Medications: Test 3
Fractures: Narcotics, NSAIDs, Stool Softener Osteoporosis: -
Estrogen replacement therapy (ERT) -
Used to prevent and treat osteoporosis
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For surgical menopause before age 50
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Decreases osteoclastic activity & increases osteoblastic activity
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Can increase risk of endometrial cancer.
Advantages: increases bone density, decreases risk of fractures, relief of hot flashes, vaginal dryness, decreases LDL, increases HDL
Disadvantages: increased risk of urterine ca (if unopposed), increased risk of DVT, possible increased risk of breast and endometrial cancer
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Dose: EstrogenEstrogen - 0.625 mg, qd, 0.3 mg; ProgesteroneProgesterone- 2.5 mg, qd, (if uterus is present)
Selective estrogen receptor modulators (SERM) -
Treatment and prevention of osteoporosis by mimicking estrogen beneficial effects on bone density.
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Decreases bone resorption
Advantages: increases bone density, decreases fracture risk, no stimulation o f breast or endometrial tissue, decreases LDL
Disadvantages: increased risk of DVT-not for women with history of blood clots, doesn’t treat post menopausal symptoms-may increase hot flashes, no effect on HDLs
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Dose: Raloxifene (Evista) 60 mg, qd
Bisphosphonates
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Alendronate (Fosamax) 5-70 mg once a week dosing
Risendronate (Actonel) 5-30 mg once a week dosing
Ibandronate (Boniva) 150 mg once a month
Primidronate (Aredia) & Zoledronic (IV prep)
Prevention & treatment of osteoporosis in post menopausal women. Prevention and treatment of steroid-induced osteoporosis both in men & women, Paget’s disease, hypercalcemia of malignancy
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It absorbs to hydroxypatite and becomes a part of the bone structure. Bisphosphonates prevent bone resorption by i nhibiting osteoclast activity.
Take on empty stomach. Take first thing in the morning (30 min befo re meal). No food or other meds 30 mi nutes after taking Bisphosphonates. Take with 8 oz of water only. Remain in an upright position for at least 30 minutes after taking the drug-result in esophagitis and GI distress. Instruct patient to report chest pain or dysphagia. Separate Ca, Al, and Mg containing meds by at least 4 hours.
Advantages: increases BMD, decreases fracture risk, no increased risk of breast and uterine ca or thromboembolic events, weekly or monthly dosing.
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Disadvantages: risk of GI disorders, contraindicated in renal failure
Calcitonin -
Increase in blood calcium increases secretion of calcitonin decrease in blood calcium increases secretion of parathyroid hormone
Principal effects are to lower serum calcium and phosphate
Salmon calcitonin (Miacalcin, Calcimar) Nasal spray o
It inhibits osteoclast activity, decreases bone resorption t hus lowers serum calcium and phosphate and reduces bone pain, it increases BMD in the spine.
o
Paget’s disease, osteoporosis, hypercalcemia.
Side effects: sore, itching, rhinitis. Transient ANV, urinary frequency, flushing o f face, palms and soles of feet. Risk of anaphylaxis.
Take adequate amount of calcium and vitamin D. take in evening. Warm to room temperature, use alternate nostril. ANV may occur. Report nose bleeds.
Arthritis: -
Osteo: Acetaminophen, NSAIDs, Glucocorticoids-maybe injected directly into the joint directly (not more than every 4-6 months)
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Rheumatoid: Acetaminophen, NSAIDs, glucocorticoids -
Disease Modifying Anti-Rheumatic Drugs (DMARD)
Gold salts, hydroxychloroquine (Plaquenil)-base (Plaquenil)- base line eye exam every 6 mo nths, Sulfasalazine (Azulfidine) & Dpenicillamine (Cuprimine)
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Immunosuppressant agents
Imuran, Cytoxan, Rheumatrex
Biologic immunosuppressant
Gouty: Chemotherapy, thiazide diuretics, aspirin, TB drugs, NSAIDs, corticosteroids, cholchicine, allopurinol -
Colchicine:
Anti-inflammatory effects limited to gout.
Inhibits crystal-induced production of chemotactic factors
Side effects: PO-abdominal cramping, diarrhea, nausea, vomiting. IV- local pain, DIC, tissue damage on extravasation. Contraindicated- GI, renal, hepatic, or cardiac disease
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Urate lowering drugs
Goal is for serum urate concentrated to be <8 mg/dL
Xanthine oxidase inhibitors-blocks conversion to uric acid o
Allopurinol
Uricosuric drugs- inhibits tubular absorption o
Probenecid or Sulfinpyrazone
Knee & Hip Replacements: pre-antibiotics, enoxaparin (lovenox), fondaparinux (arixtra), Coumadin (Warfarin) Alzheimer’s Disease: -
Acetylcholinesterase Inhibitors: selectively inhibits acetylcholinesterase which enzymatically degrades acetylcholine which is needed to be a neurotransmitter dealing with learning a nd memory. -
Tacrine (Cognex)-one (Cognex)- one hour before meals (hepatoxic); (Aricept)- at bed time; (hepatoxic); Donepezil (Aricept)-at time; Rivastigmine (Exelon); Galantamine (Razadyne)-with (Razadyne)-with food, substrate of p450
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Adverse effects: Cholinergic related problems: urinary retention, seizure, bradycardia, GI bleeding.
NMDA-receptor Antagonists - blocks the activation of glutamate receptors and minimizes the adverse effects of excess glutamate -
Metamantine has shown to slow rate of memory loss in both vascular-associated and Alzheimer’s dementia.
Well tolerated. Side effects: confusion, agitation, restlessness, indistinguishable from AD symptoms
CVA: -
Thrombolytics and/or heparin-not heparin -not for hemorrhagic
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TPA: TPA: 3 hours of onset of symptoms to dissolve the clot
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Edema: mannitol, loop diuretics
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Seizures; dilantin, valium, ativan, Phenobarbitals
Increased ICP: -
Stress ulcers: H2 blockers, Esomeprozole
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Furosemide & MannitolMannitol - draw water from edematous tissues into vascular space, Phenytoin
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Glucocorticoids –help relieve cerebral edema
Epilepsy: -
Anti-Epileptic Drugs (AEDs) -
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Modification of ion conductances.
Decrease in Sodium, Calcium influx (delay depolarization/prolong repolarization)
Increased Chloride influx (hyperpolarizes membranes)
Increase inhibitory (GABAergic) transmission
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Increased Chloride influx (hyperpolarize membrane)
Decrease excitatory (glutamatergic) activity
Decrease sodium, calcium influx (delay depolarization/prolong repolarization)
Many CNS drugs act on GABA receptors to effect the frequency and duration of action potentials! Choosing Antiepileptic Drugs: -
Monotherapy for Partial Seizures: -
Best evidence and FDA indication:
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Similar efficacy, likely better tolerated:
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Best evidence & FDA indication:
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Valproate, Topiramate
Also shown to be effective:
Zonisamide, Levetiracetam (Keppra)
Phenytoin (Dilantin), Carbamazepine (may exacerbate absence and myoclonic sz)
Lamotrigine (may exacerbate myoclonic sz of symptomatic generalized epilepsies)
Absence seizures -
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Best evidence:
Ethosuximide (limited spectrum, absence only)
Valproate (Depakote)
Also shown to be effective:
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Lamotrigine (Lamictal)
May be considered as second-line:
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Zonisamide, Pregabalin
Monotherapy for Generalized-Onset Tonic/Clonic Seizures -
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Valproate (Depakote), Phenobarbital, Felbamate, Lacosamide
Limited data but commonly used;
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Lamotrigine (Lamictal), Cabapentin (Neurontin), Levetiracetam (Keppra)
As shown to be effective:
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Carbamazepine (Tegretol), Oxcarbazepine, Phenytoin (Dilantin), Topiramate (Topamax)
Zonisamide, Levetiracetam, Topiramate, Felbamate, Clonazepam
Myoclonic Seizures -
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Best evidence:
Valproate (Depakote)
Levetiracetam (Keppra) (FDA indication as adjunctive tx)
Clonazepam (Klonopin) (FDA indication as adjunctive tx)
Possibly effective:
Zonisamide, Topiramate (Topamax)
Common Side Effects of AEDs: -
Often dose related: dizziness, fatigue, ataxia, diplopia, ir ritability-Keppra, word-finding difficulty-Topamax
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Weight loss/anorexia: topiramate, zonisamide, felbamate
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Weight gain: valproate (also associated with polycystic ovarian syndrome in young women)
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Carbamazepine, gabapentin, pregabalin
Serious Side Effects: -
Typically idiosyncratic: renal stones (topiramate, zonisamide); hyponatremia (carbamazepine, oxcarbazepine), aplastic anemia (felbamate, zonisamide, valproate, carbamazepine); agranulocytosis (Carabamazepine (Tegretol)); hepatic failure (valproate, felbamate, lamotrigine, phenobarbital); Anhydrosis, heat stroke (topiramate); Acute closed-angle glaucoma (topiramate)
Phenytoin Adverse Effects: -
Acute toxicity: high IV rate: cardiac arrhythmias + o r – hypotension &CNS depression. Acute oral overdose: cerebellar and vestibular symptoms and signs: nystagmus, ataxia, diplopia vertigo
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Chronic toxicity: dose related vestibular/cerebellar effects, behavio ral changes, gingival hyperplasia, GI disturbances, Sexual endocrine effects, osteoporosis, hirsutism, hyperglycemia -
Drug Interactions:
Sulfonamides, valproate and phenylbutazone: displace phenytoin from binding sites Cimetidine, disulfiram, doxycycline, isoniazid, phenylbutazone, sulfas, Warfarin, chloramphenicol: inhibits phenytoin metabolism
Barbiturates & carbamazepine, pyridoxine, theophylline, alcohol: enhance phenytoin metabolism
Phenytoin decreases serum levels of: carbamazepine, chloramphenicol, corticosteroids, haloperidol, quinidine, theophylline, oral contraceptives, Warfarin
Valproates: -
Precautions & Contraindications: -
Pregnancy category D associated with spina bifida. Uncommon but may impair platelet aggregation (bleeding time maybe prolonged). Can cause bone marrow suppression (Baseline CBC & regular monitoring). Can cause fal se positive ketone urine test in diabetic patients. Heptotoxicity and liver failure-Do not take with alcohol!
Carbamazepine Drug Interactions: -
Increase carbamazepine levels via decreased metabolism: cimetidine, erythromycin, isoniazid
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Decrease carbamazepine levels via increase metabolism: phenytoi n, valproic acid
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Carbamazepine decreases drug levels: Warfarin, oral contraceptives, doxycycline, phenytoin, haloperidol
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Carbamazepine increases drug levels: cimetidine, isoniazid
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Lithium induces carbamazepine toxicity
Phenobarbital Drug Interactions: -
Increase Phenobarbital levels, acute ethanol ingestion, chloramphenicol, valproic acid
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Decreases Phenobarbital levels via increased metabolism, chronic alcohol ingestion, pyridoxine, rifampin
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Barbiturates decrease serum levels: tricyclics, Warfarin, beta bloc kers, oral contraceptives, digoxin, doxycycline, metronidazole, theophylline
Multiple Sclerosis Immunomodulators -
4 drugs currently available. Recommended for all patients with relapsing-remitting MS and with secondary progressive MS experiencing acute exacerbations. Self injected. -
Inferferon Beta 1a (Avonex and Rebif): is a protein that is a re plica of human interferon. It suppresses the immune system and helps to maintain the blood-brain barrier. You inject Avonex into the muscle once a week and Re bif is injected under the skin 3 times a week. This drug is useful to people who have definite progressive MS. (T cells can’t get back in, suppresses anti-
inflammatory cytokine. Cytokines communicate between WBCs). -
Interferon Beta 1b (Betaseron): (Betaseron): is slightly different from our own interferon. This medication does the same thing as beta 1a, but is injected just under the skin every 2 days. This is also given to people who have definite progressive MS.
Adverse Effects of Interferon:
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Flu-like reaction, hepatotoxicity, myelosuppression, injection-site reactions, depression
Glatiramer Acetate (Copaxone): “is a small fragment of a protei n that resembles a protein in myeli n.” Protects myelin by inhibiting immune response to myelin basic protein (competitive binding to APC). It decreases the reoc currence of relapse. It is injected just under the skin every day-patient teaching! There is no flu like sympt oms but occasional redness may occur at the injection site. A few amount of people do experience brief shortness of breath.
Immunosuppressants: -
Only 1 approved by the FDA-Mitoxantrone FDA-Mitoxantrone (Novatrone)
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More toxic than immunomodulators. Produces greater suppression of immune function: myleosuppression, hepatotoxicity, cardiotoxicity, fetal harm, Pancytopenia (risk for bleeding, infection & anemia) -
Monitor: perform CBC at baseline and prior to each dose. Perform LFT at baseline and prior to each dose. Perform pregnancy st
test prior to each dose. Determine LVEF: prior to 1 dose, prior to all doses once the cumulative do se has been reached. Whenever signs of CHF develop (signs at 30% of ejection function; normal at 60-70%) -
Imuran; Cytoxan: Cytoxan : suppresses immune system. Watch for bone marrow suppression (Pancytopenia-infections, fatigue/anemia, bleeding)
Supportive Drugs for MS: Spasticity-Baclofen, Spasticity-Baclofen, Tizanidine, Diazepam (Valium), Dantrolene Optic Neuritis-Methylprednisolone, Neuritis-Methylprednisolone, Oral steroids Fatigue-antidepressant, Fatigue-antidepressant, amantadine Pain-Codeine, Pain-Codeine, Aspirin Sexual dysfunction-Viagra dysfunction-Viagra Tremor-Primidone, Tremor-Primidone, Propanolol
Parkinson’s Disease 2 major categories: 1)
Dopaminergic agents a.
By far the most commonly used f or PD. Promotes activation of dopamine receptors
b.
Levodopa (Dopar) & Lepodopa/Carbidopa (Sinemet)
Dopamine + Carbidopa (Sinemet): Dopamine (DA) cannot cross BBB. Given as its precursor, levodopa or L-dopa, which is converted to DA by dopa-decarboxylase.
Levodopa (L-dopa)-can cross BBB! Dopamine (DA) by dopa-decarboxylase
Carbidopa inhibits peripheral decarboxyalse which is an enzyme that breaks down L-dopa. Thus, lower doses with fewer systemic side effects have the same beneficial CNS effects. Drug of choice (most effective agent to date). Most effective for bradykinesia, poor for tremor.
Side Effects: o
“Wearing off effect”-effectiveness wanes after 2-5 years. Initially, L-dopa effects last 6 hours after
PO dose. Reduces to 3 hours after 2 years. Only 2 hours after 5 years of use. Remedy: “drug holiday” taper off over 3-4 days. o
“On-off phenomenon”-fluctuating response to medication. Patient typically worsens suddenly for
half hour then improves. Remedy: decrease dose and increase frequency. Sustained release Sinemet-CR may help. Bromocriptine, pergolide and selegiline may help. Palidotomy may help (surgery). o
N/V common, psychiatric disturbances: hallucinations, confusion, nightmares are common. Tardive Dyskinesia (Michael J Fox)-orofacial in elderly, lip smacking, eye rolling, limb chorea/dystonia in younger patients. Overdose-GI upset, choreic movements. Can cause increase in IOP-contraindicated for glaucoma patients, can cause cardiac Dysrhythmias, hypertension
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(B6)-increases peripheral breakdown of levodopa. Concomitant administration with Mono Interaction of Sinemet: Pyridoxine (B6)-increases Amine Oxidase Inhibitor (MAOI)-antidepressant
Can lead to hypertensive crisis.
Levodopa: Levodopa: promotes dopamine synthesis Dopamine agonists: stimulate dopamine receptors directly. U sed for patients requiring larger doses of levodopa. Those experiencing motor fluctuations. -
Ergot Derivatives: Derivatives: -
Bromocriptine (Parlodel): (Parlodel) : stimulates primarily D2 DA post synaptic receptors. Acts as weak D1 antagonist. Causes Vasospasm!Contraindicated in patient with P VD/CAD!!*
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Pergolide (Permax): more potent than bromocriptine. Directly sti mulates both D1 & D2 receptors. May reduce “on -off” phenomenon. Hypertensive patients shouldn’t take this.
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Non-Ergot Derivatives: -
Bind selectively to dopamine D2-like receptors and activate D3 receptors which have unknown function.
Parmipexole (Mirapex): (Mirapex): has activity at D2 & D3 receptors
Ropinirole (Requip): (Requip) : Strong D2 receptor agonist. Does not cause vasospasm. For patient with PVD.
Selegiline (Eldepryl) & Rasagiline: Rasagiline: inhibits dopamine breakdown in the brain by inhibiting MAO type B. Selegiline metaboliz ed into amphetamine Amantadine (Apokyn): (Apokyn) : promotes dopamine release. These drugs stimulate the actions of dopamine in the brain, reducing the symptoms of Parkinson’s disease (PD). 0.2-0.6 mL sub-Q prn maximum 5 times per day. R escue med for acute, intermittent hypomobility, and off episodes (end
of dose wearing off and unpredictable on/off episodes). Significant improvement in mobility at 20 minutes. Half life 40 minutes. Pregnancy category C. RESCUE MED.
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Cross sensitivity with Zofran. Severe N/V-start Tigan 3 days prior to initiation of therapy. Hallucinations, sudden sleep episodes, syncope, MI, Cardiac arrest, Priapism, Abuse potential
COMT inhibitors: enhances effects of levodopa by blocking it s degredation -
Methylation of Levodopa by this enzyme i s a minor pathway of levodopa metabolism. This enzyme i ncreases to compensate for a decrease in Dopa-decarboxylase with Carbidopa. Blocking COMT will increase peripheral blood level of levodopa and greater concentration of brain dopamine. Entacapone & Tolcapone
2)
Anticholinergic agents a.
Prevents activation of cholinergic receptors. Blockage of cholinergic transmission produces effects similar to augmenting dopaminergic transmission (balances dopamine/Ach ratio).
b.
Benztropine (Cogentin)
Myasthenia Gravis (MG) (Tensilon) - Rapid onset of 30 seconds. Short duration 5 minutes. Draw up 10 mg, Administer 2 mg . Monitro Anticholinesterase Test: Edrophonium (Tensilon)for adverse symptoms. Administer remaining 8 mg. Improvement of weak muscles that last 5-10 mi nutes. Test positive. Anticholinesterase Drugs: first line treatment for symptoms of MG. Do not treat the u nderlying disease.Pyridostigmine disease.Pyridostigmine (Mestinon) no standard dose. Neostigmine (Prostigmin)(Prostigmin)- seldom use. *Atropine antidote for choli nesterase (ChE) inhibitor drugs. Must be available. -
Pyridostigmine (Mestinon): (Mestinon): last 3 to 6 hours. Goal to produce maximal muscle strength with minimal side effects.
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Muscarinic ReceptorsReceptors - cholinergic (parasympathetic acetylcholine) receptors come in variety of types. One type is muscarinic receptors or mAChRs. Main end receptor stimulated by acetylcholine released from postganglionic fibers in the parasympathetic nervous system. Stimulation of muscarinic receptors causes parasympathetic ANS responses. -
Side effects: GI: heartburn, belching, abd cramps, increased peristalsis, diarrhea, N&V. GU: involuntary micturiction, increased tone and motility of uterus. CV: bradycardia, Vision: blurred, constricted pupils. Pulm: bronchoconstriction/bronchospasm, increased bronchial secretions, wheezing cough. Other: profuse sweating, increased salivation.
Immunosupapression: For those who do not respond to anticholinesterase drugs: Pre dnisone, Azathioprine (Imuran), Cyclophosphamide (Cytoxan)
Guillain Barre Plasmapheresis (Plasma exchange) Intravenous Immune Globin-use as immunosuppressant IVIg
