GENERAL PHARMACOLOGY Pharmacodynamics
: - What drug does to body.
Pharmacokinetics
: - What body does to the drug.
Phar Pharma maco coth ther erap apeu euti tics cs
: - Use Use of of dru drugs gs in prev preven enti tion on & tre treat atme ment nt of dise diseas ase. e.
Clin Clinic ical al phar pharma maco colo logy gy
: - Scie Scient ntif ific ic study tudy of drug drugss in man. man.
o!icology
: - "spect of pharmacology deals #ith adverse effects of $rugs.
Phar Pharma maco cody dyna nami micc agen agents ts : - $esi $esign gned ed to have have phar pharma maco cody dyna nami micc effec ffectts in the the recipient. Chemot Chemother herape apeuti uticc agents agents : - $esig $esigned ned to inhibi inhibit%k t%kill ill parasit parasites% es%mal malign ignant ant cells cells & does does not have or #ith minimal pharmacodynamic effects effects in recipient. rphan drugs : - $rugs or 'iological Products for diagnosis%treatment% Prevention of a rare disease. (.g.:- )iothyronine *+, $esmopressin $esmopressin 'aclofen $igo!in $igo!in "ntibody. "ntibody. outes of drug "dministration "dministration /, ral ral 0, Pare Parent ntra rall 1n2ections:", 1ntrad 1ntraderm ermal: al: - given given in to layers layers of skin. skin. (.g.:(.g.:- 'C3 vaccin vaccine e for testin testing g drug drug sensitivity. ', S.C:S.C:- nly nly non-ir non-irrit ritant ant drug are given given absorpti absorption on can be enhanc enhanced ed by en4yme en4yme 5yalurinase S.C.drug implants can act as depot therapy. (.g.:- steroid hormones. 1n children saline is in2ected in large 6uantities 7 5ypodermalysis. 5ypodermalysis. C, 1.8:- 8ild irritants irritants suspensions suspensions & colloids colloids can be in2ected by this route. $, 1.9: 1.9:- $irectly $irectly to vein. vein. (, 1ntra 1ntra arteri arterial: al: - nly nly used used for diagnost diagnostic ic studie studies. s. (.g.:(.g.:- "ngiog "ngiogram rams s embol embolism ism therapy. , 1ntrathecal: - Spinal anaesthetics anaesthetics in to subarachinoid subarachinoid space. space.
3, 1ntra medullary: medullary: - $rug introduced to 'one marro#. marro#. 5, 1ntr 1ntraa arti articu cula larr & 1ntr 1ntraa tens tensio iona nal: l: - $rug $rug admi admini nist ster ered ed into into 2oin 2oints ts.. (.g. (.g.::5ydrocortisone acetate in rheumatoid arthritis. Page 1 of 67
PHARMACOKINETICS
"bsorption of $rugs:", Simple Simple diffusion: diffusion: - 'idirecti 'idirectional onal process process rate of transfer across across the membrane membrane is proportional to concn gradient. (.g.:- 50; soluble drugs #ith lo# mol-#t lipid soluble drugs. ', "cti "ctive ve tran transp spor ort: t: - re6u re6uir ires es ener energy gy 7 inde indepe pend nden entt of phys physic ical al prop proper erti ties es of membrane. (.g.:- 50; soluble drugs #ith high mol-#t. Carrier mediated transport: - (.g.:- 1ntestinal absorption of Ca0<. C, Pinocytosis: - 1mportant in unicellular organisms organisms like like "moeba. "moeba. 'ioavailability: - "mount of drug reaches systemic circulation follo#ing a non-vascular drug administration. "uc oral = "uc iv 'arriers:'.'.':- made up of choroid cells *strong 'arrier,. estis 'arrier: - made up of seroid cells. Placental 'arrier: - made up of sertoli cells *#eak 'arrier,. (ndothelial 'arrier: - in all blood cells *very #eak,. or absorption of vit'/0 IF factor is re6uired #hich is synthesi4ed by parietal cells> Solubility of drugs:1oni4ed form 7 soluble Unioni4ed form 7 more absorbed $istribution of drugs:Plasma protein binding: - many drugs have affinity to#ards plasma proteins "cidic drugs to#a to#ard rdss "lbum lbumin in 'asi 'asicc drug drugss to#a to#ard rdss acid acid 3lyc 3lycop opro rote tein in Prot Prothr hrom ombi bin n and and hromboplastin. adioligand binding: - is used to determine drug in protein comple!. / PP' 9d issue issue storage of drugs:Skeletal muscle 5eart: - $igo!in emetine )iver: - Chloro6uine tetracycline?s tetracycline?s digo!in @idney: - Chloro6uine digo!in emetine hyroid: - 1odine 'rain: - CPA "ceta4olamide 1sonia4id etina: - Chloro6uine 1ris: - (phedrine "tropine "tropine 'one & eeth: - 5eavymetals etracycline?s Page 2 of 67
"dipose tissue: - Pheno!y 'en4amine 8inocycline ether hiopentane. hiopentane. 8etabolism of drugs :- * 'iotransformation % $eto!ification, Chemical alteration of drug in physiological system /. 1nac 1nacti tive ve form form 0. "ctive "ctive metabolit metabolite e (.g.:(.g.:- Codeine Codeine to morphine morphine +. Prodrug Prodrug to active active drug (.g.:(.g.:- )-$opa )-$opa to $opamine $opamine Phase 1 metabolism: - Bonsynthetic eaction !dn edn 5ydrolysis Cyclisation $ecyclisation
(n4yme 8onoo!ygenases cytpD; in lives eductases (sterases
(!amples $rugs #ith E5F & EC5Fgroups 5alothane trichloroethand )idocaine procainide 'en4ocaine Proguanil to cycloguanil Phenobarbitone & Phenytoin
Phase 11 8etabolism: - Synthetic or Con2ugation Con2ugation /. 3lucouronide 0. "cetylation
(ndogenous substrate 3lucouronic acid *glucose, "cetyl co-" *Citric acid cycle, +. 8ethylation 8ethionine . Sulphate Sulfokinases D. 3lycine*rarely 3lycine occur, G. 3lutathione H. ibonucleotide
Prodrug )evodopa (nalpril )-8ethyldopa
(!amples EhF & EC5F group drugs EB50F & 5ydra4ine group drugs EB50F & Phenol group drugs Phenolic compds & Steroids Salicylates & EC EC5F gr group drugs Paracetamol Purine & Pyrimidine antimetabolites
"ctive form $opamine (nalaprilat )8ethylnorepinephrine $ipivefrine (pinephrine 'enorylate "spirin
"ctive drug Chloralhydrate Phenacetin Primidone
"ctive 8etabolite richloroethanol Paracetamol Phenobarbitone
$igito!in Codeine Spironolactone "mitryptiline $ia4epam
Sulphasala4ine
rimethadione
$igo!in 8orphine Canrenone Bor-tryptiline $esmethyl o!a4epam $imethadione
D-amino sal salicylic aci acid
8icrosomal en4ymes: - hese are inducible 8onoo!ygenases 3lucouronyl transferase etc.
by
drugs
diet
dia4epam
(.g.:-
cytPD;
Page 3 of 67
Catalyses many o!dn redn 5ydrolysis & glucouronide con2ugations. Bon 8icrosomal en4ymes: - (.g.:- lavoprotein o!idases esterases amidases & con2ugases. Catalyses some o!dn & redn many hydrolytic reactions & all con2ugations e!cept glucouronidation. 5ofmann elimination: - 1nactivation of drug in body fluids by spontaneous molecular rearrangement #ithout en4ymes. (.g.:- "tracurium. (n4yme inducers: - Phenytoin 'arbiturates ifampicin Carbama4epine. (n4yme 1nhibitors: - Cimetidine erythromycin chloramphenicol ciproflo!acin 8" inhibitors sulfonamides verapamil 1B5 $isulfiram etc. (!cretion of drugs: - elimination of drug in inactive form Urine 7 50; soluble drugs eces 7 Unabsorbed drugs *comple! drugs insoluble drugs, S#ets 7 salts & heavy metals Saliva 7 5m )ead SCB )ithium & etracycline?s )ungs 7 gaseous drugs "lcohol paraldehyde etc. )acrimal 7 drugs applied to eye.
Clearance =
ate of elimination plasma concn of drug
PHARMACODYNAMICS
$rug produces action by stimulation depression irritation replacements cytoto!ic action. 8echanism of drug action:-
Physical
Properties 8ass of drug
$rugs 'ulk la!atives protectives Page 4 of 67
"dsorptive property smotic activity adioactivity adio opacity Chemical Beutrali4ing germicidal chelating
charcoal kaolin mgso mannitol 1/+/ & other isotope 'aso urografin "ntacids @nmo 10 ($" Penicillamine
hrough en4ymes: - $rugs may also increase or decrease rate of en4ymatically mediated reactions. Stimulation: - e.g.:- "drenaline stimulates "denyl cyclase pyrido!ine increases decarbo!ylase activity. a, 1nhibition :/, Bon specific inhibition: - 8any drugs act by denaturing proteins. (.g.:- 5m "cid & "lkalies "lcohol ormaldehyde Phenol etc. 0, Specific inhibition :i, Competitive: - Physostigmine & neostigmine #ith "ch for sulfonamides #ith P"'" for folatesynthetase "llopurinol #ith 5ypo!anthine for !anthine o!idase carbidopa & methyldopa #ith ) 7 $opa for dopa decorbo!ylase. ii, Bon-competitive:- "ch & Papaverine on smooth muscles "ch & $ecamethionine on BmI. hrough receptors:/, Clark-"rheneous theory *occupation theory,:- he effect of drug is proportional to fraction of receptors occupied by drug & ma!imum effect results #hen all receptors are occupied. 0, aton?s theory *ate theory,:- he effect of drug is a function of receptor occupation & the rate of drug receptor combination. 5ere response depends on rate of "ssociation bet#een drug molecule & receptor. 3 proteins are 5eterotrimeric proteins involved in receptor transduction it has + subunits. P"! = - log *", ! P"0 = - log *", 0 P$0 = - log *a, 0 Where *", = molar concn of antagonist #here *a, = molar concn of against. (udismic ratio: - ratio of the activities of active enantiomer *eutomer, and inactive enantiomer *distomer, in chiral pharmocodynamics.
Page 5 of 67
AUTONOMIC NERVOUS SYSTEM Sympathetic or "drenergic system enables the individual to ad2ust to stress & prepares the body for Jight or light? response. Parasympathetic or Cholinergic mainly participate in tissue building reactions. 'oth sympathetic & parasympathetic nervous system consists of myelinated preganglionic fibre #hich forms a synapse #ith the cell body of non-myelinated post ganglionic fibre. Syna!": - 1t is the structure formed by the close opposition of a neuron either #ith another neuron or #ith effector cells. he synapse b%# preganglionic & postganglionic fibres is termed as 3anglion he synapse b%# postganglionic &receptors is termed as Beuroeffector 2unction. N"#$%&#'%$a( )$an!'*!!*%n: - he transmission of an impulse across the synapse in central & peripheral nervous system occurs as a result of release of a neurohumoral transmitter substance in to the synaptic cleft. +#n,)*%na( )$an!'*!!*%n: - he arrival of an action potential at the a!onal terminals initiates the series of events that put in to effect neurohumoral transmission of an e!citatory%inhibitory impulse across the synapse % neuroeffector 2unction. A-$"n"$.*, $",")%$!:-
ecep "gonist tor a1 8etho!amine
a2
Clonidine
"ntagonist
issue
Kuina4oline 'lood vessel derivatives* Pra Smooth muscle 4osin, )iver Lohimbine.au 1slet cells losine Platelets
esponse
8olecular mechanism 9asoconstriction Stimulation of Contraction phospholipase1ncreased blood C & formation glucose level of 1P+ %$"3 $ecreased 1nhibition of insulin "denylcyclase Page 6 of 67
/1
/2
/3
$obutamine
9ascular smooth muscles 5eart Iu!ta glomerular cells
"ggregation Contraction
& neuronal ca0< channels "ctiv ctivaatio tion of "denylcyclase
"tenolol"ceb utolol 'isoprolol8et oprolol erbutalinesalbut 'uto!amine Smooth "cti "ctiva vati tion on of amol 8ethyl muscles "denylcyclase Propranalol Sibutramine* "nti -------------"dipose tissue )ipolysis "ctivation of -obesity, "denylcyclase "drenergic receptors are membrane bound 3- Protein coupled receptors #hich function primarily by increasing%decreasing increasing%decreasing the intracellular production of secondary messengers? c"8P%1P +- $"3. 1n some cases the activated 3-Protein itself operates @ <%Ca0< channels or increases prostaglandin production. C(a!!*0*,a)*%n %0 A-$"n"$.*, -$#.!:". herapeutic classificationclassification/. Pressor drugs: - "drenaline B" 8etarminol 0. 1notropic agents: - $opamine $opamine $obutamine $obutamine 1soprenaline& 1soprenaline& Mamoterol +. CBS Stimulants:-"mphetamine Stimulants:-"mphetamine . Smooth Smooth muscle muscle rela!ants:-"drenaline rela!ants:-"drenaline 1soprenaline 1so!suprine& /2 stimulants *Salbutamol, D. $rugs used in allergy: - "drenaline "drenaline & ephedrine G. )ocal vasoconstrictor effect:-"drenaline effect:-"drenaline Bapho4oline Phenylephrine H. Basal Basal decongestants: decongestants: - !ymeta4oline !ymeta4oline uaminoheptanesulfat uaminoheptanesulfatee N. "norectics: "norectics: - enfluramine enfluramine de!fenfluramine&Phenteramine de!fenfluramine&Phenteramine O. "ntiobesity: "ntiobesity: - Sibutramine
'.Chemical classification:classification:/. Catecholamines Catecholamines 7 "drenaline "drenaline B" B" $opamine $opamine D-5 & 1soprenaline 1soprenaline 0. Bon-Catecholamines Bon-Catecholamines 7 "mphetamine "mphetamine (phedrine 1so!suprine 8ephentamine P&a$'a,%(%.*,a( A,)*%n! :/. H"a$): - $ue to its stimulant action on /1 receptors causes < ve inotropic actions. his is associated #ith increased metabolism of myocardium & increased 0 consumption thus decreasing cardiac efficiency.
0. (%%- "!!"(!: - aises systolic '.P. by its cardiac actions lo#ers diastolic '.P. by its peripheral actions & hence not suitable suitable in 5ypotensive 5ypotensive shock 1n moderate doses rise in '.P. is follo#ed by a fall as it activates both the receptors. his is called as J'iphasic response?. 'y prior administration of a blockers *ergot, leads to stimulation of only /2 receptors & thus causes a fall in '.p. his phenomenon is called as J$ale?s vasomotor reversal? Compared to "drenaline the B" has feeble actions on /2 receptors. Page 7 of 67
+. S'%%)& '#!,("!: - rela!es bronchial muscles Produce Produce contraction contraction of spleemic spleemic capsule capsule producing producing a release release of erythrocytes erythrocytes in to the Peripheral circulation. his serves as protective mechanism during stress such as hypo!ia & 5emorrhage . Ey": - 8ydria 8ydriasis sis due to contra contracti ction on of radial radial muscle muscle fibres fibres of 11S. 11S. n topica topicall application do not produce 8ydriasis but cause reduction in intraocular tension. D. R"!*$a)*%n: - 'ronchodilator & #eak stimulant G. M")a/%(*, "00",)! : - 1ncreases 'lood glucose 'lood lactate free fatty acids. 1nhibits insulin release. H. CNS: - Catecholamines cannot cross ''' N. M*!,"((an"%#!: - Skeletal muscle contraction "ccelerates 'lood coagulation Platelet aggregati aggregation on )eucocyto )eucocytosis& sis& (osonopeni (osonopenia. a. 1nhibit 1nhibit cellular cellular anaphylac anaphylactic tic mechanis mechanism& m& prevent release of allergic mediators mediators *5istamine *5istamine from mast cells, cells, 8a2or e!cretory products are 9anillin mandelic acid TU!"!:/. Ba in elevating '.P. in shock 0. 1n glaucoma. o control control hemorrhage +. Cardiac resuscitation . 'ronchial asthma D. irst line drug in 5ypersensitivity G. "long #ith )ocal anaesthetics to prolong their action. N%)": - 8etyltyrosine%8etyrosine%0-methyl p-tyrosine inhibits yrosine hydro!ylase in synthesis of catecholamines & used in treatment of Pheocytochroma.
Catecholamines Bot effective effective orally $o not cross ''' Susceptible to 8"
Bon-catecholamines rally effective Crosses ''' elatively resistant to 8"
Na!a( -",%n."!)an)!: - 8ost of the Sympathetic amines on topical application produce )ocal vasoconstriction & used as $econgestants $econgestants (.g. !ymeta4oline !ymeta4oline Aylometa4oline Aylometa4oline Bapho4oline.tuaminoheptanesulfate Bapho4oline.tuaminoheptanesulfate
Potency of agonists at a&/ receptors area- "drenaline B" 1soprenaline b- 1soprenaline "drenaline B" /2 !"(",)*" !"(",)*" $", $",")%$ ")%$ !)*'#(an)! !)*'#(an)!: - 1soprenaline used in "sthma #ill cause adverse cardiac effects due to action on // herefore selective /0 stimulants are used in "sthma & as ocolytics Page of 67
(.g.Bylidrin.1so!suprine D$#.! #!"- *n CCF:$opamine& $ope!amine acts on a&/ receptors as #ell as $ /&$0 receptor. $obutamine acts only on a&/ receptor Mamoterol has selective /1agonist action.
A-$"n"$.*, (%,*n. A."n)!:-
Classification:'lockers:a/./- 5aloalkylamines5aloalkylamines- $ibenamine& Pheno!yben4amine 0. 1mida4oline derivatives- ola4oline& ola4oline& Phentolamine +. Kuina4olines- Pra4osin tera4osin trema4osin . Batural & dehydrogenated ergot alkaloids D. 8iscellaneous- yohimbine 1ndoramine Cp4 he receptor blockade produced by $ibenamine& Pheno!yben4amine is ir-reversible type type.. Phen Pheno! o!yb yben en4a 4ami mine ne is G-/; G-/; time timess more more pote potent nt than than $ibe $ibena nami mine ne but but has has be converted to active metabolite. T&"$a"#)*,! U!"!: - 1n pheocytochroma 5ypertension Secondary shock C5 '5P 8ale se!ual dysfunction Scorpion 'ite. b-
'lockers:/. Specific /- 'lockers- imolol imolol Badolol 0. 'lockers #ith membrane stabili4ing action: - Propranalol !yprenolol Pindolol +. 'lockers #ith cardioselective action: - "tenolol "tenolol "cebutolol 8etoprolol&(smolol 8etoprolol&(smolol . 'oth a&/ blockers: - )abetolol Carvedilol $ilevilol&8edro!olol $ilevilol&8edro!olol "tenolol #ith poor lipid solubility does not cross ''' at all. Propra Propranol nolol ol "lpreno lprenolol lol&8 &8eto etopro prolol lol are metabo metaboli4 li4ed ed by liver liver Pract Practolo ololl is larg largely ely e!creted unchanged by kidneys. Pindolol "tenolol "cebutolol& imolol by both the routes. hey hey are contra contraind indica icated ted in the myocar myocardia diall insuff insuffici icien ency cy 'radyc 'radycard ardia ia "sthma sthma 5eartblock& 1nsulin dependent diabetes. TU!"!:-"n :-"ngi gina nape pect ctor oris is 81 81 Card Cardia iacc arrh arrhyt ythm hmia ia 5ype 5ypert rten ensi sion on hyr hyrot oto! o!ic icos osis is Pheocytochroma to decrease cardiac symptoms prior to important speech%meetings. Propranalol is useful in prevention of 8igrane & treatment of (ssential tumor.
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CHOLINERGIC DRUGS "ch produces its dual actions as 8uscarinic actions on 8uscarinic & Bicotinic actions on nicotinic receptors. 8uscarinic receptors *mol #t-N;;;;, belong to g-Protein coupled receptors. Bicotinic receptors are Pentameric proteins. eceptor "gonist s
"ntagonist
Bm
Phenyl trimethyl ammonia $imethyl phenyl pipera4inu m
$-c B8I a- 'angaroto!in
8/
!ytremon ium
Piren4epine elen4epine "tropine
"utonomic 3anglia 3astric 3lands
80
8ethacholi ne
8ethocrotamine "tropine
5eart
8+
'ethnecol
"tropine Smooth 5e!ahydrosilede 8uscles nifol Secretory 3lands
Bn
issue
rimethophan "utonomic 5e!amethonium 3anglia Succinylcholine "drenal medulla
esponse
8olecular 8echanis m (nd plate pening depolari4ation of cation channels $epolari4ation& pening firing of Post of cation ganglionic channels neurons. Secretion of catecholamines $epolarisation & Stimulatio )ate (PSP. n of 5istamine release phospholi pase-C & formation of 1P+ %$"3 Begative 1notropic 1nhibition effect of "denylcyc lase Contraction Stimulatio n of 1ncreased secretion phospholi pase-C & formation of 1P+ %$"3
C(a!!*0*,a)*%n:-
/. (sters of Choline 7 "ch 8ethacholine Carbachol& 'ethnechol 0. Cholinomimetic "lkaloids 7 Pilocarpine 8uscarine&"recholine +. Cholinesterase inhibitors 7 a, eversible: - Physostigmine *Batural, Beostigmine.Pyridostigmine demecarium acrine *"cridine, used in "l4hmeir?s disease. Page 1 of 67
b, 1r-reversible: - $i-isopropylflurophosphate *therapeutically useful, 8PP 8alathion Parathion Berve gases *abun sarin& Soman, Propo!ur *carbamates,
P&a$'a,%(%.*,a( a,)*%n!:- Undergoes 5ydrolysis in Beutral or "lkaline medium & hence preserved in "cidic medium. n oral administration gets destroyed by 31 & hence given by 1.v. here is no circulating "ch in the 'lood.
M#!,a$*n*, a,)*%n! 7 /. CVS: - Begative 1notropic actions $ilates 'lood vessels Coronary arteries&veins. 1ncreases tone & rhythmic activity of smooth muscles of 31 & enhance Peristalsis.
0. S",$")*%n!: - 1ncreases Basal 'ronchial 3astric salivary Pancreatic & 1ntestinal secretions. +. Ey": - on instillation no effect. 'ut on in2ection to carotid arteries producesConstriction of Pupil *8iosis, 7 'y contracting circular fibres of sphincter pupillae Spasm of accommodation 7 $ue to contraction of ciliary muscle resulting in rela!ation of suspensory ligament of lens. N*,%)*n*, a,)*%n! 7 /. 1ncreases output of "ch&B" from Post ganglionic sympathetic & Parasympathetic nerve endings & increases '.p.
0. Produce paralysis of skeletal muscles at B8I C%n)$a*n-*,a)*%n! %0 ,&%(*n" "!)"$!: - 5yperthyroidism 'ronchial asthma Peptic ulcer& 81 TU!"!: - 3laucoma Post operative paralytic ileus & abdominal distension An)*,&%(*n"!)"$a!"!: - they act by inhibiting true & Pseudo cholinesterases thus causing accumulation of "ch at various sites. MOA: - "ch is inactivated by combination of 0 sites on en4yme Cholinesterase. "nionic site bearing 7 ve charge attracts Kuaternary nitrogen atom of "ch (steratic site #hich attracts carbo!ylic acid group of "ch. "s a result of union of "ch #ith cholinesterase the esteratic site of en4yme is acetylated & this results in splitting of choline. he acetyl group in combination #ith esteratic site is 5o#ever immediately removed as a result of combination #ith #ater forming "cetic acid. his sets esteratic site of en4yme free for further inactivation of "ch.
Page 11 of 67
R""$!*/(" An)*,&%(*n"!)"$a!"!: - hese are structurally similar to "ch & combine #ith "nionic & esteratic sites of cholinesterase as #ell as #ith "ch receptor. 5o#ever the comple! #ith esteratic site is much readily hydrolysed compared to "ch. his produces temporary inhibition of the en4yme. Uses 7 3laucoma 8yasthenia gravis Snake venomPoisonimg Curare Poisoning& "l4hmeir?s disease. I$8$""$!*/(" : - hese organophosphorous compounds combine only #ith esteratic site of cholinesterase & conse6uently esteratic site is phosphorylated. he hydrolysis of esteratic site is e!tremely slo# %does not occur at all. his #ill lead to 8orbidity & 8ortality to overcome this #e use cholinesterase reactivators like Pralido!ime $iacetylmono!ime&bido!ime chloride. N%)": - (drophonium forms reversible comple! only #ith "nionic site & 5ence shorter duration of action. (chothiopate forms comple! #ith both "nionic & esteratic sites & hence is much more potent than other compounds.
ANTI8CHOLINERGIC DRUGS hey 'lock only 8uscarinic actions but not the 3anglionic & skeletal neuromuscular actions of "ch. C(a!!*0*,a)*%n:/. Batural alkaloids 7 "tropine Scopalamine 0. Semisynthetic derivatives 7 5omatropine 1patropium +. Synthetic compounds 7 a, 8ydriatics: - Cyclopentolate ropicamide ', "ntisecretory: - Propantheine Piren4epine MOA: - 'elladonna alkaloids block muscarinic effects of "ch. he antagonism is of competitive type #hich is reversed by an increase in "ch concentration at the cholinergic nerve endings Pa,)*%n!:- "tropine & scopolamine have 6ualitatively similar actions e!cept that "tropine is CBS stimulant While Scopalamine is CBS $epressant. /. S",$")*%n! 7 $ecreases gastric secretions including total acidity & en4ymes leading to decreased motility $ecreases Basal 'ronchial & other secretions
0. S'%%)& '#!,("! 7 ela!ation Causes Urinary retention +. Ey" - 8ydriatic */Q, ciliary smooth muscle is paraly4ed& produces tightening of suspensory ligament resulting in flattening of lens #ith conse6uent increase in focal length. hus individual is able to see only at long distance *paralysis of accommodation%cycloplegia, Page 12 of 67
'ecause of sphincter paralysis he cannot constrict the pupils for vie#ing near ob2ects clearly in response to 'right light *Photophobia,. . CNS 7 "tropine due to stimulation of medullary vagal nuclei & higher cerebral centers produces bradycardia increase rate & depth of respiration produced by "nticholinesterases. Scopolamine by S.C.depresses "S & Produces euphoria"mnesia&dreamless sleep. T&"$a"#)*, #!"!:♣ o control hypermotility Colicky pain ♣ rganophosphorous compound poisoning ♣ "s "ntisecretory in Pre anaesthetic medication Peptic ulcer& pulmonary embolism ♣ 8otion sickness *scopolamine, ♣ Parkinsonism ♣ "s 8ydriatic& cycloplegic ♣ "s "ntispasmodic in drug induced diarrhoea Spastic constipation 3astritis&$ysmenorrhoea. C%n)$a*n-*,a)*%n!:♣ 8ay cause Congestive glaucoma in patients over ;yrs ♣ CC #ith tachycardia ♣ Pyloric obstruction pylorospasm&Cardiospasm Gan.(*%n*, S)*'#(an)!: /. Bicotine lobeline 0. Synthetic compounds *8" $8PP, "ctivation of Bicotinic receptors facilitate the release of "ch B" dopamine D-5 & / (ndorphin ♣ Bicotine releases 35 Prolactin & "C5 ♣ 1ncreases muscle t#itching follo#ed by paralysis of myoneuronal transmission ♣ 1nduces 5epatic microsomal en4ymes ♣ 1ncreases '8 reduces body #eight & "ppetite ♣ Causes lipolysis & releases free fatty acids (!cessive release of cortisol affect mood & contribute to steoporosis ♣ 9omitting due to action on CA releases "$5 by stimulating Supraoptic nuclei of 5ypothalamus ♣ "cidic urine 1ncreases e!cretion of free nicotine 8" & $8PP are e!creted unchanged ♣ ".:- 'ronchitis (mphysema obacco "mlobia Cigarette contains 7 Bicotine Pyridine.C urfural 9olatile acids& polycyclic hydrocarbons "ntidepressant like 'upropion is used to 6uit smoking in some individuals. Page 13 of 67
Bote: - 8ydriatics 7 5omatropine (ucatropine & cyclopentolate ther "ntimuscarinics 7 "tropine methanitrate 8ethoscopalmine bromide%Bitrates Propantheline *probanthine, 7 used in peptic ulcer 8ethantheline *'anthine, $icyclomine Piren4epine *3astro4epin, 7 in duodenal ulcer lavo!ate *Uripas, & !ybutynine *$itropan, 7 1n $ysurea 1n urinary fre6uencies olteridine 7 8+ antagonist in Urinary incontinence. Gan.(*%n*, (%,*n. a."n)!: - 'locks transmission across "utonomic ganglia *'oth sympathetic & Parasympathetic, (.g.5e!amethonium trimethomine&5e!amylamine S"(")a( '#!,(" $"(a9an)! : - Used to treat spasm%spasicity Spasm 7 1nvoluntary contraction of muscle or group of muscles usually accompanied by pain & limited function.
Spasticity 7 due to increased skeletal muscle tone associated #ith decrease in skeletal muscle po#er due to damage to the corticonotoneuronic path#ays as in CBS in2ury cerebral palsy stroke or 8ultiple sclerosis. C(a!!*0*,a)*%n:/. $rugs acting centrally 7 dia4epam 'aclofen& 8ephenesin 0. $rugs acting peripherally at B8I 7 a, Competitive 'lockers: - $-C b, $epolari4ation blockers: - Succinyl choline c, 1nhibitors of release of "ch from the motor nerve terminals: 'otulinum o!in 7 " & "ntibiotics *etracycline& "minoglycosides, +. $rugs directly acting on Skeletal muscles: - $antrolene P&y!*%(%.y %0 !"(")a( '#!,(" ,%n)$a,)*%n :-
/.$ue to nerve action potential releases "ch from synaptic vesicles of motor nerve in to synaptic cleft in large 6uantities While in absence of B"P "ch is released due to miniature end plate potential * 8(PP , in small 6uantities. 0. he released "ch binds to nicotinic receptors on the motor endplate resulting in )ocalised depolari4ation & development of (nd plate polari4ation *(PP,. $epolari4ation is due to influ! of Ba< & (fflu! of @ < ions from motor endplate. +. When (PP is achieved the surround area of muscle fibre gets e!cited resulting in development of muscle action potential *8"P, #hich initiates contraction of a muscle as a result of release of ca 0< in to the Sarcoplasm. . "ch is metaboli4ed enabling repolarisation of motor endplate& muscle fibre membrane. his is achieved by reversal of ionic flu!es. he polari4ed muscle is no# capable of responding to fresh nerve impulse. Skeletal muscle contraction can be blocked as follo#s 7 /. 'locking transmission of impulse across the motor nerve 7 local anaesthetics Page 14 of 67
0. 1nhibit the synthesis of "ch in motor nerve 7 5emicholinum +. 1nhibit the release of "ch 7 'otulinum o!in-" & antibiotics *tetracyclines& "minoglycosides, . 8odifying the motor endplate so that it does not respond to "ch 7 dantrolene D8T,: - de!trorotatory 6uaternary ammonium alkaloid from Chondrodendron omentosum ela!es smooth muscles eleases 5istamine n repeated "dministration produces cumulative to!icity. $o not cross ''' & Placental 'arrier. $i-8ethyl ubocurarine has slightly longer duration of action
ther drugs: - "lcuranium Chloride- Similar to $-c Pancuranium & "tracuranium 7 D times more potent than $-c 9ercuranium Similar to Pancuranium but duration of action is less. 3allamine 7 Similar to $-C less potent completely e!creted by @idneys in Unchanged form.
DRUGS USED IN PARKINSONISM (!tra pyramidal motor disorder characteri4ed by igidity tremor & "kinesia. 5ere $opamine level decreases *responsible for "kinesia, & "ch level increases *igidity remor,. Pa)&%(%.y: - here is a degeneration of neurons in substantial nigra & Bigrostatial *$opaminergic, ract. he cause for this degeneration is due to the formation of free radical *8etabolism of $opamine by 8"-',. 1n normal Protective mechanisms ree radical are 6uenched by glutathione & other protective mechanisms. 1f this fails the free radical #ill cause $B" damage. " synthetic to!in n-methyl -phenyl tetrahydropyridine is responsible for damage to Bigrostatial tract. C(a!!*0*,a)*%n:-
". $rugs acting on dopaminergic system:/. Precursors of dopamine 7 )-$opa 0. $rugs inhibit $opamine 8etabolism 7 ", 8ao inhibitors: - Selelegine ', Comt inhibitors:-olcapone& (ntacapone +. $rugs that release dopamine 7 "mantidine . $opamine agonists 7 'romocryptine )ysuride ropinrole Pergolide Pirebedil Page 15 of 67
'. "nticholinergics: - rihe!yphenidyl 'en4ohe!ol 'en4atropine C. "ntihistaminics: - Prometha4ine L8D%a:- Pharmacologically inert While its metabolite is active. nly /Q enters CBS 8ost of the drugs get decarbo!ylated in 31& liver 1t is e!creted in urine partly unchanged& partly as 5omovanilic acid. 3ives Positive Comb?s test even though hemolytic anemia is not reported. 'lood urea nitrogen & S3 sho# a transient rise. C%n)$a*n-*,a)*%n!:Pyrido!ine accelerates Peripheral decarbo!ylation of )-$P". eserpine & Phenothia4ines block the effects of dopamine to #hich )-$opa is Converted. 8ethyldopa intensifies the adverse effects of )-$opa. "nticholinergics increase the stay of )-dopa in stomach & increase its degradation & hence if needed must be taken 0hrs before taking )-$opa. D%a -",a$/%9y(a!" *n&*/*)%$! :DCI;<8 Pharmacologically inactive but on combined "dministration #ith )-$opa they do not enter ''' 'ut decreases peripheral decarbo!ylation f )-$opa (.g. Carbidopa 'ensera4ide L8-%a 7 Carbidopa combination results in control of symptoms smoother dose of )dopa Can be reduced up to HDQ Pyrido!ine does not antagoni4e the actions of )- $opa. S"("(".*n" :D"$"ny(;<8 1nhibits 8"-' *responsible for dopamine metabolism, )-dopa 7 Carbidopa 7 Selelegine combination must be avoided. Bote 7 8"-" is responsible for !idative deamination of B" & D-5. A'an)*-*n": - )iberate dopamine from residual intact nerve endings & produces rapid response than )-$opa. D%a'*n" A.%n*!)!: - Crosses ''' & need not to be converted to active metabolite. Causes nausea& severe neuropsychatric adverse effects.
Page 16 of 67
CENTRAL NERVOUS SYSTEM
$rugs act on CBS in follo#ing #ays:/. hey may act directly on neurons & modify neuronal functions. 0. hey may act refle!ly by sending afferent impulses to the CBS via chemoreceptors 'aroreceptors & peripheral nerves. +. hey may affect the nutrition & o!ygen supply of the CBS by altering its 'lood supply or affecting its metabolism. N"#$%)$an!'*))"$!: - Which stimulate%1nhibit the post synaptic neurons after a brief latency & have short duration of action. "mines 7 "ch B" D-5 5istamine& $opamine "minoacids 7 l-3lutamic acid "spartic acid 3"'" &3lycine Peptides 7 Substance-P Cholecytokinin
Bote: - 3lutamate & "spartate are e!citatory amino acids. While 3"'" is inhibitory aminoacid. N"#$%'%-#(a)%$!: - #hich act on the post synaptic neurons #ith a longer latency have a longer duration of action & modify the responsiveness of the target neurons to the action of the neurotransmitters. A(*&a)*, A(,%&%(!:(thanol in H;Q acts as antiseptic in ;-D;Q as rubifacient & mild irritant action 'y dissolving in the lipid membrane of the neurons & altering the functions of ion channels & other proteins. 1t increases 3"'"-mediated synaptic inhibition. 1t also inhibits B8$" glutamate receptors. & depress CBS in descending order. 1mpairs 3luconeogenesis educes synthesis of "lbumin & ransferrin 1ncreases synthesis of 9)$) #ith conse6uent 5ypertriglyceredemia&$iminishes fatty acid o!idation. "lcohol causes liver damage & cause Cirrhosis. (levated 3amma glutamyl transpeptidase *33P, is the most sensitive indication of "lcohol liver disease. Uses: - "ppeti4er in methanol poisoning.
reatment of "cute alcohol poisoning: - 1.v glucose D;Q 1.v.hiamine /;;mg *'olus, 1.v. 8gSo 0-gm reatment of Chronic alcoholism: - $isulfiram *"ntabuse, & Citrated calcium cyanamide *Carbimide, D*!#(0*$a' 7 1t interferes #ith the o!idation of acetaldehyde formed during the metabolism of alcohol. 1t also inhibits dopamine- / !idase & thus interferes #ith the synthesis of B". his causes depletion of catecholamines. -8ethyl pyra4ole *inhibitor of alcohol dehydrogenase, used in treatment of methanol & ethylene glycol poisoning. Page 17 of 67
GENERAL ANAESTHETICS hey bring about loss of all 8odalities of sensation in particularly pain along #ith a reversible loss of consciousness. 8inimum "lveolar concentration: - 1t is the minimum amount of the anaesthetic in pulmonary alveoli re6uired to produce immobility in response to a painful stimuli used in dose fi!ation& Capacity of anaesthetic is measured. C(a!!*0*,a)*%n:".1nhalational "naesthetics 7 /. 9olatile li6uids:-Chloroform $iethyl ether richloroethylene 5alothane (nflurane & 1soflurane 0. 3ases: - Cyclopropane Bitrous o!ide chloroform & Cyclopropane
'. Bon 7 volatile *1.v., "naesthetics 7 /. 1nducing agents: - hiopentone sodium Propafol (tomidate 0. Slo#er acting drugs: - a, 'en4odia4epines 7 $ia4epam )ora4epam&8ida4olam b, $issociative "naesthetics: - @etamine c, Beurolept "nalgesia: - entanyl < $roperdiol *"nalgesic, *'utyrophenone, Page 1 of 67
MOA.:- 8ost of the general anaesthetics acts by blocking synaptic transmission but some act by blocking e!citatory transmission but some act by prolonging the synaptic inhibition * Potentiaion of 3"'"-" , thus depressing all the functional elements of CBS. 1nhalational anaesthetics 'arbiturates & 'en4odia4epines act by potentiating the action of the inhibitory neurotransmitter 3"'" at 3"'"" receptor. @etamine selectively inhibits the e!citatory B8$" type of glutamate receptor. S)a."! %0 Ana(."!*a:/. Stage of analgesia 7 8inor surgical procedures such as incision of "bcess dental e!traction "re carried successfully in this stage. 0. Stage of delirium 7 must be avoided. +. Stage of surgical anaesthesia 7 1ncludes Planes. . Stage of respiratory Paralysis 7 P$"8Ana"!)&")*, '"-*,a)*%n: - erm applied to the use of drugs prior to the administration of an anaesthetic agent #ith the ob2ective of making anaesthesia safer & more agreeable to the patient. /. poid analgesics 7 8orphinePethidine'uprenorphine to reduce an!iety & apprehension of the patient.
0. Sedative & ran6uili4ers 7 'en4odia4epines& 'arbiturates +. "nticholinergics 7 "tropine or Scopalamine . "ntiemetics 7 Phenothia4ines*Prometha4ine & trimepra4ine, 8etoclopramide D. 50 'lockers 7 anitidine & famotidine to avoid gastric regurgitation & aspiration pneumonia G. Beuroleptics 7 Cp4 trifluproma4ine A(&a9%(%n" is a steroidal drug having anaesthetic property.
Page 1 of 67
SEDATIVE = HYPNOTICS Sedative reduces e!citement & is commonly used as an "n!iolytic 5ypnotic produces sleep resembling natural sleep. C(a!!*0*,a)*%n:/. 'arbiturates 7 )ong acting *Phenobarbitone & mephobarbitone, Short acting *'utobarbitone Secobarbitone and Pentobarbitone, Ultra short acting *hiopentone 8ethohe!itone& 5e!obarbitone, 0. 'en4odia4epines 7 "nticonvulsant *$ia4epam Clona4epam& Cloba4epam, "ntian!iety *$ia4epam o!a4epam lora4epam alpra4olam Chlordia4epo!ide, 5ypnotics *$ia4epam nitra4epam flura4epam tema4epam mida4olam, +. "lcohols 7 chloralhydrate (thchlorvynol . "ldehydes 7 Paraldehyde D. "cetylated carbinols 7 (thinamate 8eprobamate G. 1mida4opyridine 7 4olpidem H. Cyclopyralone 7 Aopiclone N. !a4olidine $iones 7 Paramethadione & rimethadione O. 8iscellaneous 7 8etha6ualone antihistaminics & scopolamine MOA:'arbiturates 7 hey act primarily at the 3"'": 'A$ receptor 7 Cl - channel comple! & they potentiate 3"'"ergic inhibition by inducing the opening of the chloride channel.
'en4odia4epines 7 hey act by enhancing presynaptic%postsynaptic inhibition through a specific 'A$ receptor #hich is an integral part of the 3"'" " receptor 7 Cl- channel comple!. he binding site for 3"'" is located in the / subunit #hile the a subunit contains the 'A$ binding site. he modulatory 'A$ receptor increases the fre6uency of cl- channel opening.
Page 2 of 67
$rugs affecting 3"'"" receptor- Cl- channel comple! are 3"'"" 3"'"' (ndogenous 3"'" 3"'" agonist "gonist 8uscimol 'aclofen Competitive 'icculine Saclofen antagonist 1nverse agonist
'A$ site*a site,
'A$ lumena4il / carboline
ANTI > CONVULSANTS hese are the agents used to treat convulsions "gents that produce convulsions are 'icculine Pentylene tetra4ole Strychnine& Picroto!in C(a!!*0*,a)*%n:/. 5ydantoin derivatives 7 Phenytoin8ethatoin & ethatoin 0. 'arbiturates 7 Phenobarbitone & Primidone +. 1minostilbines 7 Carbama4epine . Succinimides 7 (thosu!imide & 8ethsu!imide D. 3"'" ransaminase inhibitors 7 Sodium 9alproate 9igabatrin Page 21 of 67
G. 3"'" reuptake inhibitors 7 iagabin H. 3"'" "gonists 7 3abapentin N. 'en4odia4epines 7 $ia4epamClona4epam&Cloba4epam O. 8iscellaneous7 )amotrigine"ceta4olamideSultiame*Sulphonamide, "mphetamine /. Hy-an)%*n -"$*a)*"!:8..". 7 1t acts by inhibiting the spread of sei4ure discharges in the 'rain & Shortens the duration of after discharge. he drug causes dose-dependent block of sodium channels thus reducing the neuronal sodium concentration leading to a reduction in Post titanic potentiation *PP, & to increase the neuronal Potassium concentration. " 7 5yperplasia 5ypertropy of gums steomalacia 5yperosmolar&non-@etotic Coma. Uses 7 3randmal ocal cortical epilepsy. Psychomotor sei4ures & Beuralgia 0. a$/*)#$a)"!R8..". 7 Potentiates 3"'"ergic inhibition " 7 9it-@depletion 8egaloblastic "naemia & osteomalacia hey are used in the treatment of resistant grandmal cortical sei4ures. P$*'*-%n" is a $eo!y 'arbiturate converted in the liver to 0 active metabolites Phenobarbitone & Phenyl ethyl malonamide.
+ I'*n%!)*(/*n"!: - 1t increases threshold to PA & (lectroshock convulsions " 7 Peripheral neuritis "granulocytosis bstructive 2aundice "plastic anaemia & hrombocytosis $iplopia 9ertiga "ta!ia & )upus like Syndrome. Uses 7 emporal lobe & 3randmal epilepsy rigeminal neuralgia $iabetes insipidus & "lternative to )ithium C + in 8ania. . S#,,*n*'*-"!: - 1t acts by suppressing -Current " 7 'lood dyscrasiasis S)( Psychic disturbances & 31 disturbances. Used in emporal lobe epilepsy D. GAA )$an!a'*na!" In&*/*)%$!: - Potentiates Post synaptic 3"'" activity & decrease brain levels of ("". G. O9a?%(*-*n" D*%n"!: - aises threshold to Sei4ures " 7 5emeralopia @idney damage Used in Petitmal epilepsy M*!,"((an"%#!:H. )amotrigine 7 blocks voltage sensitive sodium channel "ceta4olamide 7 1nhibits C" & acts by increasing C0 levels in the 'rain or by decreasing sodium there by increasing Sei4ure threshold.
Page 22 of 67
ANTIPSYCHOTICS "ntipsychotics% ran6uili4ers% "taractics are the drugs reduce "pomorphine induced Sterotype & "mphetamine induced 5yperactivity & also inhibit conditional avoidance response and cause some "ta!ia. C(a!!*0*,a)*%n:/. Phenothia4ine derivatives 7 a, "liphatic side chain: - CPA trifluproma4ine b, Piperidine side chain: - hiorida4ine & 8esorida4ine c, Pipera4ine side chain: - triflupera4ine luphena4ine&thiopropera4ine 0. 'utyrophenones 7 5aloperidol rifluperidol $roperdiol&Penfluridol +.au#olfia "lkaloids 7 eserpine . hio!anthines 7 Chlorprethi!ene hiothi!ene& lupenthi!ol D. 1ndole derivatives 7 8olindone G. Substituted 'en4amides 7 Sulpiride H. "typical neuroleptics 7 Clo4apine *$iben4odia4epines, eserpidone N. 8iscellaneous 7 !ypertine )o!apine Pimo4ide MOA:-8ost of them act by follo#ing + #ays/. Cause 'lockade mainly of post synaptic $opaminergic *$0, receptors & to a small e!tent D-5 receptors. 0. 8odify functions of 8esolimbic system. +. educe incoming sensory stimuli by acting on the brain stem reticular formation.
"ll "ntipsychotics e!cept clo4apine have potent $opamine *$0, blocking action. $opamine acts as an e!citatory neurotransmitter at $ / & $ D #hile $opamine acts as an inhibitory neurotransmitter at $0 $+& $ receptors. Clo4apine acts by D-50 as #ell as a/ 'lockade. eserpidone acts by D-50 as #ell as $ 0 'lockade. Page 23 of 67
"- "nticholinergic effect (!trapyrimidal effects Weight gain
ANTI8AN@IETY AGENTS E("a)"- (#! Ma?" )"!) is used to evaluate "nti-an!iety agents.
Class $rugs 'en4odia4epine $ia4epam"lpro4olam!a4epa s m )ora4epamChlordia4epo!ide "4apirone 'uspirone3epirone1psapirone thers
8eprobamate5ydro!y4ine
/- blockers
Propranolol
8..". Potentiates 1nhibition.
3"'"ergic
Stimulates Presynaptic D5/" "utoreceptors. "ntihistaminic #ith sedative antimuscarinic & Spasmolytic actions. 'y reducing '.p. tremor & palpitation.
A00",)*" D*!%$-"$!
efers to pathological change in mood state. he 0 (!tremes are 8ania & $epression. $rugs like "ntidepressants & "ntimanics *8ood stabili4ers, are used.
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An)*8D"$"!!an)!:".8" 1nhibitors /. Bon-selective a, 5ydra4ines: - Phenel4ine 1socarbo!a4id& ipronia4id ', Bon-5ydra4ine:- ranylcypromine
1rreversible
c, eversible: - 8oclobemide 0. 1soen4yme Selective a, 8"-" 1nhibitor: - Clorgiline 8oclobemide b, 8"-' 1nhibitor: - Selelegine *$eprenyl, '. ricyclic "ntidepressants /. Bor-"drenaline & D-5 reuptake 1nhibitors 1mipramine "mitryptiline rimipramine $o!epin Clomipramine $othiepin & 9enlafle!in 0. Bor-"drenaline reuptake 1nhibitors Bortryptyline $esipramine Protryptiline "mo!apine +. Selective D-5 reuptake 1nhibitors luo!etine luvo!amine Paro!etine sertraline & "lpacrolate . "typical "ntidepressants ra4odone 'upropion 8ianserin ianeptine MOA:- 8" 1nhibitors act by inhibiting 8" *(n4yme responsible for degradation of Catecholamines,. ricyclic "ntidepressants 1nhibit active uptake of 'iogenic amines B" & D-5 in to their respective neurons & thus potentiate them. An)*'an*,! M%%- !)a/*(*?*n. -$#.!:L*)&*#' ,a$/%na)" 7 hey act by replacing Ba < by )i< this affects ionic flu!es across 'rain cells or modify the property of cellular membranes. hey decrease the release of B" & dopamine in the 'rain #ith out affecting D-5 release. hey inhibit action of "$5 on distal tubules & causes diabetes insipidus like state.
"lternatives used as "ntimanics 7 Carbama4epine Sodium valproate. Ha((#,*n%."ns: - *Psychomimetics% Psychedelics% Psychodysleptics% Psychotogens,
hese drugs alter mood behavior thought & perception in a manner similar to that seen in Psychosis. C(a!!*0*,a)*%n:-
/. 1ndole amines: - )S$ Psilocybin 5armine 'ufotenine & dimethyltyrptamine 0. Phenyl alkylamines: - 8escaline Page 25 of 67
+. "rylcyclo5e!ylamines: - Phencyclidine . Cannabinoids: - etrahydro Cannabinol Phencyclidine is a 5allucinogen structurally similar to @etamine. P!y,&%'%)%$ !)*'#(an)!: - Caffeine "mphetamine & Piperidyl derivatives *Pipradrol & 8ethyl phenidate,. Used in Barcolepsy Catople!y & "ttention deficit 5yperactivity disorder *"$5$,.
OPIOID ANALGESICS he opioid drugs produce their effects by combining #ith opioid receptors #hich are #idely distributed in CBS & other tissues. piods & their "ntagonists act at 8u receptors. he side effects such as vomiting S#eating & 5allucinations are due to action of drugs on subtype of @appa receptors.
(ndogenous agonists (!ogenous agonists Selective agonists
' (ndomorphin /&0 /-(ndorphin *+/a.a, 8orphine /-unaltre!amine '1-nalo!ana4ine
B )eu%8eth (nkephalein *Da.a,
$ynorphin "
8orphine
@etocycla4ocine Borbinaltorphimine
8En-%$&*n is a pain modulator in the CBS derived from Pro-opio-8elanocortin
pium alkaloids are divided as Page 26 of 67
/. Phenanthrene group 0. 'en4yl iso6uinoline 7 Papaverine Boscapine $evoid of analgesic activity 1ntracarvenosal in2ection of papaverine causes penile errection. Boscapine is a potent releaser of 5istamine. & large doses cause 5ypotension. 8orphine 7 Used as sulfate%5Cl salt Produces "nalgesia (uphoria sedation& 5ypnosis. Causes direct depressant action on 'rain stem respiratory centre & reduce the sensitivity of medullary respiratory centre to increased plasma C 0 concentration. With to!ic doses breathing is entirely maintained by J5ypo!ic $rive? mediated through the carotid & aortic body chemoreceptors & results in JCheyne Stokes espiration?. Causes 8iosis Bausea Cough suppression Stimulates 9agus nuclei (!cites spinal cord & raises CS.1t also releases "$5. 31: - spasms follo#ed by increase in intrabiliary pressure. .uses 7 Po#erful analgesic sedative Pre-anaesthetic medication general anaesthetic Contraindications- 1n hypopitutarism "ddison?s disease 5ead in2uries impaired kidney & liver functions. Codeine 7 $evoid of respiratory depression enhances analgesic effect in combination #ith "spirin. Bote: - "ll the + types of receptors are antagoni4ed by pioid antagonists such as Balo!one & Baltre!one. he drugs #hich act as partial agonist-antagonists at the opioid receptors are Balorphine )evallorphan and Penta4ocine&Balbuphine. NSAIDS: - (!tensively protein bound drugs. C(a!!*0*,a)*%n 7 /. Salicylates:0. p-"minophenol derivatives: - Phenacetin Paracetamol & "cetanilide +. Pyra4olone derivatives: - Phenyl 'uta4one . 1ndole & related drugs: - 1ndomethacin Sulindac D. 5eterocyclic "ryl acetic acid derivatives: - $iclofenac olmetin&@eterolac G. Propionic acid derivatives: - 1buprofen fenoprofen Bapro!en @etoprofen H. enamates: - lufenamic acid & 8efenamic acid N. !icams: - piro!icam O. Sulfonanilides: - Bimesulide MOA:- Co!-/ is present in Stomach @idney& 'lood vessels. Where as Co!-0 in inflammatory cells& activated leucocytes.BS"1$S act by inhibiting CM responsible for the conversion of arachidonic acid to Prostaglandins. Sa(*,y(a)"!: - prevent the release of 5istamine )o#ers (S *erythrocyte sedimentation rate, 1nhibits platelet aggregation. 1n small doses elevate plasma urate levels #hile in large doses causes uricosuria. 1nduces release of adrenaline from adrenal medulla. 1n case of salicylate poisoning supplement of 9it-k is given along #ith other formalities. russes 7 "ntirheumatic Page 27 of 67
"ntiplatelet "nalgesic "ntipyretic Counterirritant @eratolytic fungistatic "ntiseptic "ntiinflammatory. S"(",)*" C%982 *n&*/*)%$!: - Bimesulide celeco!ib rofeco!ib melo!icam GASTROINTESTINAL DRUGS
"chlorhydria: - "bsence in production of 5C) leading to improper digestion. 1t can be treated by /;ml of /;Q 5C) diluted /;;ml 50;. 5ypochlorhydria: - decreased production of 5C). Sialorrhoea: - increased salivary production S: - ral rehydration solution. 3lucose 7 0;g Bacl 7 +.Dg @cl 7 /.Dg Ba5Co +*0.Dg, or tri sodium citrate *0.Og, 7 distilled #ater */-),. 8umps: - infectious inflammatory s#elling of paratoid & other salivary glands. 5ydragogue: - $rug #hich produces #atery stools. $yspepsia: - disorder of abdomen or chest #ith flatulence nausea etc. "chyliagestrica: - "bsence of 5C). 'itters: - hey increase appetite by promoting gastric acid secretion. (.g.:- gentian chirata picrorrhi4a "lcohol & 0 other "ntihistaminics *cyproheptidine 'ucli4ine, also acts as appetite stimulants. "nore!ia nervosa: - Chronic disease characteri4ed by loss of appetite #eight loss physiological & psychological alterations. $igestants: - #hich aid in digestion in 31. (.g.:- $iastase & aka diastase 7 "mylolytic Papain 7 Proteolytic Pancreatin 7 "mylolytic & Proteolytic 'romelain 7 "mylolytic lipolytic & proteolytic )ipase 7 )ipolytic. Carminatives: - e!pels gas #ith rela!ation of sphincters. (.g.:- 9olatile oils & Spices. 3all stone dissolving drugs: - Ursodiol & chenodiol 'ile salts are essential for digestion of cholesterol #hen the amount of cholesterol in body increases they form gall stones and thereby bile acids are used for dissolving gall stones.
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'ile acids: - Chenodiol *cholic acid, & Ursodiol *taurocholic acid, both inhibit absorption of cholesterol. 'ile salts: - Sodium glycocholate & sodium taurocholate. 'ile pigments: - 'ilurubin 'iliverdin Stercobilin & Stercobilinogen. Peptic ulcer: - due to imbalance bet#een aggressive factors *acid pepsin & 5-pylori, & defensive factors *gastric mucus & bicarbonate secretions P3?S innate resistance of the mucosal cells,. 8ethods of treating peptic ulcer:/. 'y reducing gastric acid secretion :-
Class 50 'lockers
$rugs Cimetidine ranitidine o!atidine famotidine Proton pump mepra4ole inhibitors )ansopra4ole Pantopra4ole "nticholinergies piren4epine Propantheline P3 "nalogues 8isoprostol ioprostil (nprostil
8.." 'lacks 50 receptors
".. Cimetidine causes gynacomastia & inhibiting cytpD;
5<@< inhibits "tpase Bausea headache present in parietal cells loose stools $ecreases cholinergic secretions 1nhibit acid secretion & promote mucus & bicarbonate secretion 1nhibit gastrin production
1ntolerable effects Contraindicated pregnancy
side in
Cimetidine Produces "nti "ndrogen (ffect by displacing the $ihydro testosterone from the cytoplasmic receptors 1ncreases plasma prolactin level & inhibits the metabolism of (strogens. 0. Beutrali4ation of gastric acid: - Systemic antacids 7 Ba5co+ Bon Systemic antacids 7 "l *o5,+ 8g *o5,0. 8"3")$"( 7 5ydrated comple! of 5ydro!y 8agnesium "luminate. "cid neutrali4ing capacity: - Bumber of milli e6uivalents of /B 5C) that is brought to P5 +.D in /D mins by unit dose of the preparation. +. Ulcer protectives :Sucralfate 7 "luminium salt of sulfated sucrose at p5 7 it polymeri4es to form a gel & gets deposited on the #all of stomach. Colloidal 'ismuth Sub citrate 7 increases Pg synthesis. hey also destroy 5.Pylori
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. Ulcer healing drugs: - Carbeno!olone sodium $eglycyrrhi4inised licorice. D. "nti.5.Pylori :- 8etronida4ole inida4ole. Combination therapy = Clarithromycin < "mo!ycillin < mepra4ole. Polymethyl silo!ane: - Collapes froth improves dispersion of "ntacid reduces gastro esophageal reflu! & thus relieves 5eart 'urn. $rug contraindicated in glucocorticoids BS"1$S.
peptic
ulcer:
-
Caffeine
reserpine
"minophylline
EMETICS (metine "pomorphine 5ypertonic saline solution mustard *sinigrin, An)* "'")*,!:"nticholinergies 7 5yoscine $icyclomine
5/ "ntihistaminics 7 Prometha4ine diphenhydramineCycli4ineCinnara4ine Beuroleptics 7 CPA 5aloperidol Prochlorpera4ine Prokinetic drugs 7 8etoclopramide $omperidone D5+ antagonists 7 ndansetron granisetron
Page 3 of 67
D$#.! a,)*n. %n $"!*$a)%$y !y!)"'
espiratory 6uotient: - ratio of o!ygen consumed to the carbondio!ide evolved. /. Pharyngeal demulcents: - sooth the throat directly as #ell as by promoting salivation (.g.:- )o4enges 3lycerine )i6uorice. 0. (!pectorants *mucokinetics, :- $irectly acting :- eucalyptus & lemon oil 3uainaphenesin 9asaka. +. efle!ly acting: - saline e!pectorants *B5cl @1 @-citrate, . "ntitussives :♣ pioids 7 Codeine morphine. 7 Boscapine $e!trometrorphan Clophedianol ♣ Bon-pioids Carbetopentane & !eladin D. "ntihistaminics 7 Chlorpheniramine diphenhydraminePrometha4ine G. 8ucolytic agents: - decreases viscosity of sputum. (.g.:- "cetylcysteine bromohe!ine "mbro!ol pancreatic dornase. H. Basal decongestants: - ephedrine phenyl ephrine Bapha4oline & !ymeta4oline.
Page 31 of 67
$%n,&%-*(a)%$!<8
/. Sympathominetics 7 ephedrine adrenaline salmeterol 0. 8ethyl !anthines 7 heophylline +. "nticholinergics 7 1pratropium bromide "tropine methonitrate. Cromolyn sodium is a prophylactic agent that stabili4es most cells in asthma. ♣ Prednisolone is life saving in serve status asthamaticus & inhibitor of phospholipase "0. ♣ 1pratropium is bronchodilator in chronic obstructive pulmonary disease #ith least cardiac effects. ♣ @etotifen 7 rally active Prophylactic agent in 'ronchial "sthma & "llergic disorders. ♣ 1nhalational Steroids 7 'eclomethasone dipropionate& 'udesonide. Catarrh: - state of irritation of mucous membranes associated #ith a copious secretion of mucus. ♣
CVS
Cardiac glycosides: - hese glycosides have cardiac inotropic activity. hey increase myocardial contractility & output #ithout proportionate increase in 0 consumption. (.g.:- $igito!in $igo!in )anatoside 7 C 6uabain 8..":- Cardiac glycosides selectively bind to membrane bound Ba <%@ < "Pase pump. his results in accumulation of Ba< intracellularly and this indirectly results in intracellular accumulation of Ca0< this leads to increased myocardial contractility. herapeutic inde! = /.D 7 +.; *$igitalis Page 32 of 67
Properties $igito!in $igo!in )anatoride 7 c Kuabain ral absorption (!cellent 3ood )o# )o# PP' OD Q 0DQ 0DQ Poor 0plasma t/%0 H days 0 days 0 days / day Potency )ess 1ntermediate 1ntermediate 5igh (limination 5epatic enal enal enal Uses: - CC cardiac arrhytmias such as atrial flutter & atrial fibrillation. Cardiac arrhythmias: - refers to changes in Cardiac rhythm.
Page 33 of 67
"ntiarrhythmic drugs: 1 7 Sodium channel 'lockers Class 8.." (!amples 1" Prolongs repolarisation Kuinidine Procainamide $isopyramide. 1' Shortens repolarisation )idocaine Phenytoin tocainide. 1C Slo#s conduction (ncainide lecainide Propafenone. "ffinity to#ards Ba
irst line drugs "denosine%9erpamil "tropine Kuinidine 9erapamil )idocaine "miodarone%lecainide
ANTI8ANGINAL DRUGS
Used to treat "ngina pectoris "ngina pectoris: - #here the 0 demand of the myocardium e!ceeds that of the supply. Stable angina: - generally caused due to stress Unstable angina: - due to occlusion of coronary arteries by plague.
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9ariant % Prin4metal angina: - 1t occurs at rest due to recurrent locali4ed coronary vasospasms.
Page 35 of 67
Classification:". rganic nitrates: - i, short acting: - glyceryl trinitrate. ii, )ong acting: - 1S$B 1S8B. '. ' 7 'lockers: - Propranalol. C. Ca0< channel 'lockers: - 9erapamil Bifedepine $iltia4em. $. @< channel openers: - Bicorandil mino!idil. (. "ntiplatelet drugs: - "spirin $ipyridamole. . Cytoprotectives: - rimeta4idine. Bitric o!ide *($, is synthesi4ed in body from )-arginine as follo#s 7 ♣ )-arginine B..synthetase B..
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ANTIHYPERTENSIVE DRUGS< hese are drugs used to lo#er 'P in 5ypertension. 'lood pressure is the product of cardiac output and peripheral resistance. Cardiac output is the amount of blood pumped by the heart in one minute and is therefore the product of stroke volume and the heart rate. Stroke volume refers to the volume of blood pumped during each contraction. '.P = C. .P. C. = stroke volume 5eart rate. hus it can be observed that most of the antihypertensive drugs act by either decreasing peripheral resistance or by decreasing cardiac output.
Class "C( inhibitor
$rugs
8echanism of action (nalpril *prodrug, hey inhibit "C( )isinorpril*prodrug, essential for the amipril*prodrug, conversion of "-1 Captopril*nonprodrug, to "-11 #hich is a Saralasin potent vasoconstrictor.
"dverse effects $ry cough angioedema urticaria and taste disturbance.
Page 37 of 67
"ngiotensin receptor antagonist
)osartan irbesatran hey antagoni4e Usually #ell valsartan telmisatran the action of "-11 tolerated. candesartan *peptide at the angiotensin analogue,. receptor. Calcium channel 9erapamil nifedepine hey lo#er b.p by "gents such as blockers amlodepine decreasing diltia4em%verapamil peripheral have negative resistance inotropic action. $iuretics Chlorthia4ide hey induce hia4ide diuretics furosemide diuresis that cause hypokalemia spironolactone. reduces plasma and also volume #hich in hyperglycemia in turn reduces C. diabetics. leading to a drop in b.p. ' 'lockers 8etoprolol propranolol hey decrease 8yocardial sinus rhythm insufficiency #hich leads to a 'radycardia "sthma decrease in heart 5eart block. 1nsulin rate #hich leads dependent diabetics. to a drop in b.p. a "drenergic Pra4osin tera4osin hey block the 1mpotence postural blockers action of hypo tension adrenaline at the a receptor present in blood vessels thereby leading to vasodilatation Central 8ethyldopa clonidine he-nor methyl Sedation lethargy and sympatholytics *h0 agonist, adrenaline formed reduced mental from methyldopa capacity. acts as false neuro transmitter on a0 and decreases efferent sympathetic activity. Beurotransmitter 3uanethedine reserpine $isplaces B.. depletors from synapse increases B..metabolism 9asodilators 5ydrala4ine mino!idil 9asodilatation 5ydrala4ine on leads to a decrease prolonged use causes in peripheral S)( *Systematic resistance #hich lupus in turn leads to fall erythrematosus, Page 3 of 67
in b.p.
hirsustism peripheral pooling of blood. (thacyranic acid is contraindicated in "ngina in "sthma '0 blockers is avoided.
ANTIHYPERLIPIDEMIC DRUGS< hese drugs lo#er the levels of lipoproteins and lipids in blood. he different types of hyperlipoproteinemia are:
ype $isorder 1
)ipoprotein lipase deficiency
11a
19
amilial hypercholesterolemia Polygenic hypercholesterolemia amilial $ysbetalipoproteinemia 5ypertriglycereridemia
9
5yperlipedemia
11b 111
(levated lipoprotein Chylomicron
plasma (levated plasma lipids Cholesterol triglycerides Cholesterol
&
Cholesterol increase, 1$) chylomicron Cholesterol remnants triglycerides 9)$) *pre-' riglycerides lipoprotein, 9)$) )$) Cholesterol triglycerides
*moderate
)$) )$) *'-lipoprotein,
he classification of hypolipedemic drug is as follo#s: Class $rugs 8echanism of action 583-Co" )ovastatin hey inhibit the en4yme eductase atorvastatin 583-Co" eductase inhibitors simvastatin essential for the conversion of 583-Co" to mevalonate and thus inhibit synthesis of cholesterol. 'ile acid Cholestyramine hese are ion e!change resins se6uestrants colestipol that bind bile acids in the intestine inhibit their enterohepatic circulation. Cholesterol is absorbed #ith the help of bile acids and in their absence it is e!creted. ibric acid Clofibrate hey activate lipoprotein derivatives 3emfibro4il lipase #hich is essential for fenofibrate the degradation 9)$) resulting in lo#ering of 3?s.
&
&
"dverse effects 5eadache rise in serum transaminase rise in CP@ levels.
Unpalatable and may cause nausea flatulence heartburn constipation.
1ncreased appetite and #eight gain myalgia and increased incidence Page 3 of 67
thers
♣ ♣ ♣
Beomycin gugulipid probucol
of gallstones. Beomycin lo#ers )$)-C5 by Beomycin may comple!ing #ith bile acids in ho#ever damage the intestine. 3uggul lipid intestinal mucosa. probucol acts as "ntio!idant )oose stools.
Comniphora molmol 7 myrh *antiseptic, Comniphora mukul 7 guggul *antihyperlipedemic,. $romotropic 7 $rug affects conductivity of impulses in neuronal cells.
HORMONES hey are mediator molecules act as chemical messengers. hey are released in one part of the body & regulates activity of cells in other ports of the 'ody. 5ormones are secreted by endocrine or ductless glands. 8ost hormones enter interstitial fluid & then the 'loodstream. 8..":- 5ormones like neurotransmitters influence their target cells by chemically binding to specific protein or glycoprotein receptors.
Site of action:"t cell membrane receptors 7 (.g.:- "drenaline glucagons S5 )5 S5 "C5 calcitonin vasopressin o!ytocin insulin etc. "t cytoplasmic receptors 7 (.g.:- steroidal 5ormones. Page 4 of 67
"t nuclear receptors 7 hyroid 5ormones. $o#n regulation: - #hen hormone is present in e!cess the no. of target cells receptors decreases. his makes target cells less responsive to the hormone. Up regulation :- #hen there is a deficiency in hormone is the no. of receptors may increase. his makes target cells more sensitive to hormone Classification of hormones: - he endocrine glands include pituitary hyroid Parathyroid "drenal and pineal glands. Water soluble hormones :- protein eicosanoid hormones. )ipid soluble hormones: - Steroid hyroid & gaseous hormone *Bitric o!ide,. Placental hormones: - Chronic gonadotropin 7 Prolactin (strogens 7 Progesterone Placental lactogen 7 Chorionic thyrotropin. 5ormones of the "nterior & Posterior Pituitary:H%$'%n"
S",$")"- /y
R"("a!*n. H%$'%n" In&*/*)*n. :!)*'#(a)"! !",$")*%n; &%$'%n" :!#$"!!"! !",$")*%n; 5uman gro#th Somatotrophs 3ro#th hormone-releasing 3ro#th hormone *h35, or hormone *355, or harmonesomatotropin somatocrinin *".", inhibiting */O/aminoacid, hormone *3515, or somatostain */"", hyroid-stimulating hyrotrophs hyrotropin releasing 3ro#th hormone *S5, or hormone*tripeptide, hormonethyrotropin inhibiting hormone somatostatin ollicle-stimulating 3onadotrophs 3onadotrophic releasing --------harmone *S5, harmone*decapeptide, )uteini4ing harmone 3onadotrophs 3onadotrophic releasing --------*)5, harmone Prolactin *P), )actotrophs Prolactin releasing harmone Prolactin */ONaminoacid, inhibiting harmone or dopamine "drenocorticotropic Corticotrophs Corticotropin releasing ---------harmone *"C5, or harmone*/aminoacids, corticotrophin 8ealanocyteCorticotrophs Corticotropin releasing $opamine stimulating harmone harmone */O/aminoacid,
Page 41 of 67
♣ ♣ ♣ ♣ ♣
)euprolide is a synthetic non-peptide of 35. $ropamine antagonist not given in lactating #omen because it inhibits prolactin. (nuresis 7 'ed #etting *$esmopressin, 8elatonin 7 *responsible for normal sleep, Posterior pituitary or neurohypophysis does not synthesi4e harmonesR it stores and releases t#o harmones o!ytocin and antidiuretic harmones *vasopressin,.
5ormone Principal actions 5uman gro#th harmone Stimulates liver muscle cartilage bone and other tissues to *h35, or somatotropin synthesi4e and secrete insulin like gro#th factors. *13?s,R 13s promote gro#th of body cells protein synthesis tissue repair lipolysis and elevation of blood glucose concentration. hyroid-stimulating Stimulates synthesis and secretion of thyroid harmones by harmone *S5, or thyroid gland thyrotropin ollicle-stimulating 1n females initiates development of oocytes and induces harmone *S5, ovarian secretion of estrogens. 1n males stimulates testes to produce sperm. )uteini4ing harmone *)5, 1n females stimulates secretion of estrogens and progesterone ovulation and formulation of corpus luteum. 1n males stimulates interstitial cells in testes to develop and produce testosterone. Prolactin *P), more ogether #ith other harmones promotes milk secretion by active in presence of the mammary glands. o!ytocin "drenocorticotropic Stimulates secretion of glucocorticoids *mainly coritsol, by harmone *"C5, or adrenal corte!. corticotrophin 8elanocyte-stimulating (!act role in humans is unkno#n but may influence brain harmone activity #hen present in e!cess can cause darkening of skin. !ytocin *, Stimulates contraction of smooth muscle cells of uterus during childbirthR stimulates contraction of myoepithelial cells in mammary glands to cause milk e2ection. "ntidiuretic harmone Conserves body #ater by decreasing urine volumeR *"$5, or vasopressin decreases #ater loss through perspirationR raises blood pressure by constricting arterioles.
Pitutary harmone derivates:Page 42 of 67
"nalogue 'romocriptine Prolactin inhibitor $esmopressin "$5 3asrelin coryntropin )euprolide "C5 8enotropins urofollitin S5 )5 Baferelin 3B5 creolide Somatostatin
3onadal harmones amo!ifen $iethylstilbesterol (strogen & progesterone Borgesterol & medro!yprogesterone 8ifepristone !andralone
Uses Cancer therapy $iabetes insipidus 1nfantile spasms 1nfertility Cancer 1nfertility 1nhibits glandular
Uses 'reast cancer "fter contraception ral contraception chronic contraception "bortifacient "nabolic
5L1$ 3)"B$:he follicular cells produce t#o harmonesR thyro!ine *tetraiodothyronine, and triiodothyronine #hich are kno#n as thyroid harmones. Synthesis and secretion of + and occurs as follo#s: a. 1odine trapping: ollicular cells trap iodine ions by an active transport mechanism. b. Synthesis of thyroglobulin: While the follicular cells are trapping iodide ions they are also producing thyroglobulin *3',. c. !idation of iodide: 1odine ions are o!idi4ed by pero!idase to form iodine *10,. d. 1odination of tyrosine: as iodine molecules form they react #ith tyrosines that are part of thyroglobulin molecules. 'inding of one iodine atom #ith tyrosine yields mono-iodotyrosine */, #hile t#o iodine atoms yields diiodotyrosine *0, e. Coupling of / and 0: t#o 0 molecules combine to form #hile one / and one 0 combine to form + in the presence of pero!idase. Calcitonin: - 1t is a harmone produced by the parafollicular cells of the thyroid gland. 1t decreases the level of calcium in blood by inhibiting the action of osteoclasts the cells that break do#n bone matri!. Parathormone: - 1t is secreted by the parathyroid glands and it increases blood calcium and magnesium levels #hile it decreases phosphate levels. he harmones produced by the adrenal corte! are of three types: a. 8ineral corticoids : "ldosterone b. 3lucocorticoids: Cortisol Coorticosterone & Cortisone. c. "ndrogens: $ehydroepidandrosterone. Page 43 of 67
he harmones produced by the chromaffin cell of the adrenal medulla are (pinephrine and nor epinephrine. he four types of pancreatic islets that produce harmones are:a. " cells secrete glucagons. b. ' cells secrete insulin. c. $ cells secrete somatostatin. d. cells secrete pancreatic polypeptide. 5ormone hyroid harmone
Control of secretion Secretion is increased by thyrotopin-releasing harmone and high thyroid iodine levels suppresses secretion. Calcitonin 5igh blood calcium levels stimulates secretion lo# levels suppresses secretion. Parathyroid )o# blood calcium levels hormone stimulate secretionR 5igh blood calcium levels inhibit secretion. 8ineral corticoids 1ncreased blood @< level and angiotensin 11 stimulates secretion. 3lucocorticoids "C5 stimulates release. "ndrogens
"C5 stimulates release.
(pinephrine and Sympathetic preganglionic Bor epinephrine neurons release acetylcholine #hich stimulates secretion. 3lucagon
1nsulin
Somatostatin
Pancreatic polypeptide
$ecreased blood level of glucose e!ercise and mainly protein meals stimulate secretion. 1ncreased blood level of glucose acetylcholine arginine and leucine glucagon 31P h35 and "C5 stimulate secretion. Pancreatic polypeptide inhibits secretion.
Principal actions 1ncrease basal metabolic rate stimulate synthesis of proteins and increase use of glucose. )o#ers blood levels calcium and phosphate.
of
ionic
1ncreases blood calcium and magnesium levels and decreases phosphate levels. 1ncreases blood levels of Ba< and #ater and decrease blood level of @<. 1ncrease protein breakdo#n stimulate gluconeogenesis. "ssist in early gro#th of a!illary and public hair. Produce effects that enhance those of the sympathetic division of the automatic nervous system during stress. aises blood glucose level by accelerating breakdo#n of glycogen into glucose in liver.
)o#ers blood glucose level by accelerating transport of glucose into cells converting glucose into glycogen and stimulates protein synthesis. 1nhibits secretion of insulin and glucagon and slo#s absorption of nutrients from the gastrointestinal tract. 8eals containing protein 1nhibits somatostatin secretion fasting e!ercise and acute gallbladder contraction and Page 44 of 67
hypoglycemia secretion.
stimulate secretion of pancreatic digestive en4yme.
5ormones affecting calcium homeostasis:♣ Calciferol *0D 5ydro!y 9it-$+, ♣ Calcitrol */ 0D dihydro!y 9it-$+, ♣ Cholecalciferol *9it-$+, ♣ Secalcifediol *0 0D dihydro!y vit$+, ♣ (rgocalciferol *9it$0, ♣ "ndrogens: - estosterone !androlone Stano4olol. ♣ "ntiandrogens: - inasteride *synthetic inhibitors,. ♣ "ntiprogestins: - 8ifepristone.
CHEMOTHERAPY Page 45 of 67
1t deals #ith the use of chemical agent to arrest the progress of infectious diseases by destroying infective parasites or microbes #ithout damaging the host tissues. 8..":/. 1nhibiting protein synthesis by binding to ribosomal subunit & destroying the bacterial cell. (.g.:- 3entamycin & streptomycin. 0. eversible inhibition of protein synthesis by action on ribosome. (.g.:- 'road spectrum "ntibiotics. +. by detergent action *leakage of cell constituents, ". $irect cell membrane. (.g.:- Colistin Polymy!in '. $rug binding to cell #all sterols. (.g.:- Bystatin "mphotercin. . 1nhibition of cell #all synthesis: - (.g.:- Penicillins Cephalosporins sulphonamides. D. $rugs affecting nucleicacid metabolism:". 1nhibition of $B" dependent B" polymerase. (.g.:- efampicin. '. 1nhibition of $B" supercoiling & $B" synthesis. (.g.:- Kuinolones & luoro6uinolones. $rug resistance:/. Batural: - rganisms do not have target sit for drugs to act. (.g.:- "ntifungals in 'acterial infections. 0. "c6uired: - rganisms are e!posed to the drug in such a manner that it develops resistance. Cross resistance: - $evelopment of resistance to one substance may also sho# resistance to another substance to #hich the organism has not been e!posed. (.g.:- resistance bet#een Sulphonamides resistance bet#een etracycline?s resistance bet#een etracycline?s & Chloramphenicol. here is no cross resistance bet#een "nimoglycosides. Super infection%Supra infection: - 1t is due to the use of 'road spectrum antibiotics. here is no. of microorganisms inhabiting 31 & these organisms constitute the microbial flora. hey are called as EcommensalsF under normal conditionsR these organisms compete #ith another for nutrients. & therefore they are unable to proliferate rapidly. When a 'road spectrum antibiotic such as chloramphenical % tetracycline is administered it might kill most of the microbial flora barring a fe# organisms. Bo# these fe# microbes are free to proliferate rapidly in the absence of competition & they multiply spread all over the body & cause infections called super infections. "ntimicrobial agent: - "n agent #hich kills 8.. or suppresses their gro#th. he susceptibility of "8" is determined by /. adiometric method 0. esistance ratio method *raditional,. Sulfonamides & Sulfones hese are derived from prontosil red *dye, & are effective against pyogenic 'acterial 1nfections. Classification:/. Short acting: - Sulfadia4ine Sulfiso!a4ole. Page 46 of 67
0. +. . D. G.
1ntermediate: - Sulfametho!a4ole. )ong acting: - Sulfado!ine Sulfamethopyra4ine. 1n intestinal infections: - Sulfasala4ine. 1n 'urn therapy: - Silver sulfadia4ine mafenide. 1n ophthalmic infection: - Sulfacetamide.
8..":3uanosineTTTT P"'" $ihydropteroic acid Several steps *-, Sulfonamides *-,rimethoprim VTTTTT $ihydrofolic acid folate reductase folic acid $ihydro folate reductase etrahydrofolic acid ------------BD B/; methylene "5 BDformyla5 -------- B/; formyl "5 BDformyl"5 BDB/; methylene "5 B/;formyl"5 is very essential for several 'iosynthetic path#ays in humans & 'acteria. he gro#th and cell division in bacteria can be stopped if any drug blocks 'iosynthesis of folate co-en4ymes. olate co-en4ymes are biosynthesi4ed from dietary folic acid in humans & other animals. Sulfonamides act as competitive inhibitors for the incorporation of P"'" to form $ihydropteroic acid. rimethoprim is an inhibitor of dihydrofolate reductase re6uired for the conversion of dihydrofolic acid in to tetrahydrofolic acid in bacteria. 8echanism of resistance: - 1t may be due to /. 1ncreased production of P"'" by resistant bacteria 0. $ecrease the affinity of folate synthetase en4yme for sulfonamides. +. "dopts an alternative path#ay in folate metabolism. (.g.:- gonococci pneumococci (.coli S.aureus etc Cotrimo!a4ole: - fi!ed dose combination of trimethoprim and sulfametho!a4ole in a ratio of */:D,. "s this inhibits 0 different steps in path#ay the development of resistance is reduced. "dverse reactions:/. Stevens Iohnson?s syndrome 0. 5emolytic anemia +. @ernicterus *neonatal 5yperbilirubinemia, . Skinrash Urticaria D. Crystalluria is due to crystals of sulfanilamide his can be presented by i, "lkalani4ing the urine ii, 'y increasing the urine flo# iii, 'y reducing P@a of drug. Page 47 of 67
8etabolism: - 1t occurs by acetylation at B they are e!creted as mi!tures of unmetabolised drugs B acetates & glucouronides. Sulfones: - less active than sulfonamides 8..":- similar to sulfonamides. (.g.:- $apsone
UINOLONES (.g.:- Balidi!ic acid luoro6uinolones: - hese are more potent than 6uinolones. irst generation: Borflo!acin flo!acin Ciproflo!acin Perflo!acin. Second generation: Sparflo!acin )omeflo!acin. 8..":- hey inhibit 'acterial $B" gyrase *"n en4yme responsible for introducing negative supercoiling in to circular duple! $B"., Begative super coiling relieves the tortional stress of un#inding helical $B" & thereby allo#s transcription & replication to occur. 5umans have opoisamerase 11 in place of gyrase & this accounts for the lo# to!icity of K?s to the host cells. esistance: - $ue to chromosomal mutation producing a $B" gyrase #ith reduced affinity for Ks. ": - 5ypersensitivity reactions 5emolytic anemia 31 disturbances. Uses: - yphoid soft tissue infection U1. La,)a' An)*/*%)*,! (.g.:- Pencillins & Cephalosporins
8..":- microorganism synthesi4e t#o pentapeptides 7 /. U$P-B-acetyl muramic acid *B"8", 0. U$P-B-acetyl glucosamine *B"3", hese peptidoglycon residues are linked together in forming long strands & the U$P is split off. he final step is cleavage of the terminal $-"lanine by Jtranspeptidase?. he energy released is utili4ed for establishment of crosslinkages bet#een peptide chains of the neighbouring strands.
'eta lactam "ntibiotics inhibit the en4yme Jtranspeptidase? so that crosslinking does not take place. hese en4ymes constitute the pencillin binding proteins #hich are located in the bacterial cell membrane. When 'acteria divide in presence of a '-lactam antibiotic cell #all deficient forms are produced & these forms burst resulting in cell lysis. Page 4 of 67
'lood pus & tissues fluids do not interfere #ith the antibacterial action of '-lactam "ntibiotics.
Classification of penicillin?s:♣ Batural: - Penicillin-3 procaine penicillin3 ♣ "cid resistant: - Penicillin 9 *pheno!ymethyl penicillin, ♣ 'road spectrum: - "mpicillin "mo!icillin Piperacillin 8ethicillin ♣ ' lactamase inhibitors: - clavulonic acid sulbactam ♣ 8onobactams: - "4treonam ♣ Carbapenems: - 1mipenam hienamycin 'acterial resistance: - gram positive organisms develop resistance by producing 'lactamases. *pens ' lactam ring & inactivates, 1n methicillin resistant S.aureus the penicillin 'inding proteins has been mutated. So that it does not binds methicillin efficiently. ": - penicillin allergy due to formation of "ntigenic penicilloyl proteins. Iarisch-5er!hemier reaction is Syphilis patient. $egradation of penicillin can be controlled by ad2usting the P5 of a6-solutions bet#een G.; 7 G.N. Uses: - gonorrhea Syphilis $iphtheria & coccal infections. "ugmentin = Clavulanic acid < "mo!icillin Unasyn = Sulbactam < "mpicillin C(a!!*0*,a)*%n %0 C"&a(a!%$*n!<8
Cephalosporin = ' lactam ring < dihydrothia4ine ring Penicillin = ' lactam ring < thia4olidine ring. 1 Cephale!in
11 ral "!etal Cefaclor Cefuro!ime Parentral Cephadro!il Cefomandole Cefonacid "ntipseudomonal Cephalosporins: Cefti4o!ime & Ceftria!one.
-
111 Cefi!ime Cefpodo!ime Cefoto!ime Ceftria!one Cefopera4one 8o!alactam
19 --Cefepime Cefota!ime
$isulfiram effect: - Cefomandole cefopera4one cefometa4one cefotetan & mo!olactam due to tetra4ole group produce $isulfiram effect #hen taken #ith alcohol. "4treonam is used to treat hospital ac6uired infections *Bosocomical infections,. Page 4 of 67
T")$a,y,(*n"! C&(%$a'&"n*,%( A'*n%.(y,%!*-" an- Ma,$%(*-" an)*/*%)*,! 1n order to understand the mechanism of the above antibiotics it is essential to understand the process of protein synthesis:
n a specific signal from the cytoplasm the $B" in the nucleus un#inds itself #ith the help of the en4yme $B" gyrate or topoisomerase *humans,. ne of the strands of the $B" acts a template for the synthesis of a complimentary strand of mB" in the presence of B" polymerase. he synthesis of mB" from $B" is called transcription. he mB" #hich no# contains the code for protein synthesis comes out of the nucleus and attaches itself to the +;?s ribosomal subunit. his is follo#ed by the attachment of the D;?s ribosomal subunit to the mB"-ribosomal comple!. here are t#o sites present on the D;?s ribosomal subunit the acceptor site and the peptidyl site. Protein synthesis does not begin until the mB" has the initiator codon "U3 *codes for formylmethionine, on it. nce the mB" e!poses the initiator codon "U3 a specific tB" carrying the amino acid formylmethionine #ill arrive at the acceptor site of D;?s subunit. he tB" carrying the amino acid is no# transferred to the peptidyl site #here the tB" dissociates leaving the amino acid at the peptidyl site. he ribosome no# moves along the mB" to e!pose the ne!t coon. $epending upon the codon the corresponding amino acid is brought to the acceptor site by a specific tB". he tB" carrying the amino acid is no# transferred to the peptidyl site #here the tB" dissociates leaving the amino acid at the peptidyl site. "gain the ribosome no# moves along the mB" to e!pose the ne!t codon and this process continues until the mB" sho#s one of the terminatory codons U"" or U"3 or U3". hese terminatory codons are called non-sense codons as they do not code for any particular amino acid. he transfer of data contained in the mB" to form proteins is called translation. When only one ribosome is attached to the mB" it is called monosome #hen there are more than one ribosome attached to the mB" it is called polysome. "ntibiotic Source Spectrum activity 8echanism action
8echanism esistance
etracycline Soil actinomycetes S.aureofaciens of 'road spectrum
Chloramphenicol Streptomyces 9ene4uelae 'road Spectrum
of 'inds to the +;?s ribosomal subunit and inhibits the attachment of aminoacid-tB" comple! to the mB"-ribosomal comple!.
1t acts by interfering #ith the transfer of the elongating peptide chain to the ne#ly attached amino acid at the ribosome mB" comple!. herefore it inhibits peptide bond formation. 1t specifically attaches to D;?s ribosome. esistant organisms produce Chloramphenicol acetyl transferase #hich inactivates
of $ue to plasma mediated synthesis of a protection protein that protects the ribosomal
"minoglycoside Streptomycin- S .griseus
8acrolide (rythromycin- S .erythreus
"ctive only against aerobes. 'actericidal 1t binds to the +;?s subunit the D;?s subunit as #ell to the +;sD;s interface. hey free4e initiation of protein synthesis prevent polysome formation. 'inding to the +;s-D;s interface causes distortion of the mB" codon resulting in #rong amino acids entering the peptide chain and these defective proteins affect the integrity of the cell membrane resulting in cell death.
"ctive against mainly gram < organis 1t combines #ith D;s ribosomal interferes #ith translocation of t peptide chain back to the peptid ribosome fails to move along the m the ne!t codon and thus protein terminated prematurely.
". 1nactivating en4ymes that esistant organisms produce adenylate%acetylate or esterase that inactivates the drug or t phosphorylate the become less permeable to the drug. antibiotic. '. $ecrease in the affinity of
Page 5 of 67
binding site from C?s. Posess cross resistance #ith chloramphenicol. Pharmacokinetics C?s have chelating propertyform insoluble and unabsorbable comple!es #ith calcium and other metals. "dverse (ffects a. )iver anchony damage syndrome. b. @idney Sho#n by only damage do!ycycline c. Photo to!icity d. $eposition of calcium tetracycline chelate in bones and teeth. e. 9estibular to!icity-"ta!ia vertigo and nystagmus *involuntary eye ball moment,. f. $iabetes insipidus$emeclocyclin Uses a. Used to treat infections #hen the causative organism is unkno#n. b. venereal diseases c. Cholera plague 'rucellosis etc.
the drug.
ral form is Chloramphenicol palmitate. Parenteral form is Chloramphenicol Succinate. a. 3ray baby syndrome: seen in infants because they lack the glucoronic acid re6uired for con2ugation #ith Chloramphenico l. b. Super infections c. 'onemarro# depressionaplasticanemia agranulocytosis thrombocytopeni a.
the ribosomal protein that binds the antibiotic. C. Porins become less permeable to the drug. "ll ioni4e in solution and are not absorbed orally. (!creted unchanged in urine.
a.
toto!icity Cochlear damage ♣ 9estibular damage ♣ b. Bephroto!icity c. Beuromuscular blockade
(rythromycin is acid labile. o prote gastric acid it is given an enteric coat.
a.3astrointestinal distress a.
hepatitis.
a. yphoid *enteric a. uberculosis a. "typical pneumonia caused by fever, b. S"'( pneumoniae b. 5.influen4ae c. Plague b. $iphtheria tetanus Syphilis etc... meningitis d. ularemia sub acute c. "naerobic 'acterial endocarditis *sabe, infections $.1ntraocular infections.
etracyclines:8ore stable & long acting ------ G-deo!y tetracycline methacycline do!ycline minocycline. Page 51 of 67
8iscellaneous "ntibiotics:/, )incosamide antibiotics: - clindamycin 8.." & spectrum of activity is similar to erythromycin & also e!hibits partial cross resistance. 0, 3lycopeptide "ntibiotics: - (.g.:- 9ancomycin acts by inhibiting cell #all synthesis. 1t binds to the terminal dipeptide se6uence of peptidoglycon units at the cell membrane & their cross linking to form the cell #all does not take place. Uses: - 1n 8S" infections. +. Polypeptide "ntibiotics: - 'actericidal agents have detergent like action on cell membrane. hey have high affinity for phospholipids & thus they orient bet#een phospholipid & the protein layers in gram negative organisms resulting in formation of pseudopore. "s a result aminoacids leak out leading to cell death. (.g.:- Polymy!in ' 'acitracin Colistin hyrotricin Capreomycin Bespirocin. Urinary "ntiseptics: - Bitrofurantoin 5e!amine Urinary "nalgesic: - Phena4opyridine 5C).
ANTITUERCULAR AGENTS
uberculosis is caused by mycobacterium tuberculosis. irst line drugs: - 1B5 ifampicin Pyra4inamide (thambutol. Second line drugs: - Ciproflo!acin "4ithromycin. $rug P-amino salicylic acid
8.." Prevents incorporation P"'"
Pharmacokinetics ". 1t undergoes 5ypersensitivity of "cetylation "t reactions lo#P5decarbo!ylation "t highP5-o!idation Page 52 of 67
1B5
ifampicin
1nhibits the synthesis of mycolic acid *imp component of mycobacterial cell #all, 1nhibits $B" dependent B" polymerase
Pyra4inamide
Bot kno#n penetrates inflamed meninges in treatment of tuberculosis meningitis. (thambutol *d 1nterferes #ith isomer is more mycolic acid patent, incorporation in cell #all & inhibits B" synthesis.
"cetylated by liver.
Peripheral neuritis due to renal e!cretion of vit 'G 5epatitis
8etaboli4ed in liver 5epatitis respiratory to an active syndrome Cutaneous deacteylated syndrome lu metabolite. syndrome "bdominal syndrome. Penetrates CS & 5epatato!icity metabolised in liver. 5yperuricaemia *due to inhibition of uric acid tubular secretion,
HDQ of oral dose is )oss of visual acuity absorbed & field effects due to optic temporarily stored in neuritis. .'.C.
"ntitubercular "ntibiotics: - Cycloserine Capreomycin 9iomycin ifampicin. (ffective treatment :- *Sterili4ation period,. 1B5 +;;mg ifampicin G;;mg Pyra4inamide 0Dmg%kg *for N #eeks, *8aintainance period, 1B5 & ifampicin *for /G #eeks,
ANTILEPROTIC AGENTS )eprosy is called by Mycobacterium leprae. $rug $apsone
Cycloserine
Clofa4imine *dye,
8.." 1nhibits incorporation P"'" in to folic acid
Pharmacokinetics of Completely absorbed orally gets concentrated in skin liver & kidney. 1nhibits bacterial cell #all synthesis by inhibiting the en4yme that racemises halanine and links t#o $"lanine residues. 'inds #ith nucleic acids & 3ets accumulated in concentrate in tissues especially in reticuloendothelial tissue & crystalline form. interfere #ith template
". 8ild 5emolytic anemia gastric intolerance.
Well tolerated reddish 'lock discolouration of skin Page 53 of 67
function of $B".
ANTIFUNGAL AGENTS
Classification:/. "4oles: - Clotrima4ole @etacona4ole 8icona4ole. 0. "llylamine & related compounds: - olnafate erbinafine. +. atty acids: - Propionic acid riacetin Salicylic acid. . Phenol & their derivatives: - 5aloprogin Cyclopiro!. D. Bucleosides: - lucytosine. G. "ntibiotics: - Bystatin "mphotericin Candidicin. H. 5eterocyclic 'en4ofuran: - 3riseofulvum.
Page 54 of 67
$rug
"mphotericin ' 8echanism of 5as high action affinity for ergosterol present in fungal cell membrane. 'inds to it forming a micropore through #hich amino acids leak out leading to cell death. Spectrum of Candida activity albicans 5istoplasma capsulatum etc.
3riseofulvin
1mida4oles and tria4oles. 1t interferes hey inhibit #ith mitosis the fungal and causes cytochrome abnormal PD; en4yme metaphase lanosterol /configurations. demethylase he daughter re6uired for nuclei fail to conversion of move apart and lanosterol to thus cell ergosterol. division is his results in arrested at membrane metaphase. abnormalities in the fungus. $ermatophytes $ermatophyt such as es candida (pidermophyto albicans n nocardia richophyton leishmania microsporum etc. etc. Pharmacokineti "dministered 3ets deposited cs both orally in the @eratin and forming cells prarenterally. of skin hair and nails. "bsorption is enhanced by micronisation. "dverse effects Bephroto!icit Peripheral 1nhibits y-a4otemia neuritis CLP+" reduced g.f.r transient thereby acidosis. leukopenia raising the albuminuria. blood levels of drugs like #arfarin terfenadine. Uses Systemic $ermatophytos Systematic mycoses and is. and topical )eishmaniasi infections. s.
lucytosine
olnafate
1t is taken up by fungal cells and then converted into D-U and then to Dfluorodeo!yuridylic acid #hich is an inhibitor of thymidylate synthetase re6uired for the synthesis of thymidylic acid #hich is a component of $B". Cryptococcus neoformans candida torula aspergilllus chromoblastomyces .
1nterfere #ith fungal ergosterol 'iosynthesis by epo!idation of s6ualene by the en4yme s6ualene epo!idase.
$ermatophyt es candida.
"dministered orally
)eucopenia thrombocytopenia.
Chromoblastomyco sis.
"thlete?s foot ring#orm.
"ntiviral agents 1nfectious virus particle is called virion. $B" containing virus "denovirus 5erpes virus
8any types espiratory tract & eye infections 5.simple! 1 & 11 vercilla 4oster (ncephalitis chicken po! shingles 5erpes 4oster Page 55 of 67
Papora virus Po! virus
5uman #art virus polyoma virus 9accine
5uman #art salivary gland infection Small po! chicken po! co# po! ec4ema.
B" containing virus:rthomy!ovirus Picornovirus etrovirus
1nfluen4a "'$ hinovirus ype C ype ' ype $ 519 habdovirus abies virus ogavirus ubella virus Unclassified virus 5epatitis "'&C viruses
1nfluen4a "'$ espiratory disease poliomyletis )eukemia 8ammary tumor 8onkey "ids "1$S abies ubella 5epatitis
Classification:". "nti-herpes virus. 8ost of the antiviral drugs of this class act by inhibiting $B" polymerase. (.g.:- 1do!uridine acyclovir 3anciclovir oscarnet. '. "nti-retro virus. Bon-nucleoside reverse transcriptase inhibitors. (.g.:Aidovudine *"A, $idanosine and Aalcitabine. Bevirapine $elaviridine. Protease inhibitors. (.g.:- Sa6uinavir 1ndinavir. C. "nti-influen4a virus. (.g.:- amantadine. $. thers. (.g.:- interferons ribavirin. $rug
8echanism of 8echanism "dverse action of resistance effects 1do!uridine 1t is esistant phosphorylated by viruses viral thymidylate decrease the kinase to amount of monophosphate thymidylate then to kinase triphosphate. he re6uired for triphosphate is an the inhibitor of viral activation of $B" polymerase the drug. causing inhibition $ecrease in of viral $B" the affinity synthesis and it is of $B" also incorporated polymerase in the $B" for the drug. resulting in faulty $B" #hich code for #rong proteins.
Uses /.5.simple! keratocon2uctivities. *Cytomegalblasto virus,
Page 56 of 67
oscarnet
" phosphonoformate derivative binds to the pyrophosphate binding sites of viral $B" polymerase and reverse transcriptase to prevent the incorporation of nucleotides into $B". Aidovudine n Stavudine phosphorylation in the body into 4idovudine triphosphate it inhibits the en4yme viral reverse transcriptase #hich is re6uired for the synthesis of $B" from viral B". Sa6uinavir "n aspartic en4yme protease encoded by 519 is involved in the production of structural protein and en4ymes of the virus. 1nhibition of the aspartic en4yme by Sa6uinavir #ill deprive the virus of the essential proteins. "mantadine 1t acts on an ion channel 80 and interferes #ith the step of uncoating. ibavirn 1ts mono and triphosphate
5ypokalemia C89 retinitis varicella hypomagnesia 4oster infections. renal to!icity.
$ecrease in "naemia the affinity neutropenia of reverse myopathy. transcriptase for the drug.
"1$S
3.i.t intolerance asthenia paresthesia and e!acerbation of diabetes.
Used to treat later stages of "1$S infections.
1nsomnia di44iness hallucination.
influen4a"0 Parkinson?s.
1nfluen4a" measles.
&
'
Page 57 of 67
"cylclovir
derivatives inhibit 3P and viral B" synthesis. Converted to monophosphate by viral thymidine kinase.
5erpes infections.
1nterferons: - are the cytokines produced by the body in response to viral infections. hey bind to cell specific receptors and interfere #ith various stages of viral replication such as uncoating penetration of virus into the host cell synthesis of viral protein. 1nterferon?s bind to receptors and induce production of 1nterferon induced protein that has antiviral effects. hey are active against both $B" & B" viruses. hey are host specific. hey are indicated for:♣ Chronic hepatitis ' & C ♣ "1$S related @aposi sarcoma *cancer & aids, ♣ 5airy cell leukemia. ♣ hinoviral cold. "dverse effects include myelosupression neuroto!icity etc. ANTIMALARIAL AGENTS
8alaria is caused by four species namely plasmodium viva! P.falciparum P.malariae and P.ovale. P.falciparum does not have secondary Schi4ontic stage. Classification:/. Cinchona "lkaloids: - Kuinine 0. "mino 6uinoline: - Chloro6uine "modia6uine +. N "mino 6uinoline :- Prima6uine pama6uine . O "mino "cridines: - Kuinacrine D. 'iguanides & dihydrotria4ines: - Chlorguanide G. Pyrimidines: - Pyrimethamine H. Sulfonamides: - Sulfado!ine $apsone Sulfamethopyra4ine N. Kuinoline methanol: - 8eflo6uine O. Phenanthrene methanol: - 5alofantrine /;. 8iscellaneous: - Kinghaosu tetracycline?s.
$rug
Chloro6uine
8eflo6uine
Kuinine
Chloroguanide proguanil 8echanism 1t moves into 1nhibits the 1nhibits the 1t is cyclised in of action acidic vesicles of en4yme haem en4yme the body to a the parasite raises polymerase. haempolymerase. tria4ine p5 and inhibits derivative the degradation of #hich inhibits 5emoglobin by plasmodial Page 5 of 67
esistance
Spectrum of activity
"dverse effects
Uses
1ysosomal products. 1t inhibits the en4yme haempolymerase that polymeri4es to!ic free haem to nonto!ic haem4oin. 1t occurs due to the increased efflu! of the drug from the parasitic vesicles.
1ncreased e!pression of an efflu! transporter similar to human transporter Pglycoprotein. (rythrocytic 'lood stages of all the Schi4onticide four plasmodial "gainst species. P.alciparum & P.viva!. )iver damage. 3astrointestinal disturbance giddiness insomnia. Prolongation of K intervals leading to arrhythmias.
dihydrofolate reductase #hich is essential for the synthesis of folate coen4ymes.
1ncreased e!pression of an efflu! transporter similar to human transporter Pglycoprotein.
'lood schi4onticide on all the four plasmodial species. Cinchonismtinnitus paraplegia metallic taste. Cardiac arrhytmias blood dyscriasis can also occur.*bone marro# depression, "lso active reatment of an esistant (ntamoeba acute attack. falciparum histolytica & malaria cerebral 3iardia lamblia. malaria.
1t occurs mutation resulting decrease in affinity of $5ase drug.
by in the the for
Slo# acting (rythrocytic Schi4onticide.
8ild abdominal upset hematuria.
Prophla!is malaria.
of
Pyrimethamine also acts by inhibiting plasmodial dihydrofolate reductase and it is a more potent than chlorguanide. Prima6uine acts on the e!oerythrocytic stages and is highly active against the gametocytes and hypno4oites. 1t causes hemolytic anemia in patients #ith 3G-P$ deficiency. 5alofantrine a blood schi4onticidal agent is active against multiresistant. P.falciparum. Cross-resistance is seen bet#een 5alofantrine and meflo6uine. Page 5 of 67
"rtemesinin a ses6uiterpine lactone is active against multiresistant. P.falciparum. 1t acts by interacting #ith haem and generated free radicals that binds to the membrane proteins and damages the parasite.
ANTIAMOEIC DRUGS
"meobiasis is a proto4oal disease caused by (ntamoeba 5istolytica. 1ntestinal amoebiasis: - 5ere (.5istolytica invade the intestinal #all of the colon. (!tra intestinal amoebiasis: - 1t affects liver lungs & 'rain. (.5istolytica e!ists in t#o forms /. Cysts: - inactive form 0. ropho4ite: - active form Classification:". issue amoebicides ♣ or both intestinal and e!tra intestinal amoebiasis. Bitroimida4oles. (.g.: 8etronida4ole tinido4ole rhimostro4ole. "lkaloids. (.g. : emetine ♣ or e!tra intestinal amoebiasis only. (.g. : chloro6uine
Page 6 of 67
'. )uminal amoebicides ♣ "mide. (.g. : $ilo!anide furoate ♣ N-5ydro!y6uinolines. (.g.: Kuiniodochlor $iiodohydro!y6uin clio6uinol. ♣ "ntibiotics. (.g.: etracycline?s. $rug
8etronida4ole tinido4ole 8echanism he nitro group of action of the compound is reduced to intermediate compounds that cause cytoto!icity by damaging $B". Spectrum "naerobic of activity organisms.
"dverse effects
Uses
(metine 1t inhibits protein by arresting the intraribosomal translocation of peptidyl tB" aminoacid comple!.
@ills tropho4oites but has no action on cysts. 3.i.t 5ypo tension disturbances tachycardia CBS symptoms. (C3 changes and myocarditis. "moebiasis )iver fluke 3iardiasis infestation Ulcerative gingivitis 5.Pylori infections.
$ilo!anide Kuiniodochlor furoate $iiodohydro!y6uin 1t prevents the @ill the cyst forming formation of tropho4oites in the cysts. rom intestinal tract by tropho4oites. chelating ferrous 1nterferes #ith ions #hich are protein essential for synthesis. proto4oal metabolism. @ills tropho4oites responsible for cyst formation. latulence itching is occasional.
"symptomatic amoebiasis.
"ctive against entamoeba 3iardia trichomonas and some fungi. 1odism. Prolonged use caused Jsub acute myelopatic neuropathy? *S8B,. "moebiasis 3iardiasis monolial vaginitis fungal infections.
Suramin sodium: - anionic in nature & binds #ith cationic sites in proteins & en4ymes in glycolytic path#ay. Sodium stilbogluconate: - hese pentavalent antimonials get converted to trivalent antimonials #hich inhibit phosphofructokinase an en4yme catalyses a limiting step in glycolysis. )eishmaniasis is caused by )eishmania donovani and the drugs used to treat are Sodium Stilbogluconate 8eglumine pentamidine "mphotericin ' @etocona4ole and allopurinol. Severe form of leishmaniasis is @ala-a4ar.
Page 61 of 67
ANTHELMINTICS
hese agents destroy or eliminate parasitic #orms *helmints, from 31%body tissues. "nthelmintic may act as:/, 9ermifuge :- e!pels #orms by paraly4ing them 0, 9ermicide :- kill #orms in the body +, Some may also impair the egg production process in #orms. $rug
8ebenda4ole%"lbenda4o le 8echanis 1nhibit glucose uptake m of thereby depleting action glycogen stores. 'ind #ith affinity to micro tubular protein '-tubulin and inhibit its polymeri4ation.
Pyrantel Pipera4ine pamoate 1t causes 1t causes activation of neuromuscular nicotinic blockade by cholinergic antagoni4ing receptors in "ch action and the #orm causes resulting in hyperpolarisatio persistent n #hich leads to depolari4ation paralysis. Worms #hich leads are then to paralysis. e!pelled. Worms are then e!pelled. ound #orm hook 5ook #orm ound #orm #orm tirichuriasis ound #orm pin#orm & guinea thread #orm. #orm.
$iethyl carbama4ine "lteration of the 8icrofilariae *8, membrane so that they are readily phagocytose d by tissue fi!ed monocytes.
Spectrum of activity
8f of Wuchereria bancrofti 'rugia malayi o.volvulus.
$rug )evamisole 8echanism 1t is an of action immunomodulatorrestores -cell function
Biclosamide 1t inhibits o!idative phosphorylationin mitochondria and thereby interferes
Pra4i6uantel Causes leakage of intracellular calcium from the membranes leading to
1vermectin Potentiation of 3"'"ergic transmission in #orms Page 62 of 67
Spectrum of activity
"scaris stronglyloides larvae.
#ith anaerobic paralysis. he generation of "P. lose grip of the intestine and are e!pelled. & aenia saginata . ape #orms solium schistosomiasis. hymenlepsis nana.
leading to paralysis.
nchocerca volvulus #hich causes river blindness.
hiabenda4ole acts by inhibiting fumarate reductase. 1n .C.". cycle useful in strongylodias.
ANTICANCER AGENTS
hese are cytoto!ic drugs either kill cancer cells or modify their gro#th cell cycle: G 1
(pre-synthetic phase)
S – Synthesis of DNA G 2 – Post synthetic phase M - Mitosis phase Page 63 of 67
G 1 G 1 (daughter cells) G – !esting phase
he cells in resting stage are those that are non-proliferating. hese remain 6uiescent but they can be recruited in the cell cycle #hen stimulated later. Cytoto!ic drugs are either cell cycle specific or cell cycle non-specific *they kill both resting as #ell as dividing cells,. Cytoto!ic drugs that are cell cycle specific include drugs like 8ethotre!ate Cytarabine G-8ercaptopurine G-hioguanine 8itomycin $o!orubicin act on the S phase drugs like $aunorubicin 'leomycin etoposide that act on the 30 drugs like vincristine 9inblastine and paclita!el that act on the 8 phase. Cytoto!ic drugs that are cell cycle nonspecific include nitrogen mustards cyclophosphomide Chlorambucil D-U )-asparginine Cisplatin Procarba4ine $acarba4ine etc. Classification: ". "lkylating agents: hese can be further classified into: a. Bitrogen mustards. (.g.: 8ustine Cyclophosphamide 1fosfamide chlorambucil b. (thyleneimine. (.g.: hiotepa c. "lkylsulfonate. (.g.: 'usulphan d. Bitrosourea. (.g.: Carmustine )omustine *they cross '.'.' & used in 'rain tumors, e. ria4ine. (.g.: $acarba4ine. f. 5ydra4ine. (.g.: Procarba4ine '. "ntimetabolites a. olate antagonist. (.g.: 8ethotre!ate *amethopterin, b. Purine antagonist. (.g.: G-8ercaptopurine "4athiopurine G-hioguanine c. Pyrimidine antagonist. (.g.: D-luorouracil Cytarabine. C. 9inca alkaloids. (.g.: 9incristine *oncovin, 9inblastine. $. a!anes. (.g.: paclita!el a!otere. (. (pipodophylloto!in. (.g.: etoposide eniposide $aunorubicin. . "ntibiotics. (.g.: "ctinomycin $ *$actinomycin, $o!orubicin 'leomycins 8itomycin. 3.8iscellaneous. (.g.: cisplatin )-asparaginase. o!icity of "nticancer drugs:- hey have a profound effect on rapidly proliferating cells the most important target of action are the nucleic acids and their precursorsR rapid nucleic acid synthesis occurs during cell division. he different o!icities that arise from "nticancer agents are:Page 64 of 67
/. 'one marro# depression *8yelo suppression % 'lood dyscriasis, resulting in granulocytopenia agranulocytosis thrombocytopenia "plastic anemia 0. )ymphocytopenia and the suppression of 5umoral & Cell mediated immunity. +. Stomatitis diaarohea shedding of mucosa hemmorages . Skin: "lopecia D. 1nhibition of gonadal cells causes oligo4oospermia& impotence in males. G. eratogenic in nature. H. 5yperuricaemia 9irus: - (pstein barr virus is responsible for production of cancer 3enes: - ncogene is responsible for production of cancer A(y(a)*n. a."n)!< 8 hese compounds produce highly reactive carbonium intermediates #hich transfer alkyl groups to cellular macromolecules by forming covalent bonds. he position H of guanine residues in $B" is highly susceptible because it is highly nucleophilic .his results in cross linking % abnormal base pairing % scission of $B" strand. Crosslinking of nucleic acids can also take place. 1n case of 8eclorethamine *mustine, "4iridinium is the intermediate formed. 1n case of Cyclophosphamide Phosphoramide & "crolein are the intermediates formed. Phosphoramide is the active metaboliteR While "crolein is to!ic to the Urinary bladder. *8ercapto sulphonic acid is given to avoid damage of urinary bladder due to "crolein, 1fosfamide is the congener of Cyclophosphamide. hiotepa produces "4iridinium as an intermediate. "lkyl sulfonates undergo a process kno#n as ESulphur StrippingF to react #ith cellular macromolecules & is used in 8yeloid )eukemia. Carmustine & )omustine crosses '.'.'. and hence used in treatment of 'rain umors An)*'")a/%(*)"!< 8 hese compounds prevent biosynthesis or utili4ation of normal cellular macromolecules. F%(a)" An)a.%n*!)!< 8 8ethotre!ate *"methopterine, % "minopterine act by inhibiting dihydrofolate reductase *$5, #hich is essential for the conversion of $ihydrofolic acid to etrahydrofolic acid & step #hich has to occur if synthesis of folate co-en4ymes has to proceed. hus they inhibit the synthesis of thymidilic acid #hich is a component of the $B". "dministration of olinic acid counteracts to!icity of 8ethotre!ate. 8ethotre!ate acts on S phase of the cell division. P#$*n" an)a.%n*!)!< 8 G-mercaptopurine G-thioguanine are converted to monoribonucleotide by 5ypo!anthine guanine phosphoribosyl transferase *53P,. umor cells lack the en4yme 53P develop resistance to the above drugs.8onoribonucleotides inhibit the conversion of DPhosphoribosylpyrophosphate to D-phosphoribosylamine #hich is re6uired for the synthesis of purines. Py$*'*-*n" an)a.%n*!)!< - D-fluorouracil is converted in the body to the corresponding nucleotide. % Page 65 of 67
58fluro-0-deo!yuridine monophosphate #hich inhibits thymidilate synthetase & blocks the conversion of deo!yuridilic acid to deo!y thymidilic acid. hus it inhibits the synthesis of $B". luorouracil itself gets incorporated in to nucleic acids and this may contribute to its to!icity. Cytarabine: - 1t is phosphorylated in the body to the corresponding nucleotide #hich inhibits $B" synthesis. he triphosphate of cytarabine is an inhibitor of $B" polymerase & blocks the generation of cytidilic acid. V*n,a a(a(%*-!< 8 hese are mitotic inhibitors that bind to the micro tubular protein EtubulinF prevent its polymeri4ation & assembly of microtubules &thus cause disruption of mitotic spindle &interfere #ith cytoskeletal function .herefore the chromosomes fail to move apart during mitosis. hey are cell cycle specific and they act in metaphase phase. (.g.: vincristine & vinblastine Ta9an"!< - paclita!el enhances polymeri4ation of tubulin. "s a result the microtubules are stabili4ed & their depolymerisation is prevented.his stability results 1U inhibition of normal dynamic reorgani4ation of the microtubule net#ork that is essential for vital interphase & mitotic functions. "bnormal arrays or bundles of microtubules are produced throughout the cell cycle. he ma2or adverse effects seen are Estocking & gloveF neuropathy. (pipodophylloto!ins such as etoposide arrest cells in the 3 0 Phase & causes $B" breaks by stimulating $B" topoisomerase-0
$U3 "ctinomycin $ * $actinomycin ,
8echanism of action 1t inhibits $B" topoisomerase-0 & also interrelates in $B" causing $B" breaks $aunorubicin*ubidomycin,$o!orubicin 1t inhibits $B" topoisomerase-0& generates 6uinone type free radicals. 8itomycin 1t is converted in the body to act as an alkylating agent. 5ydro!yurea 1t blocks the conversion of ribonucleotides to deo!y ribonucleotides by inhibiting the en4yme ribonucleoside diphosphate reductase & thus interferes #ith $B" synthesis. Procarba4ine "fter metabolic activation it depolymerises $B" & causes chromosomal damage. 1nhibition of $B" synthesis occurs. )-asparginase he en4yme )-"sparginase degrades lasparginase to )- aspartic acid depriving leukemic cells of an essential metabolite & this may cause cell death. Cisplatin " platinum co-ordination comple! is Page 66 of 67
