensive emergencies (obsolete)

Postural hypotension, dry mouth, blurred vision, constipation, sexual dysfunction

first successful agents in treating HTN

Non-selective, direct acting sympathomimetic; activates A and B adrenergic receptors; A1 vasoconstriction and increased BP; B1 - increased HR, conduction and contractility; B2 - bronchodilatation ; used for Cardiac arrest, anaphylaxis, asthma, COPD, Hemostasis Non-selective, direct acting sympathomimetic; activates A and B adrenergic receptors; A1 vasoconstriction and increased BP; B1 - increased HR, conduction and contractility; B2 - bronchodilatation ; used for Neurogenic shock, cardiogenic shock

Hypertension, tachycardia, ischemia, hyperglycemia

DOC for Anaphylaxis ; inactive per orem ; do not enter CNS significantly ; short DOA

Extreme vasospasm, tissue necrosis, excessive BP increase, arrhythmias, infarction, reflex bradycardia

Compensatory vagal reflexes tend to overcome the direct postive chronotropic effects ; alpha activity > beta activity; inactive per orem ; do not enter CNS significantly ; short DOA

Non-selective, direct acting sympathomimetic; activates A, B and D1 adrenergic receptors; A1 vasoconstriction and increased BP; B1 - increased HR, conduction and contractility; D1 - vasodilation in splanchnic and renal blood vessels ; for cardiogenic Shock and heart failure

Cardiovascular disturbances, arrhythmias

inactive per orem ; do not enter CNS significantly ; short DOA; very effective in renal failure associated with shock

Sympathomimetics i. Epinephrine

ii. Norepinephrine

iii. Dopamine

iv. Isoproterenol

Beta nonselective sympathomimetic; nonselectively activates B adrenergic receptors; B1 - increased HR, conduction and contractility; B2- bronchodilatation ; for Asthma

Cardiovascular disturbances, arrhythmias

synthetic catecholamine, not readily taken up into nerve endings

vi. Phenylephrine

A1 agonist used for short term maintenance of BP in acute hypotension; also used intranasally to produce local vasoconstriction as a decongestant ; mydriatic, for drug-induced hypotension, spinal shock

Rebound nasal congestion (Rhinitis medicamentosa), hypertension, stroke, MI

Mydriasis without cycloplegia

vii. Clonidine

A2 agonist that inhibits adenylyl cyclase and interacts with other intracellular pathways; marked vasodilation by central sympatholytic effect ; for Hypertension, Cancer pain, opioid withdrawal

Sedation, rebound hypertension, dry mouth

When taken per orem, there is initial inc in BP then will go down once the drug enters the CNS

viii. Methyldopa, Guanfacine and Guanabenz

Central sympatholytics analogous to clonidine ; Methyldopa is used for Pre-eclampsia

Sedation, positive Coomb's test (Hemolytic anemia)

Methyldopa - positive Coomb's test (Hemolytic anemia)

xi. Apraclonidine, Brimonidine

A2 agonist; reserved for ophthalmologic use in glaucoma for reduction of intraocular pressure

eye discomfort, hyperemia and pruritus, blurred vision

NONE

xii. Dobutamine

B1 agonist that activates adenylyl cyclase, increasing myocardial contractility; with positive inotropic effect ; Clinically used for cardiogenic shock and acute heart failure

Tachyarrhythmia, Hypertension, Eosinophilic myocarditis, Premature ventricular beats, Angina, Dyspnea, Fever, Headache, Nausea, Palpitation

Beta1 selective

xiii. Albuterol/Salbutamol

B2 agonist with adenylyl cyclase activation; results to bronchial smooth muscle dilation ; for Bronchial Asthma D1 agonist that activates adenylyl cyclase; results to vascular smooth muscle relaxation ; for Hypertension

Nausea , Fever, Bronchospasm, Vomiting, Headache, Dizziness, Cough, Allergic reactions

Rapid development of tolerance; DOC as Asthma reliever

Angina, Cardiac dysrhythmia, Dizziness, Flushing, Heart failure, Hypotension, Myocardial infarction, Tachycardia

D1 agonist

D2 agonist that inhibits adenylyl cyclase and interacts with other intracellular pathways; restores dopamine actions in the CNS for Parkinson's disease, prolactinemia

Nausea, Hypotension, Headache, Dizziness

D2 agonist

i. Phenoxybenzamine

Irreversibly blocks A1 and A2 receptors resulting to indirect baroreflex activation. Decreases blood pressure but increases heart rate due to baroreflex activation ; for Pheochromocytoma

Orthostatic hypotension, Reflex tachycardia, GI irritation

Irreversible blockade

ii. Phentolamine

Reversible A1 and A2 receptor antagonist with low

Orthostatic hypotension, Reflex tachycardia, GI irritation

Reversible blockade

xiv. Fenoldopam

xv. Bromocriptine

Sympatholytics

iii. Prazosin, Doxazosin, Terazosin

Blocks A1 but not A2 receptors; leads to reduction in blood pressure ; for Benign Prostatic Hyperplasia, Hypertension

Dizziness, Drowsiness, Headache, Weakness, Asthenia, Nausea, Palpitation, Edema, Orthostatic hypotension

Used in patients with HTN and BPH at the same time

iv. Tamsulosin

Slightly selective A1a blockade causing relaxation of prostatic smooth muscles > vascular smooth muscle ; for BPH

Headache, Orthostatic hypotension, Rhinitis, Abnormal ejaculation, Dizziness, Arthralgia, Infection

Slightly selective A1a blockade causing relaxation of prostatic smooth muscles > vascular smooth muscle

vi. Labetalol

Beta blockade > A1 blockade; still with BP depressant effects and limited HR increase

safe in pregnant patients

vii. Propranolol, Nadolol, Timolol

Blocks B1 and B2 receptors; lowers both HR and BP and reduces the release of renin ; for Angina prophylaxis, hypertension, arrhythmias, migraine, performance anxiety, hyperthyroidism

Bronchospasm, cardiac depression, AV block, hypotension, dizziness, headache; Use in caution with DM Px: Masks symptoms of hypoglycemia in diabetics

Propranolol has local anesthetic effect

viii. Metoprolol, Atenolol, Alprenolol, Betaxolol, Nebivolol

B1 > B2 blockade; lowers both HR and BP, reduces the release of renin BUT is considered safer for patients with asthma ; for Angina prophylaxis, hypertension, arrhythmias, migraine, performance anxiety, hyperthyroidism

Nebivolol has vasodilating effect ; metoprolol reduce moratlity in heart failure

x. Pindolol, Acebutolol, Carteolol, Bopindolol, Oxprenolol, Celiprolol, Penbutolol

B1, B2 with intrinsic sympathomimetic (partial agonist) effect; lowers BP with modest reduction in HR

Pindolol is a partial agonist, therefore safer in bronchial asthma

xi. Carvedilol, Medoxalol, Bucindolol, Labetalol

Beta blockade > A1 blockade; still with BP depressant effects and limited HR increase ; for Heart Failure

Carvedilol reduce mortality in heart failure

xii. Esmolol

B1 > B2 blockade; for rapid control of BP and arrhythmias, thyrotoxicosis and myocardial ischemia intraoperatively ; for Supraventricular tachycardia

Used in for perioperative thyroid storm

2. CARDIOVASCULAR-RENAL DRUGS Antihypertensives A. Diuretics

i.Thiazide: Hydrochlorothiazide, Chlorthalidone,

lower BP by decreasing volume and a direct vascular effect that is not yet fully understood Inhibit Na/Cl transporter in distal convoluted tubule. Cause moderate diuresis and reduced excretion of calcium; for mild to moderate hypertension (FIRST LINE), Heart failure, Nephrogenic Diabetes Insipidius,

Hypokalemic metabolic alkalosis, Dilutional hyponatremia, Potassium wasting, hyperlipidemia, hyperuricemia, sulfa allergy,

causes hypercalcemia in contrast with loop diuretics which cause hypocalcemia ; FIRST LINE for mild

Inhibit Na/K/2Cl transporter in thick ascending limb of loop of Henle, Cause powerful diuresis and increased CA excretion; for heart failure, hypertension, acute renal failure, Pulmonary edema, hypercalcemia, Anion overdose decrease venous return, decrease HR, decrease contractile force, decrease cardiac output, decrease TPR

Hypokalemic metabolic alkalosis, Potassium wasting, ototoxicity, hyperuricemia, nephrotoxicity, dehydration, hypomagnesemia, sulfa allergy

causes hypocalcemia in contrast with thiazide diuretics which cause hypercalcemia

i.Sympathetic Outflow Blocker: Clonidine, Methyldopa

activates a2 adrenergic receptors ; for hypertensive urgency (clonidine), pre eclampsia (methyldopa)

dry mouth, sedation, rebound hypertension, hemolytic anemia: (+) Coomb's test (methyldopa), sedation

Taper use prior to discontinuation to avoid rebound hypertension ; readily enter the CNS

ii. Ganglion blockers: Hexamethonium,Trimethaphan

competetively blocks Nn nicotinic Ach receptors; for hypertension (obsolete), hypertensive emergencies

Postural hypotension, blurred vision, constipation, dry mouth, sexual dysfunction

NONE

Reserpine Irreversibly blocks the vesicular monoamine transporter (VMAT) while Guanethidine and Guanadrel inhibit the vesicular release of NE from the presynaptic neuron; for Hypertension (obsolete)

Sedation, suicidal ideation, severe psychiatric depression

ii. Loop: Furosemide, Torsemide, Bumetanide, Ethacrynic Acid

B. Sympathoplegics

iii. Nerve terminal blockers: Reserpine, Guanethidine, Guanadrel

iv. Adrenergic antagonists: Prazosin,Doxazosin, Terazosin, Tamsulosin, Silodosin

selectively blocks a1 adrenergic receptors; for hypertension, benign prostatic hyperplasia

NONE

Reflex tachycardia (less chance), first dose o rthostatic hypotension

Tamsulosin is most selective for prostatic smooth muscle ; Doxazosin and Terazosin has longer duration of action than prazosin

Edema, myocardial ischemia, drug induced lupus (hydralazine), reflex tachycardia

combination treatment with ISDN for heart failure is more effective than ACEIs in blacks

Edema, Angina, Reflex tachycardia, Pulmonary hypertension, Pericarditis, Hirsutism, salt and water retention

require concomitant use of diuretics and BBs to block compensatory responses

Constipation, Nausea, flushing,gingival hyperplasia, AV block, sinus node depression, Pretibial edema, dizziness

excessive cardiac depression may occur

C. Vasodilators

i. Oral Vasolidator: Hydralazine

Minoxidil

Release NO from endothelial cells, Relaxes arteriolar smooth muscle, causing vasolidation. Decreases afterload ; for pre-eclampsia, hypertension, heart failure Opens K+ channels in vascular smooth muscle, causing hyperpolarization, muscle relaxation and vasolidation; for alopecia / male pattern baldness, hypertension

ii. Calcium Channel Blockers Non-dihydropyridine calcium channel blocker: Verapamil, Diltiazem Dihydropyridine calcium channel blocker: Nifedipine,

block voltage-gated L-type calcium channels (cardiac > vascular); for Angina, Supraventricular tachycardia, migraine, hypertension

iii. Parenteral Vasodilators

hypotension, headache, CN toxicity

not commonly used because it is very light sensitive, has short Duration of action ; given as continuous infusion

Diazoxide

Opens K+ channels in vascular smooth muscle, causing hyperpolarization, muscle relaxation and vasolidation; for hypertension

hypotension, headache

a thiazide derivative without a diuretic effect ; also reduces insulin release (can be used to treat hypoglycemia in insulin-producing tumors)

Fenoldopam

causes arteriolar vasolidation of the afferent and efferent arterioles. Increases renal blood flow; for hypertensive emergency

hypotension, hypokalemia

short duration of action: 10mins

i. ACE inhibitors: Captopril, Enalapril, L isinopril, Benazepril

inhibit angiotensin converting enzyme ; for hypertension, heart failure

cough, hyperkalemia, rash, hypotension, palpitations, renal damage in patients with preexisting renal vascular disease but is protective for DM nephropathy ; CI in pregnancy

slows down the progression of DM nephropathy and cardiac remodelling in heart failure

ii. Angiotensin receptor blocker: Losartan, Valsartan, Irbesartan, Candesartan

competetively blocks Angiotensin 1 receptor site ; for hypertension

fatigue / weakness, hypoglycemia, anemia, diarrhea, cough, CI in pregnancy

as effective as ACEi but less cough

inhibitor of renin's action on its substrate angiotensinogen

diarrhea, cough, rash, hyperkalemia, increase in serum c reatinine, renal impairment, angioedema

no reproductive toxicity but is also CI because of the toxicity of ACEi and ARBs

releases nitric oxide (NO), relaxes smooth muscle, especially vascular, increases cGMP (cyclic guanosine monophosphate); for cyanide poisoning

Reflex tachycardia, Orthostatic hypotension, methemoglobinemia

inhalational route, but now rarely used

Reflex tachycardia, orthostatic hypotension, headache, tolerance (transdermal)

Dangerous hypotension with PDE inhibitors such as Sildenafil ; First Pass effect is ~90% (NTG), NTG also decrease platelet aggregation

Nitroprusside

relaxes venous and arteriolar smooth muscle; for acute heart failure, controlled hypotension, cardiogenic shock, hypertensive emergency

D. Angiotensin antagonists and renin inhibitor

iii. Renin inhibitor: Aliskerin Vasodilators and anti-Angina Pectoris A. Nitrates

i. Ultrashort-acting nitrate: Amyl Nitrite

ii. Short-acting nitrate: Nitroglycerin, Isosorbide Dinitrate, Isosorbide Mononitrate

releases nitric oxide (NO), increases cGMP (cyclic guanosine monophosphate) and relaxes smooth muscle especially vascular; for Angina, acute c oronary syndromes

B. Calcium Channel Blockers i. Non-dihydropyridine calcium channel blocker: Verapamil, Diltiazem

block voltage-gated L-type calcium channels (cardiac > vascular); for Angina, Supraventricular tachycardia, migraine, hypertension

Constipation, Nausea, flushing,gingival hyperplasia, AV block, sinus node depression, Pretibial edema, dizziness

excessive cardiac depression may occur

ii. Dihydropyridine calcium channel blocker: Nifedipine, Amlodipine, Nicardipine, Nisoldipine, Isradipine, Felodipine

block voltage-gated L-type calcium channels (vascular > cardiac); for Angina, hypertension

Nausea, Flushing, dizziness, pretibial edema, constipation

greater vasodilator effect that cardiodepressant effect

inhibits Na/K ATPase; increases intracellular Ca, increasing cardiac contractility; for heart failure, Nodal arrythmias

Narrow therapeutic index, Arrhythmias, diarrhea, vomiting, visual changes

Arrhythmogenesis increased by hypokalemia, hypercalcemia, hypomagnesemia

Use- and state-dependent block of INa c hannels; some block of Ik channels. Slowed conduction velocity and pacemaker activity; prolonged action potential duration and refractory period; for atrial and ventricular arrhythmias especially after myocardial infarction

Arrhythmias, lupus-like syndrome (procainamide), hypotension, cinchonism (quinidine), thrombocytopenia (quinidine), antimuscarinic effect (disopyramide), quinidine reduces digoxin clearance

Hyperkalemia exacerbates cardiac toxicity

CNS stimulation, Allergy, Arrhythmias, depression, Agranulocytosis

Hyperkalemia, exacerbates cardiac toxicity. Lidocaine is the least cardiotoxic among conventional anti-arrhythmics ; only affect ischemic tissue; lidocaine is never given P.O due to significant first pass effect

Drugs used in Heart Failure

A. Cardiac Glycoside

i. Digoxin

Other drugs for heart failure include Diuretics (Furosemide is the DOC for acute heart failure), Angiotensin Antagonists (ACEi is the DOC for chronic heart failure), Beta1 blockers (dopamine and dobutamine), Non-selective Beta Blockers (Carvedilol, Labetalol, Metoprolol), PDEi (Inamrinone, Milrinone), Vasodilators (Nitroprusside, Nitroglycerin)

Anti-Arrhythmics A. Class 1 Antiarryhtmics

i. Class 1A: Proc ainamide, Disopyramide, Quinidine,

ii. Class 1B: Lidocaine, Mexiletene, Tocainide, Phenytoin

highly selective use and state-dependent INa block; minimal effect in normal tissue; no effect on IK; DOC for ventricular arrhythmia post-myocardial infarction, Digoxin-induced arrhythmia ; Mexilitine can be used for neuropathic pain Selective use and state-dependent block of INa;

hyperkalemia exacerbates cardiac

B. Class 2 Antiarrythmics

i. Propranolol, Esmolol

Block of beta-receptors, decrease in cAMP results to decreased Na and Ca current and suppression of cardiac pacemaker activity; for Post MI prophylaxis against sudden death, thyrotoxicosis, acute perioperative and thyrotoxic arrhythmias, Supraventricular tachycardia

Bronchospasm, AV block, Hypotension, Cardiac depression

C. Class 3 Arrhythmics

In CHF, reduces progression and decreases incidence of potentially fatal arrhythmias. Sotalol is a betablocker anti arrhythmic that has class 3 properties Group with the greatest risk for TDP

ii. Sotalol

Selective Ik block ; prolonged action potential and QT interval; for treatment and prophylaxis of atrial fibrillation Ik block and beta-adrenoceptor block; for ventricular arrhythmias, Supraventricular tachycardia, Atrial fibrillation

iii. Amiodarone, Dronedarone

Strong Ik block produces marked prolongation of action potential and refractory period. Group 1 activity slows conduction velocity; groups 2 and 4 activity confer additional anti arrhythmic activity; for refractory arrhythmia, used off label in many arrhythmia

Microcrystalline deposits in cornea and skin, paresthesias, Pulmonary fibrosis, Tremor, Thyroid dysfunction (hyper- or hypo-)

Amiodarone has Class 1, 2 3 and 4 activity therefore is the MOST EFFICACIOUS of all anti-arrhythmics, amiodarone has longest among all anti-arrhythmics (1-10 weeks)

Block voltage-gated L-type calcium channels (cardiac >vascular), decreased AV conduction velocity ; for Angina, Hypertension, Supraventricular tachycardia, migraine, Raynaud's Phenomenon, Vasospasm

Constipation, Pretibial edema, Nausea, Flushing, Gingival hyperplasia, heart failure, AV block, dizziness, sinus node depression

should be avoided in Ventricular tachycardia

Increase in diastolic Ik of AV node that causes marked hyperpolarization and conduction block; reduced ICa; For AV nodal arrhythmias, DOC for paroxysmal supraventricular tachycardia

Flushing, Transient chest pain, Dyspnea, Hypotension

DOC for paroxysmal supraventricular tachycardia, Duration of action is only 15sec

Inhibits carbonic anhydrase. In proximal tubule, In glaucoma, secretion of aqueous humor is reduced and in mountain sickness, metabolic acidosis increases respiration; for glaucoma, diuresis for edema with

Drowsiness, Sulfa Allergy, Renal calcium stones, Paresthesias, hyperchloremic metabolic acidosis, hepatic encephalopathy in

diuresis is self-limiting after 2-3

i. Dofetilide, Ibutilide,

Torsade de pointes

NONE

Dose-related torsade de pointes, excessive beta-blockade (sinus bradycardia, asthma)

NONE

D. Class 4 Antiarrythmatics

i. Non-dihydropyridine calcium channel blocker: Verapamil, Diltiazem E.Miscellaneous Antiarrythmics

i. Adenosine Diuretics A. Carbonic Anhydrase Inhibitors

i. Acetazolamide, Dorzolamide, Brinzolamide,

B. Loop Diuretic

Hypokalemic metabolic alkasis, dehydration, Ototoxicity, Potassium wasting, Sulfa allergy, Hyperuricemia, Hypocalcemia, Hypomagnesemia, Nephritis

Synergistic ototoxicity with aminoglycosides. Efficacy decreased by NSAIDs ; causes hypocalcemia in contrast with thiazide diuretics which cause hypercalcemia

Inhibit Na/Cl transporter in distal convolutes tubes. Causes moderate diuresis and reduced excretion of calcium; For hypertension Hypercalciuria, Heart failure, Nephrogenic diabetes insipidius, renal calcium stones

Hypokalemic metabolic alkalosis, Potassium wasting, dilutional hyponatremia, Hyperglycemia, hyperuricemia, sulfa allergy, hyperlipidemia

Synergistic effect with loop diurectics. Efficacy decreased by NSAIDs ; causes hypercalcemia in contrast with loop diuretics which cause hypocalcemia

i. Spironolactone, Eplerenone (Aldosterone Antagonist)

Steroid inhibitors of cytoplasmic aldosterone receptor in cortical collecting ducts. Reduce K excretion; for Hyperaldosteronism, Heart failure, Hypokalemia, Hypertension

Hyperkalemia, impotence, Benign prostatic hyperplasia, Hyperchloremic metabolic acidosis, anti-androgenic effect (Spironolactione)

Eplerenone reduces progression of DM nephropathy and reduces mortality post MI

ii. Amiloride, Triamterene (Na channel Blocker)

Inhibitor of ENaC (Epithelial sodium channels) in cortical collecting duct, reduces Na reabsorption and K excretion; for hypokalemia

Hyperkalemia, kidney stones, metabolic acidosis, Acute renal failure (with indomethacin), should never be given with potassium supplements

should never be given with potassium supplements

Osmotically retains water in tubule by reducing reabsorption in proximal tubule, descending limb of Henle's loop, and collecting ducts; in the periphery, mannitol extracts water from cells; for Rhabdomyolysis, Hemolysis, Increased intracranial pressure, Acute glaucoma

Transient volume expansion (hyponatremia, pulmonary edema; followed by hypernatremia) nausea, headache, dehydration, vomiting

used to maintain high urine flow

Hypertension, Hyponatremia

Increases the factor VIII activity of patients with mild hemophilia A or von Willebrand disease

i.Furosemide, Bumetanide, Torsemide

Inhibit Na/K/2Cl transporter in thick ascending limb of loop of Henle, Cause powerful diuresis and increased Ca excretion; for Heart failure, Hypertension, Pulmonary Edema, Hypercalcemia, Acute renal failure, Anion overdose

C. Thiazide Diuretics

i. Hydrochlorothiazide, Chlorthalidone, Indapamide, Metolazone D. Potassium-Sparing Diuretics

E. Osmotic Diuretics

i. Mannitol, Glycerin, Isosorbide, Urea F. ADH Agonists/ Antagonists

i. Antidiuretic hormone, Desmopressin, Vasopressin

Agonists at V1 and V2 ADH receptors. Activate insertion of aquaporin water channels in c ollecting tubule. Vasoconstriction; For central diabetes insipidus, hemophilia, Nocturnal enuresis, von Willebrand's disease

G. ADH Antagonists: Conivaptan, Tolvaptan, Lixivaptan, Demeclocycline, Lithium

Antagonist at V1, V2 receptors; for SIADH and Hyponatremia

Infusion site reactions, hyperkalemia, Nephrogenic diabetes insipidus, Bone and Teeth abnormalities(demeclocycline), Renal failure (Lithium, demeclocycline)

Central Pontine Myelinosis may occur with rapid correction of hyponatremia

3. DRUGS WITH IMPORTANT ACTION ON SMOOTH MUSCLES Histamine, Serotonin and the Ergot Alkaloids A. H1 antagonists

diminish or abolish the major actions of histamine in the body by competitive, reversible blockade of histamine H1-receptor sites on tissues ; used primarily for the alleviation of conditions such as urticarial rashes and nasal allergy that are characterised by type I hypersensitivity ; are of value in preventing urticaria and are used to treat urticarial rashes and mild angioedema

Sedation, should not be given to neonates because they are more susceptible to antimuscarinic effects

Possess antimuscarinic, adrenalineantagonising, serotonin antagonising, and local anaesthetic effects. Some have calcium-channel blocking activity ; Sedating antihistamines may enhance the sedative effects of CNS depressants including alcohol, barbiturates, hypnotics, opioid analgesics, anxiolytic sedatives, and antipsychotics ; all are PO but can be given topical (nose and eyes) ; negligible effect on H2 receptors

i. 1st Generation: Diphenhydramine, Dimenhydrinate, Chlorpheniramine, Meclizine, Promethazine

Reversible blockade of histamine H1-receptor sites on tissues ; anti-nausea and antiparkinsonism effect, for allergic reactions, for sedation and motion sickness (Diphenhydramine Dimenhydrinate, Cyclizine, Meclizine, Promethazine), for chemotherapy-induced vomiting (Diphenhydramine)

Anticholinergic effects, orthostatic hypotension (promethazine), sedation

more likely to block autonomic receptors, also has alpha1 blocking and local anesthetic effect ; Cyclizine (more anti-motion sickness action less sedative and and autonomic effects); Promethazine (less anti-motion sickness, more sedative and autonomic effects ; Usual half-life: 4-12h

ii. 2nd G eneration: Loratadine, Desloratadine, Cetirizine, Levocertirizine, Fexofenadine

Reversible blockade of histamine H1-receptor sites on tissues ; for allergic reactions

headache, dry mouth, hyperkinesia, malaise, may cause arrhythmia due to blockade of cardiac potassium channels (acrivastine, astemizole, cetirizine, loratadine, and terfenadine)

No sedation and antimuscarinic effects ; usual half-life: 12-24h

B. H2 antagonists

No blocking action on H1 receptor

i. Cimetidine, Ranitidine, Famotidine, Nizatidine

Surmountable competitive pharmacologic block of H2 receptors, reduction of nocturnal acid secretion in gastirc and duodenal ulcer, accelerate healing and prevent recurrences ; for PUD, GERD and ZES

CYP450 inhibitor, antiandrogen effects, decreased hepatic blood flow (cimetidine), weak enzyme inhibitory effect (Ranitidine)

used in the ICU setting to prevent gastric erosion and hemorrhage ; usual half-life: 1-3h

Agonist at the 5HT1D receptor in the blood vessels causing vasocontriction ; 1st line treatment for Acute migraine and cluster headache attacks

Injection site reaction, paresthesia, dizziness, warm/hot sensation, chest pain, coronary vasospasm

all are per orem only except for Sumatriptan which can also be given intranasally, transdermal and IV ; All has 2-27hrs DOA exc for sumatriptan DOA: 2-4h

i. 5HT3 receptor antagonist: Ondansetron, Granisetron, Dolasetron, Alosetron

Selectively block 5HT3 receptors ; For antiemesis in patients post-chemotherapy or post-operation

Constipation, headache, malaise

Dolasetron can increase QRS and QT (proarrhythmic effect) duration so never use in patients with heart disease

E. Ergot Alkaloids

most are partial agonists at alpha receptors and 5HT receptors but some are potent agonist at dopamine receptors

C. Serotonin Agonists i. 5HT1D receptor agonist: Sumatriptan, Naratriptan, Almotriptan, Eletriptan, Frovatriptan, Rizatriptan, Zolmitriptan

D. Serotonin Antagonists

i. Vasoselective: Ergotamine

Mixed partial agonist effects at 5-HT2 and aadrenoceptors, causes vasoconstriction; For Migraine attacks (but 5HT1D are preferred)

gangrene (secondary to ischemia) in overdose, unusual hyperplasia of the retroperitoneal, retropleural or subendocardial cavity --> hydronephrosis, cardiac valvular and c onduction system malfunction

can cause epinephrine reversal due to partial agonist effect on alpha receptors (REMEMBER: All partial agonist will act as antagonist in the present of a full agonist)

ii. Uteroselective: Ergonovine

Mixed partial agonist effects at 5-HT2 and aadrenoceptors, causes vasoconstriction; For control of post-partum bleeding

marked uterine contraction, GI upset (nausea, vomiting, diarrhea)

uterus becomes more sensitive to ergots during pregnancy, produce very powerful and long-lasting contraction leading to decreased bleeding, Never give before delivery of placenta

The Eicosanoids: Prostaglandins, Thromoboxanes, Leukotrienes and related compounds A. Prostaglandin E1 analog i. Misoprostol, Gemeprost

PGE1 analogue, activated EP receptor, causes increased HCO3 and mucus secretion in stomach and uterine contraction; For prevention of ulcer in patients who take high doses of NSAIDs due to arthritis, abortifacient

Abdominal pain, Uterine cramping, teratogen, miscarriage

Misoprostol's intended use is for NSAID-induced gastritis, may also be used together with Mifepristone or Methotrexate as safe abortifacient

ii. Alprostadil

PGE1 analogue, causes vascular smooth muscle relaxation and vasolidation; For Maintenance of patent ductus arteriosus (PDA), Erectile dysfunction

Apnea, hypotension, priapism, lightheadedness, arrhythmia

given as injection into the cavernosa for erectile dysfunction

Low concentrations contract, higher concentrations relax uterine and cervical smooth muscle, soften cervix at term before induction with oxytocin; For cervical ripening, induction of labor, abortifacient

Cramping, Fetal trauma

approved abortifacient in the 2nd trimester, although effective in inducing labor, it produces more SE than other oxytocics

PGF2a analogue, increases outflow of aqueous humor thus reduces intraocular pressure; For glaucoma

vomiting, diarrhea, transient bronchoconstriction

Latanoprost may cause changes in the color of the iris and may lengthen eyelashes

PGI2 analogue, activates IP receptor, causes vasolidation and reduces platelet aggregation; For severe pulmonary Hypertension and reducing platelet aggregation in dialysis machines

Hypotension, headache, flusing

used primarily for pulmonary hypertension (esp Treprostinil IV)

B. Prostaglandin E2 analog i. Dinoprostone, Sulprostone

C. Prostaglandin F2a analog i. Latanoprost, Arboprost, Bimatoprost, Travoprost, Unoprostone D. Prostaglandin I2 analog i. Epoprostenol, Beraprost, Iloprost, Treprostinil

E. Leukotriene antagonists i. Lipoxygenase inhibitor: Zileuton

see entry on Drugs used for Asthma

ii. LT receptor blocker: Montelukast, Zafirlukast


F. Corticosteroids


G. Non-steroidal anti-inflammatory drugs

see entry on Analgesics

Drugs used in Asthma A. Beta2-selective agonist (short-acting) i. Albuterol/Salbutamol, Levalbuterol, Terbutaline, Metaproterenol, Pirbuterol, Procaterol, Fenoterol

Activates beta2-receptors in bronchial smooth muscle leading to bronchodilation ; DOC for acute asthma attacks

Tachycardia, Nervousness, tremors, restlessness, arrhythmias when used excessively, loss of responsiveness (tolerance, tachyphylaxis)

Increase toxicity when used for COPD (May precipitate arrythmias) and in patients with heart disease; usual DOA: 2-4hrs, all are given inhalational, Salbutamol and terbutaline is also available PO, terbutaline can also be given IV

Activates beta2-receptors in bronchial smooth muscle leading to bronchodilation, potentiates corticosteroid action; For Asthma prophylaxis

Tachycardia, Nervousness, tremors, restlessness, arrhythmia when used excessively, loss of responsiveness (tolerance, tachyphylaxis)

Increase asthma mortality when used alone; May precipitate arrhythmias; usual DOA: 12hrs

Blocks muscarinic receptors in bronchial smooth muscle and prevent bronchoconstriction mediated by vagal discharge; For acute BA attack and COPD

anti-muscarinic effects (dry mouth, blurred vision etc.)

More effective and less toxic than beta agonists for COPD, Tiotropium has longer DOA than Ipratropium, Ipratropium given as aerosol has little systemic effects, has no effect on the chronic inflammation aspect of BA

Phosphodiesterase inhibitor, Adenosine receptor antagonist, causes bronchodilation and increased strength of contraction of diaphragm; For asthma especially in nocturnal attacks, Intermittent claudication (pentoxifylline), very useful in COPD

CNS stimulation (Insomnia, seizure, Anorexia), Cardiac stimulation (Arrhythmias), Tremors, increased BP, diuresis, inc GI motility

Antidote in overdosage is BB. Higher clearance in adolescents and smokers. Narrow therapeutic window; usual DOA: 12hrs

Prevents calcium influx and stabilizes mast cells, preventing degranulation and release of histamine, leukotrienes and mediators; for Asthma prophylaxis and allergies (oral, nasal and ophthalmic drops)

Cough, Airway irritation

No bronchodilator action but can prevent bronchoconstriction caused by antigens (both in the early and late BA responses), unusually

B. Beta2-selective agonist (long acting) ii. Salmeterol, Formoterol, Cleneterol, Bambuterol

C. Muscarinic receptor agonist i. Ipratropium, Tiotropium

C. Methylxanthine i. Theophylline, Aminophylline, Pentoxifylline

D. Mast cell Stabilizer i. Cromolyn, Nedocromil, Lodoxamide

E. Corticosteroid i. Fluticasone, Beclomethasone, Budesonide, Flunisolide, Mometasone, Triamcinolone, Ciclosenide

Inhibit synthesis of arachidonic acid by inhibiting Phospholipase A2, Reduces expression of COX and LT, inc responsiveness of Beta receptors in the a irway, bind to intracellular receptors and activate Glucocorticoid response elements in the nucleus leading to synthesis of substances that prevent full expression of inflammation and allergy ; DOC for Asthma prophylaxis, First line treatment for moderate to severe BA, COPD, Allergic rhinitis, also used as anti-inflammatory for other conditions such as auto-immune diseases and cancer, also f or immune suppression

Oropharyngeal candidiasis, mild growth retardation observed in children, Minimal systemic steroid steroid toxicity (eg, adrenal suppression), Mild growth retardation

For status asthmaticus: use IV prednisolone or hydrocortisone ; prednisolone is the active metabolite of prednisone

Inhibitor of 5-lipoxygenase. Reduces synthesis of leukotrienes. Prevents airway inflammation and bronchoconstriction; For asthma prophylaxis

Flulike syndrome, headache, drowsiness, dyspepsia, hepatitis, elevation of liver enzymes (more than LT receptor blockers)

No bronchodilator action, not recommended for acute BA attack

Blocks leukotriene-1 receptor, prevents airway inflammation and bronchoconstriction; For asthma prophylaxis

Gastrointestinal upset, Insomnia, elevation of liver enzymes

No bronchodilator action, not recommended for acute BA attack

Binds IgE antibodies on sensitized mast cells and prevents activation by BA triggers and subsequent release of inflammatory mediators; For prophylaxis of severe, refractory asthma not responsive to all other drugs

Long term toxicity not yet well documented

humanized murine monoclonal antibody, very expensive and only administered IV

F. Leukotriene synthesis inhibitor i. Zileuton

G. Leukotriene Antagonist i. Montelukast, Zafirlukast, Pranlukast

H. Anti-IgE antibody i. Omalizumab

4. DRUGS THAT ACT ON THE CENTRAL NERVOUS SYSTEM Sedative-Hypnotics A. Short-acting benzodiazepines bind GABA-A receptor subunits to increase frequency of chloride channel opening which causes membrane hyperpolarization ; For acute anxiety, panic attacks,

causes anterograde amnesia, decreased psychomotor skills,

additive CNS depression if used with ethanol, antihistamines, antipsychotics, opioids and TCAs, decreased REM sleep, use lower

B. Intermediate-acting benzodiazepines

i. Lorazepam, Alprazolam, Estazolam, Clonazepam, Lormetazepam, Nitrazepam, Temazepam

bind GABA-A receptor subunits to increase frequency of chloride channel opening which causes membrane hyperpolarization; For anxiety disorders even panic disorders (Alprazolam and Clonazepam), insomnia (Estazolam), skeletal muscle relaxation, seizure disorders (Clonazepam), status epilepticus (Lorazepam), tranquilizers, Bipolar disorder (Clonazepam), infantile spasm (Clonazepam)

causes anterograde amnesia, decreased psychomotor skills, unwanted daytime sedation, tolerance, dependence liability and unwanted daytime sedation.

additive CNS depression if used with ethanol etc, decreased REM sleep, High dose BZD and Barbs may suppress seizure but at the expenses of marked sedation EXCEPT Clonazepam and Phenobarbital, Lorazepam is preferred over Diazepam in Status Epilepticus due to its long distribution halflife, use lower doses in the elderly when used for insomnia

causes anterograde amnesia, decreased psychomotor skills (esp Diazepam and Flurazepam), unwanted daytime sedation, tolerance, dependence liability and rebound insomnia or anxiety.

additive CNS depression if used with ethanol etc., decreased REM sleep, Flunitrazepam is used as a date-rape drug, use lower doses in the elderly when used for insomnia

agitation, confusion, and precipitates benzodiazepine withdrawal syndrome for those with benzodiazepine dependence.

Seizures and arrhythmias may occur when administered in patients who took both TCAs and benzodiazepines

dependence liability is greater than benzodiazepine, acute intermittent porphyria.

additive CNS depression if used with ethanol etc., CYP450 inducer, Thiopental has highest lipid solubility

C. Long-acting Benzodiazepine

i. Diazepam, chlorazepate, chlordiazepoxide, flurazepam, quazepam, flunitrazepam

bind GABA-A receptor subunits to increase frequency of chloride channel opening which causes membrane hyperpolarization; For anxiety disorders, insomnia (Flurazepam), skeletal muscle relaxation (e.g. cerebral palsy - Diazepam), seizure disorders, tranquilizers, for status epilepticus (Diazepam), anesthesia (Diazepam), alcohol withdrawal (Diazepam and Chlordiazepoxide)

D. Benzodiazepine antagonist

i. Flumazenil

antagonist at benzodiazepine sites on GABA-A receptor ; for benzodiazepine overdose.

E. Ultrashort-acting barbiturates

i. Thiopental, Methohexital, Thiamylal F. Short and intermediate-acting barbiturates

bind to GABA-A receptor sites (distinct from benzodiazepines) to increase duration of chloride channel opening, block glutamic acid neurotransmission, at high doses can block NA channels ; For anesthesia induction (esp Thiopental)

i. Pentobarbital, secobarbital, amobarbital, butalbital, butabarbital, talbutal, aprobarbital

bind to GABA-A receptor sites (distinct from benzodiazepines) to increase duration of chloride channel opening, block glutamic acid neurotransmission, at high doses can block Na channels ; For insomnia and preoperative sedation (Secobarbital), for status epilepticus (Phenobarbital)

dependence liability is greater than benzodiazepine, acute intermittent porphyria.

additive CNS depression if used with ethanol etc., CYP450 inducer

dependence liability is greater than benzodiazepine, acute intermittent porphyria, severe respiratory and cardiovascular depression

additive CNS depression if used with ethanol, CYP450 inducer, Phenobarbital may be excreted unchanged in the urine, High dose BZD and Barbs may suppress seizure but at the expenses of marked sedation EXCEPT Clonazepam and Phenobarbital

day-after psychomotor depression, few amnestic effects; tolerance, dependence liability and withdrawal symptoms is less than that of benzodiazepines

lack anti-convulsant, anti-anxiety and muscle relaxant effects, effects are reversed with Flumazenil, very rapid onset of action, may dec. REM sleep, rebound inc on withdrawal from chronic use, increasing use due to rapid onset with minimal effects on the sleep pattern and cause less daytime cognitive impairment as compared to BZD

non-specific chest pain, tachycardia, palpitations, dizziness, nervousness, tinnitus, GI distress, paresthesias, dose-dependent pupillary constriction

minimal abuse liability, minimal CNS depressant effects, tolerance and withdrawal ; no anticonvulsant or muscle relaxant property ; slow onset of action (>1week), metabolized by CYP3A4, safe for pregnant patients

G. Long-acting barbiturate

i. Phenobarbital, mephobarbital, primidone

bind to GABA-A receptor sites (distinct from benzodiazepines) to increase duration of chloride channel opening, block glutamic acid neurotransmission, at high doses can block Na channels ; For insomnia, seizure disorders (Phenobarbital), status epilepticus (Phenobarbital)

H. Imidazopyridine sedative-hypnotics

i. Zolpidem, Zaleplon, Eszopiclone

bind selectively to a subgroup of GABA-A receptors, acting like benzodiazepines to enhance membrane hyperpolarization, only interact with GABA-A receptors with alpha-1 subunit ; For insomnia and sleep disorder esp. when sleep onset is delayed

I. Atypical Sedative-Hypnotics

i. Partial Serotonin Agonist: Buspirone

partial agonist at 5-HT1A receptors and possibly D2 receptors, precise MOA of anxiolytic effect is unkown ; For generalized anxiety disorders

ii. Melatonin receptor agonist: Ramelteon

activates melatonin receptors (MT1 and MT2 receptors) in the suprachiasmatic nuclei in the CNS --> decreased latency of sleep onset

Dizziness, fatigue, decreased testosterone, increased prolactin

minimal rebound insomnia or withdrawal symptoms, minimal abuse liability, metabolized by CYP450 (increased levels in the presence of CYP1A2 or CYP2D6 inhibitors

nystagmus, diplopia, sedation, gingival hyperplasia, hirsutism, anemias, peripheral neuropathy (absent DTRs), osteoporosis, fetal hydantoin syndrome, abnormalities in Vit D metabolism

CYP450 inducer , metabolism is non-linear (elimination shift from 1st order to zero order at moderate to high dose levels) , Fosphenytion is a water-soluble prodrug of phenytoin ; phenytoin is preferred in prolonged therapy for status epilepticus because it is less sedating.

diplopia, cognitive dysfunction, drowsiness, ataxia, blood dyscrasias, Stevens-Johnson syndrome, erythematous rash, teratogen (spina bifida and craniofacial anomalies), hyponatremia (Oxcarbazepine)

CYP450 inducer, Oxcarbazepine has less drug interactions, metabolism may be inhibited by other drugs such as Propoxyphene and valproic acid ; may be used for acute manic phase and as prophylaxis in the depressive phase

drowsiness, nausea, tremor, alopecia, weight gain, hepatotoxicity (esp in infants), neural tube defects

CYP450 inhibitor ; also have the same effect on Ca currents like Ethosuximide ; Other MOA include enhancing K channel permeability ; BZDs are commonly required at initiation therapy of valproic acid ; DOC for acute manic illness

cognitive dysfunction, dependence

May also act on Na channels and as antagonist at some glutamate receptors ; primary anticonvulsant in infants, children and pregnant patients

Antiseizure Drugs

i. Phenytoin, Fosyphenytoin, Mephenytoin, Ethotoin

ii. Carbamazepine, Oxcarbazepine

iii. Valproic acid

iv. Phenobarbital

block voltage-gated Na channel ; DOC for generalized tonic-clonic seizures, DOC for partial seizures, status epilepticus, arrhythmias, migraine

block voltage-gated Na channels and decreases glutamate release ; DOC for trigeminal neuralgia, DOC for generalized tonic-clonic seizures, DOC for partial seizures, for bipolar disorders

blocks high-frequency firing of neurons which modifies amino acid metabolism ; DOC for bipolar disorder (acute mania), DOC for generalized tonicclonic seizures and absence seizure, partial seizures, myoclonic seizures, also used for Bipolar disorders

see notes above ; For status epilepticus in children inhibit low threshold (T-type) Ca c urrents esp in

vi. Diazepam

see entry on Sedative-Hypnotics

viii. Lamotrigine, Zonisamide

blocks Ca++ channels, increases GABA release ; For neuropathic pain such as postherpetic neuralgia, partial seizures, migraine blocks Na and Ca++ channels and decreases glutamate , Zonisamide only blocks Na channels ; For generalized tonic-clonic seizures, DOC for partial seizures, myoclonic seizures, absence seizures, bipolar disorder.

ix. Levetiracetam

Bind synaptic protein selectively inhibiting hypersynchronization of epileptiform burst firing ; For generalized tonic-clonic seizures, partial seizures

vii. Gabapentin, Pregabalin

dizziness, ataxia, nausea, rash, SJS / TE N (lamotrigine), severe skin reaction (Zonisamide)

eliminated in the kidneys in their unchanged form ; structural analogues of GABA but does not activate GABA receptor directly ; also have the same effect on Ca currents like Ethosuximide primarily undergoes glucuronidation reaction ; Lamotrigine may be used for ac ute manic phase and as prophylaxis in the depressive phase

dizziness, sedation, weakness, irritability, hallucinations, psychosis

It is not metabolized by CYP450 enzymes, eliminated in the kidneys in their unchanged form

dizziness, sedation, ataxia, nystagmus, tremor

drowsiness, dizziness, ataxia, psychomotor slowing, memory impairment, paresthesias, weight loss, acute myopia, glaucoma, myopia, urolithiasis ; felbamate causes hepatic failure and hematotoxic (can cause ITP, aplastic anemia)

Antiseizure drugs with the most number of MOA, undergo both hepatic and renal metabolism, Topiramate can also block Na channels and potentitae action of GABA and block glutamate receptor, Felbamate may also block glutamate receptors

xi. Vigabatrin

multiple actions on synaptic function, probably via actions on phosphorylation (Na, Ca, GABA, AMPAglutamate, carbonic anhydrase), Felbamate also facilitate the inhibitory actions of GABA but its exact MOA is still unknown ; For generalized tonic-clonic seizures, partial seizures, absence seizures, migraine ; Felbamate is only for severe refractory seizure states Irreversibly inactivates GABA aminotransaminase (GABA-T) which terminates the action of GABA ; For GTC seizure

visual field defects

None

xii. Tiagabine

Inhibits GABA transporter (GAT-1) in neurons and glia thus inhibiting its reuptake, leading to prolongation of GABA effects ; For partial seizures

asthenia or weakness, dizzines

None

x. Topiramate, Felbamate

General Anesthetics This group in general increase the threshold for firing of CNS neurons

A. Inhalational General Anesthetics

i. Nitrous Oxide

Facilitates GABA-mediated inhibition, block brain NMDA and Ach-N receptors; used as anesthesia for minor surgery and dental procedures

megaloblastic anemia on prolonged exposure; Euphoria (laughing gas), bronchodilation

Lowest Potency (highest MAC) and least cardiotoxic; additive CNS depression with many agents especially opioids and sedativehypnotics

ii. Desflurane

Facilitates GABA-mediated inhibition, block brain NMDA and Ach-N receptors ; For general anesthesia

bronchospasm, peripheral vasodilation

additive CNS depression with many agents especially opioids and sedative-hypnotics ; all inhaled anesthetcis cause bronchodilation except Desflurane

iii. Sevoflurane

Facilitates GABA-mediated inhibition, block brain NMDA and Ach-N receptors; For general anesthesia

peripheral vasodilation, renal insufficiency (due to Flourine release), bronchodilation

additive CNS depression with many agents especially opioids and sedative-hypnotics

iv. Isoflurane


catecholamine-induced arrhythmias, peripheral vasodilation, bronchodilation


v. Enflurane


spike-and-wave activity in EEG, muscle twitching, breath-holding, myocardial depression, renal insufficiency (due to Flourine release), dec cardiac output, bronchodilation

additive CNS depression with many agents especially opioids and sedative-hypnotics ; has pungent odor which limits its use

vi. Halothane


catecholamine-induced arrhythmias, myocardial depression, postoperative hepatitis, dec cardiac output, bronchodilation



renal insufficiency (due to Flourine release), bronchodilation

Highest potency and lowest MAC (very slow onset and recovery); additive CNS depression with many agents especially opioids and sedative-hypnotics

see notes above

are respiratory and circulatory depressants --> dec cerebral blood flow --> dec ICP

rapid entry into the brain (<1min)

see notes above

see notes above

Midazolam is a usual adjunct with inhalational anesthetics and IV opioids, has a slow onset but longer DOA

Blocks excitation by glutamate at NMDA receptors; For dissociative anesthesia (analgesia, amnesia and catatonia but with retained consciousness)

CV stimulation, hypertension, increased ICP, delirium, Dissociative anesthesia, post-op effects: disorientation, hallucination, excitation

Reduces delirium by pretreatment with benzodiazepine, congener of Phencyclidine / angel dust

Modulates GABA-A receptors containing beta3 subunits; For general anesthesia to patients with

pain at injection site, myoclonus, postoperative nausea and vomiting, adrenocortical suppression (on prolonged

Minimal effects on CV and respiratory functions, no analgesic

vii. Methoxyflurane B. Intravenous General Anesthetics i. Barbiturates: Thiopental, Methohexital, Thiamylal

ii. Benzodiazepine: Midazolam, Brotizolam, Triazolam, Oxazepam, Etizolam

iii. Phencyclidine derivative: Ketamine

v. Opioid analgesics: Fentanyl, morphine, alfentanil, remifentanil

vi. Propofol, Fospropofol

Interacts with mu, sigma, kappa receptors for endogenous opioid peptides ; For high r isk patients who might not survive general anesthesia

Potentiates GABA-A receptors, blocks Na c hannels; For prolonged sedation esp in ICU patients and also in OPD surgeries

respiratory depression, chest wall rigidity (which may cause impaired ventilation) and constipation

Antidote is Naloxone / Naltrexone ; Neuroleptanesthesia (analgesia + amnesia) happens when Fentanyl, Droperidol and Nitrous oxide are given together ; faster recovery with remifentanil ; these drugs have fast onset of action

bradycardia, vasodilation, hypotension, negative inotropism, pain at injection site, anterograde amnesia, dystonia, priapism, paresthesia (Fospropofol)

"milk of anesthesia", additive effects with sedative-hypnotic drugs ; as rapid as thiopental and also with fast recovery ; antiemetic action ; Fospropofol is the watersoluble prodrug form of propofol but with slower onset and recovery

Local Anesthetics this group can cause antibody formation in some patients

A. Ester Local Anesthetics i. Procaine

Blockade of Na channels slows which prevents axon potential propagation; For local anesthesia

light-headedness, sedation, restlessness, nystagmus, seizures, respiratory, CV depression

Shortest half-life among local anesthetics

ii. Benzocaine

Blockade of Na channels slows which prevents axon potential propagation; For local anesthesia, topical anesthesia


Use cautiously in sunburns, Topical only

iii. Cocaine

Blockade of Na channels slows which prevents axon potential propagation, with intrinsic sympathomimetic activity; For local anesthesia, topical anesthesia

light-headedness, sedation, restlessness, nystagmus, seizures, respiratory, CV depression, abuse liability, severe hypertension, cerebral hemorrhage, cardiac arrhythmia, MI

with intrinsic sympathomimetic activity so it does not need an alpha agonist (like epinephrine) to limit its systemic absorption; causes mood elevation due to action on dopamine receptor ; All local anesthetics are vasodilators EXCEPT cocaine ; Topical only

iv. Tetracaine

Blockade of Na channels slows which prevents axon potential propagation; For local anesthesia, spinal anesthesia, epidural anesthesia, topical ophthalmic anesthesia


also available as Ophthalmic solution

B. Amide Local Anesthetics

i. Lidocaine

Blockade of Na channels slows which prevents axon potential propagation; For local anesthesia, antiarrhythmia (group 1B activity), used for post-MI and for digitalis toxicity


Frequently administered with Epinephrine to avoid systemic absorption

ii. Prilocaine

Blockade of Na channels slows which prevents axon potential propagation; For local anesthesia, dental anesthesia


causes methemoglobinemia (antidote: methylene blue)

iii. Bupivacaine

Blockade of Na channels slows which prevents axon potential propagation; For local anesthesia, epidural anesthesia, intrathecal anesthesia

light-headedness, sedation, restlessness, nystagmus, seizures, respiratory, CV depression, severe CV toxicity, hypotension and arrhythmias

Use with caution in pregnant women and patients with cardiac disease (may cause heartblock, arrhyhtmia and hypotension)

iv. Ropivacaine

Blockade of Na channels slows which prevents axon potential propagation; For local anesthesia, epidural anesthesia

light-headedness, sedation, restlessness, nystagmus, seizures, respiratory, CV depression, cardiotoxicity

Longest half-life among local anesthesia

Agonist at Ach-N receptors causing initial twitch then persistent depolarization ; For skeletal muscle relaxation during intubation and general anesthesia

muscle pain, hyperkalemia, increased intragastric pressure leading to regurgitation (aspiration), increased intraocular pressure, malignant hyperthermia

Metabolized by pseudocholinesterase ; may cause malignant hyperthermia if given together with inhaled anesthetics

a common SE for this group is Histamine release

effects are easily reversed by giving AChE inhibitors such as Neostigmine

respiratory paralysis, apnea, and moderate histamine release

Metabolized by pseudocholinesterase; reverse effects with Neostigmine

respiratory paralysis, apnea, and moderate histamine release and bronchospasm

Undergoes Hoffman elimination (rapid spontaneous breakdown); reverse effects with Neostigmine ; converted to Laudanosine which can cause seizures

respiratory paralysis and apnea

Undergoes elimination in bile; reverse effects with Neostigmine

Skeletal Muscle Relaxant A. Depolarizing Neuromuscular Blocker

i. Succinylcholine

B. Non-Depolarizing Neuromuscular Blocker

i. Mivacurium (short-acting: 10-20mins DOA)

ii. Atracurium (intermediate-acting)

iii. Vecuronium (intermediate-acting)

Competitive antagonists at skeletal muscle nicotinic acetylcholine receptors; For skeletal muscle relaxation during intubation and general anesthesia

respiratory paralysis and apnea, hypersensitivity

reverse effects with Neostigmine; Suggamadex is a novel reversal agent for rocuronium; most rapid onset time (60-120 sec)

respiratory paralysis, apnea, hypotension and recurarization

Relatively contraindicated in myocardial ischemia; reverse effects with neostigmine

respiratory paralysis, apnea, tachycardia, hypertension, recurarization

Reverse effects with Neostigmine, may cause heart block

Levodopa is a dopamine precursor, c arbidopa inhibits peripheral metabolism via dopa decarboxylase; Drug of choice for parkinson’s disease

GI upset (emesis), dyskinesia (choreoathetosis), behavioural changes (anxiety, agitation, confusion, delusion), on-off phenomena, wearing-off phenomena, postural hypotension, tachycardia

Contraindicated in patients with history of psychosis; hypertensive crisis occurs when used with MAO inhibitors, ameliorates signs of parkinsonism and decreases mortality rate ; patient response decreases with time but is improved when given together with COMT inhibitors

Partial agonist at dopamine D2 receptors in brain; For Parkinson’s disease which is levodopa intolerance, hyperprolactinemia

anorexia, nausea, vomiting, dyskinesia, postural hypotension, behavioural changes, erythromelalgia (Bromocriptine), pulmonary infiltrate (Bromocriptine)

Ergot alkaloids

anorexia, nausea, vomiting, dyskinesia, postural hypotension, behavioural changes (more prominent compared to levodopa)

Contraindicated for patients with active peptic ulcer disease, psychotic illnesss or recent MI ; decrease dose in renal dysfunction ; Neuroprotective ; Ropirinole is metabolized by CYP1A2

iv. Rocuronium (intermediate-acting)

v. Tubocurarine (long-acting)

vi. Pancuronium (long-acting)

Competitive antagonists at skeletal muscle nicotinic acetylcholine receptors; For skeletal muscle relaxation during intubation and general anesthesia, euthanasia, lethal injection, strychnine poisoning

Anti-Parkinsonism and other drugs for movement disorders A. Dopamine Precursor

i. Levodopa-carbidopa B. Dopamine Agonist

i. Bromocriptine, Pergolide

ii. Pramipexole, Ropinirole

Partial agonist at dopamine D3 receptors in brain, Roprinole is a D2 agonist; For Parkinson’s disease

iii. Apomorphine

Partial agonist at dopamine D3 receptors, antagonist at 5-HT and alpha adrenoceptors; For off-periods of Parkinson’s disease, alcoholism, opiate addiction, erectile dysfunction, alzheimer’s disease

severe nausea, dyskinesia, hypotension, drowsiness and sweating

Premedicate with Trimethobenzamide to prevent severe nausea

Selective inhibitors of MAO type B leading to decreased degradation of dopamine, increases response to levodopa/carbidopa; Only as adjunct to levodopa for parkinson’s disease but Rasigiline can be given alone (more potent)

insomnia, mood changes, dyskinesias, GI distress and hypotension

serotonin syndrome occurs when used with SSRI and Meperidine ; Selegiline is hepatically metabolized into desmethyl selegiline (which is neuroprotective) and amphetamine

Block L-dopa metabolism by inhibiting catechol-Omethyltransferase in periphery and CNS, prolongs response to levodopa; used in the wearing-off phenomena of parkinson’s disease, as adjuncts to levodopa

dyskinesias, GI distress, postural hypotension, sleep disturbance, orange discoloration of urine, hepatotoxicity (tolcapone only), neuroleptic malignant syndrome, rhabdomyolysis

Entacapone only acts in the periphery while Tolcapone acts both in the periphery and CNS.

enhances dopaminergic transmission by unknown mechanism, maybe by influencing the synthesis, release or reuptake of dopamine; For Parkinson’s disease and influenza

behavioural changes (restlessness, agitation, insomnia, hallucination, psychosis), livedo reticularis, GI disturbances, urinary retention, postural hypotension, peripheral edema

May improve bradykinesia, rigidity and tremor ; has antimuscarinic action

drowsiness, inattention, confusion, delusions, hallucinations, atropine-like effects

Exacerbate tardive dyskinesias that result from prolonged use of antipsychotic drugs; improve tremor and rigidity with little effect on bradykinesia

C. MAO type B inhibitor

i. Selegiline, Rasagiline D. COMT inhibitor

i. Entacapone, Tolcapone E. Antiviral

i. Amantadine F. Anticholinergic

i. Benztropine, Biperiden, Trihexyphenidyl, Orphenadrine

Decrease the excitatory actions of cholinergic neurons on cells in the striatum by blocking muscarinic receptors; as adjunct for parkinson’s disease and extrapyramidal symptoms caused by antipsychotics

Antipsychotics and Lithium A. Typical Antipsyhotics

i. Phenothiazine: Chlorpromazine

may also be used for pruritus and as sedatives

Blocks D2 receptors >> 5-HT2 receptors; For schizophrenia and other psychotic disorders

has no effect on negative symptoms extrapyramidal dysfunction, tardive dyskinesia, hyperprolactinemia, atropine-like effects, failure of ejaculation, postural hypotension, marked sedation, corneal and lens deposits, neuroleptic malignant syndrome, contact dermatitis

prototype of all typical antipsychotics

ii. Other Phenothiazines: Thioridazine, Fluphenazine, Perphenazine, Prochlorperazine, Trifluoperazine

iii. Butyrophenol: Haloperidol, Droperidol B. Atypical Antipsychotics

Blocks D2 receptors >> 5-HT2 receptors; For schizophrenia and other psychotic disorders, antiemesis (prochlorperazine) Blocks D2 receptors >> 5-HT2 receptors; For schizophrenia and other psychotic disorders, huntington’s disease and tourette’s syndrome

extrapyramidal dysfunction, tardive dyskinesia, hyperprolactinemia, atropine-like effects, failure of ejaculation, postural hypotension, retinal deposits (thioridazine), cardiotoxicity (arrhythmias - thioridazine)

Thioridazine has the Strongest autonomic effects; only antipsychotic with fatal overdose ; Fluphenazine and Trifluoperazine have very significant parkinson-like effect ; Fluphenazine has less sedation compared to other antipsychotics

extrapyramidal dysfunction, tardive dyskinesia, hyperprolactinemia, neuroleptic malignant syndrome

causes the most extrapyramidal symptoms of all typical antipsychotics ; has the weakest autonomic effects

may be used for mania and psychotic symptoms in Alzheimer's dementia and Parkinsons disease

cure both negative and positive symptoms

i. Clozapine

Blocks 5-HT2 receptors >> D2 receptors; For schizophrenia (refractory, suicidal) and other psychotic disorders

Extrapyramidal dysfunction (less), hyperprolactinemia (less), postural hypotension, weight gain, hyperglycemia, hyperlipidemia, myocarditis, agranulocytosis, seizures, ileus, hypersalivation (sialorrhea)

Only antipsychotic that reduces the risk of suicide ; may be effective for drug-resistant types ; weight gain, agranulocytosis, seizure and hyperglycemia is prominent

ii. Olanzapine

Blocks 5-HT2 receptors >> D2 receptors; For schizophrenia, bipolar disorders, anorexia nervosa and depression

Extrapyramidal dysfunction (less), hyperprolactinemia (less), postural hypotension, weight gain, hyperglycemia, hyperlipidemia

weight gain and hyperglycemia is prominent, safe in pregnancy

iii. Quetiapine

Blocks 5-HT2 receptors >> D2 receptors; For schizophrenia, bipolar disorders (manic)

Extrapyramidal dysfunction (less), hyperprolactinemia (less), postural hypotension, weight gain, somnolence, fatigue, sleep paralysis, hypnagogic hallucinations, cataracts, priapism, QT prolongation (TDP)

can cause TDP, safe in pregnancy

iv. Risperidone

Blocks 5-HT2 receptors >> D2 receptors; For schizophrenia, bipolar disorders, depression, intractable hiccups, tourette syndrome

Extrapyramidal dysfunction (less), hyperprolactinemia (marked), insomnia, photosensitivity

Only antipsychotic approved for schizophrenia in the youth

v. Ziprasidone

Blocks 5-HT2 receptors >> D2 receptors; For schizophrenia, bipolar disorders (acute mania)

Extrapyramidal dysfunction (less), postural hypotension, QT prolongation (TDP)

Increased mortality in elderly patients with dementia-related psychosis ; can cause TDP

vi. Aripiprazole

Blocks 5-HT2 receptors >> D2 receptors; For schizophrenia, bipolar disorders, depression, autism, cocaine dependence

Extrapyramidal dysfunction (less), GI upset, tremor, hypersensitivity (rare)

Least sedating atypical antipsychotics

vii. Lithium (mood stabilizer)

Uncertain MOA but the proposed MOA is by inhibiting the enzyme involved in the recycling of neuronal membrane phosphoinositides which causes depletion of phosphatidylinositol bisphosphate, thus consequently decreasing IP3 and DAG --> decrease in neurotransmission ; For bipolar disorder, recurrent depression, schizoaffective disorder

Tremor, sedation, ataxia, aphasia, thyroid enlargement, hypothyroidism, reversible nephrogenic diabetes insipidus, edema, acneiform skin eruption, leukocytosis, teratogen (ebstein’s anomaly), bradycardia, some drugs (NSAIDs, ACEi, diuretis etc) can increase Lithium toxicity while caffeine and theophylline can decrease its toxicity

Contraindicated in sick sinus syndrome; treat overdose with hemodialysis ; high volume of distribution ; clinical benefit is seen only after weeks of use ; antipsychotic agents or BZDs are commonly required at initiation therapy of Li and valproic acid ; Contraindicated in lactation ; Natriuresis stimulates reflex increase in the reabsorption of Li and Na in the PCT

excessive sedation, fatigue, confusion, sympathomimetic effects, atropine-like effects, orthostatic hypotension, cardiomyopathies, arrhythmias, tremors, paresthesias, weight gain ; 3Cs of overdose: Coma, Cardiotoxicity, Convulsions

Additive depression of the CNS with other central depressants ; Imipramine is metabolized to desipramine while amitriptyline is metabolized to nortriptyline ; longterm use may lead to downregulation of Beta receptors leading to a decrease in BP and depression of cardiac conduction ; has significant muscarinic receptor blocking effect esp Amitriptyline ; lower seizure threshold ; may interfere with antihypertensive action of Clonidine

nausea, vomiting, headache, anxiety, agitation, drowsiness, insomnia, erectile dysfunction, EPS, QT prolongation ( citalopram),

Serotonin syndrome when used with MAOIs ; minimal inhibitory effect on cholinergic or adrenergic receptors ; lower seizure threshold ; this group can decrease appetite leading to weight loss ; Increased risk for suicide in children and adolescents ; Fluoxetine, Fluvoxamine and Paroxetine are

Antidepressants A. Tricyclic Antidepressants

i. Imipramine, Clomipramine, Desipramine, Amitryptyline, Nortryptiline

Block NE and 5-HT transporters leading to potentiation of NT action at postsynaptic receptors; For MDD (most effective), bipolar disorder, ac ute panic attacks, ADHD, chronic pain states, as sleeping aid, OCD (Clomipramine) ; this group is very useful for patients with psychomotor retardation, sleep disturbance, poor appetite and weight loss

B. SSRI

i. Fluoxetine, Paroxetine, Citalopram, Escitalopram,

Inhibits neuronal reuptake of serotonin by inhibiting Serotonin Transporter (SERT); DOC for OCD, for MDD, anxiety, panic attacks, phobias, PTSD, GAD, bulimia,

C. SNRI

i. Venlafaxine, Duloxetine, Desvenlafaxine

Inhibits neuronal reuptake of serotonin and norepinephrine by binding to transporters for both 5HT and NE; For MDD, fibromyalgia, neuropathic pain, menopausal symptoms

dizziness, insomnia, sedation, GI distress, hypertension (venlafaxine), hepatotoxicity (duloxetine), withdrawal syndrome even in just one missed dose, CNS stimulation (Venlafaxine), liver dysfunction (Duloxetine)

venlafaxine has less affinity for NE transporter than desvenlafaxine and duloxetine ; differ from TCA in lacking blockade of H1, M and alpha receptors ; Increased risk for suicide in children and adolescents

sedation, GI disturbance, orthostatic hypotension, priapism, hyperprolactinemia, liver dysfunction (nefazodone)

May cause arrhythmias in px with pre-existing cardiac disease ; short t1/2 so given BID to TID, has significant muscarinic receptor blocking effect esp Nefazodone ; CYP450 inhibitors ; Trazodone also has significant alpha1 and H1 blocking effect

D. Serotonin antagonist

i. Trazodone, Nefazodone

Blocks 5-HT2A receptors, weak inhibitor of NE and 5HT transporters; For MDD, as sleeping aid (trazodone)

Increased risk for suicide in children and adolescents

E. Tetracyclics

i. Amoxapine

Strong norepinephrine reuptake inhibitor and weak serotonin reuptake inhibitor, blocks dopamine D2 receptors; For MDD

autonomic effects, akathisia, parkinsonism (due to dopamine receptor blockade), seizures, cardiotoxicity

Lowers seizure threshold, has significant muscarinic receptor blocking effect

ii. Mirtazapine

Increases amine release from nerve endings by antagonism of presynaptic a2 adrenoceptors, also blocks serotonin 5-HT2A receptors; For MDD, appetite stimulation, as sleeping aid

weight gain, marked sedation, dizziness, blurred vision and nightmares

has significant muscarinic receptor and alpha2 blocking effect

iii. Bupropion

Inhibits neuronal reuptake of dopamine and norepinephrine, increase dopamine and norepinephrine activity; For MDD and smoking cessation, alcohol dependence

weight loss, agitation, anxiety, dizziness, dry mouth, aggravation of psychosis, seizures, priapism

Lowers seizure threshold, for smoking cessation ; no effect on 5HT or NE receptors or amine transporters ; CYP450 inhibitor

F. MAO Inhibitors

dizziness, insomnia, orthostatic hypotension, blurred vision, arrhythmia, diarrhea, hyperthermia, CNS stimulation, seizure

Hypertensive crisis when taken with tyramine-rich food, serotonin syndrome when taken with SSRI ; this group is structurally related to amphetamine ; CYP450 inhibitors ; longterm use may lead to downregulation of Beta receptors (leading to decrase in BP) ; lower seizure threshold ; selegiline may be given as skin patch

TRIAD: miosis, coma, respiratory depression

Additive CNS depression with other depressants

i. Morphine

Strong agonist at u receptors; For severe pain, pain associated with acute MI, for pulmonary edema

miosis, restlessness, respiratory depression, increased ICP, postural hypotension, urinary retention, pruritus, addiction liability

Exerts hemodynamic effects on the pulmonary circulation ; significant first-pass effect ; metabolized in the body to morphine-6-glucuronide which has equal analgesic activity as morphine

ii. Fentanyl

Strong agonist at u receptors; For severe pain, adjunct in anesthesia, chronic pain and breakthrough cancer pain

restlessness, respiratory depression, increased ICP, postural hypotension, urinary retention, pruritus, addiction liability

May be given transdermally or via lollipop; ohmefentanyl is the most potent opioid

restlessness, respiratory depression, increased ICP, postural hypotension, urinary retention, pruritus, addiction liability, seizures

Only opioid that does not cause miosis and biliary contraction ; opioid of choice for pain relief in pancreatitis ; metabolized to normeperidine which can cause seizure therefore contraindicated in patients with seizure disorder ; if given with MAOi --> Hyperpyrexic coma, if given with SSRI --> Serotonin syndrome


Used in methadone maintenance therapy (MMT) for opioid dependence; currently being investigated as a novel treatment for leukemia

i. Phenelzine, tranylcypromine, selegiline

Inhibits MAO type A and type B, increases CNS levels of NE and serotonin, Phenelzine and Tranylcypromine are nonselective MAO inhibitors while Selegiline is a MAO-B selective inhibitor; For MDD unresponsive to other agents ; useful in patients with significant anxiety, phobic features and hypochondriasis

Opioid Analgesics and Antagonists A. Full Agonist

iii. Meperidine

Strong agonist at u and k receptors, inhibits pain neurotransmission, muscarinic blocking actions; For moderate to severe pain, labor analgesia, spasmodic pain (biliary, renal), preoperative sedation

iv. Methadone

Strong agonist at u receptors, i nhibits pain neurotransmission, binds NMDA receptors and antagonizes the effects of glutamate; For moderate to severe pain, opioid dependence, opioid withdrawal

i. Hydrocodone, oxycodone

Strong agonist at u receptors, i nhibits pain neurotransmission, binds NMDA receptors and antagonises the effects of glutamate; For moderate to severe pain, opioid dependence, opioid withdrawal


there is genetic variation in the metabolism of codeine and its derivatives

ii. Dextrometorphan, codeine

Decreases sensitivity of cough receptors, depressing the medullary cough center through sigma receptors stimulation; For cough suppression

hallucination, confusion, excitation, increased or decreased pupil size, nystagmus, seizures, coma, respiratory depression, addiction liability

codeine is metabolized by CYP2D6 to morphine

Weak agonist at u receptors, inhibits pain neurotransmission; For mild to moderate pain, restless leg syndrome

miosis, respiratory depression, increased ICP, postural hypotension, urinary retention, pruritus, addiction liability, fatal arrythmias

Withdrawn because of fatal cardiotoxicity

Strong agonist at k receptors, weak antagonist activity at u receptors; For moderate to severe pain, opioid dependence, alcohol dependence, balance anesthesia, for opioid withdrawal states (buprenorphine)

sedation, dizziness, sweating, nausea, anxiety, hallucinations, nightmares, respiratory depression (less), tolerance, dependence liability

Buprenorphine reduces craving in alcohol dependence, buprenorphine and nalbuphine is resistant to Naloxone

pruritus, nausea, vomiting

Precipitates abstinence syndrome in Px with opioid dependence ; Naloxone and Nalmefene is IV (DOA: 12-24 hrs) while Naltrexone is PO (DOA: 48h)

seizures, nausea, dizziness, pruritus, constipation

Lower seizure threshold ; CI in Px taking SSRI and those with history of seizure

C. Weak Agonist i. Propoxyphene, levopropoxyphene, dextropropoxyphene D. Mixed Agonist-Antagonist

i. Nalbuphine, buprenorphine, butorphanol, pentazocine E. Opioid Antagonist

i. Naloxone, naltrexone, nalmefene

Competitively blocks u, sigma and k receptors, rapidly reverses effects of opioid agonists; For opioid overdose, opioid and alcohol dependence (naltrexone)

F. Dual-acting

i. Tramadol

Weak agonist at u receptors, inhibits neuronal reuptake of serotonin and norepinephrine; For moderate pain, chronic pain syndrome, neuropathic pain

5. DRUGS USED TO TREAT DISEASES OF THE BLOOD, INFLAMMATION, & GOUT Agents Used in Anemias and Hematopoietic Growth Factors A. Hematopoietic growth factor i. Ferrous sulfate, Ferrous gluconate, Ferrous Fumarate,

Required for the biosynthesis of heme and heme containing proteins, including hemoglobin and

Black stools, shock, lethargy, dyspnea, abdominal pain, necrotizing

B. Heavy metal chelator i. Deferoxamine, Deferasirox

Chelates excess iron; For acute and chronic iron poisoning

Hypotension, Neurotoxicity, ARDS, Increased susceptibility to infections

None

Cofactor required for essential enzymatic reactions that form tetrahydrofolate, convert homocysteine to methionine and metabolize methylmalonyl-CoA; For vitamin B12 deficiency, megaloblastic anemia

No significant toxicity

Hydroxocobalamin has a longer t1/2 than cyanocobalamin ; has a storage of up to 5yrs in the liver

Precursor of an essential donor of methyl groups used for synthesis of amino acids, purines and deoxynucleotide; For Megaloblastic anemia, prevention of neutral tube defects (spina bifida), prevention of coronary artery disease

No significant toxicity

only modest amounts are stored in the body

Agonist of erythropoietin receptors expressed by red cell progenitors; For Anemia, associated with c hronic renal failure, cancer, HIV infection and prematurity

Hypertension, Thrombosis, Pure red cell aplasia

Performance-enhancing drug in athletes ; darbepoietin is once a week administration, while Methoxy Polyethylene GlycolEpoetin Beta is 1-2x per month administration

Binds receptors on myeloid progenitors and stimulates cell maturation and proliferation ; Accelerates neutrophil recovery and reduces incidence of infection; For neutropenia associated with chemotherapy, myelodysplasia, and aplastic anemia

Edema, Fever, Arthralgia

Pegfilgrastim has longer t1/2

Recombinant form of an endogenous cytokine; activates IL -11 receptors ; For secondary prevention of thrombocytopenia in patients undergoing chemotheraphy

fatigue, headache, anemia, fluid accumulation in the lungs, dizziness, transient atrialarrythmias

given SC OD

C. Hematopoietic growth factor

i. Cyanocobalamin, Hydroxocobalamin D. Hematopoietic growth factor

i. Folic acid, Folacin (Pteroylglutamic acid), Folinic acid E. Hematopoietic growth factor

i. Epoetin Alfa, Darbepoetin alfa, Methoxy Polyethylene Glycol- Epoetin Beta F. Myeloid growth factor

i. (G-CSF) Filgrastim, Sargamostim (GM-CSF), Pegfilgrastim G. Megakaryocyte growth factor

i. Oprelvekin(IL-11), Thrombopoietin

Agents Used in Dyslipidemia

Hepatoxicity, Myopathy, Rhabdomyolysis, Gastrointestinal distress, Teratogen

has direct anti-atherosclerotic effect, and can prevent bone loss ; Increased risk of myopathy and rhabdomyolysis when used with fibrates ; Given before bedtime because cholesterol synthesis predominantly occurs at night ; simvastatin and lovastatin are prodrugs, all the rest are in their active form already ; Rosuvastatin, Atorvastatin and Simvastatin have greater maximal effect than other statins ; if given together with r esins give at least 1hr before or 4hrs after resin administration (resins decrease the absorption of statins) ; has CYP450 dependent metabolism

B. Bile Acid Binding Resin: Colesevelam, Colestipol, Cholestyramine

non-absorbable polymers that bind bile acids and similar steroids in the intestines preventing their reabsorption, increases cholesterol utilization for replacement, modestly lowers LDL levels by increasing hepatic LDL receptors ; For hypercholesterolemia (high LDL), pruritus in cholestasis, digitalis toxicity

Constipation, Bloating, Gritty taste, Gallstone fo rmation, steatorrhea, malabsortion of fat soluble substances (vitamin k, folate)

Increases TGs and VLDL in patients with high TGs and combined hyperlipidemia ; Treat constipation with fiber supplements/psyllium ; Avoid in patients with diverticulitis

C. NPC1L1 transporter inhibitor: Ezetimibe

Selective inhibitor of the NPC1L1 transporter decreasing intestinal absorption of cholesterol and other phytosterols, decreases cholesterol hepatic pool, increases hepatic LDL receptors ; For Hypercholesterolemia (High LDL), phytosterolemia

Hepatoxicity (increased with statin use), Myositis

Synergistic LDL-lowering effect with statins ; is a prodrug

D. Sterol absorption blocker: Sitosterol

Cholesterol analog, takes the place of dietary and billiary cholesterol, decreasing intestinal absorption of cholesterol and other phytosterols ; For Hypercholesterolemia (high LDL), phytosterolemia

Gastrointestinal upset, bloating, impotence (rare), coronary events

NONE

A. HMG-CoA Reductase Inhibitors: Simvastatin, Atorvastatin, Rosuvastatin, Fluvastatin, Pravastatin, Lovastatin, Pitavastatin, Cerivastatin,

Inhibits rate-limiting enzyme in cholesterol biosynthesis (HMG-CoA reductase), Increased hepatic cholesterol uptake, Increased high affinity LDL receptors which leads to decreased LDL levels ; DOC for hypercholesterolemia (high LDL), decreases risk of acute coronary syndromes, ischemic stroke

E. Nicotinic Acid derivatives: Niacin

F. Fibrates: Gemfibrozil, Fenofibrate, Bezafibrate

Decreases VLDL synthesis and LDL cholesterol concentrations, decreases hormone-sensitive lipase activity leading to decreased LDL levels, Increases HDL cholesterol by decreasing its catabolism ; DOC for increasing HDL levels, for Hypercholesterolemia (low HDL, high LDL/VLDL), hypertriglyceridemia

Activates PPAR- α and increases expression of lipoprotein lipase and apolipoproteins (apoA-I, apoAII) leading to enhanced clearance of TG-rich lipoproteins, Lowers triglycerides, Increases HDL ; DOC for hypertriglyceridemia

Flushing, nausea, vomiting, Pruritus, Acanthosis nigricans, Rashes, Gastrointestinal irritation, Hepatoxicity (mild), Hyperuricemia, Impaired glucose tolerance, Arrhythmias, Ambylopia

decreases fibrinogen and increases t-PA ; NSAIDs pre-treatment reduces flushing ; Avoid in patients with peptic ulcer disease ; Potentiates effects of antihypertensives (vasodilators, ganglion blockers)

Nausea, Rashes, Leukopenia, nausea, vomiting, increased risk of cholesterol gallstones

Increased risk of myopathy and rhabdomyolysis when used with statins ; Avoided in patients with hepatic or renal dysfunction ; may increase LDL in patients with familial combined hyperlipoproteinemia ; has little or no effect on LDL ; higher risk of gallstone formation if given together with resins

Gastrointestinal toxicity, nephrotoxicity, tinnitus, hyperventilation, hypersensitivity, HAGMA, Increased bleeding time, Nephrotoxicity (AKI and Interstitial Nephritis)

Uncoupler of oxidative phosphorylation, associated with Reye syndrome in children ; Do not use as NSAID for gout

Bleeding, Thrombocytopenia

Adjunct to thrombolysis

Headache, palpitations

additional MOA: inhibit uptake of adenosine by endothelial cells and RBC, thus increasing adenosine levels leading to inhibition of platelet aggregation ; Cilostazol is contraindicated in heart failure

Drugs for Coagulation A. Antiplatelet

For arterial thrombosis only

ii. GPIIb-IIIa inhibitor: Abciximab, Eptifibatide,Tirofiban

Nonselective, irreversible COX 1&2 inhibitor. Reduces platelet production of thromboxane A2, temporarily inhibit Prostacyclin synthesis ; For prevention or arterial thrombosis (MI, TIA, CVD), Inflammatory disorders (rheumatic fever, juvenile rheumatoid arthritis, kawasaki disease) Reversbily inhibits the binding of fibrin and other ligands to the platelet GPIIb-IIIa receptor ; For antithrombosis during PCI, Acute coronary syndromes (unstable angina, NSTEMI)

iii. PDE III inhibitor: Dipyridamole, Cilostazol

Inhibits phosphodiesterase III and increases cAMP in platelets and blood vessels, Inhibits platelet aggregation and causes vasolidation ; For prevention of thromboembolic complications of cardiac valve replacement (as adjunct to warfarin), secondary prevention of ischemic stroke (with aspirin), Intermittent claudication (Cilostazol only)

i. Aspirin

iv. ADP inhibitor: Clopidogrel,Ticlopidine, Prasugel B. Anticoagulant

i. Heparin (indirect thrombin inhibitor)

Irreversibly inhibits binding of ADP to platelet receptors,thus reducing platelet aggregation ; For prevention and treatment of arterial thrombosis (stroke, TIA, unstable angina), Acute coronary syndromes, Prevention of re-stenosis after PCI

Bleeding, nausea, hematologic (neutropenia, leukopenia), thrombotic thrombocytopenic purpura (Ticlopidine), dyspepsia

GI & Hematologic SE are more common with ticlopidine. Additive effects with aspirin

Bleeding, transient Heparin-induced thrombocytopenia, Osteoporosis with chronic use

DOC for anticoagulation during pregnancy ; administered IV or SC ; Monitor with aPTT, Antidote: Protamine Sulfate

For both venous and arterial thrombosis Activates antithrombin III which Inactivates thrombin or factor IIa, factor IXa & factor Xa by forming stable complexes with them ; For deep venous thrombosis, myocardial dysfunction, Pulmonary embolism, adjuvant to percutaneous coronary intervention (PCI) and thrombolytics, Atrial fibrillation, Pulmonary embolism, given with thrombolytics for revascularization procedures, given with GPIIb-IIIa inhibitors for angioplasty and stent placement

ii. LMWH: Enoxaparin, Dalteparin, Tinzaparin, Fondaparinux

Binds and potentiates effect of antithrombin III on factor Xa (more selective for Xa); For Deep venous thrombosis, Pulmonary embolism, unstable angina, myocardial infarction, adjuvant to percutaneous coronary intervention (PCI) and thrombolytics, Atrial fibrillation

Bleeding, less risk of thrombocytopenia

Does not require aPTT monitoring, Protamine sulfate is only partially effective in reversing effects ; advantage over regular heparin is higher bioavailability and t1/2 ; Fondaparinux is given SC OD

iii. Direct Thrombin Inhibitors: Lepirudin, Desirudin, Bivalirudin, Argatroban, Dabigatran

Binds to thrombin's ative site and inhibits its enzymatic action; For anticoagulation in patients with heparin induced thrombocytopenia (HIT), percutaneous coronary angioplasty (Bivalirudin with aspirin)

Bleeding, Anaphylactic reactions, Effect-prolonging antibodies

Monitor with aPTT. No reversal agents exist ; Dabigatran is PO while all the rest are parenteral ; Bivalirudin also inhibits platelet activation

iv. Direct Oral Factor Xa inhibitor: Rivaroxaban, Apixaban

bind to free and bound factor Xa ; For prevention of Venous thrombosis, in stroke patients with Afib

bleeding

No reversal agent

v. Warfarin, Dicumarol

Inhibits vitamin K epoxide reductase (responsible for y-carboxylation of the vitamin K- dependent clotting (factors II, VII, IX, X, Protein C & Protein S) ; For chronic anticoagulation (DVT, atrial fibrillation, valve replacement) EXCEPT in pregnancy

Bleeding, Teratogen (bone defects, hemorrhage), warfarininduced skin necrosis (transient hypercoagulability)

Monitor effects with PT-INR. Antidote is vitamin K or FFP. Narrow therapeutic window ; 99% proteinbound

C. Antidote Chemical antagonist of heparin. Reverses excessive anticlotting activity of unfractionated heparin; For

ii. Endogenous Vitamin: Vitamin K1, K2, K3 (Phytonadione, Menaquinone, Menadione)

Increases supply of reduced vitamin K, which is required for synthesis of functional vitamin Kdependent clotting and anticlotting factors ; For Vitamin K deficiency, Antidote to warfarin, prevention of hemorrhagic diatheses in newborns

Severe infusion reaction when administered at a fast rate (dyspnea, chest and back pain)

Vit K1 may be given PO or IV

Bleeding, Reperfusion, Cerebral hemorrhage, Arrhythmias ; Loss of effectiveness (on 2nd use) and allergic reactions (streptokinase)

Tx should be done within 6 hrs, better if within 3hrs ; Antidote is AMINOCAPROIC ACID ; Streptokinase forms a complex with endogenous plasminogen, thus catalyzing the conversion of plasminogen to plasmin ; tPA is selective for fibrin-bound plasminogen

D. Thrombolytic: Alteplase, Anistreplase, Reteplase, Streptokinase, Tenecteplase, Urokinase

Tissue plasminogen activator analog. Converts plasminogen to plasmin, which degrades the fibrin and fibrinogen, causing thrombolysis ; For acute myocardial infarction, pulmonary embolism, Ischemic stroke

E. Antiplasmin drug: Tranexamic acid

Competitively inhibits plasminogen activation thus inhibiting fibrinolysis ; For prevention and treatment of acute bleeding episodes in patients with high risk of bleeding (hemophilia, intracranial aneurysms, menstrual, obstetrics, thrombolytics, postperative)

Thrombosis, hypotension, Myopathy, Diarrhea

Contraindicated in disseminated intravascualr coagulation (DIC) and genitourinary bleeding

F. ADH agonist: Desmopressin

Vasopressin V2 receptor agonist, Increases factor VIII activity of patients with mild hemophilia A or VWD; For hemophillia A, von Willebrand's disease, central diabetes insipidus

headaches, nausea, flushing, seizures, hyponatremia

may cause immunologic reactions and infections

Non-steroidal Anti-Inflammatory Drugs, Disease-Modifying Anti-rheumatic Drugs, Non-opioid Analgesics & Drugs Used in Gout A.Non-selective NSAID

i. Aspirin, Sodium Salicylate

See entry on Drugs for caogulation Disorder

See entry on Drugs for caogulation Disorder

low doses undergo first order kinetics while high doses undergo zero order reaction ; Long term use reduces the risk of colon cancer

Nonselective reversible COX-1 and COX-2 inhibitor. Inhibits prostaglandin and thromboxane synthesis ; For analgesia, fever and as anti inflammatory

Gastrointestinal bleeding (less than aspirin), Nephrotoxicity (AKI and Interstitial Nephritis), Hypersensitivity reaction

Ibuprofen and Indomethacin can be used to close PDA ; Ibuprofen and naproxen have moderate effectiveness ; Ibuprofen is relatively safe but with short halflife of 2hrs ; Naproxen and Piroxicam have longer half-lives ; Ketorolac has significant analgesic effect but not anti-inflammatory effect ; use Ketorolac only for 72hrs due to GI and renal damage ; NSAIDs may interfere with ASA's antithrombotic action

Nonselective reversible COX-1 and COX-2 inhibitor. Inhibits prostaglandin synthesis and inhibit crystal phagocytosis by macrophages ; For anti inflammatory (gout arthritis, ankylosing spondylitis), for closing PDA

Gastrointestinal toxicity, pancreatitis, Nephrotoxicity, Serious hematologic reactions, BM suppression

Indomethacin has greater antiinflammatory effect compared to other NSAIDs

B. COX-2 Selective NSAID: Celecoxib, Etoricoxib, Parecoxib

Selective COX-2 inhibitor. Inhibits prostaglandin synthesis ; For Analgesia, Anti inflammatory, Antipyretic

Gastrointestinal bleeding, Nephrotoxicity (same risk as nonselective NSAIDs), Myocardial infarction and stroke

Rofecoxib and Valdecoxib withdrawn due to incereased incidence of thrombosis

C. Non-opioid Analgesic (COX3 inhibitor) Paracetamol (Acetaminophen)

Selectively inhibits COX-3 in the CNS, Weak C OX-1 and COX-2 inhibitor in the periphery, Inhibits prostaglandin synthesis ; For Analgesia and antipyretic

Hepatoxicity (antidote: NAC), Renal papillary necrosis and Interstitial nephritis, Methemoglobinemia, Hemolytic anemia

Preferred antipyretic in children (does not cause reye's syndrome) ; t1/2 is only 2-3h

Inhibits AICAR transformylase and thymidylate synthase, with secondary effects on polymorphonuclear chemotaxis ; For rheumatoid arthritis, SLE, JRA, psoriatic arthritis, Ankylosing spondylitis, Polymyositis

Nausea, Mucosal ulcers, hepatoxicity, hypersensitivty, Pseudolymphomatous reaction, teratogen, hematotoxicity

DMARD of choice for Rheumatoid arthritis, Rescue agent: Leucovorin (Folinic acid)

Binds or inhibits to TNF-a ; For Crohn's disease, rheumatoid arthritis, other rheumatic disease

Bacterial infections (URTIs), reactivation of latent tuberculosis, lymphoma, Demyelination, Reactivation of Hepatitis B, Auto antibody formation (ANA, anti dsDNA), infusion reactions, hepatoxicity, hematotoxicity, cardiotoxicity

Synergistic effects with methotrexate

ii. Ibuprofen, Diclofenac, Diflunisal, Etodolac, Fenoprofen, Flurbiprofen, Ketoprofen, Meloxicam, Nabumetone, Naproxen, Oxaprozin, Piroxicam, Sulinidac, Tolemtin, Mefenamic acid, Ketorolac

iii. Indomethacin

D. Disease Modifying Anti-Rheumatic Drug

i. Methotrexate

ii. TNF-alpha inhibitor: Infliximab, Adalimumab, Etanercept

iii. Azathioprine

Forms 6-thioguanine, suppressing inosinic acid synthesis, B-cell and T-cell function, Immunoglobulin production and interleukin-2 secretion ; For rheumatoid arthritis, psoriatic arthritis, reactive arthritis, polymyositis, SLE

Bone marrow supression, increased risk of infections, increased incidence of lymphoma, Fever, rash, hepatotoxicity, allergic reactions

Cannot give allopurinol with azathioprine (allopurinol reduces xanthine oxidase catabolism of purine analogs, increasing 6thioguanine nucleotides, leading to severe leukopenia)

iv. Chloroquine, Hydroxychloroquine

Suppression of T-lymphocyte leading to decreased leukocyte chemotaxis, stabilization of lysosomal enzymes, inhibition of DNA and RNA synthesis, trapping of free radicals ; For rheumatiod arthritis, SLE, Sjogren's syndrome, Malaria

Ocular toxicity, Dyspepsia, Nausea, vomiting, abdominal pain, rashes, nightmares, myopathy, neuropathy, ocular toxicity

safe for pregnant women

v. Cyclophosphamide

Forms phospharamide mustard, which cross links DNA to prevent cell replication, Supresses T-cell and B-cell function ; For Rheumatoid arthritis, SLE vasculitis, Wegener's granulomatosis, severe rheumatic diseases

Hemorrhagic cystitis

Hemorrhagic cystitis, Rescue agent is Mesna

vi. Cyclosporine

Inhibits interleukin-1 and iterleukin-2 receptor production and secondarily inhibits macrophage-T-cell interaction and T-cell responsiveness ; For rheumatoid arthritis, SLE, Tissue transplantation

Nephrotoxicity, hypertension, hyperkalemia, hepatoxicity, Gingival hyperplasia, hirsutism

NONE

vii. Mycophenolate Mofetil

active product inhibits inosine monophosphate dehydrogenase and inhibits T-cell lymphocyte proliferation ; For SLE nephritis, vasculitis, Wegener's granulomatosis, rheumatoid arthritis

Gastrointestinal disturbances, headache, hypertension, reversible myelosupression

NONE

viii. Sulfasalazine

active metabolite inhibits the release of inflammatory bowel cytokines; For rheumatoid arthritis, inflammatory bowel disease, JRA, ankylosing spondylitis

Nausea, vomiting headache,rash, hemolytic anemia, methemoglobinemia, neutropenia, leukopenia, thrombocytopenia, pulmonary toxicity, autoantibody formation (anti dsDNA), Reversible infertility in men

anti-IBD drugs

E. Antigout drugs

i. Microtubule assembly inhibtor: Colchicine

ii. Uricosuric agent: Probenecid, Sulfinpyrazone

iii. Xanthine oxidase inhibitor: Allopurinol, Febuxostat

Inhibits microtubule assembly and LTB4 production leading to decreased macrophage migration and phagocytosis ; For gout

are weak acids that compete with uric acid for reabsorption in the PCT leading to increased uric acid excretion ; For gout

Active metabolite (alloxanthine) irreversibly inhibits xanthine oxidase and lowers production of uric acid; 1st line treatment of chronic gout, tumor lysis syndrome

Diarrhea, nausea, vomiting, abdominal pain, hepatic necrosis, acute renal failure, disseminated intravascular coagulation, seizures, hair loss, bone marrow depression, peripheral neuritis, myopathy

a general mitotic poison, may also be used for Familial Mediterranean Fever ; diarrhea is the adverse effect which signals toxicity from colchicine

Gastrointestinal irritation, rashes, nephrotic syndrome, aplastic anemia ; sulfa allergy

May precipitate acute gout during early phase of drug action (prevent by coadministering with colchicine or indomethacin) ; may be given together with antimicrobial agents (particularly Penicillins) to prolong therapeutic effect by inhibiting renal tubular secretion of antibiotics

Gastrointestinal upset, Rash, Peripheral neuritis, Vasculitis, bone marrow dysfunction, Aplastic anemia, liver dysfunction (Febuxostat)

Inhibits metabolism of mercaptopurine and azathioprine. Witheld for 1-2 wk after an acute episode of gouty arthritis (coadministered with colcichine or indomethacin to avoid an acute attack) ; Feboxustat is a newer nonpurine inhbitor of Xanthine Oxidase ; Febuxostat is more effective than Allopurinol

6. ENDOCRINE DRUGS Hypothalamic and Pituitary Hormones

i. Somatropin

Recombinant Growth hormone, Increases release of IGF-1 in the liver and carilage, stimulates skeletal muscle growth, amino acid transport, protein synthesis and cell proliferation ; For GH deficiency in children and genetic disease associated with short stature (Turner syndrome, Prader-Willi syndrome), failure to thrive due to chronic renal failure or SGA, AIDS wasting, improve GI function in patients who underwent intestinal resection that led to malabsorption syndrome

Peripheral edema, Myalgia, Arthralgia, Intracranial hypertension, pseudotumor cerebri, slipped capital femoral epiphysis, progression of scoliosis, hyperglycemia

used as Performance enhancing drug since it increases muscle mass ; given SC

ii. Mecasermin

Recombinant IGF-1 ; For children unresponsive to GH therapy

Hypoglycemia, increased LFT, intracranial HTN

remedy to hypoglycemia: give patient some snacks prior to dose

iii. Octreotide, Lanreotide

Somatostatin analog, suppresses the release of growth hormones, glucagon, insulin, gastrin, IGF-1, serotonin and gastrointestinal peptides ; For Acromegaly, pituitary adenoma, carcinoid, gastrinoma, glucagonoma, variceal bleeding

GI upset, gallstone, cardiac condution abnormality

regular release: given BID-QID SC, if slow release: every 4wks IM ; are long-acting synthetic analogs of somatostatin

iv. Pegvisomant

GH receptor antagonist ; For acromegaly

Diarrhea, nausea, flu-like syndrome, elevated LFTs, hypesensitivity reaction

v. Follitropin alfa, Follitropin beta, Urofollitropin

Gonadotropin analog (FSH analog); activates FSH receptors and mimics effects of endogenous FSH ; For Controlled ovarian hyperstimulation, infertility due to hypogonadism in men

Headache, depression, edema, ovarian hyperstimulation syndrome (ovarian enlargement, ascites, hypovolemia, shock), multiple pregnancies in women, gynecomastia in men

onset of action is expected within 2wks of use Follitropin alfa and beta are recombinant FSH forms while Urofollitropin is a purified preparation from urine of postmenopausal women

Headache, depression, edema, ovarian hyperstimulation syndrome, multiple pregnancies in women, gynecomastia in men

menotropins are mixtures of FSH and LH from postmenopausal women ; Choriogondaotropin alfa is a recombinant hCG while Lutropin is a recombinant LH ; hCG given IM

vi. Menotropins, Human chorionic gonadotropin (HCG), Choriogondaotropin alfa, Lutropin

Gonadotropin analog (LH analog); activates LH receptors and mimics effects of endogenous LH ; For Controlled ovarian hyperstimulation (ovulation induction), hypogonadotripic hypogonadism

Hot flushes, sweats, headaches, osteoporosis, gynecomastia, reduced libido, decreased hematocrit

there is exacerbation of symptoms in males with prostate CA and children with precocious puberty during the first few weeks of therapy (remedy: co-administer Flutamide, an androgen receptor antagonist) ; Gonadorelin is a synthetic human GnRH ; Leuprolide has a long agonist activity

viii. Ganirelix, Cetrorelix, Degarelix

GnRH antagonist, blocks GnRH receptors, reduces endogenous production of LH and FSH ; For Controlled ovarian hyperstimulation (prevents premature LH surge), advanced prostate CA

Nausea, headache, hypersensitivity, hot flushes, gynecomastia, decreased libido, decreased hematocrit, osteoporosis

Does NOT cause tumor flare-up whe used for treatment of advanced prostate cancer, also less likely to cause ovarian hyperstimulation syndrome ; Degarelix is used for prostate CA while Ganirelix prevent LH surge in controlled ovulation

ix. Bromocriptine, Carbegoline

Dopamine agonist, partial agonist at dopamine D2 receptors in brain, inhibits prolactin release ; For Hyperprolactinemia, Pituitary adenoma, acromegaly, Parkinson's disease

Nausea, headache, lightheadedness, orthostatic hypotension, fatigue, behavioral changes, erythromelalgia, Raynaud's phenomenon, pulmonary infiltrates

Slightly inhibits GH release if g iven in high doses ; CI in patients with history of psychotic illness

x. Oxytocin

Activates oxytocin receptors, stimulates uterine contraction and labor, stimulates mammary glands, lactation and milk let-down ; For Labor induction, labor augmentation, control of uterine hemorrhage post-delivery

Fetal distress, placental abruption, uterine rupture, fluid retention, hyponatremia, heart failure, seizures, hypotension

ATOSIBAN - an oxytocin antagonist used in preterm labor

xi. Desmopressin, Vasopressin

ADH agonist, Vasopressin V2 receptor agonist which causes insertion of water channels in the collecting duct leading to more water reabsoprtion, also regulates the release of factor VIII and VWF ; For Central DI, Hemophilia A, von Willebrand's disease, Variceal bleeding, colon diverticula, primary nocturnal seizures

Headaches, flushing, nausea, hyponatremia, seizures

also contracts vascular smooth muscles via V1 receptor leading to vasoconstriction, used as treatment for esophageal varices or colon diverticula

vii. Leuprolide, Gonadorelin, Goserelin, Histrelin, Nafarelin, Triptorelin

GnRH analog, increased LH and FSH secretion with intermittent administration , reduced LH and FSH secretion with prolonged continuous administration (due to downregulation of GnRH receptors in the pituitary cells that normally release LH and FSH ; For Controlled ovarian hyperstimulation, endometriosis, myoma uteri, precocious puberty, prostate CA

xii. Conivaptan, Tolvaptan, Lixivaptan

ADH antagonist, Antagonist at V1a and V2 receptors ; For SIADH, Hyponatremia, offset fluid retention in acute heart failure and SIADH which causes hyponatremia (dilutional)

Infusion site reactions, hyperkalemia

Central pontine myelinolysis may occur with rapid correction of hyponatremia, tolvaptan is more selective for V2 receptors

Thryoid hormone, activation of nuclear receptors results in gene expression with RNA f ormation and protein synthesis ; For Hypothyroidism, myxedema coma

Dry skin, sweatng, tachycardia, nervousness, tremor, weight loss, weakness, heat intolerance

T4 dose must be lowered in patients with cardiovascular disease or longstanding hypothyroidism (increased cardiosensitivity) ; Liothyronine has a faster onset but shorter half-life

Inhibits thyroid peroxidase reactions, blocks iodine organification, inhibits peripheral conversion of T4 into T3 ; For Hyperthyroidism, thyroid storm

Maculopapular pruritic rash, gastrointestinal distress, fulminant hepatitis, agranulocytosis, urticaria, vasculitis, lupus-like syndrome, lymphadenopathy, hypoprothrombinemia, Exfoliative dermatitis, polyserositis, arthralgia, hypothyroidism

Drug of choice for pregnant hyperthyroid patients (does not eneter placenta and breastmilk); slow onset of action (3-4 weeks for full effect)

Inhibits thyroid peroxidase reactions, blocks iodine organification ; For Hyperthyroidism, thyroid storm

Maculopapular pruritic rash, gastrointestinal distress, fulminant hepatitis, dose-dependent, agranulocytosis, urticaria, vasculitis, lupus-like syndrome, lymphadenopathy, hypoprothrombinemia, Exfoliative dermatitis, polyserositis, arthralgia, hypothyroidism

Methimazole and Carbimazole are teratogens (causes Aplasia Cutis Congenita) ; given as once daily dosing

Iodism, acneiform rash, swollen salivary glands, mucous membrane ulcerations, conjunctivitis, rhinorrhea, drug fever, metallic taste, bleeding disorders, anaphylactoid reactions

onset is more rapid (2-7 days) but effect is transient (thyroid gland escapes iodide block after several weeks of treatment) ; Should not be used alone (escape in 2-8 weeks); prevents radiation induced thryoid damage; prenatal exposure causes fetal goiter

Thryoid & Antithyroid Drugs

i. Levothyroxine (T4), Liothyronine (T3)

ii. Propylthiouracil (PTU)

iii. Methimazole, Carbimazole

iv. Lugol Solution (Iodine in Potssium Iodide), Potassium Iodide

Inhibit iodine organification and hormone release leading to reduced size and vascularity of thyroid gland ; For Hyperthyroidism, thyroid storm, preparation for surgical thyroidectomy to reduce the size and vascularity of the thyroid gland, radiation prophylaxis

v. Propranolol, Esmolol, Metoprolol, Atenolol

Beta blocker control HR and other cardiac abnormalities of severe thyrotoxicosis, slows pacemaker activity; inhibits peripheral conversion of T4 into T3 ; For Hyperthyroidism, thyroid storm, post MI prophylaxis, hypertension

Bronchospasm, cardiac depression, AV block, hypotension

vi. Radioactive Iodine

Iodide, emits beta rays causing destruction of thyroid parenchyma ; For hyperthyroidism, permanent cure of thyrotoxicosis without surgery and no effect on other tissues

Permanent hypothyroidism, sore throat

Esmolol may be used to treat thyrotoxicosis-related arrhythmias; causes clinical improvement WITHOUT altering thyroid hormone levels Preferred treatment for most patients due to ease of administration, effectiveness, low expense and absence of pain; contraindicated in pregnant women or nursing mothers

Adrenal suppression, growth inhibition, DM, muscle wasting, osteoporosis, salt retention, glucose intolerance, behavioral changes

Effects: stimulate gluconeogenesis, increased fat deposition, muscle protein and bone catabolism, lymphoid connective tissue fat and skin wasting inhibit cell-mediated immunologic functions, lymphotoxic, increased neutrophils, decreased lymphocytes eosinophils basophils and monocytes, inhibit leukocyte migration, inhibit PLA2, delay rejection in transplant patients, increased GI acid secretion (ulcer) ; Biochemical effects: induced synthesis of an inhibitor of PLA2, decreased mRNA for COX2, decrease in IL-2 and IL-3 and decrease in Platelet Activating Factor (PAF)

Adrenal suppression, growth inhibition, muscle wasting, osteoporosis, salt retention, glucose intolerance, behavioral

prednisolone is the active metabolite of prednisone ; this group has a long t1/2, reduced saltretaining effect and better

Adrenocorticosteroids & Adrenocortical Antagonists i. Low Potency: Desonide ii. Med Potency: Fluticasone, Mometasone

iii. High Potency: Desoximetasone, Clobetasol

iv. Synthetic GCs: Prednisone, Prednisolone, Methylprednisolone, Meprednisone, Dexamethasone, Betamethasone, Triamcinolone, Beclomethasone,

Glucocorticoid, activates glucocorticoid receptors, leading to altered gene transcription, Suppresses inflammation, Replaces cortisol when deficient ; For Acute adrenal insufficiency associated with lifethreatening shock, chronic adrenal insufficiency (Addison's disease), congenital adrenal hyperplasia, insect bites, contact dermatitis, status asthmaticus, thyroid storm

Glucocorticoid; For supressession of inflammation and immune response, hematopoeitic cancers, transplant rejection, collagen and rheumatic disease, lung maturation in preterm labor (betamethasone and dexamethasone), bronchial asthma, chemotherapy-

v. Mineralocorticoid: Fludrocortisone, Deoxycorticosterone

strong agonist of mineralocorticoid receptors and moderate activation of glucorticoid receptors, Increases Na reabsorption, K and H excretion ; For Chronic adrenal insufficiency (Addison's disease), Congenital adrenal hyperplasia, adrenal r eplacement therapy post-adrenalectomy

Salt and fluid retention, Hypokalemia, Congestive heart failure, muscle wastng, osteoporosis, glucose intolerance, behavioral changes

Additive hypokalemia with loop diurectics and thiazides ; Deoxycorticosterone is the precursor of aldosterone ; Fludrocortisone also has significant glucocorticoid activity ; Aldosterone is implicated in myocardial and vascular fibrosis and baroreceptor dysfunction

Skin rash, hepatotoxicity, hypothyroidism

Also inhibits synthesis of all hormonally active steroids

Corticosteroid Antagonists

vi. Aminoglutethimide

vii. Ketoconazole

viii. Metyrapone

ix. Mifepristone (RU486)

x. Spironolactone, Eplerenone

Glucorticoid synthesis inhibitor, inhibits desmolase activity, blocking conversion of cholesterol to pregnenolone ; For Breast CA, Cushing syndrome Glucorticoid synthesis inhibitor; azole antifungal; inhibits cholesterol side chain cleavage, cytochrome P450 enzymes and other enzymes necessary for synthesis of all steroids ; For Adrenal CA, Hirsutism, Breast CA, steroid-responsive metastatic Prostate CA, Cushing's syndrome, Fungal infections, hirsutism

Hepatotoxicity, many drug interactions, androgenic effect

Potent inhibitor of CYP450 enzymes

Glucorticoid synthesis inhibitor, selective inhibitor of steroid-11 hydroxylation, interfering with cortisol and corticosterone synthesis ; As diagnostic test for adrenal function

Dizziness, GI disturbances

DOC for pregnant patients with Cushing's syndrome

competitive inhibitor at the GC receptor as well as progesterone receptor ; For Cushing's syndrome

abdominal pain and cramping, uterine cramping, nausea, headache, vomiting, diarrhea, dizziness, vaginal bleeding

also used as an approved abortifacient for medical abortion (usually together with misoprostol)

Aldoesterone antagonist ; For hypokalemia due to other diuretics, for post-MI, hyperaldoteronism- see entry -

Hyperkalemia, gynecomastia (spironolactone) - see entry -

also with weak antagonist effect at the androgen receptor

Gonadal Hormones and Inhbitors A. Estrogen compounds

Activates etrogen receptors, leads to changes in rates of trasncription of estrogen-regulated genes ; For Primary hypogonadism, Postmenopausal hormonal replacement therapy, Osteoporosis and prevention of bone loss, Contraception, Intractable dysmenorrhea

breakthrough bleeding, nausea, breast tenderness, migraine, thromboembolism (DVTs), gallbladder disease, hypertriglyceridemia, hypertension, premature closure of the epiphysis in young females, increased risk of breast and endometrial cancer (remedy: add progesterone to the preparation)

Increases risk of endometrial cancer and breast cancer ; Ethinyl Estradiol has low bioavailability, PO/TD/IM/Intravaginal ; Estradiol cypionate is IM with longer t1/2 ; Premarin is a mixture of conjugated estrogen used in HRT ; Ethinyl estradiol undergoes enterohepatic recirculation ; Effects of Estrogen: growth of genital structures and secondary sexual characteristics, modifies serum protein levels and decrease bone resorption, enhances coagulability of blood, increases TG and HDL levels while decreasing LDL levels, if given as continuous infusion will inhibt FSH and LH release

Synthetic estrogen (nonsteroid); activates estrogen receptors; leads to changes in rates of transcription of estrogen-regulated genes ; For Atrophic vaginitis, hormone replacement therapy, prevention of adverse pregnancy outcomes, metastatic prostate CA

breakthrough bleeding, nausea, breast tenderness, migraine, thromboembolism (DVTs), gallbladder disease, hypertriglyceridemia, hypertension, premature closure of the epiphysis in young females, increased risk of breast and endometrial cancer (remedy: add progesterone to the preparation)

associated with Infertility, ectopic pregnancy, clear cell vaginal adenocarcinoma in daughters of women treated with DES

i. Ethinyl Estradiol, Mestranol, Estradiol cypionate, Premarin

ii. Diethylstilbestrol

B. Progestins

i. Norgestrel, Medroxyprogesterone, Norethindrone, Norgestimate, Desogestrel, Megestrol activates progesterone receptors, changes rate of transcription of progesterone-regulated genes ; For Hormone replacement therapy (given together with Estrogen, to prevent estrogen-induced endometrial cancer), contraception, assisted reproduction (for maintenance of pregnancy), anovulation induction (given in high doses to suppress FSH and LH)

Hypertension, decreased HDL, weight gain, reversible decrease in bone mineral density, delayed resumption of ovulation after use

C. Combined Hormonal Contraceptives

Prevents estrogen induced endometrial cancer when used in combination with estrogens; Megesterol is used as an a ppetite stimulant ; given PO or as vaginal cream ; Medroxyprogesterone has a better oral bioavilability ; LNorgestrel and Norethindrone has more androgenic effect ; Norgestrel undergoes enterohepatic recirculation ; Effects of progesterone: induces secretory changes in the endometrium, stabilize the endometrium, affect carbohydrate metabolism and stimulate deposition of fat, high doses suppress FSH and LH secretion maybe PO/IM/TD/vaginal rings/IUD

iv. Ethinyl Estradiol + Noregistmate

Combined oral contraceptive, activates estrogen and progesterone receptors, inhibits ovulation, effects on cervical mucus gland, uterine tubes and endometrium lead to decreased fertility, inhibit ovulation when given before the LH surge ; For Contraception, hypogonadism, acne, hirsutism, dysmenorrhea, endometriosis

breakthrough bleeding, nausea, breast tenderness, migraine, thromboembolism (DVTs), breast cancer (earlier onset), headache, skin pigmentation, depression, weight gain acne and hirsutism for older OCPs

Lifetime risk of breast cancer is NOT changed; Norethindrone is a testosterone derivative while Drospirenone is a spironolactone derivative that is antiandrogenic ; Norgestimate and Desogestrel are newer progestins ; combined OCPs may be used for androgen-induced hirsutism ; Mestranol (Estrogen) may also be used in OCPs

v. Medroxyprogesterone Acetate

Progestin-only contraceptive, activates progresterone receptors, Prevents conception by altering cervical mucus and creating a hostile endometrium ; For Contraception, hormone replacement therapy

Breakthrough bleeding, hair loss, dysmenorrhea, delayed return of fertility, osteoporosis

IM depot preparation

vi. Levonorgestrel

Postcoital contraceptive, activates estrogen and/or progesterone receptors, thickens cervical mucus, inhibits ovulation ; For Emergency contraception

Severe nausea, vomiting, breast tenderness, irregular bleeding, headache, dizziness (fewer SE compared to estrogen alone and combi contraceptives)

Must be taken within 72 hours of unprotected sexual intercourse

i. Estradiol + Norethindrone ii. Ethinyl Estradiol + Desogestrel iii. Ethinyl Estradiol + Drospirenone

i. Tamoxifen, Torimefene

Estrogen antagonist actions in breast tissue and CNS, Estrogen agonist effects in uterus, liver and bone ; For Hormone responsive breast CA, prophylaxis of breast CA esp. in those with high risk

Hot flushes, thromboembolism, endometrial hyperplasia, endometrial cancer

prevent osteoporosis in postmenopausal women ; Torimefene is structurally related to Tamoxifen

ii. Raloxifene

Estrogen antagonist actions in breast tissue, uterus, and CNS, Estrogen agonist effects in liver and bone. Increases bone mineral density ; For Osteoporosis esp on post menopausal women, breast CA prevention

Hot flushes, thromboembolism

No estrogenic effect on endometrial tissue unlike tamoxifen

iii. Clomiphene

Partial agonist in pituitary, reduces negative feedback by estradiol, increases FSH and LH output ; For Induction of ovulation in women who want to become pregnant

Hot flushes, afterimages, headache, constipation, reversible hair loss, ovarian enlargement

may cause multiple pregnancies ; FULVESTRANT: pure estrogen receptor anatgonist in all tissues used in breast CA resistant to tamoxifen

iv. Anastrozole, Letrozole, Exemestane

Reduces estrogen synthesis by inhibiting aromatase ; For breast CA, precocious puberty

Hot flushes, musculoskeletal disorders, osteoporosis, joint pains

Effective against brest CA that have become tamoxifen-resistant ; Exemestane is an IRREVERSIBLE inhibitor

v. Danazol

Ovarian inhibitor, weak cytochrome P450 inhibitor and partial agonist of progestin a nd androgen receptors ; For Endometriosis, Fibrocystic disease, Hemophilia, Angioneurotic edema

Acne, hirsutism, weight gain, menstrual disturbances, hepatic dysfunction

May also act on Glucocorticoid receptors

vi. Mifepristone (RU486)

Glucocorticoid receptor antagonist, progesterone receptor antagonist ; For Medical abortion, Cushing's syndrome

Vaginal bleeding, abdominal pain, GI upset (vomiting, diarrhea), uterine cramping, nausea, vomiting, headache, dizziness, diarrhea

Combined with misoprostol results in abortion of 95% of early pregnancies ; as abortifacient in early pregnancy (may be used up to 49days after menses) ; complication: failure to induce complete abortion

vii. Leuprolide and Ganirelix

see entry

see entry

see entry

E. Androgens

may be given IV or as TD

i. Testosterone, Fluoxymesterone, Methyltestosterone

Activates androgen receptors, promotes development of male characteristics, increases body muscle bulk and RBC production ; For Male hypogonadism, delayed puberty, wasting syndromes (for weight gain), certain types of anemias

Virilization and menstrual irregularities in females, paradoxical feminization in males, cholestatic jaundice, elevated LFTs

Effects of androgen: secondary sexual characteristics, fertility and libido, male pattern baldness, increases muscle mass, increased RBC production, decreased urea nitrogen excretion, maintains normal bone density ; used illegally by atheletes as performance enhancer

ii. Oxandrolone, Stanozolol, Nandrolone

Activates androgen receptors, promotes development of male characteristics, increases body muscle bulk and RBC production; increased ratio of anabolic-toandrogenic activity in animals

Virilization in females, paradoxical feminization in males; cholestatic jaundice, elevated liver enzymes, hepatocellular CA

this group is called "anabolic steroids"

F. Anti-androgens

For benign and malignant prostate disease, precocious puberty, hair loss and hirsutism

i. Flutamide, Bicalutamide, Nilutamide

Competitive antagonist at androgen receptor ; For Prostate CA, surgical castration

Gynecomastia, hot flushes, impotence, hepatotoxicity

GnRH analogs must be coadministered with flutamide to prevent acute flareups of prostate CA ; Bicalutamide and Nilutamide have less heaptotoxicity

ii. Cyproterone

Antagonist at androgen receptor. Marked progestational effect that suppresses the feedback enhancement of LH and FSH ; for Hirsutism, component of combined oral contraceptives, decreased sexual drive in men

Hepatotoxicity, Adrenal suppression, depression, gynecomastia, galactorrhea, thromboembolism

Orphan drug status

iii. Finasteride, Dutasteride

Androgen synthesis inhibitor, inhibits 5a reducase enzyme that converts testosterone to dihydrotestosterone ; For BPH, Male pattern baldness. Hirsutism

Impotence, gynecomastia, depression

Dutasteride is newer with longer t1/2 ; this group is less likely to cause impotence, infertility and decreased libido

iv. GnRH agonist and antagonists

see entry

see entry

see entry

v. Spironolactone

for treatment of hirsutism in women

P ancreatic Hormones & Antidiabetic Drugs A. Insulins

Activates insulin receptors leading to a reducting of circulating glucose: promotes glucose transport and oxidation; glycogen, lipid, protein synthesis and regulation of gene expression ; For Diabetes mellitus, diabetic emergencies like DKA, HHS (rapid-acting), Hyperkalemia

Hypoglycemia (antidote: sugar or candy, IV glucose, IM glucagon), insulin allergy, immune insulin resistance, lipodystrophy at injection site

Effects of insulin: increased glycogen and protein synthesis, decreased protein catabolism, increased TG storage ; rapid acting insulins are injected a few mins prior to meals and they are the preferred insulin for continuous SC infusion devices ; short-acting insulins are injected more than an hour before a meal ; intermediate acting insulins are often combined with regular and rapid acting insulins ; long acting insulins are called "peakless" insulins

2nd generation sulfonylurea, acts as an insulin secretagogue, increases insulin secretion from pancreatic beta cells by closing ATP sensitive K+ channels leading to depolarization of the B cell; For Type 2 Diabetes Mellitus

Less hypoglycemia, weight gain, photosensitivity, cholestatic jaundice (glibenclamide)

Not effective in patients with functional B cells

1st generation sulfonylurea, acts as an insulin secretagogue; increases insulin secretion from pancreatic beta cells by losing ATP sensitive K+ channels ; for Type 2 Diabetes Mellitus

Hypoglycemia, weight gain, disulfiram reaction, hyperemic flush, dilutional hyponatremia, hematologic toxicity

tolbutamide and chlorpropamide are highly protein bound drugs, which may also cause allergic reactions and rash

i. Repaglinide

Insulin Secretagogue, similar to sulfonylureas with some overlap in binding sites, reduces c irculating glucose, increases glycogen, fat and protein formation and gene regulation ; For Type 2 Diabetes Mellitus

Least hypoglycemia, headache, URTI

Least Hypoglycemia, rapid onset and short DOA

ii. Nateglinide

Insulin Secretagogue, similar to sulfonylureas with some overlap in binding sites, reduces circ ulating glucose, increases glycogen, fat and protein formation and gene regulation ; For Type 2 Diabetes Mellitus

Least hypoglycemia, headache, URTI

Has least incidence of hypoglycemia, may be used in CKD patients ; rapid onset and short DOA

i. Rapid Acting Insulin: Lispro, Aspart, Glulisine ii. Short Acting Insulin: Regular iii. Intermediate Acting: NPH, Lente iv. Long Acting Insulin: Detemir, Glargine, Ultralente, Lantus B. Sulfonylureas

i. Glipizide, Glibenclamide, Glimepiride, Gliclazide, Glyburide

ii. Tolazamide, Tolbutamide, Chlorpropamide C. Meglitinides

D. Biguanides

i. Metformin

Reduced hepatic and renal gluconeogenesis with decreased endogenous glucose production, activates AMP-stimulated protein kinase leading to inhibition of gluconeogenesis ; For Type 2 DM, Diabetes prevention, PCOS

GI disturbance, weight loss, lactic acidosis (esp in renally and hepatically impaired patients), Vit B12 malabsorption

DOC for obese diabetics ; may also cause slowing of glucose absorption from GIT, decreased plasma glucagon ; causes a decrease in endogenous insulin production by increasing insulin sensitivity of tissues "Insulin Sparing Effect" therefore does not have weight gain as a SE ; do NOT cause hypoglycemia

GI disturbance, hypoglycemia, increased liver enzymes, flatulence, diarrhea, abdominal pain

relatively minor glucose lowering effects ; impaired absoprtion of sucrose ; taken immediately before a meal

E. Alpha Glucosidase Inhibitors

i. Acarbose, Miglitol

Inhibits intestinal alpha-glucosidases , reduces conversion of starch and disacchardies to monosaccharidea, reduces post prandial hyperglycemia ; For Type 2 DM, Diabetes prevention

F. Thiazolidinediones

i. Pioglitazone

Regulates gene expression by binding to PPA R-gamma and PPAR-alpha which increases tissue sensitivity, increases glucose uptake in muscle and adipose tissue, inhibits hepatic gluconeogenesis, effects on lipid metabolism and distribution of body fat, control of fasting and postprandial glucose, decreased risk of DM in high-risk patients ; For Type 2 DM, Diabetes prevention

ii. Rosiglitazone

Regulates gene expression by binding to PPAR- gamma ONLY ; for Type 2 DM, Diabetes prevention

Fluid retention, weight gain, congestive heart failure, fractures esp in women, cardiovascular events, hepatotoxicity (Troglitazone), macular edema, dyslipidemia, increased risk of MI (Rosiglitazone)

binds to PPAR-gamma ONLY

i. Exenatide

Analog of GLP-1, Binds to GLP-1 receptors which leads to reducetion of post-meal glucose excursions, increases glucose-mediated insulin release, lowers glucagon levels, slows gastric emptying time, produces satiety ; For Type 2 DM

Hypoglycemia, acute pancreatitis, GI upset, nausea, vomiting

usually combined with SU or metformin ; long-acting injectables

ii. Sitagliptin, Linagliptin

Dipeptidyl Peptidase-4 Inhibitors, blocks degradation of GLP-1, raises circulating GLP-1 levels, reduces postmeal glucose excursions, increases glucose mediated insulin release, lowers glucagon levels, slows gastric emptying time, decreases appetite For Type 2 DM

Headache, nasopharyngitis, URTI

often combined with metformin

binds to PPAR-gamma and PPARalpha ; PPAR regulates transcription of genes encoding proteins involved in carbohydrate and lipid metabolism ; may increase risk for developing Bladder Cancer

G. Novel Antidiabetic Agents

iii. Pramlintide

Analog of amylin, Binds to amylin receptors, reduce post-meal glucose excursions, lowers glucagon levels, slows gastric emptying, decreases appetite ; For Type 2 DM

Hypoglycemia, GI disturbances

used with insulin to control postprandial glucose

iv. Colesevelam hydrochloride

Bile acid binder, lowers glucose through unknown mechanisms ; For Type 2 DM

constipation, dyspepsia, myalgia, asthenia

None

Hypercalcemia, hyperphosphatemia, hypercalciuria

given topically for psoriasis ; given with calcium supplements for osteoporosis

Hypercalcemia, hyperphosphatemia, hypercalciuria ; Doxercalciferol, Paricalcitol and Calcipotriene cause less hypercalcemia and hypercalciuria

The active form Calcitriol is preferred in patients with CKD, chronic liver disease and hypoparathyroidism ; Doxercalciferol is a prodrug that is converted in the liver to 1,25dihydroxyvitaminD ; Paricalcitol, Calcipotriene are analogs of calcitriol and are used topically for psoriasis and are being investigated for malignancies and inflammatory disorders

Agents That Affect Bone Mineral Homeostasis A. Vitamin D Metabolites and Analogs

i. Cholecalciferol, Ergocalciferol

ii. Calcitriol, Doxercalciferol, Paricalcitol, Calcipotriene

INACTIVE Vitamin D; Regulates gene tanscription via the vitamin D receptor; stimulates intestinal calcium absorption, bone resorption, renal calcium and phosphate reabsorption, decreases PTH, promote innate immunity ; For Vitamin D deficiency states (intestinal osteodystrophy, CKD, chronic liver disease, hypoparathyroidism, nephrotic syndrome) osteoporosis, psoriasis

ACTIVE Vitamin D; Regulates gene tanscription via the vitamin D receptor; stimulates intestinal calcium absorption, bone resorption, rena calcium and phosphate reabsorption, decreases PTH, promote innate immunity ; For Secondary hyperparathyroidism in CKD, hypocalcemia in hypoparathyroidism, psoriasis

B. Bisphosphonates

Suppress the activity of osteoclasts in part via inhibition of farnesyl pyrophosphate synthesis, inhibit resorption and formation of bone by ac ting on the basic hydroxyapatite crystal structure ; For Paget's disease of the bone, Hypercalcemia esp in malignancies, Osteoporosis

Adynamic bone, Esophagitis, Osteonecrosis of the Jaw, renal impairment, GI irritation (remedy: take lots of water and keep patient in an upright position for 30mins after intake of drug)

Pamidronate, Zoledronic acid and Etidronate are used IV for hypercalcemia in Paget's disease and cancer ; all other preparations and Etidronate can be given PO but with low bioavailability (<10%) ; Treatment regimen: oral OD (alendronate, risedronate, ibandronate), weekly PO (alendronate, risedronate), monthly PO (ibandronate), quarterly injection (ibandronate), annual IV (zoledronate)

i. Teriparatide

Recombinant PTH, Acts via cognate G protein coupled receptors, stimulates bone formation when given in low intermittent doses

hypercalcemia, arthralgia, rhinitis, nausea, weakness, dizziness, pharyngitis, dyspepsia, rash

used IV for osteoporosis

ii. Calcitonin

Acts via cognate G protein coupled receptors; suppresses bone resorption ; For Paget's disease of the bone, hypercalcemia, osteoporosis, tumor marker for thyroid CA

Rhinitis, Nausea, vomiting, facial flushing

given as injection or as nasal spray ; used for osteoporosis but is less effective than bisphosphonates and teriparatide

Interacts selectively with estrogen receptors, inhibits PTH-stimulated bone resorption without stimulating breast or endometrial hyperplasia, delay bone loss in post-menopausal women

see entry

see entry

Monoclonal antibody, binds to RANKL and prevents it from stimulating osteoclast differentiation and function, blocks bone resorption ; For postmenopausal osteoporosis

increased risk of infection

as potent as bisphosphonates ; given SC every 6months which avoid the GI SE

Activates the calcium sensing receptors in the parathyroid gland, inhibits PTH secretion ; For secondary hyperparathyroidism in CKD,

hypocalcemia, adynamic bone disease (profound decreae in bone

considered a Calcimimetic

i. Alendronate, Risedronate, Ibandronate, Pamidronate, Zoledronate, Etidronate, Tiludronate, Zoledronic acid C. Hormones

D. Selective Estrogen Receptor Modulators (SERMs)

i. Raloxifene E. Rank Ligand (RANKL) Inhibitor

i. Denosumab F. Calcium Receptor Antagonist

7. CHEMOTHERAPEUTIC DRUGS Beta-Lactam & Other Cell Wall-Active & Membrane-Active Antibiotics Bactericidal ; excreted unchanged in the urine ; capable of entering the blood brain barrier

A. Penicillin

i. Natural Penicillins: Penicillin G, Penicillin V (narrow spectrum penicillin)

ii. Anti-Staphylococcal Penicillins: Methicillin, nafcillin, oxacillin, cloxacillin (very narrow spectrum)

iii. Extended Spectrum Penicillin: Ampicillin, Amoxicillin

iv. Antipseudomonal Penicillin: Piperacillin, ticarcillin, carbenicillin

Binds to penicillin-binding proteins, inhibits transpeptidation in bacterial cell walls ; DOC for syphillis, for streptococcal, meningococcal, G+ bacilli, spirochete infection

Binds to penicillin-binding proteins, inhibits transpeptidation in bacterial cell walls; For staphylococcal infections

Binds to penicillin-binding proteins, inhibits transpeptidation in bacterial cell walls ; For enterococci, Listeria, E. coli, Proteus, H. influenza, Moraxella

Binds to penicillin-binding proteins, inhibits transpeptidation in bacterial cell walls ; For Pseudomonas, Enterobacter, Klebsiella

hypersensitivity, GI disturbances, interstitial nephritis (methicillin), neutropenia (nafcillin)

Resistant to inactivation by betalactamase (penicillinase) ; all penicillins are excreted unchanged in the urine EXCEPT for Nafcillin which is excreted in the bile

hypersensitivity, GI disturbances, pseudomembranous colitis (ampicillin), rash (ampicillin)

Inactivated by beta-lactamase (penicillinase), enhanced effect when used with beta-lactamase inhibitors (clavulanic acid, sulbactam) ; ampicillin undergoes enterohepatic recirculation ; synergistic effect with aminoglycosides

hypersensitivity, GI disturbances

Inactivated by beta-lactamase (penicillinase), enhanced effect when used with beta-lactamase inhibitors (clavulanic acid, tazobactam) Bactericidal ; mostly IV ; all have renal excretion EXCEPT Cefoperazone and Ceftriaxone

B. Cephalosporins

i.First Generation: Cefazolin, cefadroxil, cephalothin, cephapirin, cephradine, cephalexin

hypersensitivity, GI disturbances

Inactivated by beta-lactamase (penicillinase) ; given IM but Pen V can be given PO ; increased activity against enterococci when given together with aminoglycosides

Binds to penicillin-binding proteins, inhibits transpeptidation in bacterial cell walls ; For surgical prophylaxis, bone infections, infections due to staph

Increases nephrotoxicity of aminoglycosides ; do not cross the BBB ; minimal activity against Gcocci, enterococci, MRSA and most

ii. Second Generation: Cefamandole, cefaclor, cefonicid, cefuroxime, cefprozil, loracarbef, ceforanide, cefoxitin, cefmetazole, cefotetan

Binds to penicillin-binding proteins, inhibits transpeptidation in bacterial cell walls ; For surgical prophylaxis, bone infections, infections due to staph strep and E. coli, Enterobacter, Neisseria, infections against anaerobes (Bacteroides), sinus ear and respiratory infections by Klebsiella andHemophilus

hypersensitivity, injection site reactions, phlebitis, GI upset, Hypoprothrombinemia and Disulfiram rection (cefamandole, cefotetan)

Increases nephrotoxicity of aminoglycosides ; do not cross the BBB ; slight less activity against G + but extended G- activity ; Cefuroxime has improved action against pneumococcus and H. influenzae ; Cefotetan and Cefoxitin have good activity against B. fragilis and thus are used for abdominal and pelvic infections

hypersensitivity, GI upset, Hypoprothrombinemia and Disulfiram rection (cefoperazone)

Synergistic effect with aminoglycosides ; all have renal excretion EXCEPT Cefoperazone and Ceftriaxone ; all can penetrate the BBB EXCEPT Cefoperazone and Cefixime ; Ceftriaxone and Cefotaxime are the most active Cephs against Penicillin resistant Streptococcus pneumoniae ; Ceftizoxime is commonly used against Bacteroides ; should be reserved against serious infection EXCEPT ceftriaxone and cefixime ; Ceftriaxone has very good CNS penetration ; Ceftazidime has very good action on Pseudomonas

iii. Third Generation: Cefoperazone, cefotaxime, ceftizoxime, ceftriaxone, cefixime, cefpodoxime proxetil, cefdinir, ceftibuten

Binds to penicillin-binding proteins, inhibits transpeptidation in bacterial cell walls ; decreased gram + coverage, increased gram – activity (pseudomonas, bacteroides), against Providencia, Serratia, Neiserria, Haemophilus ; DOC for gonorrhea (Ceftriaxone and Cefixime)

hypersensitivity, GI upset

More resistant to beta-lactamase produced by Enterobacter, Haemophilus, Neisseria and Pneumococcal ; Has improved stability to chromosomal lactamase ; Ceftaroline used for MRSA

hypersensitivity, GI upset, CNS toxicity (confusion, encephalopathy, seizures)

Reserved for serious ife-threatening infections; cilastatin inhibits renal metabolism of imipenem ; given IV ; low susceptibility to B-lactamases ; active against Pseudomonas and Acinetobacter EXCEPT Ertapenem ; Imipenem given with Cilastatin which acts as Dehydropeptidase enzyme inhibitor ; Partial crossallergenicity with Penicillins ; Ertapenem has longer t1/2 but less active against Enterococci and Pseudomonas

GI upset, superinfection, vertigo, headache, skin rash and hepatotoxicity

Resistant to beta-lactamase, no activity against gram + bacteria or anaerobes ; given IV ; synergistic with AG ; renal excretion ; No crossallergenicity with Pens

hypersensitivity and cholestatic jaundice

Most active against plasmid encoded B lactamases (Gonococci, Streptococci, E coli and H. Influenzae ; not good inhibitor of inducible chromosomal B lactamases (Enterobacter,Pseudomonas, Serratia)

iv. Fourth Generation: Cefipime, Ceftaroline Binds to penicillin-binding proteins, inhibits transpeptidation in bacterial cell walls ; wide c overage against gram + and gram - bacteria C. Other Beta-Lactams

i. Carbapenems: Imipenem-cilastatin , ertapenem, meropenem Binds to penicillin-binding proteins, inhibits transpeptidation in bacterial cell walls, wide coverage against gram + gram - bacteria and anaerobes ; For infections resistant to other antibiotics EXCEPT MRSA, DOC for Enterobacter, Citrobacter and Serratia

ii.Monobactam: Aztreonam

iii. Beta-Lactamase Inhibitors: Clavulanic acid , sulbactam, tazobactam

Binds to penicillin-binding proteins, inhibits transpeptidation in bacterial cell walls ; used agai nst Gram – like klebsiella, pseudomonas and Serratia

Inhibits inactivation of penicillins by bacterial betalactamase (penicillinase); used against beta-lactamase producing gonococci, streptococci, E. coli and H. influenza

D. Other Cell Wall Synthesis Inhibitors

Inhibits cell wall synthesis by binding to the D-Ala-DAla terminus of nascent peptidoglycan --> inhibit transglycosylation --> prevent elongation and crosslinking of peptidoglycan chain ; For MRSA, PRSP, as alternative for pseudomembranous colitis

red man syndrome, nephrotoxicity, ototoxicity, chills, fever, phlebitis

Narrow spectrum Treat red man syndrome by slowing the rate of infusion ; VRSA and VRE are due to D-Ala-D-Lactate formation ; teicoplanin and telavancin are not absorbed in the GIT thus used for bacterial enterocolitis, they are also eliminated unchanged in the urine ; decrease dose for renally impaired patients ; Dalbavancin has very long t1/2 (6-11 days) which permits once-weekly dosing and is more active than Vancomycin

ii. Peptide Antibiotic: Bacitracin

Interferes with a late stage oin cell wall synthesis in gram + organisms ; For gram + bacteria

nephrotoxicity

Reserved for topical use only due to marked nephrotoxicity

iii. Antimetabolite: Cycloserine

Blocks incorporation of D-Ala into the pentapeptide side chain of the peptidoglycan ; For drug-resistant TB

neurotoxicity (tremors, seizures and psychosis)

only used as a second-line agent in TB

iv. Antimetabolite: Fosfomycin

inhibits cytosolic enolpyruvate transferase --> prevents formation of N-acetylmuramic acid (a peptidoglycan precursor molecule)

Diarrhea

renal excretion ; resistance emerges rapidly ; synergistic with Beta lactam and quinolones

myopathy

monitoring of CPK is needed, NOT Bactericidal (only destabilizes bacterial cell membrane)

GI disturbance, aplastic anemia, gray baby syndrome

given PO and IV ; able to cross the placenta and BBB ; Inhibits hepatic drug-metabolizing enzymes causing many drug interactions ; resistance is due to the formation of acetyltransferase that inactivates drug ; usually used as topical agent

i. Glycopeptides: Vancomycin, teicoplanin, telavancin, dalbavancin

v. Cyclic lipopeptide: Daptomycin

same spectrum of activity as Vancomycin ; For VRE, VRSA, for G+ acitivity, against endocarditis and sepsis

Tetracyclines, Macrolides, Clindamycin, Chloramphenicol, Streptogramins & Oxazolidinones

A. Chloramphenicol (broad spectrum protein synthesis inhibitor)

Inhibits transpeptidation (catalyzed by peptidyl transferase) by blocking the binding of aminoacyl moiety of the charged tRNA to the acceptor site o mRNA at 50S subunit, basteriostatic ; For meningitis (Strep pneumonia, H influenza, Neisseria meningitides), back up for Salmonella, Rickettsia, Bacteroides, Wide spectrum antibiotic

B. Tetracyclines: Tetracycline, doxycycline, minocycline, tigecycline, demeclocycline

Binds 30s ribosomal subunit thus preveting the binding of tRNA to mRNA, bacteriostatic ; Broad/Wide Spectrum (G+ and G-), For infections caused by Mycoplasma pneumonia, Chlamydia, Rickettsia, Vibrio, Spirochetes such as Leptospira, Peptic ulcer disease, Lyme disease, Malaria prophylaxis, Amoebiasis, Acne, Doxycycline is an alternative to macrolides as initial treatment of CAP, Alternative in syphilis, treatment of respiratory infection caused by susceptible organism, prophylaxis against infection in chronic bronchitis ; Selective uses: Tetracycline (H. Pylori PUD), Doxycycline (Lyme disease and malaria prevention), Minocycline (Meningococcal carrier state), Demeclocycline (SIADH), Tigecycline (more broad spectrum - MRSA, VRE, B-lactamase producing G- bacteria, anaerobes, Chlamydiae, Mycobacteria)

GI disturbances (enetrocolitis, nausea, diarrhea, vomiting), teratogen (tooth enamel dysplasia/discoloration), hepatotoxicity, nephrotoxicity, photosensitivity n(esp. demeclocycline), vestibulotoxicity, candidiasis, bacterial superinfection with S. aureus and C. difficile, Fanconi syndrome

Tigecycline has the broadest spectrum and has the longest t1/2 (30-36hrs); do not drink with milk (decreased absorption with divalent cations like calcium) ; high Vd, cross the placenta, enterohepatic recycling ; all are excreted renally EXCEPT Doxycycline (bile) ; Resistance is due to development of efflux pumps for active extrusion of tetracyclines and the formation of ribosomal protection proteins that interfere with tetracycline binding (but not present with Tigecycline EXCEPT in Proteus and Pseudomonas) ; Tigecycline is given IV only and is unaffected by common tetracyclie resistace mechanisms

C. Macrolides

Binds 30s ribosomal subunit, inhibit transpeptidation, bacteriostatic ; For community-acquired pneumonia, pertussis, diphtheria, chlamydial infections ; Eryhthromycin (Campylobacter, Chlamydia, Mycoplasma, Legionella, Corynebacterium, Chlamydophila, Legionella, Ureaplasma, Bordetella, G+ cocci, some G-), Clarithromycin and Azithromycin (coverage of Erythromycin plus greater activity against Chlamydia, Mycobacterium avium, Toxoplasma, Helicobacter, Haemophilus, Moraxella, Neiserria) ; Azithromycin is used as an alternative Ceftriaxone in Gonorrhea and to Pen G in syphilis

GI disturbance, cholestatic hepatitis, QT prolongation, drug interaction

good oral bioavilability but azithromycin absoprtion is impeded by food ; All macrolides inhibit CYP450 except azithromycin; azithromycin has highest Vd and slowest elimination; telithromycin is used for macrolide-resistance ; Halflives: Erythromycin (2hrs), Clarithromycin (6hrs), Azithromycin (24-48hrs) ; Resistance is due to development of efflux pumps and production of methylase enzyme ; Cross-resistance among macrolides: complete or partial resistance with drugs acting on the 50S

ii. Fidaxomicin

a narrow spectrum macrolide, for G+ and anaerobe, low oral bioavailability

GI upset, rashes, eosinophilia, acute cholestatic hepatitis, enzyme inhibitor

as effective as Vancomycin as treatment for C. difficile possibly with lower relapse rate

iii. Telithromycin

Ketolide, structurally related to macrolide, same MOA and spectrum as erythromycin but macrolide-resistant organisms are susceptible to telithromycin ; For CAP

QT prolongation, enzyme inhibitor, hepatic dysfunction

For CAP including multi-drug resistant organisms, A ketolide not a macrolide in chemical structure

GI disturbance, skin rash, neutropenia, hepatic dysfunction, possible superinfection (Pseudomembranous colitis - C. diff icile overgrowth)

Cross-resistance between clindamycin and macrolides is common ; Resistance is due to methylation of binding sites and enzymatic inactivation ; G- aerobes are resistant because of poor penetration through th eouter membrane

Injection site reaction, anthralgia-myalgia syndrome

Inhibits CYP450 enzymes causing multiple drug interactions ; BACTERICIDAL

i. Erythromycin, azithromycin, clarithromycin, telithromycin

D. Lincosamides: Clindamycin, lincomycin

Binds 30s ribosomal subunit, inhibit transpeptidation, bacteriostatic ; For anaerobic infections (Bacteroides), alternative against gram + cocci (MRSA), endocarditis prophylaxis esp in those allergic to Pens, PCP pneumonia, toxoplasmosis (+ Pyrimethamine), skin and soft tissue infection

E. Streptogramin: Quinupristin-Dalfopristin

Binds 50s ribosomal subunit, constricting the channel where polypeptides are extruded thus tRNA synthetase is also inhibited --> decreased free tRNA ; For infections caused by drug-resistant gram + cocci (MRSA, VRSA, PRSP, resistant E. faecium)

F. Oxazolidinone: Linezolid

Binds 23S rRNA of 50s ribosomal subunit, inhibit initiation by blockin formation of the tRNA-ribosomemRNA ternary complex, bacteriostatic ; Reserved for infections caused by drug-resistant gram + cocci (MRSA, VRE, PRSP), Listeria, Corynebacteria

Thrombocytopenia, neutropenia, serotonin syndrome, neuropathy, optic neuritis

Inhibits CYP450 enzymes causing multiple drug interactions ; Resistance is due to decreasedaffinity of drug to binding site

nephrotoxicity (reversible - Acute Tubular Necrosis esp in elderly, if given with Amphotericin B, Cephalosporin and Vancomycin)), ototoxicity (irreversible), neuromuscular blockade (Curare-like block --> respiratory paralysis. Remedy: Calcium, Neostigmine and Mechanical Ventilator) ; S. pneumoniae is resistant to Gentamicin, Enterococci is resistant to amikacin, gentamicin, tobramycin but NOT streptomycin

AG are given IM or IV only, have concentration dependent killing, is not capabale of penetrating the blood brain barrier, low tissue penetration, SYNERGISTIC effect with cell wall synthesis inhibitors due to enhancement of transport to the inside of the bacterial cell ; mechanism of resistance of AG: plasmid-mediated formation of inactivating enzymes "group transferase" --> catalyze the acetylation of amine functions and the transfer of phosphoryl or adenylyl groups to the oxygen atoms of the hydroxyl groups of AG, For Streptomycin, resistance is due to changes in the ribosomal binding site ; Gentamicin and tobramycin are the most vestibulotoxic and nephrotoxic

nephrotoxicity (reversible), ototoxicity (irreversible), neuromuscular blockade

Least resistance and narrowest therapeutic window ; used for streptomycin-resistant TB

hypersensitivity, nephrotoxicity (reversible), ototoxicity (irreversible), neuromuscular blockade, teratogen (congenital deafness), injection site reactions

Administered intramuscularly ; if given together with Pens can be used for enterococcal endocarditis, TB plague and tularemia

Aminoglycosides & Spectinomycin

B. Amikacin

General MOA of all aminoglycosides (AG) is by inhibiting protein synthesis by binding to 30s subunit: (1) block formation of the initiation complex (2) cause misreading of the code on the mRNA template (3) inhibit translocation, bactericidal ; For serious infections caused by aerobic gram – bacteria (E.coli, Enterobacter, Klebsiella, Proteus, Providencia, Pseudomonas, Serratia, Haemophilus, Moraxella, Shigella), endocarditis, ocular infections ; If given together with Pens, may be used f or Listeria, Enterococcus and G+ cocci Inhibits protein synthesis by binding to 30s subunit, bactericidal ; For serious infections caused by aerobic gram – bacteria (E.coli, Enterobacter, Klebsiella, Proteus, Providencia, Pseudomonas, Serratia, Haemophilus, Moraxella, Shigella), endocarditis, ocular infections, multidrug resistant TB (2nd line) ; If given together with Pens, may be used for Listeria, Enterococcus and G+ cocci

C. Streptomycin

Inhibits protein synthesis by binding to 30s subunit, bactericidal ; For TB, tularaemia, bubonic plague, brucellosis

A. Gentamycin, tobramycin

D. Neomycin, kanamycin, paromomycin

Inhibits protein synthesis by binding to 30s subunit, bactericidal ; For skin infections, bowel preparations for elective surgeries, hepatic encephalopathy, visceral leishmaniasis (paromomycin)

hypersensitivity, nephrotoxicity (reversible), ototoxicity (irreversible), neuromuscular blockade

Limited to topical and oral use due to nephrotoxicity, kanamycin is most ototoxic ; Neomycin has the most skin reactions (allergic reactions, contact dermatitis)

E. Spectinomycin

Inhibits protein synthesis by binding to 30s subunit, bactericidal ; For drug-resistant gonorrhoea, gonorrhoea in penicillin allergic patients

nephrotoxicity (reversible), ototoxicity (irreversible), neuromuscular blockade

Ototoxcity of AG's can be increased by loop diuretics

F. Netilmicin

Inhibits protein synthesis by binding to 30s subunit, bactericidal ; For serious infections caused by aerobic gram – bacteria

hypersensitivity, nephrotoxicity (reversible), ototoxicity (irreversible), neuromuscular blockade

For Treatment of serious infections caused by organisms resistant to other aminoglycosides

Inhibits dihydropteroate synthase, bacteriostatic ; For burn infections, for G=, G-, Chlamydia and Nocardia, Simple oral sulfas (UTI), Sulfacetamide (ocular infection, topical), Mafenide and Silver sulfadiazine (burn infection, topical), Sulfasalazine (Ulcerative colitis and RA, oral), Sulfadizaine + Pyrimethamine + Folinic acid (Toxoplasmosis, oral)

GI upset, mild hepatic dysfunction, acute hemolysis in G6PD deficiency, nephrotoxicity (precipitate in the urine at acidic pH --> crystalluria, hematuria), hypersensitivity (cross-allergenicity with other related drugs such OHAs and diurectics), exfoliative dermatitis, polyarteritis nodosa, SJS, hematotoxicity (granulocytopenia, thrombocytopenia, aplactis anemia), kernicterus ; Drug Interactions: warfarin, methotrexate, bilirubin

low solubility in acidic urine causing formation of stones ; Resistance is due to plasmin-mediated (decreased intracellular accumulation of the drug, increased production of PABA by bacteria, decreased sensitivity of dihydropteroate synthetase to sulfas and production of dihydrofolate reductase that has decreased affnity for the drug ; sulfonamides are formulated in a 5:1 ratio with trimethoprim

B. Combination: Co-trimoxazole (Sulfamethoxazole + Trimethoprim)

Sequential blockade of dihydropteroate synthase (sulfamethoxazole) and dihydrofolate reductase (trimethoprim), bactericidal ; For UTI, respiratory, ear and sinus infections (Hemophilus, Moraxella, Aeromonas), DOC for P. jiroveci pneumonia and Nocardiosis, toxoplasmosis, Back-up for cholera typhoid fever shigellosis, G- sepsis, MRSA, Listeria

GI upset, acute hemolysis in G6P D deficiency, nephrotoxicity, hypersensitivity, hematotoxicity, kernicterus ; trimethoprim toxicity: antifolate effects (megaloblastic anemia, leukopenia, granulocytopenia)

Sulfonamides are weakly acidic while Trimethroprim is a weak base ; remedy for antifolate effects: Folinic acid supplement

C. Fluoroquinolones

Avoid in pregnancy due to absence of safety data

Sulfonamides, Trimethoprim & Quinolones A. Sulfonamides: Silver sulfadiazine, mafenide acetate i. Short acting: Sulfisoxazole ii. Intermediate acting: Sulfamethoxazole

iii. Long acting: Sulfadoxine

i. First Generation Fluoroquinolones: Norfloxacin, Nalidixic acid

Inhibits DNA replication by binding to DNA gyrase and topoisomerase IV (G+) and Topoisomerase II (G-), bactericidal, inhibition of Topoisomerase II results in blockade of relaxation of supercoiled DNA that is catalyzed by DNA gyrase while inhibition of Topoisomerase IV interferes with the separation of replicated chromosomal DNA during cell division ; General use of FQs: For infections of the urogenital and GI tract by G- (gonococci, E. coli, Klebsiela, Campylobacter, Enterobacter, Pseudomonas, Salmonella, Shigella), respiratory tract, skin and soft tissue infection ; may be used against meningococcal carrier state, for treatment of TB and prophylaxis in neutropenic patients

ii. Second Generation Fluoroquinolones: Ciprofloxacin, ofloxacin, Enoxacin Norfloxacin

Inhibits DNA replication by binding to DNA gyrase and topoisomerase IV (G+) and Topoisomerase II (G-), bactericidal, bactericidal ; For UTI and GIT infections (gram – rods, gonococci, gram + cocci), atypical pneumonia (Mycoplasma, Chlamydophila), Mycobacteria ; increased activity against G-

General SE: GI distress, skin rashes, HA, dizziness, insomnia, increased LFT, phototoxicity, CNS effects (dizziness, headache), tendinitis and tendon rupture, opportunistic infection by Candida and Streptococci ; CI in pregnancy and in children (damage growing cartilage --> arthropathy), enhance toxicity of methylxanthines (theophylline) ; Mechanism of resistance for Quinolones: decreased intracellular accumulation via efflux pumps, change in porin structure, c hnages in sensitivity of target enzyme svia point mutations in the antibiotic binding region, mutations in the quinolone resistance determining region of the gyrA gene that encodes for DNA gyrase

General properties of quinolones: good oral bioavailability, high Vd, t1/2 3-8hrs, absorption is impeded by antacids, elimination is via kidneys by tubular secretion (may compete with probenecid for excretion) EXCEPT for MOXIFLOXACIN ; Norfloxacin does not achieve adequte plasma levels for use in systemic infections

GI distress, skin rashes, HA, dizziness, insomnia, increased LFT, phototoxicity, CNS effects (dizziness, headache), tendinitis and tendon rupture, opportunistic infection by Candida and Streptococci ; CI in pregnancy and in children (damage growing cartilage --> arthropathy)

high resistance esp for C. jejuni, gonococci, G+ cocci like MRSA, Pseudomonas and Serratia ; are used as alternative to Ceftriaxone and Cefixime in gonorrhea ; Ofloxacin can be used against C. trachomatis

iii. Third Generation Fluoroquinolones: Levofloxacin, Gemifloxacin, Moxifloxacin, Sparfloxacin

iv. Fourth Generation Fluoroquinolones: Trovafloxacin,

Inhibits DNA replication by binding to DNA gyrase and topoisomerase IV (G+) and Topoisomerase II (G-), bactericidal, bactericidal ; For lung infections caused by gram + cocc i, atypical pneumonia (Chlamydia, mycoplasma) ; less G- activity compared to 2nd gen but increased activity against G+ cocci, enterococci, MRSA

GI distress, skin rashes, HA, dizziness, insomnia, increased LFT, phototoxicity, CNS effects (dizziness, headache), tendinitis and tendon rupture, opportunistic infection by Candida and Streptococci ; CI in pregnancy and in children (damage growing cartilage --> arthropathy)

"Respiratory Quinolones" ; Moxifloxacin and Gemifloxacin are the newest members of this family and are condisered to have the broadest spectrum of activity with increased activity aginst anaerobes ang atypical agents ; FQ elimination is via kidneys by tubular secretion (may compete with probenecid for excretion) EXCEPT Moxifloxacin ; NEVER use moxifloxacin in UTI ; Levofloxacin is used in CAP caused by Chlamydia, Mycoplasma and Legionella ; Gemifloxacin, Levofloxacin and Moxifloxacin can prolong QT ; Levofloxacin has superior activity against G(+) bacteria including S. pneumoniae ; All have relatively long t1/2 permitting once daily dosing ; Oral absorption is impaired by cations ; Gatifloxacin can cause hyperglycemia in DM Px and hypoglycemia in patients also receiving OHA and was withdrawn from the market in 2006 (USA)

Inhibits DNA replication by binding to DNA gyrase and topoisomerase IV (G+) and Topoisomerase II (G-), bactericidal, bactericidal ; has broad spectrum activity (gram – and gram +), enhanced activity against

GI distress, skin rashes, HA, dizziness, insomnia, increased LFT, phototoxicity, CNS effects (dizziness, headache), tendinitis and tendon rupture, opportunistic infection by Candida and Streptococci ; CI in pregnancy and in children (damage growing

additional SE: diabetes (gatifloxacin), hepatotoxicity

D. Miscellaneous agents

i. Metronidazole, tinidazole

Reactive reduction by ferredoxin forming free radicals that disrupt electron transport chain, bactericidal ; For anaerobic or mixed intra-abdominal infections, vaginitis (trichomonas, gardnerella), pseudomembranous colitis, brain abscess, protozoal infections

ii. Nitrofurantoin

Forms multiple reactive intermediates when acted upon by bacterial nitrofuran reductase, bactericidal ; For UTI (except Proteus and Pseudomonas)

GI irritation, metallic taste, headache, dark urine, leukopenia, dizziness, ataxia, neuropathy, seizures and disulfiram reaction

DOC for amoebiasis, giardiasis and Pseudomembranous colitis

GI irritation, skin rashes, pulmonary infiltrates, phototoxicity, neuropathies, hemolysis in patients with G6PD deficiency

single OD dose can prevent recurrent UTI ; acidification of urine enhances activity ; adjust dose in renal patients

hepatotoxicity, neurotoxicity (seizures, peripheral neuritis, insomnia, restlessness, muscle twitching), acute hemolysis in G6PD deficiency, drug-induced lupus

Most impt drug in TB, prevent neurotoxicity by giving pyridoxine (vit B6) ; structural congener of pyridoxine ; high level resistance due to deletion of KatG gene whichh codes for catalaseperoxidase enzyme involved in bioactivation of INH, low level resistance due to deletion og inhA gene which encodes the target enzyme which is an acyl protein reductase ; Potent CYP450 inhibitor

red-orange urine, light chain proteinuria, skin ra sh, thrombocytopenia, nephritis, hepatotoxicity, flulike syndrome,

Potent CYP450 inducer ; rapid development of resistance if used alone ; resistance is due to changes of drug sensitivity of the polymerase enzyme; undergoes enterohepatic recirculation ; orange-colored metabolites ; delay emergence of resistance to dapsone ; Rifabutin is equally effective as anti-mycobacterial agent with less drug interaction and it is the preferred anti-TB for AIDS patients ; Rifamixin is not absorbed in the GIT

Antimycobacterial Drugs

A. Isoniazid (nicotinic acid derivative)

B. Rifamycin derivatives: Rifampicin, rifabutin, rifapentine,

Inhibits mycolic acid synthesis, bactericidal ; For TB, for latent infection, given as a sole drug for prophylaxis of close contacts and skin test converters

Inhibits DNA-dependent RNA polymerase, bactericidal ; For TB, leprosy, prophylaxis for meningococcal and staphylococcal carrier states, drug-resistant infections (MRSA, PRSP) when given together with Vancomycin, can be used as sole drug in the treatment of latent TB in INH-intolerant patient or in close contact of

C. Ethambutol (butanol derivative)

D. Pyrazinamide (pyrazine derivative) E. Streptomycin (aminoglycoside)

Inhibits arabinosyl transferases involved in the synthesis of arabinogalactan in mycobacterial cell wall, bacteriostatic ; For TB

Unknow MOA, bacteriostatic but can be bactericidal on actively dividing mycobacteria, is metabolozed to pyrazinoic acid, t 1/2 is increased in liver and kidney disease ; For TB for MDRTB (TB meningitis, miliary TB, severe organ TB)

dose-dependent visual disturbances (decreased visual acuity, red green color blindness, retrobulbar neuritis, retinal damage, optic neuritis), headache, confusion, hyperuricemia, peripheral neuritis

Resistance is due to mutation in emb gene ; dose adjustment id needed in renal patients ; always used in combination with other drugs for TB

hepatotoxicity, nongouty polyarhtralgia, asymptomatic hyperuricemia, myalgia, GIT irritation, maculopapular rash, porphyria, photosensitivity ; CI in pregnancy

Most hepatotoxic anti-TB drug, also known as sterilizing agent ; r equire metabolic conversion via pyrazinamidases in MTb ; resistance is via mutation in pncA gene which codes for pyrazinamidases and increased efflux systems ; decrease dose in hepatic and renal patients

see entry

see entry

Drugs for Leprosy

A. Sulfones: Dapsone, acedapsone

Inhibition of folic acid synthesis, bacteriostatic ; For leprosy, alternative for PCP pneumonia

GI irritation, fever, skin rashes, methemoglobinemia, acute hemolysis in G6PD deficiency patients

Most active drug against M. leprae ; used in combination with rifampicin and clofazimine ; Acedapsone is a repository form of dapsone which has drug action that can last for several months

B. Clofazimine

Binds to guanine bases in bacterial DNA, bactericidal ; For leprosy

GI irritation, skin discoloration

a phenazine dye

infusion reactions (chills, fever, muscle spasms, vomiting, hypotension), dose limiting nephrotoxicity (decreased GFR, ATN

Control infusion reactions by slowing the rate of infusion and premedication with antihistamines, additive nephrotoxicity with other nephrotoxic drugs (aminoglycosides) ; highly lipid soluble, poorly absorbed in the GIT ; high Vd except in the CNS with a t1/2 of 2weeks ; resistance is due to decreased level of ergosterol or

Antifungal Agents

Binds to ergosterol in fungal cell membranes, forming artificial pores, fungicidal, WIDEST antifungal spectrum ; For systemic fungal infections (aspergillus, blastomyces, candida, Cryptococcus, histoplasma, mucor), for initial induction before followup

B. Flucytosine

Accumulated in fungal cells by the action of permease and converted by cytosine deaminase to 5-FU, which inhibits thimidylate synthase, pyrimidine antimetabolite, fungistatic ; given together with ampho B and Triazoles - For cryptococcal infection, systemic candidal infections, chromoblastomycosis

reversible myelosuppresion, alopecia, hepatotoxicity

decrease dose in renal patients ; resistance is due to decreased activity of fungal permease and deaminase ; has synergistic effect when given with ampho B and Triazoles.

GI disturbances (vomiting, diarrhea), rash, hepatotoxicity, drug interaction, gynecomastia, menstrual irregularities and infertility

Limited to topical use because of systemic toxicity ; narrow antifungal spectrum ; resistance is due to chnages in the sensitivity of target enzyme ; Potent CYP450 inhibitor ; Ketoconazole is rarely used due to drug interactions and narrow spectrum

GI disturbances (vomiting, diarrhea), rash, hepatotoxicity

alternative to Ampho B in the treatment of C. neoformans, as effective as Ampho B in c andidemia


may also be used for subcutaneous chromoblastomycosis

GI disturbances (vomiting, diarrhea), rash, hepatotoxicity, blurring of vision in 30% of patients, CI in pregnancy

wider specturm azole

C. Azole Antifungals

i. Ketoconazole (Imidazole)

Inhibit 14α -demethylase --> decreased ergosterol production --> increased permeability of cell membrane, Inhibits fungal P450- dependent enzymes blocking ergosterol synthesis, fungistatic ; For chronic mucocutaneous candidiasis, dermatophytosis

iii. Itraconazole (Triazole)

Inhibit 14α -demethylase --> decreased ergosterol production --> increased permeability of cell membrane, Inhibits fungal P450- dependent enzymes blocking ergosterol synthesis, fungistatic ; DOC for candidiasis (esophageal, oropharyngeal, vulvovaginitis), coccidioidomycosis, cryptococcal meningitis (treatment and prophylaxis) Inhibit 14α -demethylase --> decreased ergosterol production --> increased permeability of cell membrane, Inhibits fungal P450- dependent enzymes blocking ergosterol synthesis, fungistatic ; DOC for blastomycosis, sporotrichosis, dermatophytosis esp onchomycosis, chromoblastomycosis ; alternative for infections due to Aspergillus, Coccidioides, Cryptococcus and Histoplasma , for esophageal candidiasis resistant to fluconazole

iv. Voriconazole (Triazole)

Inhibit 14α -demethylase --> decreased ergosterol production --> increased permeability of cell membrane, Inhibits fungal P450- dependent enzymes blocking ergosterol synthesis, fungistatic ; co-DOC for invasive aspergillosis, alternative in candidemia, for fluconazole-resistant organisms, for candidal esophagitis and stomatitis in AIDS patients

ii. Fluconazole (Triazole)

v. Posaconazole (Triazole)

Inhibit 14α -demethylase --> decreased ergosterol production --> increased permeability of cell membrane, Inhibits fungal P450- dependent enzymes blocking ergosterol synthesis, fungistatic ; For Candida and Aspergillus, as prophylaxis of fungal infection during cancer chemotherapy, salvage therapy in invasive aspergillosis


BROADEST spectrum triazole ; the only azole with activity against Rhizopus sp. (mucormycosis) ; Potent CYP450 inhibitor

vi. Clotrimazole, miconazole, ketoconazole

Inhibit 14α -demethylase --> decreased ergosterol production --> increased permeability of cell membrane, Inhibits fungal P450- dependent enzymes blocking ergosterol synthesis, fungistatic ; For mucocutaneous candidiasis, dermatophytosis, seborrheic dermatitis, pityriasis versicolor

None when administered topically

Limited to topical use because of systemic toxicity

Inhibit beta- glucan synthase which produces β(1 -->2) glycan which is a cellwall component, thus decreasing fungal cell wall synthesis, fungostatic ; For disseminated and mucocutaneous candidiasis who fail to respond to amphoB, for mucormycosis, salvage therapy for invasive aspergillosis

headache, GI distress, rash, fever, flushing ( histamine release), elevated liver enzymes

all are given IV ; micafungin can increase levels of cyclosporine and tacrolimus

headache, mental confusion, GI irritation, photosensitivity, hepatotoxicity, disulfiram reaction, drug interactions (decreases bioavialability of warfarin) ; contraindicated in porphyria

given PO ; Accumulates in keratin ; potent CYP450 inducer ; absorption is increased by intake of f atty meal ; resistance is due to decreased transport of drug into the fungal cell wall

GI upset, rash, headache, taste disturbances

given PO and topical, also accumulates in keratin, more effective than griseofulvin in onchomycosis

nephrotoxicity (severe)

Minimal mucocutaneous absorption, available as swish and swallow preparation

D: Echinocandins: Caspofungin, anidulafungin, micafungin

E. Griseofulvin

F. Terbinafine

G. Nystatin (polyene)

Interferes with microtubule function in dermatophytes, inhibits synthesis and polymerization of nucleic acids, fungistatic ; For dermatophytosis Inhibits withg ergosterol synthesis by inhibiting fungal squalene oxidase leading to increased squalene which interferes with ergosterol synthesis, fungicidal ; For dermatophytosis, onchomycosis Binds to ergosterol in fungal cell membranes, forming artificial pores, fungicidal ; For candidiasis ((oropharyngeal, esophageal and vaginal), for GI fungal infections in patients with impaired defense mechanisms

Antiviral Agents A. Anti-Herpes

i. Acyclovir, valacyclovir, penciclovir, famciclovir, docosanol

ii. Docosanol

Activated by viral thymidine kinase (TK) to f orms that inhibit viral DNA polymerase, guanosine analog, competitive substrate for DNA polymerase, causes chain termination after its incorporation into the viral DNA ; For infections due to HSV1, HSV2, VZV (mucocutaneous and genital herpes, prophylaxis in AIDS and in other Immunocompromised states such as organ transplant patients, herpes encephalitis, neonatal HSV infection etc. Inhibits fusion between the HSV envelope and plasma membrane, prevents viral entry and subsequent replication

iii. Ganciclovir, valganciclovir (anti-CMV)

Inhibits viral DNA polymerase causing chain termination, guanosine derivative ; For infections due to CMV, HSV1, HSV2, VZV ; For prohylaxis and treatment of CMV retinitis and other CMV infections in the immunocompromised patients

iv. Cifodovir (anti-CMV)

Inhibits viral DNA polymerase causing chain termination ; For CMV retinitis, mucocutaneous HSV infections, acyclovir-resistance, ganciclovir-resistance, genital warts and molluscum contangiosum

nausea, diarrhea, headache, delirium, tremor, seizures, hypotension, nephrotoxicity

given PO, topical and IV ; dose adjustment in renal patients ; No activity against strains of HSV with absent thymidine kinase activity ; resistance is due to changes in viral DNA polymerase ; Valacyclovir is a prodrug that is converted to Acyclovir and reached plams levels 3-5x (longer t1/2) more than acyclovir ; Penciclovir does not cause chain termination ; Famciclovir is a prodrug which is converted to Penciclovir in vivo

nausea, diarrhea, headache, delirium, tremor, seizures, hypotension, nephrotoxicity

topical preparation shortens healing time

leukopenia, thrombocytopenia, mucositis, hepatotoxicity, seizures, neutropenia

given as IV or intraocular implant (for CMV retinitis) ; No activity against strains of HSV with absent thymidine kinase activity ; CMV resistance is due to mutation in viral DNA polymerase and in the genes that code for the activating viral phosphotransferase ; Valganciclovir is a prodrug of ganciclovir with increased oral bioavialability

nephrotoxicity

Active against strains of HSV with absent thymidine kinase activity ; resistance is due to mutation in DNA polymerase ; dose adjustment in renal patients

v. Foscarnet (anti-CMV)

Inhibits viral RNA polymerase, DNA polymerase, and HIV reverse transcriptase, binds to pyrophosphate binding site ; as alternative for prophylaxis and treatment of CMV retinitis, gancyclovir-resistant strains of CMV, HSV infection in patients with AIDS, also used in organ transplantation

nephrotoxicity, electrolyte abnormalities (hypocalcemia), GU ulcerations, CNS effects (headache, hallucination, seizures)

Active against strains of HSV with absent thymidine kinase activity ; does not require phosphorylation for antiviral activity ; resistance is due to mutations in DNA polymerase gene ; dose adjusment in renal patients

vi. Vidarabine

adenine analog ; For HSV, VZV, CMV

GI irritation, paresthesia, tremor, convulsion, hepatic dysfunction, CI in pregnancy

used topically only because it is rapidly metabolized into the inactive form and because it has a toxic potential

vii. Idoxuridine, trifluridine

pyrimidine analogs ; For herpes keratitis (HSV-1)

irritation, blurred vision, photophobia

topical only because it is too toxic fo systemic use

iritis, vitritis, increased IOP, changes in vision

injected intravitreally ; concurrent systemic use of anti-CMV in threapy is recommended to protect against extraocular and contralateral retinal CMV disease

Inhibit HIV reverse transcriptase after phosphorylation by cellular enzymes, acts as chain terminators via insertion into the growing DNA chain ; For HIV infection, prevention of maternal-fetal HIV transmission

see specific drugs below

these are prodrugs converted by host cell kinases tp triphosphates causing competitive binding of natural nulecotides to the dNTPbinding site of Reverse Transcriptase ; resistance is due to mutation in pol gene

guanosine analog

hypersensitivity reaction

good oral bioavailability, T1/2 is 1224hrs, resistance is slow

b. Didanosine (ddI)

NRTI

acute pancreatitis, peripheral neuropathy, diarrhea, hepatic dysfunction, hyperuricemia, CNS effects

oral bioavailability is decreased by food and chelating agents ; dose adjustment in renal patients

c. Emtricitabine

NRTI

aesthenia, GI upset, headache, hyperpigmentation of palms of soles, CI in pregnancy, children, renal and hepatic and patients

per orem once a day treatment, dose adjustment in renal patients

viii. Fomivirsen

antisense oligonucleotide that binds to mRNA of CMV causing inhibition of early protein synthesis ; For CMV retinitis

B. Drugs for HIV

i. NRTI: a. Abacavir

d. Lamivudine (3TC)

NRTI

GI upset, headache, fatigue, insomnia

80% oral bioavailability ;may also be used for Hepa B infection ; HAART, dose adjustment in renal patients

e. Stavudine (d4T)

NRTI

peripheral neuropathy esp if given together with Zalcitabine, lactic acidosis with hepatic steatosis

good oral bioavailability, dose adjustment in renal patients

f. Tenofovir

a nucleotide but acts as NRTI, competitively inhibits RT, cause chain termination after incorporation into DNA

GI upset, asthenia, headache, Fanconi syndrome, AKI

oral bioavailabilty is 25-40% ; halflife is 60hours ; also used against HBV

g. Zalcitabine (ddC)

NRTI

peripheral neuropathy, pancreatitis, esophageal ulceration, stomatitis, arthralgias

increased oral bioavailability, dose adjustment in renal patients

Azidothymidine or AZT

BM suppression (anemia, neutropenia, thrombocytopenia), acute cholestatic hepatitis, agitation, insomnia, myalgia, headache, GI upset

dose adjustment in uremic patients and cirrhosis ; affected by enzymes inducers and inhibitors

Inhibits HIV reverse transcriptase, no phosphorylation required, do not compete with nucleoside triphosphate ; For HIV infection

Delavirdine and Nevirapine (rash, increased AST/ALT, Efavirenz (teratogenicity), Etravirine (increased cholesterol and triglycerides)

binds to a different binding site ; resistance is due to mutations in pol gene

NNRTI

rashes, teratogenic

metabolized by CYP3A4 and CYP2D6, affected by enzyme inducer and inhibitor

b. Efavirenz

NNRTI

CNS dysfunction, skin rash, increased plasma c holesterol, teratogenic

enhanced absorption by fatty meals, drug interactions are common

c. Etravirine

NNRTI, for drug-resistant HIV used as a singledose to prevent HIV vertical transmission at the onset of labor and also given to the neonate

nausea, vomiting, diarrhea, increased cholesterol, triglycerides and LFTs

NEWEST NNRTI

rash, SJS, TEN

good oral bioavailability,t1/2 is >24hours

cleaves precursor polyprotein to form the final structural protein of the mature virion c ore, inhibits viral protein processing ; For HIV infection

General SE: hyperglycemia, insulin resistance, hyperlipidemia, altered body fat distribution (buffalo hump, gynecomastia, truncal obesity, facial and peripheral lipodystrophy) due to the inhibition of lipid-regulating proteins which have active sites with structural homology to that of HIV protease

Resistance is due to mutation in pol gene ; are potent CYP3A4 inhibitor esp Ritonavir

h. Zidovudine (ZDV)

ii. NNRTI: Delavirdine, efavirenz, etravirine, nevirapine

a. Delavirdine

d. Nevirapine

iii. Protease Inhibitor: Atrazanavir, Darunavir, Fosamprenavir, Indinavir, Nelfinavir, Lopinavir-Ritonavir, Saquinavir, Tipranavir

a. Atazanavir

Protease Inhibitor

peripheral neuropathy, skin rash, hyperbilirubinemia, QT prolongation

per orem absorption requires acidic environment ; can penetrate CSF and seminal fluid ; is not associated with dyslipidemia, fat deposition or metabolic syndrome ; CYP3A4 and 2C9 inhibitor

b. Darunavir

Protease Inhibitor

rash, hepatotoxicity, hypersensitivity ; CI in patients with sulfa allergy

Given together with Ritonavir in patients resistant to other PIs

Protease Inhibitor

GI upset, paresthesia, rash, CI in pregnant patients and children if drug uses propylene glycol as solvent ; does not have risk for hyperlipidemia, fat maldistribution, hyperglycaemia and insulin resistance

a prodrug that is converted to the active drug Amprenavir ; absorption is impaired by fatty food ; used with lowdose Ritonavir

d. Indinavir

Protease Inhibitor

nausea, vomiting, diarrhea, thrombocytopenia, hyperbilirubinemia, nephrolithiasis, insulin resistance

decreased bioavailability in the presence of food ; affected by enzyme inhibitors and inducers

e. Lopinavir-Ritonavir

used as a combination drug: uses subtherapeutic dose of ritonavir which inhibits CYP3A4 mediated metabolism of lopinavir

GI upset (well-tolerated side effects)

there is increased compliance with this drug ; Ritonavir has “boosting effect” on other PI due to enzyme inhibitory effect

Diarrhea

absorption is increased by food, short half-life ; has the most favorable safety profile for pregnancy

GI upset, bitter taste, paresthesia, increased LFT's

good oral bioavailability esp when taken with meals ; affected by enzyme inducer and inhibitors

nausea, vomiting, diarrhea, dyspepsia, rhinitis

affected by enzyme inducers and inhibitors

GI upset, rash, hepatotoxicity

newer drug ; induces P-glycoprotein transporters which leads to alteration of GI absorption of o ther drugs

c. Fosamprenavir

f. Nelfinavir

g. Ritonavir

h. Saquinavir

i. Tipranavir iv. Entry inhibitors:

Protease Inhibitor Protease Inhibitor ; subtherapeutic doses inhibit CYP3A4-mediated metabolism of other Pis (Indnavir, Lopinavir, Saquinavir) which permits lower dose of the other PI Protease Inhibitor ; given together with low dose Ritonavir to improve compliance and decrease GI upset

Protease Inhibitor ; given with Ritonavir for PIresistant HIV

a. Fusion Inhibitor: Enfuvirtide, Docosanol

Binds to gp41 subunit of viral envelope glycoprotein, preventing fusion of viral and c ellular membranes ; For previously drug-treated patients with persistent HIV replication despite ongoing therapy

injection site reaction, hypersensitivity reaction, increased incidence of bacterial pneumonia

subcutaneous and usually given together with other HIV agents

b. CCR5 receptor antagonist: Maraviroc

Blocks viral attachment by blocking CCR5, a transmembrane protein involved in the attachment of HIV to host cell ; For HIV infection

cough, diarrhea, muscle and joint pains, increased LFTs

good tissue penetration ; affected by enzyme inhibitors and inducers

C. Drugs for Influenza

i. Uncoating inhibitors: Amantadine, rimantadine

Inhibit early step replication and prevent uncoating by binding to M2 proton channels ; For influenza A and rubella

GI irritation, dizziness, cerebellar dysfunction (ataxia, dysarthria), livedo reticularis

ii. Neuraminidase inhibitors: Oseltamivir, Zanamivir, Peramivir

Inhibits neuraminidase which cleaves sialic acid residues from viral proteins and surface proteins of infected cells , decrease release of progeny virus ; For influenza A and B, shortens duration of symptoms

GI effects (Oseltamivir), bronchospasm in asthmatics and c ough with throat discomfort (Zanamivir )

Amantadine is also used in treating parkinsonism ; should be given within 48hrs of exposure ; Rimantadine has longer halflife and doe snot need dose-adjustment for renally-impaired Px ; there is increased resistance observed with amantadine DOC for influenza (including H1N1) ; Oseltamivir is PO while Zanamivir is intranasal ; Peramivir has been given temporary emergency use authorization by US FDA for H1N1 in 2009 but has not yet been licensed by the US FDA

cytokine, increased activity of JAKS leading to phosphorylation of signal transducers and activation of transcription (STATS) which causes increased formation of antiviral proteins , also increases NK cells that destroy infected liver cells, Degrades viral RNA via activation of host cell RNAse (ribonuclease) ; For chronic HBV, HCV infection, Kaposi sarcoma, genital warts, prevents dissemination of HZV in cancer patients and decreased CMV shedding after renal transplantation

alopecia, myalgia, severe depression, flu-like syndrome, thyroid dysfunction, reversible hearing loss, neutropenia ; Contraindications include autoimmune disease, history of cardiac arrhythmia and pregnancy

slow absorption, given IM or SC once a day 3x week but the PEGform is only given once a week, given topically for genital warts

D. Drug for HBV and HCV

i. Interferon- α

ii. Adefovir, Dipivoxil, Telbivudine, Tenofovir

Inhibits HBV DNA polymerase causing chain termination after incorporation into the viral DNA ; For lamivudine-resistant Hepatitis B infection, suppresses HBV replication and improves liver histology and fibrosis

Lactic acidosis, renal toxicity, severe hepatomegaly with steatosis

Dipiroxil is a prodrug of Adefovir ; Telbivudine is a newer drug (nucleoside analog) but develpoment of resistance is rapid, it is as effective as lamivudine ; Tenofovir is an anti-RT drug that is also effective in chronic HBV, it is active against lamivudine and entecavir-resistant strains

iii. Entecavir

guanosine nucleoside, inhibits DNA polymerase

headache, dizziness, fatigue, nausea

is as effective as lamivudine, longer t1/2 of 12hrs

see entry

Coinfection between HBV and HIV may increase the risk of pancreatitis with lamivudine use ; longer t1/2 in HBV infected cells than in HIV (lower dose required in HBV than in HIV)

haemolytic anemia, conjunctival and bronchial irritation, teratogen

given PO, IV or aerosol, avoid concomitant administration of anatcids ; Early IV administration of ribavirin decreases mortality in viral hemorrhagic fevers ; monotherapy is NOT effective

GI irritation, skin rash, headache, severe skin lesions, peripheral neuropathies, myocardial depression, retinal damage, auditory impairment, psychosis

May precipitate porphyria ; Chloroquine is 4-aminoquinoline derivative, can be given PO and has high Vd, absorption is decrease by antacids ; resistance is due to dec. intracellular accumulation via inc activation of membrane pumps, dec intravacuolar accumulation via transporter encoded by pfcrt gene

iii. Lamivudine (3TC)

see entry, also active for HBV, rapidly suppresses HBV replication

iii. Ribavirin

Inhibits guanosine triphosphate formation, prevents capping of viral mRNA, blocks RNA-dependent RNA polymerase, inhibit replication of many DNA and RNA viruses like Influenza A and B, parainfluenza, paramyxo viruses, HCV and HIV ; For HCV infection (with IFN-α) and RSV infection, decreases mortality in viral hemorrhagic fevers

Antiprotozoal Drugs A. Antimalarial drugs

i. Chloroquine, hydroxychloroquine

accumulates in the food vacuole of plasmodia —> Prevents polymerization of heme into hemozoin —> inc heme concentration which is toxic to the parasite, Blood schizonticide ; For malaria ( non-falciparum, chloroquine-sensitive), DOC for acute attacks of nonFalciparum and sensitive Falciparum malaria, used as chemoprophylaxis except in regions where P. falciparum is resistant, for autoimmune diseases such as rheumatoid arthritis, amoebic liver abscess

ii. Quinine, Quinidine gluconate

Complexes with double stranded DNA to prevent strand separation —> blocks DNA replication and transcription to RNA, blood schizonticide ; For malaria (chloroquine-resistant) and severe falciparum malaria (quinidine), given together with Doxycycline and or Clindamycin to shorten duration of disease

cinchonism (headache, tinnitus, vertigo), hemolysis in G6PD deficiency, blackwater fever, blurring of vision, GI upset, disturbance n cardiac conduction ; CI in pregnancy

Quinine is commonly used with doxycycline or clindamycin to limit toxicities, PO and IV (in severe infection) ; NEVER use as prophylaxis

iii. Mefloquine

Unknown MOA, blood schizonticide ; For chemoprophylaxis (chloroquine-resistant areas) ; 1st line drug (weekly administration) for prophylaxis in all areas with Chloroquine resistance), alternative to quinine in acute attacks and uncomplicated infections from falciparum malaria

GI distress, skin rash, headache, dizziness, cardiac conduction defects, psychiatric disorders (psychosis), neurologic symptoms, seziures

is a 4-quinoline derivatives, PO

GI distress, pruritus, headaches, methemoglobinemia, hemolysis in G6PD deficient patients ; CI in pregnancy

Eradicates hypnozoites in the liver, preventing malarial relapse, PO , should be used with a blood schizonticide, 14-day course of Tx after Tx with choloroquine

abdominal pain, nausea, vomiting, diarrhea, headache, rash, increased liver enzymes

also effective against Mefloquineresistant Falciparum infection ; Proguanil has a t1/2 12-16h ; Atovaquone is an alternative for P. jiroveci infection

GI disturbances, teratogen (enamel dysplasia and discoloration), hepatotoxicity, nephrotoxicity, photosensitivity, vestibulotoxicity, hemolysis

t1/2 is usually >100h, PO, highly protein bound ; pyrimethamine is a sporonticide

GI disturbances, teratogen (enamel dysplasia and discoloration), hepatotoxicity, nephrotoxicity, photosensitivity, vestibulotoxicity

Do not drink with milk (decreased absorption), PO

vi. Sulfadoxine-pyrimethamine (Fansidar)

8-aminoquinoline, Forms quinoline-quinone metabolites which are electron-transferring redox compounds that act as cellular oxidants, tissue schizonticides, gametocides ; For malaria, eradicates liver stages of P. vivax and P. ovale (radical cure of P. vivax and P. ovale), alternative as primary pr evention, terminal prophylaxis (vivax, ovale), PCP pneumonia Atovaquone disrupts mitochondrial electron transport, blood and tissue schizonticide, proguanil inhibits folate synthesis, sporonticide ; For treatment and chemoprophylaxis of c hloroquine-resistant falciparum, protective vs. Mefloquine-resistant falciparum Sequential blockade of folic acid synthesis (sulfadoxine blocks Dihyrodpteroate synthetase, Pyrimethamine blocks Dihydrofolate reductase, blood schizonticide and sporonticide ; For malaria (for Chloroquine-resistant)

vii. Doxycycline

Impairs progeny of malarial apicoplast g enes, resulting in abnormal cell division, blood schizonticide ; For chemoprophylaxis in multi-drug resistant strains

iv. Primaquine

v. Atovaquone-proguanil

abdominal pain, diarrhea, vomiting, cough, rash, headache, pruritus, elevated liver enzymes, c ardiotoxicity, teratogen

Lumefantrine used in combination with artemether (Co-arthem) for uncomplicated falciparum infection ; Halofantrine is never used for prophylaxis because of cardiotoxicity and embryogenecity, Lumefantrine has minimal cardiotoxicity

is metabolized in the food vacuole of protozoa —> Forms toxic free radicals in malarial food vacuole, blood schizonticide ; For malaria (falciparum and MDR strains)

nausea, vomiting, diarrhea ; SAFE in pregnancy

Co-artem is the DOC for uncomplicated falciparum malaria in the Philippines ; Combination therapy of artemesinins with one or two long-acting antimalarial drugs (amodiaquine, mefloquine, sulfadoxine/pyrimethamine or lumefantrine) is favored to retard the development and progression of drug resistance in P. falciparum ; not given as Prophylaxis due to short t1/2 (1-3h) ; the only reliably effective meds vs Quinine-resistant strains

MOA same as chloroquine (inhibits the digestion of hemoglobin) ; For chloroquine-resistant falciparum

agranulocytosis, aplastic anemia

low-cost, given as combination with Artesunate

i. Diloxanide Furoate

Unknown MOA, converted to Diloxanide freebase (active amobecide), luminal amebicide ; DOC for asymptomatic cyst carrier of E. histolytica

flatulence, nausea, abdominal cramps

converted in vivo into Diloxanide freebase which is the amoebicide

ii. Emetine, dehydroemetine

Inhibits protein synthesis by blocking ribosomal movement along messenger RNA, tissue amebicide ; back up drug for severe intestinal, hepatic and extraintestinal amebiasis

GI distress, muscle weakness, CV dysfunction (arrhythmias and CHF)

Reserved only for situations where metronidazole can’t be used , given SC or IM , usually given together with luminal amebicides

ii. Iodoquinol

halogenated hydroxyquinoline, Unknown MOA, luminal amebicide ; Alternative to Diloxanide for mild to severe intestinal amebiasis

GI distress, thyroid enlargement, skin reactions due to iodine toxicity, neurotoxicity (peripheral neuropathy, visual dysfunction)

Usually used in combination with metronidazole, PO

viii. Halofantrine , lumefantrine

ix. Artemsinin, artesunate, artemether, dihydroartemsinin x. Amiodaquine

Unknown MOA, active vs the erythrocytic stage of all 4 strains including Chloroquine-resistant, blood schizonticide ; For chloroquine-resistant malaria and severe falciparum malaria

B. Anti-amoebiasis

GI irritation, metallic taste, headache, dark urine, leukopenia, dizziness, ataxia, neuropathy, seizures, disulfiram reaction, opportunistic infections, parestheisa, CI in pregnancy

given PO, IV or topical, Metronidazole t1/2 is 6-8h, Tinidazole t1/2 is 12-14h; dose adjustment in renal patients, well distributed even in CSF ; active against protozoan and bacteria (Bacteroides and Clostridium, DOC for Pseudomembranous colitis) ; causes potentiation of warfarin action ; bets taken with meals

iv. Paromomycin

An aminoglycoside, Inhibits protein synthesis, binds to 16S ribosomal subunit, luminal amebicide ; For intestinal amebiasis, cryptosporidiosis

headaches, dizziness, rashes, arthralgia

may be given together with tetracycline in mild intestinal disease ; superior to Diloxanide in asymptomatic carries but SE limits its use

v. Nitazoxanide

Reactive reductions by ferredoxin forming free radicals that disrupt electron transport chain, tissue amebicide ; For metronidazole-resistant amebiasis, giardiasis, cryptosporidiosis (DOC)

GI distress

may also be used in helminthic infections

i. Co-trimoxazole

Sequential blockade of dihydropteroate synthase (sulfamethoxazole) and dihydrofolate reductase (trimethoprim), bactericidal ; DOC for prophylaxis and treatment of Pneumocystosis, prophylaxis (T. gondii, I. belli)

GI upset, acute hemolysis in G6P D deficiency, nephrotoxicity, hypersensitivity, hematotoxicity, kernicterus

Recommended at CD4 count < 200, given daily, PO or IV

ii. Pentamidine

Unknown MOA but may involve inhibition of glycolysis or interference with NA metabolism of Protozoans and Fungi ; For prophylaxis and treatment of pneumocystosis and trypanosomiasis

respiratory stimulation followed by depression, hypotension, hypoglycaemia, anemia, neutropenia, hepatitis, pancreatitis, inhalant route has minimal SE

Administered by nasal spray/aerosol, given once a month if used for prophylaxis, IV or IM for 21 days if for Tx of active disease

Sequential blockade of dihydropteroate synthase (sulfadiazine) and dihydrofolate reductase (pyrimethamine) ; DOC for prophylaxis and treatment of toxoplasmosis

gastric irritation, glossitis, neurologic symptoms (headache, insomnia, tremors, seizures), hematotoxicity (megaloblastic anemia, thrombocytopenia), pseudomembranous colitis (clindamycin)

an alternative drug for Toxoplasmosis is Clindamycin ,give daily for 3-4 weeks if for Tx of active toxoplasmosis , if for Toxoplasma encephalitis, give for at least 6 weeks

Atovaquone disrupts mitochondrial electron transport ; For mild to moderate PCP, as chemoprophylaxis for

abdominal pain, nausea, vomiting, diarrhea, fever, increased liver

has increased absorption in the

iii. Metronidazole, Tinidazole, Secnidazole

Reactive reduction by ferredoxin forming free radicals that disrupt electron transport chain, tissue amebicide ; DOC for severe intestinal wall disease and in hepatic abscess and other extra intestinal amebic disease, DOC for trichomoniasis, also used for giardiasis, bacterial vaginosis (Gardnerella vaginalis), anaerobic infections, H. pylori PUD

C.Drugs for Pneumocystis and Toxoplasmosis

iii. Pyrimethamine-sulfadiazine

D. Drugs for Trypanosomiasis

i. Pentamidine

Unknown MOA but may involve inhibition of glycolysis or interference with NA metabolism of Protozoans and Fungi ; For hemolymphatic stage of T. gambiense and T. rhodiense, For prophylaxis and treatment of pneumocystosis

respiratory stimulation followed by depression, hypotension, hypoglycaemia, anemia, neutropenia, hepatitis, pancreatitis, inhalant route has minimal SE

do not use for latter stages because it does not cross the BBB, also used for Kala-azar and PCP

ii. Suramin

Polyanionic compound, Unknown MOA ; DOC for early hemolymphatic stages of African sleeping sickness, Alternative to Ivermectin in onchocerciasis

fatigue, nausea, vomiting, seizures, shock fever, rash, headache, paresthesia, neuropathies, renal abnormalities (proteinuria), chronic diarrhea, haemolytic anemia and agranulocytosis

Do not cross blood brain barrier , Used in combination with melarsoprol

iii. Eflornithine

Suicide inhibitor of ornithine decarboxylase ; DOC f or advanced west African sleeping sickness

diarrhea, vomiting, anemia, thrombocytopenia, leukopenia, seizures

Crosses blood brain barrier, PO, IV

iv. Melarsoprol

Organic arsenical, inhibits enzyme sulfhydryl (-SH) groups in trypanosomes ; DOC for African sleeping sickness

GI irritation, reactive encephalopathy

Crosses BBB, administered parenterally because it causes GI upset

v. Nifurtimox

Nitrofurazone derivative, Inhibits trypanothione reductase which is unique to the parasite ; DOC for Chagas disease / American Sleeping sickness (Trypanosoma cruzi), alternative for African sleeping sickness, also for mucocutaneous leishmaniasis

nausea, vomiting, fever, rash, restlessness, insomnia, neuropathies, seizures

Does not cross BBB

GI symptoms, fever, rash, arthralgia, healdache, myalgia, sterile abscesses, cardiotoxicity

IV ; alternative for leishmaniasis are as follows: Pentamidine or Miltefosine (for visceral leishmaniasis), Fluconazole or Metronidazole (for cutaneous leishmaniasis) and Amphotericin B (for mucocutaneous leishmaniasis)

GI irritation, agranulocytosis, alopecia, Elevated liver enzymes

Greatly affected by enzyme inducers and inhibitors ; Contraindicated in pregnancy, Use cautiously in patients with Cirrhosis and children <2y.o.

Drugs for Leishmaniasis

vi. Sodium Stibogluconate

Pentavalent antimony, Inhibits glycolysis or effects on NA metabolism ; DOC for Leishmaniasis

Anthelmintics

A. Mebendazole

Selectively inhibits microtubule synthesis and glucose uptake in nematodes, ovicidal ; Whipworm infections (drug of choice), Also a primary drug (together with albendazole) for ascariasis, pinworm, Trichinosis, Visceral larval migrans (backup)

B. Albendazole

Inhibits microtubule assembly, larvicidal and ovicidal ; DOC for Ascariasis, Hookworm, Pinworm, Hydatid disease ; Also used for Whipworm infections, Cutaneous & Visceral Larva migrans, Cysticercosis (larval stages of T. solium), Angiostrongylus cantonensis, Capillaria philippinensis

reversible leukopenia, alopecia, elevation of liver function tests, bone marrow suppression

primary drug for ascariasis, ancylostomiasis, trichuriasis ; safety in pregnant and children is not yet established ; Improved penetration (> Praziquantel) of the subarachnoid space in Neurocysticersosis Should not be given to patients with Cirrhosis

C. Diethylcarbamazine

Immobilizes microfilariae by an unknown mechanism —> inc susceptibility to host defense mechanism ; DOC for filariasis and eye worm disease (Loa-Loa)

headache, malaise, weakness, anorexia, filarial fever (fever, rashes, ocular damage, joint and muscle pain, lymphangitis)

May cause mazzotti reaction when used for onchocerciasis

D. Ivermectin

Intensifies GABA-mediated neurotransmission in nematodes —> immobilizes parasites —> removal by reticuloendothelial system ; Used for Strongyloidiasis (drug of choice), Onchocerciasis, Cutaneous larva migrans, Filariasis (back up)

Mazzotti reaction (fever, headache, dizziness, rashes, pruritus, tachycardia, hypotension, pain in muscles and joints and lymph glands), corneal opacities

Antidote for Mazzoti reaction: antihistamine and NSAIDs ; CI in pregnancy, children 5 y.o. and Avoid concomitant use with other drugs that enhance GABA activity (Barbituraates, BZDs etc)

E. Pyrantel pamoate

Stimulates nicotinic receptors at NMJ of nematodes —> depolarization-induced paralysis, Causes release of ACh and inhibition of Cholinesterase, Kills adult worms not eggs ; DOC for pinworm, may be used also for Hookworm, Trichostrongylus and Ascaris infections

GI distress headache, weakness, dizziness, insomia, rash, fever,

Contraindicated in patients with hepatic dysfunction (may cause an increase in LFT) ; No study on pregnant and children <2y.o.

F. Thiabendazole

Structural congener of Mebendazole, same MOA as Mebendazole, Selectively inhibits microtubule synthesis and glucose uptake in nematodes, Inhibits fumarate reductase. Ovicidal, has anti-inflammatory and immunosuppressive action in the host ; Used for Trichinosis (drug of choice), Strongyloidiasis (backup)

Gastrointestinal irritation, Headache, Dizziness, Drowsiness, Leukopenia, Hematuria, Hypersensitivity reactions (SJS), Hepatotoxicity (intrahepatic cholestasis, liver failure), Reactions caused by dying parasites

CI in renal and liver disease and in pregnancy

G. Praziquantel

Increases membrane permeability to calcium —> contraction of trematode and cestode muscle —> muscle paralysis, vacualization and death ; DOC fo r trematodes (schistosoma, paragonimus, clonorchis, opistorchis, Fasciolopsis, Heterophyes) and cestodes (taenia, diphyllobothrium, Hymenopelsis) together with Niclosamide ; for infection by small and large intestinal flukes ; alternative to Albendazole in Cysticerci

H. Niclosamide

Uncouples oxidative phosphorylation or by activating ATPases, scoleces and segments are killed b ut NOT Ova ; alternative drug to Praziquantel for cestode infection (Taenia, Diphyllobotrium), not effective in cystecercosis (use Albendazole or Praziquantel instead) or Hydatid disease (use Albendazole), effective in the Tx of infections from small and large intestinal flukes

headache, dizziness, nausea, malaise, Inc ICP, seizure (neurocystecercosis) ; CI in pregnancy

Used with steroid when treating neurocysticercosis to dec swelling , contraindicated in ocular cysticercosis (may cause irreparable eye damage) ; May be used as an adjunct to Albendazole in Hydatid disease

GI distress, headache, rash, fever

Avoid ethanol consumption for 48 hours upon drug consumption ; Safety in children <2y.o. and pregnanct not yet established

I. Piperazine

GABA agonist —> paralyze ascaris —> expelled by normal peristalsis , block ACh at the myoneural junction --> expulsion via normal peristalsis ; As alternative for ascariasis

GI upset

Contraindicated in pregnancy, impaired renal or hepatic function or with a history of epilepsy or chronic neurologic disease

J. Bithionol

Unknown MOA ; co-DOC (with Triclabendazole) for Tx of Fascioliasis (sheep liver fluke), as alternative for paragonimiasis

Nausea,vomiting, diarrhea, abdominal cramps, phototoxicity, rash

do not use in Px <8y.o.

K. Metrifonate

an organophosphate prodrug —> Dichlorvos (AchE inhibitor) -> muscle contraction —> paralysis ; Active vs Schistosoma haemoatobium

Excess cholinergic stimulation (DUMBBELSS)

CI in pregnancy

L. Oxamniquine

effective solely in Schistosoma mansion (intestinal bilharziasis) - on male immature forms and adult schistosomal forms ; MOA is unknown

GI upset, pruritus, eosinophilia, urticaria, pulmonary infiltrates, fever, orange-red discoloration of urine ; CI in pregnancy and seizure disorder, proteinuria, microscopic hematuria,

Px is not allowed to drive within 24hrs after intake of Oxamniquine

Cancer Chemotherapy

A. Alkylating agents

i. Nitrogen Mustards: Cyclophosphamide, Chlorambucil, Mechlorethamine

ii. Platinum Analogs: Cisplatin, Carboplatin, oxaliplatin

iii. Alkyl sulfonate: Busulfan

iv. Nirtosoureas: Carmustine, lomustine

v. Others: Procarbazine, Dacarbazine B. Antimetabolites

all are Cell-cycle non-specific ; Universal MOA: form reactive molecular species that alkylate nucleophilic groups on DNA bases, particularly the N-7 of guanine leading to cross-linking of bases, abnormal base pairing and DNA strand breakage Forms DNA cross-links, resulting in inhibition of DNA synthesis and function, Cell-cycle nonspecific, Mechlorethamine has additional MOA: converts to a reactive cytotoxic product ; For nonhodgkin’s lymphoma, breast cancer, ovarian cancer, neuroblastoma, CLL Forms DNA cross-links, resulting in inhibition of DNA synthesis and function, Cell-cycle nonspecific ; component of regimen For testicular cancer, ovarian cancer, bladder cancer and lung cancer ; Oxaliplatin is used also for advanced colon CA Forms DNA cross-links, resulting in inhibition of DNA synthesis and function, Cell-cycle nonspecific ; For CML Forms DNA cross-links, resulting in inhibition of DNA synthesis and function, Cell-cycle nonspecific ; For brain tumors, melanoma, skin cancer a reactive agent which forms hydrogen peroxide, which generates free radicals that cause DNA strand scission, cell cycle non-specific ; component of reigned For Hodgkin’s lymphoma, non -hodgkin’s lymphoma, brain tumors all are cell-cycle specific , they also have immunosuppressant action

Resistance is due to increased DNA repair, decreased drug permeability and production of trapping agents such as thiols

bone marrow suppression, hemorrhagic cystitis, hepatotoxicity, alopecia, SIADH, pulmonary toxicity, cardiac dysfunction ; Mechorethamine SE include marked vesicant action, sterility, myelosuppresion, alopecia

Rescue therapy is MESNA and hydration; metabolite is acrolein which is important for Cyclophosphamide’s anti -cancer effect and also its toxicity

nausea, vomiting, nephrotoxicity, neurotoxicity (peripheral neuritis), ototoxicity (acoustic nerve damage), hematotoxicity

IV, Rescue therapy is Amifostine, decreased nephrotoxicity by giving mannitol with forced hydration ; Carboplatin is less nephrotoxic but has more myelosuppression

pulmonary fibrosis, adrenal insufficiency, skin pigmentation

Spares the bone marrow

CNS toxicity (dizziness, ataxia), nausea and vomiting, bone marrow suppression, skin flushing

Highly lipophilic allowing ease of passage through BBB into the CNS

bone marrow suppression, pulmonary toxicity, hemolysis, disulfiram reaction,skin reactions, peripheral neuropathy, CNS dysfunction

PO, can pemetrate the CSF, LEUKEMOGENIC, CPY450 inhibitor, Dacarbazine is phototoxic

i. Folate antagonist: Methotrexate

ii. Purine antagonist: 6-Mercaptopurine, 6-thioguanine, fludarabine, cladribine

iii. Pyrimidine antagonist: 5-Fluorouracil

iv. Pyrimidine antagonist: Cytarabine (ARA-C)

Inhibits dihydrofolate reductase, decreases synthesis of thymidylate, amino acids, purine nucleotides —> interfere with NA and CHON metabolism ; cell cycle specific ; For choriocarcinoma, acute leukemia, nonhodgkin, primary CNS lymphoma, breast cancer, head and neck cancer, bladder cancer ; also for psoriasis, rheumatoid arthritis, ectopic pregnancy

are activated by hypoxanthie-guanine phosphoribosyltransferase (HGPRT) to toxic nucleotides which inhibit enzymes in purine metabolism —> Inhibits de novo purine nucleotide synthesis , cell cycle specific ; For acute leukemia (AML, ALL), CML

converted to 5-fluoro- 2’-deoxyuridine-5’monophosphate (5-FdUMP) which Inhibits thymidylate synthase, incorporation inhibits DNA synthesis and function, cell cycle specific ; For bladder cancer, breast cancer, colorectal cancer, anal cancer, head and neck cancer, liver cancer and ovarian cancer, topically for keratoses and superficial basal cell skin cancer a cytosine arabinoside, activated by kinases to AraCytidine Triphosphate (AraCTP) which Inhibits DNA polymerase —> inhibition of DNA synthesis and repair, inhibits ribonucleotide reductase with reduced formation of dNTPs, cell cycle specific ; For AML, ALL, CML

bone marrow suppression, pulmonary infiltrates and fibrosis, mucositis, crystalluria, hepatotoxic

PO, IV, Rescue therapy is Leucovorin (Folinic acid) ; cytotoxic due to formation of polyglutamate derivatives ; resistance is due to decreased drug accumulation, changes in drug sensitivity or activity of DHF reductase and decreased formation of polyglutamates ; clearance is dependent on renal function therefore adequate hydration is important to prevent crystallization into stones

bone marrow suppression, hepatic dysfunction (necrosis, jaundice, cholestasis)

6-MP metabolism inhibited by allopurinol and febuxostat , Resistance is due to decreased activity of HGPRT, increased alkaline phosphatase activity (which inactivates the toxic nucleotide) , undergo significant FPE (by xanthine oxidase)

bone marrow suppression, GI irritation, alopecia

IV, can distribute to CSF, causes “thymineless” death of cells, Resistance is due to decreased activation of 5-FU, increase thymidylate synthase activity and decreased sensitivity of this enzyme ; another metabolite is 5florouridine-5’triphosphate (FUTP) which incorporates into RNA —> interfere with RNA processing and function

GI irritation, bone marrow suppression, neurotoxicity

Most specific for the S-phase of the cell cycle, Resistance is due to decreased uptake and decreased conversion to AraCTP, a cytosine arabinoside

v. Pyrimidine antagonist: Gemcitabine C. Natural Anticancer Drugs

i. Vinca alkaloid: Vincristine, Vinblastine, Vinorelbine

ii. Podophyllotoxin: Etoposide, Teniposide

iii. Camptothecins: Topotecan, Irinotecan

iv. Taxanes: Paclitaxel, Docetaxel

a deoxycytidine analog, converted to Gemcitabine diphosphate which inhibits ribonucleotide reductase with reduced formation of deoxyribonucleotide triphosphate required for DNA synthesis, Gemcitabine triphosphate is incorporated into DNA causing chain termination, cell cycle specific ; For pancreatic cancer, bladder cancer, non-small cell lung cancer, nonHodgkins lymphoma

bone marrow suppression, neutropenia, pulmonary toxicity

a deoxycytidine analog

Neurotixicity (areflexia, peripheral neuritis, paralytic ileus)

IV, highly distributed except in CSF, Acts primarily in M phase of cancer cell cycle, Resistance is due to increased efflux of drugs via membrane drug transporter

bone marrow suppression, alopecia, GI distress

PO, high Vd ; dose adjustment in renal patients ; Act on the L ate S and early G2 phase

bone marrow suppression, diarrhea

Irinotecan can be used for metastatic colorectal cancer

Paclitaxel (neutropenia, thrombocytopenia, peripheral neuropathy, hypersensitivity), Docetaxel (neurotoxicity, bone marrow suppression)

Act on M phase

all are cell-cycle specific Prevents assembly of tubulin dimers into microtubule assembly blocking the formation of mitotic spindles, causes cell arrest at metaphase, cell cycle specific ; For acute leukemias, lymphomas, wilms tumor and neuroblastoma ; Vinblastine For lymphomas, neuroblastomas, testicular carcinoma and Kaposi sarcoma ; Vinorelbine For non-small cell lung cancer and breast cancer Induces DNA breakage by inhibiting DNA topoisomerase II, inhibits mitochondrial electron transport, cell cycle specific ; Combination regimen For lung cancer, prostate cancer, testicular cancer, non-hodgkin’s lymphoma, germ cell and gastric cancer Inhibits DNA topoisomerase I which cute and relegates single DNA strands during normal DNA repair, cell cycle specific; For advanced ovarian cancer (2nd line), small cell lung cancer, Irinotecan For metastatic colorectal cancer Interferes with mitotic spindle synthesis by preventing microtubule disassembly into tubulin monomers, cell cycle specific ; For solid tumors - advanced breast and ovarian cancer, lung cancer, gastroesophageal cancer, prostate cancer, bladder cancer, head and neck cancer

D. Antitumor antibiotics

i. Anthracycline: Doxorubicin, Daunorubicin, Idarubicin, Epirubicin, Mitoxantrone

Intercalates between base pairs, inhibits topoisomerase II, generates free radicals, blocks synthesis of RNA and DNA causing DNA strand scission, causes membrane disruption, cell cycle nonspecific ; Doxorubicin For Hodgkins and Non-Hodgkins lumphoma, myelomas, sarcomas, breast cancer, endometrial cancer, lung cancer, ovarian cancer and thyroid cancer ; Daunorubicin For acute leukemias Idarubicin For AML, Epirubicin For breast cancer and gastroesophageal ; Mitoxantrine For acute myeloid leukemias, Non-Hodgkins lymphoma, breast and gastroesophageal cancer

alopecia, nausea, vomiting, Cardiotoxicity (dilated cardiomyopathy, CHF)

Rescue therapy is Dexrazoxane and liposomal formulation of the drug

pneumonitis, pulmonary fibrosis, alopecia, mucocutaneous reactions, hypersensitivity reactions

IV, inactivated by tissue aminopeptidases, Most specific for the G2 phase of cell cycle, a glycopeptide

iii. Actinomycin D

Generated free radicals which bind to DNA and causes DNA strand breaks leading to inhibition of DNA synthesis, intercalates with DNA, cell cycle specific ; Component of regimens in Hodgkins lymphoma and testicular cancer, lymphomas and squamous cell cancer, head and neck cancer, skin cancer Binds to double stranded DNA, inhibits DNAdependent RNA synthesis, cell cycle non-specific ; For melanoma, wilm’s tumor, choriocarcinoma, Kaposi sarcoma

bone marrow suppression, skin reactions, GI irritation

None

iv. Mitomycin C

Metabolized into an alkylating agent that cross-links DNA ; In combination regimens for adenocarcinoma of the cervix, stomach, pancreas and lungs

severe myelosuppression, toxic the heart, liver, lungs and kidneys

IV, used for hypoxic tumor cells

Tyrosine kinase inhibitor of the protein product of bcr-abl oncogene in CML ; For CML, GIST

diarrhea, myalgia, fluid retention, CHF

Resistance is due to mutation is bcrabl gene

recognizes a surface protein in breast CA cells that overexpress Her-2-neu receptors for epidermal growth factor

nausea, vomiting, chills, fever, headache, cardiotoxicity (CHF)

None

ii. Bleomycin

E. Miscellaneous Anticancer Drugs i. TK inhibitor: Imatinib, Dasatinib, Nilotinib ii. Growth Factor Receptor Inhibitor

a. Her-2-neu inhibitor: Trastuzumab

b. EGFR inhibitor: Cetuximab, Panitumumab, Gefitinib, Erlotinib

EGFR (Epidermal Growth Factor Receptor) regulate signaling involved in cellular proliferation, invasion and metastasis and angiogenesis, it also inhibits cytotoxic activity of some anti-cancer and radiation treatment, Gefitinib and Erlotinib are capable of inhibiting EGFR’s Tyrosine Kinase domain ; Cetuximab (+ Irinotecan and Oxalipatin) For metastatic colon cancer and Head and Neck cancer ; Panitumumab For refractory colorectal cancer ; Gefitinib and Erlotinib as second-line agents for non-small cell lung cancer VEGF (Vascular Endothelial Growth Factor) has a role in angiogenesis required for metastasis, Inhibits binding of VEGF to VEGFR leading to inhibition of VEGF signalling, inhibits tumor vascular permeability but enhances tumor blood flow and drug delivery ; Sorefenib Sunitinib and Pazopanib inhibits multiple receptor Tyrosine Kinase including those associated to VEGF ; For metastatic colorectal cancer, breast cancer, diabetic retinopathy

folliculitis, diffuse hair loss, dry skin, paronychia

Erlotinib can also be used for advanced pancreatic cancer

hypertension, arterial thrombosis, impaired wound healing, proteinuria, GI perforation

may also be used in non-small cell lung CA and renal CA

iv. Rituximab

Binds to a surface protein in NHL cells, induces complement-mediated lysis, direct cytotoxicity and induction of apoptosis ; For Non- Hodgkin’s lymphoma and other lymphomas

hypersensitivity reaction, bone marrow suppression

None

v. Interferon alpha

Endogenous glycoproteins with antineoplastic, immunosuppressive and antiviral actions ; For hairy cell leukemia, early CML, T-cell lymphoma

alopecia, myalgia, depression, thyroid dysfunction, hearing loss, bone marrow suppression

None

vi. Asparaginase

Depletes serum asparagine ; For ALL, T-cell auxotrophic CA (leukemia and lymphomas) that require asparagine for growth

acute pancreatitis, bleeding, severe hypersensitivity reaction

None

vii. All-Trans retinoic acid

Allows DNA transcription and differentiation of immature leukemic promyelocytes into mature granulocytes ; For acute promyelocytic leukemia

retinoic acid syndrome (dyspnea, fever, weight gain, peripheral edema)

Only vitamin that can cure cancer, treat retinoic acid syndrome with dexamethasone

viii. Protease Inhibitor: Bortezomib

a reversible inhibitor of 26s proteasome in mammalian cell ; For multiple myeloma

peripheral neuropathy, thrombocytoppenia

Suppresses inflammation and immune response, may trigger apoptosis and work on nondividing cancer cells

adrenal suppression, growth inhibition, muscle wasting,

c. VEGF Inhibitor: Bevacizumab, Sorafenib, Sunitinib, Pazopanib

F. Hormonal Anticancer Agents

Estrogen antagonist actions in breasts tissue and C NS, estrogen agonist effects in uterus, liver and bone ; For hormone-responsive breast cancer, Toremifene For advanced breast cancer

hot flushes, thromboembolism, endometrial hyperplasia, endometrial cancer

Prevents osteoporosis and decrease risk of atherosclerosis

gynecomastia, hot flushes, impotence

iv. GnRH analog: Leuprolide, Goserelin Nafarelin

Androgen antagonist ; For prostate cancer Increased LH, FSH secretion with intermittent administration, reduced LH and FSH secretion with prolonged continuous administration ; For prostate cancer

GnRH analogs (leuprolide) must be co-administered to prevent acute flare-up of prostate cancer

hot flushes, sweats, headache, osteoporosis, gynecomastia, gynecomastia, testicular atrophy, impotence, bone pain

see entry

v. Aromatase inhibitor: Anastrazole, Letrozole

Reduces estrogen synthesis by inhibiting aromatase; For advanced breast cancer

nausea, diarrhea, hot flushes, bone and back pain, dyspnea, peripheral edema

Effective againsts breast cancer that have become resistant to tamoxifen

ii. SERM: Tamoxifen, Toremifene

iii. Androgen antagonist: Flutamide

Drugs Used in the Treatment of Gastrointestinal Diseases [Divided into 2 classes: agents that reduce intragastric acidity and agents that promote mucosal defense

A. Antacids: Magnesium-Aluminum Hydroxide, Calcium carbonate, Sodium bicarbonate

Neutralize stomach acid by reacting with protons in the lumen ; For peptic ulcer disease, Gastroesophagal reflux

Sodium bicarbonate: Belching, metabolic alkalosis. Calcium carbonate: hypercalcemia, renal insufficiency, metabolic alkalosis (milk-alkali syndrome) exc for Aluminum Magnesium Hydroxide

Impairs absorption of tetracyclines, flouroquinolones,itraconazole and iron --> should not be given within 2 hours with these drugs ; When used regularly in large doses needed to significantly raise the stomach pH, antacids, decrease recurrence rate of peptic ulcers ; Aluminum and Magnesium are always given together to cancel out each other's adverse effects ; Avoid in renally impaired patients ; DOA: 1-2 hours

B. H2 receptor antagonist: Cimetidine, Ranitidine, Famotidine, Nizatidine

C. Proton Pump Inhibitor: Omeprazole, Lansopraole, Rabeprazole, Pantoprazole, Esomeprazole

Competitive pharmacologic block of H2 receptors ; For peptic ulcer disease, Zollinger-Ellison syndrome, Gastroesophagal reflux, dyspepsia

Irreversible blockade of H/K ATPase in active gastric parietal cells, Long lasting reduction of meal stimulated and nocturnal acid secretion ; For Peptic ulcer disease(DOC), Zollinger-Ellison syndrome, Gastroesophageal reflux, dyspepsia

Gynecomastia (cimetidine only), Diarrhea, headache, fatigue, Myalgias, constipation, Nosocomial pneumonia, Mental status changes, Bradycardia, Hypotension, Blood dyscrasias

Cimetidine is a potent inhibitor of CYP450. Highly effective in suppressing nocturnal acid secretion but only modest effect on meal- stimulated secretion ; avoid in renally and hepatically (severe) impaired patients ; are highly selective and does not affect H1 and H3 receptors, may also reduce seceretion of pepsin ; DOA: 6-10hrs ; Reduces acid secretion by 60-70%

Diarrhea, headache, abdominal pain, Malabsorption syndrome (Vit B12, Ca, Fe, Z n, Digoxin, Ketoconazole), Infections (respiratory, enteric), Hypergastrinemia, Atrophic gastritis

usually enetric coated, t1/2 is 12hrs but DOA of is around 24hrs, needs 3-4 days treatment to achieve full effectiveness ; decreases bioavailability drugs that require acidity for GI absorption ; when used for PUD together with 2 antibiotics, achieve 90% cure ; Reduces acid secretion by 90-98% ; should be taken on an empty stomach since food decreases its bioavailability by 50%

constipation, dizziness, flatulence, dry mouth

Highly insoluble, requiring frequent dosing (QID) ; chemically: Aluminum Sucrose Sulfate

D. Mucosal Protective Agent:

i. Sucralfate

polymerizes in acidic environmet —> polymers bind to injured tissue and forms a protective covering over ulcer bed, Accelerates healing of peptic ulcers and reduces recurrence rate ; For Peptic ulcer disease forms a protective coating on ulc erated tissue, stimulates mucosal protective mechanisms, direct

Infectious diarrhea

PGE1 analog, Activates EP receptors, causes increased HCO3 and mucus secretion and i nhibits acid secretion in the stomach, causes uterine contraction ; For Peptic ulcer disease, Prevention of NSAID-induced gastric mucosal injury, Abortifacient

Abdominal pain, Diarrhea, Uterine cramping, Miscarriage

see entry, decreases ulcer in NSAIDs induced ulceration

Metoclopramide and domperidone block D2 receptors, Erythromycin stimulates motilin receptor, Increases gastric emptying and intestinal motility ; As Antiemetic for post operative/chemotherapy vomiting, Diabetic gastroparesis (drug of choice), Neostigmine for acute large bowel distention

Parkinsonism, Extrapyramidal effects, Hyperprolactinemia

Domperidone does not cross the BBB (less toxic) ; Increases LES pressure (helpful in GERD)

i. Bulk-forming: Psyllium, Methylcellulose, Polycarbophil

Indigestible, hydrophilic colloids that absorb water, forming a bulky emollient gel that distends the colon and promotes peristasis ; For constipation

Diarrhea

None

ii. Stool-softener: Docusate, Glycerine, Mineral oil

Soften stool material, Permitting water and lipids to penetrate the stool ; For constipation

Diarrhea, Aspiration,(Lipid pneumonitis), Malaabsorption of fatsoluble vitamins (A, D, E, K)

None

Soluble but nonabsorbable compound that result in increased stool liquidity due to an obligate increase in fecal fluid ; For Constipation, Hepatic encephalopathy (lactulose), Preparation for endoscopy (polyethylene glycol)

Diarrhea, Flatus, Abominal cramps, Electrolyte abnormalities (hyperphosphatemia, hypocalcemia, hypernatremia, hypokalemia, hypermagnesemia)

None

Unknown. Directly stimulate enteric nervous system and colonic electrolyte and fluid secretion

Diarrhea

can cause melanosis coli

Lubiprostone is a Chloride channel activator which stimulates Cl secretion into the intestines leading to increased fecal fluid content, Methylnaltrexone and Alvimopan are Opioid receptor antagonist that block intestinal mu receptors, but not the CNS

mild nausea, stomach pain, mild diarrhoea, bloating, headache

NONE

iii. Misoprostol E. Prokinetics

i. Metoclopramide, Domperidone, Erythromycin, Neostigmine F. Laxatives

iii. Osmotic: Lactulose, Magnesium oxide, Magnesium hydroxide, Sorbitol, Magnesium citrate, Sodium phosphate, Polyethylene Glycol iv. Stimulant: Bisacodyl, Aloe, Senna, Cascara, Castor oil

v. Miscellaneous: Lubiprostone, Methylnaltrexone, Alvimopan

Activates opioid receptors in enteric nervous system. Slows motility with negligible CNS effects, Kaolin (+pectin) absorbs bacterial toxin and fluid leading to decreased stool liquidity ; for Diarrhea (nonspecific, noninfectious)

Drowsiness, Nausea, Paralytic ileus, interfere with absorption of other drugs

Do not use in children less than 4 years of age (increased chance of causing paralytic ileus), Reverse ileus by administering Betanechol. Direct m-agonist, Kaolin is hydrated Magnesium Aluminum Silicate

i. laxatives, antidiarrheals and low-dose TCA

see entry

see entry

see entry

ii. Anticholinergics: Dicylomine, Hyoscyamine

see entry ; antispasmodic for abdominal pain, f or IBS with prominent diarrhoea

see entry

see entry

iii. 5HT3 antagonist: Alosteron

see entry ; For IBS with severe diarrhoea

severe constipation, ischemic colitis

see entry

iv. Lubiprostone

see entry ; activate type2 chloride channels in small intestines ; For IBS with predominant constipation

see entry

see entry

G. Anti-diarrheals: Diphenoxylate, Loperamide, Kaolin+Pectin, Colloidal Bismuth H. Drugs for IBS

I. Anti-emetics Headache, Dizziness, Constipation, QRS and QT prolongation (Dolasetron only)

see entry

ii. Aprepitant

Blocks chemoreceptor trigger zone and enteric nervous system 5-HT3 receptors ; For Vomiting (Post chemothereaphy, postoperative) antagonist of the Neurokinin-1 receptor in the areas postrema that is activated by substance P and other tackykinins ; For post-chemotherapy nausea and vomiting

fatigue, dizziness, diarrhea

an enzyme inhibitor

iii. Scopoloamine

see entry ; For motion sickness emesis

see entry

see entry

i. Aminosalicylates: Mesalamine, Balsalazine, Olsalazine, Sulfasalazine

Unknown. Probably inhibits production of eicosanoid inflammatory mediators (PG and LT) and interfering with cytokines ; For Inflammatory bowel disease (mild to moderate)

Gastrointestinal upset,Headaches, Arthralgias, Myalgias, Bone marrow suppression, Malaise, Hypersensitivity reactions ( severe)

Not useful for treating active flare ups of disease

ii. Other agents: Antibiotics, Immunosuppressibe antimetabolites (Azathioprine, 6-MP, Methotrexate), antiTNF (Infliximab), Natalizumab

see entry ; Natalizumab is a Ma b that blocks intergrins in circulating leukocytes, restricted to severe refractory Crohn’s disease

multifocal leukoencephalopathy

see entry

i. Ondansetron, Granisetron, Dolasetron, Palonosetron

J. Drugs for IBD

K. Miscellaneous Agents

i. Pancreatic lipase: Pancreatin or Pancrealipase

For pancreatic enzyme replacement, improve digestion of fats proteins and carbohydrates ; For pancreatic insufficiency due to Cystic Fibrosis, pancreatitis and pancreatectomy a bile acid derivative that decreases cholesterol content of bile by decreasing hepatic cholesterol secretion and other effects on hepatocyte canalicular membrane ; For gallstone in patients refusing or not eligible for surgery

hyperuricemia

Taken with every meal

headache, dizziness, mild stomach pain, rhinorrhea, sore throat, rash hair loss

None

A. Mucolytics : N-acetylcysteine, Carbocysteine, Ambroxol

decrease sputum activity ; Usually derivatives of cysteine; reduce disulfide bridges that bind glycoproteins to other proteins such as albumin ; Also act as antioxidants & may reduce airway inflammation ; Orally available drugs are well-tolerated; but of little benefit in acute respiratory condition

Chest tightness, Disagreeable odor, Drowsiness, Fever, Hemoptysis, Increased volume of bronchial secretions, Irritation of tracheal or bronchial tract, Nausea, Rhinorrhea, Stomatitis, Vomiting

available as IV, PO, IM and inhalational forms

B. Expectorants: Guiafenesin

may act as an irritant to gastric vagal receptors, and recruit efferent parasympathetic reflexes that cause glandular exocytosis of a less viscous mucus mixture.

Drowsiness, Incomplete or Infrequent Bowel Movements, Inducing of a Relaxed Easy State, Stomach Cramps, dizziness or headache, a rash, or. nausea, vomiting, or stomach upset

Are often emetics (ipecac, guaifenesin)

ii. Drugs that inhibit formation of Gallstones: Ursodiol

Drugs Used For Cough

C. Antitussives

Used for dry painful cough of neoplasia or pleural disease ; Irritative cough in inflammation of the respiratory tract (epiglottitis); in hemoptysis

DO NOT suppress in bacterial lung infections, asthma, bronchiectasis (suppurating bronchial inflammation) or chronic bronchitis where antitussives can cause harmful sputum thickening & retention

Pharma Super Table

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