` DrugsAffectingANS

` CholinergicDrugs
1.CholinergicAgonist:
` DirectActing:
Cholinergic agonists (also known as parasympathomimetics) mimic the effects of
acetylcholinebybindingdirectlytocholinoceptors.
Acetylcholine,Pilocarpine,Bethanecol,Carbachol.
` IndirectActing:
Acetylcholinesterase is an enzyme that specifically cleaves acetylcholine to acetate and
cholineand,thus,terminatesitsactions.Inhibitorsofacetylcholinesteraseindirectlyprovide
acholinergicactionbyprolongingthelifetimeofacetylcholine.
Physostigmine,Neostigmine,Ecothiophate,Rivastigmine,Tacrine.
` ReactivationofActylcholineesterase:
Pralidoxime.
2.CholinergicAntagonist:
` Antimuscarinic:
Commonly known as antimuscarinics, these agents block muscarinic receptors, causing
inhibitionofallmuscarinicfunctions.
Atropine,Scopolamine,Ipratropium.
` GanglionicBolckers:
Ganglionicblockersspecificallyactonthenicotinicreceptorsofbothparasympatheticand
sympathetic autonomic ganglia. Except for nicotine, the other drugs mentioned in this
categoryarenondepolarizing,competitiveantagonists.
Mecylamine,Nicotine.
` NeuromuscularBolckers:
Theseneuromuscularblockersarestructuralanalogsofacetylcholine,andtheyacteitheras
antagonists (nondepolarizing type) or agonists (depolarizing type) at the receptors on the
endplateoftheneuromuscularjunction.Neuromuscularblockersareclinicallyusefulduring
surgeryforproducingcompletemusclerelaxation
Atracurium,Doxacurium,Succinylcholine,Tubocurarine.
` AdrenergicDrugs
1.AgrenergicAgonist:
` DirectActing:

Thesedrugsactdirectlyonorreceptors,producingeffectssimilartothosethatoccur
following stimulation of sympathetic nerves or release of the hormone epinephrine from
theadrenalmedulla.
Dopamine,Epinephrine,Norepinephrine,Phenylephrine,Sameterol,Terbutaline.
` IndirectActing:
Theseagents,whichincludeamphetamine,cocaineandtyramine,mayblocktheuptakeof
norepinephrine(uptakeblockers)oraretakenupintothepresynapticneuronandcausethe
releaseofnorepinephrinefromthecytoplasmicpoolsorvesiclesoftheadrenergicneuron.
Aswithneuronalstimulation,thenorepinephrinethentraversesthesynapseandbindsto
theorreceptors.
Amphetamine,Cocaine,Tyramine.
` Mixed:
Capacitybothtostimulateadrenoceptorsdirectlyandtoreleasenorepinephrinefromthe
adrenergicneuron.
Ephedrine,Pseudoephedrine.
2.AdrenergicAntagonist:
` Blockers:
Drugsthatblockadrenoceptorsprofoundlyaffectbloodpressure.
Doxazocin,Prazocin,Terazocin,Tamsulosin.
` Blockers:
All the clinically available Bblockers are competitive antagonists. Nonselective Bblockers
act at both B1 and B2 receptors, whereas cardioselective B antagonists primarily block B1
receptors.
Atenolol,Esmolol,Labetalol,Pindolol.
` NTUptakeorRelease:
Guanethidine,Reserpine.

` CNSDrugs
` AntiParkinsonismDrugs:
Thediseaseiscorrelatedwithdestructionofdopaminergicneuronsinthesubstantianigra.
Levodopa,Carbidopa,Amantidine,Apomorphine,Benzotropine.
` AlzheimerDrugs:
MajorcauseislossofCholinergicneurons.

Memantine,Rivastigmine,Tacrine.
` AnxiolyticDrugs:
a.Benzodiazepenes:
Alprazolam,Temazepam,Flurazepam,Lorazepam,Oxazepam.
b.Barbiturates:
Amobarbital,Phenobarbital,Pentobarbital,Thiopental.
c.OtherAnxiolytic:
Buspirone(mediatedbyserotonin(5HT1A)receptors),Hydroxyzine,Antidepressants.
` CNSStimulants:
a.PsychomotorStimulants:
Psychomotorstimulants,causeexcitementandeuphoria,decreasefeelingsoffatigue,and
increasemotoractivity.
Amphetamine,Cocaine,Caffeine,Theobromine.
b.Hallucinogens:
The hallucinogens, or psychotomimetic drugs, produce profound changes in thought
patternsandmood,withlittleeffectonthebrainstemandspinalcord.
LysergicAcidDiethylamide,TetrahydroCannabinol.
` CNSDrugs
` AntiDepressants:
a.SSRIs:
Cetalopram,Fluoxetine,Fluvoxamine.
b.SNRIs:
Duloxetine,Venlafaxine.
c.AtypicalAds:
Bupropion,Trazodone.
d.TCAs(OlderSNRIs):
Amitryptiline,Imipramine,Trimipramine.
e.MAOInhibitors:
TheMAOinhibitorsmayirreversiblyorreversiblyinactivatethemitochondrialenzyme(gut
andliver),permittingneurotransmittermoleculestoescapedegradationand,therefore,to
bothaccumulatewithinthepresynapticneuronandleakintothesynapticspace.

Phenelzine,Selegiline.
f.AntiMania&BipolarDisorders:
ValproicAcid,LithiumSalts.
` AntiEpileptics:
By a variety of mechanisms, including blockade of voltagegated channels (Na+ or Ca2+),
enhancement of inhibitory GABAergic impulses, or interference with excitatory glutamate
transmission.
Barbiturates, BZDs, Carbamezepine, Gabapentin, Ethosuximide, Levetiracetam, Felbamate,
Phenytoin,Zonisamide.
` CNSDrugs
` NeurolepticDrugs(AntiPsychoticorMajorTranquilizers):
TheyinactivateDopaminereceptors.
a.Typicalbutlowpotency:
Chlorpromazine,Prochlorperazine.
b.Typicalbuthighpotency:
Haloperidol,Thiothixene.
c.Atypical:
Clozapine,Olanzapine,Risperidone.
` Opoids:
Activation of the opoid receptor decreases the Ca2+ influx and increases the K+ efflux.
Decrease Ca+ influx decreases the release of excitatory NT and increased K+ efflux
decreasestheresponseofpostsynapticneurontoexcitatoryNT(Glutamate).
a.StrongAgonists:
Meperadine,Methadone,Heroine,Fentanyl.
b.Moderate/LowAgonists:
Codeine,Propoxyphene.
c.PartialAgonists:
Buprenorphine,Pentazocine.
d.Antagonists:
Naloxone,Naltrexone.
e.Others:

Tramadol.

` CVSDrugs
` CongestiveHeartFailure(CHF):
a.ReninAngiotensinSystemBlockers:
ThesedrugsblocktheenzymethatcleavesangiotensinItoformthepotentvasoconstrictor
angiotensinII.Alsodiminishtherateofbradykinininactivation.[Note:Vasodilationoccurs
asaresultofthecombinedeffectsoflowervasoconstrictioncausedbydiminishedlevelsof
angiotensin II and the potent vasodilating effect of increased bradykinin.] By reducing
circulating angiotensin II levels, ACE inhibitors also decrease the secretion of aldosterone,
resultingindecreasedsodiumandwaterretention.
Captopril,Lisinopril,Quinapril,Ramipril,Enalapril(ACEInhibitors)
ARBs are nonpeptide, orally active compounds that are extremely potent competitive
antagonistsoftheangiotensintype1receptor.
Losartan,Valsartan,Telmisartan(ARBs)
b.Blockers:
Atenolol,Metoprolol,Carvedilol.
c.Diuretics:
Diureticsdecreaseplasmavolumeand,subsequently,decreasevenousreturntotheheart
(preload).Thisdecreasesthecardiacworkloadandtheoxygendemand.
Bumetanide,Furesamide,Metolazone,Hydrochlorthiazide.
d.DirectVasodilators:
Hydralazine,Isosorbidedinitrate,Sodnitroprusside.
e.InotropicAgents:
Enhancecardiacmusclecontractilityand,thus,increasecardiacoutput.
Digitoxin,Digoxin,Dobutamine,Amrinone.
f.AldosteroneAntagonist:
Spironolactone.
*Dec.AngiotensinIIcausedec.Aldosteronewhichcausedecreasedwater&sodretention.
Plasmavolisdecreasedandhencepreloadalsodecreased&BPlowered.

` AntiArrythmicDrugs:
Arrhythmiasariseeitherfromaberrationsinimpulsegeneration(abnormalautomaticity)or
fromadefectinimpulseconduction.
a.Na+ChannelBlockers:
Quinidine,Procanamide,Propafenone.
b.Blockers:
InhibitsPhase4depolarizationinSA&AVnodes.
Esmolol,Propranolol,Metoprolol.
c.K+ChannelBlockers:
ProlongsPhase3repolarizationinventricularmusclefibres.
Amiodarone,Sotalol,Dofetilide.
d.Ca2+ChannelBlockers:
InhibitsactionpotentialinSA&AVnodes.
Diltiazem,Verapamil.
e.Others:
Adenosine,Digoxin.

` AntiAnginalDrugs:
a.OrganicNitrates:
Nitrates decrease coronary vasoconstriction or spasm and increase perfusion of the
myocardiumbyrelaxingcoronaryarteries.Inaddition,theyrelaxveins,decreasingpreload
andmyocardialoxygenconsumption.
Isosorbidedinitrate&mononitrate,Nitroglycerin.
b.Blockers:
Theydecreasetheoxygendemandsofthemyocardiumbyloweringboththerateandthe
forceofcontractionoftheheart.
Acebutolol,Atenolol,Metoprolol,Propranolol.

c.CaChannelBlockers:
The calciumchannel blockers protect the tissue by inhibiting the entrance of calcium into
cardiacandsmoothmusclecellsofthecoronaryandsystemicarterialbeds.
Amlodipine,Diltiazem,Verapamil,Nicardipine,Nifedipine.

` AntiHyperlipidemics:
a.HMGCoAReductaseInhibitors:
AnalogsofHMG(precursorofCholesterol).Becauseoftheirstrongaffinityfortheenzyme,
all compete effectively to inhibit HMG CoA reductase, the ratelimiting step in cholesterol
synthesis(denovosynthesis).
Atorvastatin,Lovastatin,Provastatin,Simvastatin.
b.Fibrates:
Gemfibrozil,Fenofibrate.
c.Niacin:
Niacin strongly inhibits lipolysis in adipose tissue, the primary producer of circulating free
fattyacids.
d.BileAcidSequestrants:
Colestipol,Colestyramine,Colesevelam.

e.CholesterolAbsorptionInhibitors:
It inhibits intestinal absorption of dietary and biliary cholesterol in the small intestine,
leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a
reductionofhepaticcholesterolstoresandanincreaseinclearanceofcholesterolfromthe
blood.
Ezetimibe.

` AntiHypertensives:
a.Diuretics:
Theycauseincreasedwaterandsodiumexcretionleadingtodecreasedextracellularvolume
&decreasedcardiacoutput.
Bumetanide,Furosamide,Spironolactone,Hydrochlorthiazide.
b.Blockers:
DecreaseCardiacOutput.
Atenolol,Carvedilol,Labetalol,Metoprolol.
c.ACEInhibitors:
ACE inhibitors decrease conversion into angiotensin II and increase bradykinin levels.
Vasodilationoccursasaresultofthecombinedeffectsoflowervasoconstrictioncausedby
diminished levels of angiotensin II and the potent vasodilating effect of increased
bradykinin.
Captopril,Enalapril,Fosinopril,Lisinopril,Ramipril.
d.ARBs:
SameAsACEIsbutnoCoughorAngiodema.
Candesartan,Losartan,Telmisartan,Valsartan.
e.CaChannelBlockers:
Verapamil,Nifedipine,Nicardipine,Diltiazem,Amlodipine.
f.Blockers:
They decrease peripheral vascular resistance and lower arterial blood pressure by causing
relaxationofbotharterialandvenoussmoothmuscle.
Doxazocin,Prazocin,Terazocin.
g.Others:
Clonidine,Hydralazine,Sod.nitroprusside,Minoxidil,Methyldopa.

` Diuretics:
a.Thiazides:
ThesedrugsincreasetheconcentrationofNa+andClinthetubularfluidbydecreasingthe
reabsorptionofNainthedistalconvulatedtubule.
Chlorothiazide,Chlorthalidone,Indapamide,Hydrochlorthiazide.
b.LoopDiuretics:
Loop diuretics inhibit the cotransport of Na+/K+/2Cl in the luminal membrane in the
ascending limb of the loop of Henle. Therefore, reabsorption of these ions is decreased.
Mostefficacious.
Bumetanide,Furosamide,Torsemide.
c.PotassiumSparingDiuretics:
Amiloride,Spironolactone,Triamterene.
d.CarbonicAnhydraseInhibitors:
Acetazolamide.
e.OsmoticDiuretics:
Mannitol,Urea.

` Antibiotics(Antimicrobials)
` CellWallInhibitors:
Thesedrugsinterferewiththelaststepofbacterialcellwallsynthesis(transpeptidationor
crosslinkage),resultinginexposureoftheosmoticallylessstablemembrane.Celllysiscan
thenoccur,eitherthroughosmoticpressureorthroughtheactivationofautolysins.These
drugsarethusbactericidal.
a.Blactams:
iPenicillins:
Amoxicillin,Ampicillin,Piperacillin,Oxacillin,Methicillin,Nafcillin.
iiCephalosporins:
1stGeneration(Cefadroxil,Cefalexin)
2ndGeneration(Cefaclor,Cefoxitin,Cefprozil)
3rdGeneration(Cefixime,Cefotaxime,Cefibuten,Ceftriaxone)
4thGeneration(Cefepime)
iiiCarbapenems:
Meropenem,Imipenem.
IvMonobactam:
Aztreonam.
b.OtherAntibiotics:
Bacitracin,Vancomycin,Daptomycin.

` ProteinSynthesisInhibitors:
a.Tetracyclines:
The drug binds reversibly to the 30S subunit of the bacterial ribosome, thereby blocking
accessoftheaminoacyltRNAtothemRNAribosomecomplexattheacceptorsite.Bythis
mechanism,bacterialproteinsynthesisisinhibited.
Doxycycline,Minocycline,Tetracycline.
b.Glycylcyclines:
Alsobindsreversiblytothe30Softheribosomalunit.
Tigecycline.
c. Aminoglycosides (derived from Streptomyces have mycin suffixes, whereas those
derivedfromMicromonosporaendinmicin):
Alsobindsreversiblytothe30Sribosomalsubunit&inhibitingproteintranslation.
Allaminoglycosidesshouldbegivenparenterallyexceptneomycin.
Amikacin,Gentamicin,Neomycin,Tobramycin,Streptomycin.
d.Macrolides/Ketolides:
Themacrolidesbindirreversiblytoasiteonthe50Ssubunitofthebacterialribosome,thus
inhibitingthetranslocationstepsofproteinsynthesis.
Azithromycin,Clarithromycin,Erythromycin,Telithromycin.
e.Chloramphenicol(50Ssubunit)
f.Clindamycin
g.Dalfopristin/Quinupristin(50Ssubunit)
h.Linezolid(bindstoasiteonthe50Ssubunitneartheinterfacewiththe30Ssubunit)

` Fluoroquinolones:
Thesedrugsenterthebacteriumbypassivediffusionthroughwaterfilledproteinchannels
(porins) in the outer membrane and then inhibit the replication of bacterial DNA by
interfering with the action of DNA gyrase (topoisomerase II) and topoisomerase IV during
bacterialgrowthandreproduction.
NalidixicAcid,(Ciprofloxacin,Ofloxacin,Norfloxacin),Levofloxacin,Moxifloxacin.

` FolateSynthesisInhibitors:
SilverSulfadiazene,Sulfamethoxazole,Sulfasalazine,Sulfisoxazole.

` FolateReductionInhibitors:
Pyrimethamine,Trimethoprim.

` CombinationofAbovetwo:
Cotrimoxazole.

` UTIAntiseptics:
Methenamine,Nitrofurantoin(urinediscoloration).
` WhereSulfonamidesandTrimethoprimact??
Pteridine+pABA+GlutamateDihydrofolicAcid(Sulfonamide)(microbes)
DihydrofolicAcidTetrahydrofolicAcid(Trimethoprim)(humans)
TetrahydrofolicAcidAminoAcidSynthesis+PurineSynthesis+
ThymidineSynthesis

` AntimycobacterialsAndAntifungals
` AntiTBdrugs:
Isoniazid(altering cell membrane function), Ethambutol(inhibit normal arabinogalactin cell
wall),Rifampicin(inhibitssynthesisofmRNA),Pyrazinamide(unknown).(1stlinedrugs)
Aminoglycosides,Macrolides,Cycloserine,Ethionamide,.(2ndlinedrugs)

` AntiLeprosyDrugs:
Clofazimine,Dapsone,Rifampin.

` SubcutaneousandSystemicMycoses:
AmphitericinB,Fluconazole,Ketoconazole,Micafungin,Capsofungin.

` CutaneousMycoses:
Butoconazole,Griseofulvin,Nystatin,Terbinafine.

` Antiprotozoals&Antihelminthics
` Amebiasis:
Chloroquine,Emetine,Dehydroemetine,Metronidazole,Paramomycin.

` Malaria:
Artemisinin,Primaquine,Pyrimethamine,Mefloquine,Quinine/Quinidine.

` Trypanosomiasis:
Benznidazole,Suramin,Nifurtimox,Melarsoprol.

` Leishmaniasis:
Sodiumstibogluconate.

` Toxoplasmosis:
Pyrimethamine.

` Giardiasis:
Metronidazole,Nitazoxanide,Tinidazole.

` AntiNematodes(Ascaris,Hookworms,Filarias.Enterobius,Trichinella):
Ivermectin,Pyrantelpamoate,Diethylcarbamazine.

` AntiTrematodes(Schistosomes):
Praziquantel.

` AntiCestodes(Tapeworms):
Niclosamide,Albendazole.

` AntiVirals
` RespiratoryVirusInfections:
Amantadine,Rimantadine,Ribavirin,Zanamivir.

` HepaticViralInfections:
Interferon,Adefovir,Entecavir.

` HIVInfections:
Abacavir,Didanosine,Etravirine,Fosamprenavir,Tenofovir.

` AntiCancers
` Antimetabolites:
Methotrexate,Gemcitabine,6Mercaptopurine,Cytarabine.
` Antibiotics:
Bleomycin,Doxorubicin,Daunorubicin.
` AlkylatingAgents:
Cyclophosphamide,Busulfan,Ifosfamide,Mechlorethamine,Streptozocin.

` MicrotubuleInhibitors:
Docetaxel,Vincristine,Vinblastine,Vinorelbine.

` Steroids,HormonesandtheirAntagonists:
Prednisone,Tamoxifen,Estrogens,Goserelin,Letrozole.

` MonoclonalAntibodies:
Cetuximab,Rituximab.
` Others:
Asparaginase,Interferons,Cisplatin,Etoposide,Imanitib,Topotecan,Oxaliplatin.

` AntiInflammatory
` NSAIDs:
Aspirin,Diclofenac,Indomethacin,Fenamates,Ibuprofen,Piroxicam,Sulindac.
` CoX2Inhibitors:
Celecoxib.
` OtherAnalgesics:
Acetaminophen.
` AntiArthritis:
Adalimumab,Anakinra,Infliximab,Goldsalts,DPenicillamine.
` DrugsforGout:
Allopurinol,Colchicine,Probenecid,Sufinpyrazone.

` Autocoids&TheirAntagonists
` Prostaglandins:
Misoprostol.

` H1Antihistamines:
H1 receptors present in exocrine excretion, bronchial smooth muscles, intestinal smooth
musclesandsensorynerveendings.
H1&H2receptorspresentinCVS&Skin.
H2receptorsfoundonlyinstomach.
FirstGeneration(Chlorpheniramine,Diphenhydramine,Dimenhydrinate)
SecondGeneration(Cetrizine,Fexofenadine,Loratadine)

` MigraineHeadache:
Almotriptan,Naratriptan,Riztriptan,Sumatriptan,Zolmitriptan.

FactstoRemember
` SubstancePBlocker:APREPITANT
` IsoniazidwrittenasINHrepresentsIsoNicotinicacidHydrazide.
` UterusParts:Fundus;Body;Corporis;Cervix.
` Fallopiantubeconnectsovarywithuterus.
` FemaleReproductiveSystem:Ovary;FallopianTube;Uterus;Vagina.
` Embryolifecycle:18weeks
` Fetus:After8weeks
` Uteruswalls:EndometriumMyometrium;Parametrium.
` Endo&MyometrialwallsinvolvedintheproductionofProstaglandins.
` F2:Vasoconstrictor(dysmenorrhia)
` E2:Vasodilator(menorraghia)
` I2:Myometrialrelaxation;vasodialtion;antiplatelets.
` Menarchie:FirstPeriodsofawoman(816yrs)Avg:13yrs.
` Mostregularizedperiods:2040yrs.
` Averagecycle:28days(2436days)
` AverageFlow:37days;TypicalFlow:5days
` Startslightthenheavythenagainlight.
` ACEIscontraindicatedinbilateralrenalarterystenosi.
` Desmopressineusedinnocturnalenuresis.
` Ovulation:Releaseofovafromtheovary.
` Range:Day8th20th(14thday).
` Awomanhasalmost2000daysofperiodsinherlife(400cycles)exceptpregnancy
andillness.
` Menstrualcycle:Menstruation;Proliferation;Ovulation;Secretory.
` Menstruation:Day15.
` Proliferation:Day613.
` Ovulation:Day14th.
` Secretory:Day1528.

` GraffianFolliclebeforeovulationsecreteestrogenandafterovulationisisknownas
Corpeus Luteum and secretes Progesterone which develops thick wall of uterus
(endometrium).
` Cervix:Neckofuterus.
` BasalBodyTemperature(BBT):Tempatrelaxedbodystate.
` Nociceptives:NerveEndingsthatsensepain.
` Anhedonia: An unprovoked stimuli could result in painful sensation normally not
painful.
` Gestational Diabetes: Diabetes that occurs during pregnancy and soon disappears
afterchildbirth.
` MajorAdverseeffectofAdenosineisDyspnea.
` VerapamiliscontraindicatedwithCNSDepressants.
` DailydoseofFolicAcidis400500g.
` TypesofPain:
a. Nociceptive: Pain due to sensitization of nociceptive nerve endings due to certain
tissuedamage.
b. Neuropathic: Any lesion or damage to the nerve fibres, resulting in pain. E.g.
DiabeticPeripheralNeuropathy(DPN)
c. Mixed:Lowbackpain;AnkolysingSpondylitis.
` MechanismofFeelingpain:
a. Reception:StimulationofnociceptivesbyPGs.
b. Conduction:FromNerveendingtobrain.
c. Perception:Cortex&Thallamusreceiveimpulse.
d. Suffering:Reaction.
` Pain&InflammationMediators:Histamine;Bradykinins;Kinins;SubstaceP;PGs.
` PGsincreasebloodflowtotheinjurysiteandacceleratethetransferofWBCsand
Platelets.
` Inflammation:Naturalresponsetotheinjurytoinactivatecausativeagent.
` PGs increase vascular permeability and WBCs migration and sensitization of
Nociceptives.
` PAE:Thepostantibioticeffect(PAE)isapersistentsuppressionofmicrobialgrowth
thatoccursafterlevelsofantibiotichavefallenbelowtheMIC.

` Myasthenia gravis: (Muscle weakness)Autoimmune disorder due to blockade of

cholinoceptorsbycirculatingantibodies.TreatmentbyNeostigmine,physostigmine.
` DiabetesTypeI:InsulinDependant;whenthebodystopsmakinginsulin.Alsocalled
brittleorlabilediabetes.
` DiabetesTypeII:NonInsulinDependant;bodyismakinginsulineitherininsufficient
amountorthecellsdonotrespondtobodymadeinsulin.
` Menorrhagia:ExcessBloodflowinfrequency,durationoramount;upto80ml.(20
30ml)
` PGE2:Inc.vasodilation;Dec.plateletadhesion&aggregationInc.BloodFlow.
` PGF2:Inc.vasospasm;Inc.uterinecontractionsPainfulMenses.
` Hyperalgesia:IntensedPain.
` Articular:Bones&Joints.NonArticular:Tendons;Ligaments;Bursa.
` Epicondyl:Bonyprojectionsattheendoflongbones.
` Sprains:Injurytotheligament.
` StillsDisease:JuvenileIdiopathicArthritis.
` Inenteralrouteduodenumisthemajorsitefordrugabsorption.
` Bioavailability:Fractionofthedrugthatreachesthebloodstream.
` Totalbodywaterin70kghuman=42litres.
` Intracellular(28ltrs)+Interstitial(10ltrs)+Plasma(4ltrs)=42litres.
` VolumeofDistribution:Hypotheticalvolumeoffluidsintowhichdrugisdispersed.
` Albuminhasthestrongestaffinitywithanionicandhydrophobicdrugs.
` Eachcellmayhave10,000receptorse.g.hearthasBreceptorfornorepinephrine
andmuscarinicreceptorforacetylcholine.
` PotassiumisadministeredasSlowIVinfusions.
` Receptor:Biologicalmoleculetowhichdrugbindingproducemeasurableresponse.
` ReceptorTypes:
a. LigandgatedIonChannels:GABA(Fastestreception)
b. GproteinCoupled:Sildenafil
c. EnzymeLinked:Insulin
d. IntracellularReceptors:Steroids(Slowestreception)
` Competitive Antagonism: Same site on same receptor e.g. Prazocin &
Norepinephrine.

` Noncompetitive Antagonism/Allosteric: Different sites on same receptor e.g.

Protamine&Heparin.
` Functional/PhysiologicAntagonism:Differentreceptorsinvolvede.g.Epinephrine&
Histamine.
` QuantalDoseResponse:Studyofdoseresponseonapopulationthatresponds.
` TherapeuticIndex:Ratiooftoxicdosetoeffectivedose.
` DrugswithHighTherapeuticIndexisSAFERtouse.
` Catecholamineshavebriefduration&rapidonsetofactionanddonotcrossBBB.
` Noncatecholamineshavelongerdurationofactionandcanbeadministeredorally.
` Narcolepsy: Narcolepsy is a relatively rare sleep disorder that is characterized by
uncontrollable bouts of sleepiness during the day. It is sometimes accompanied by
catalepsy,alossinmusclecontrol,orevenparalysisbroughtonbystrongemotions,
suchaslaughter.
` P450 enzyme INDUCERS: Smoking, Omeprazole, Rifampicin, Carbamazepine,
Phenytoin,Phenobarbital.
` P450enzymeINHIBITORS:Cimetidine,Fluvoxamine,IsoniazidQuinidine,Macrolides,
Chloramphenicol.
` INR:AlaboratorytesttocalledINTERNATIONALNORMALISEDRATIOmeasuresthe
timeittakesforabloodsampletoclotandcomparesitwithaverageclottingtime(5
11min). Average CT measured by Dales method (taking a blood sample in a thin
capillaryandtheendoftubeisbrokenevery30secuntilclotformed).
` BleedingTime:Itisthetimeuntilwhichthebloodcontinuesoozingfromtheinjured
site(15min). Measured by Dukes method (pricking a finger and taking the blood
sampleevery30sec.onafilterpaperuntilbloodstopscoming).
` Norepinephrineisineffectiveorally.
` AlphaMethyldopaistheonlyanihypertensiveusedinpregnancy.
` MajorsideeffectofDoxorubicinistissuenecrosis.
` OxidationisPhaseIreaction.
` InoverdosageofDigoxinweuseAntidoteFABfragment.
` DigitoxintoxicityreflectsinECGastoprolongPRinterval.
` Myxodema(Hypothyroidism)treatedbyThyroidsodium.
` VitAdailydoseis30,00050,000IU.
` VitCdailydoseis400mgforbothmenandwomen.
` Floxapen(flucloxacillin)isresistanttopenicilinnase.

` Chelatorsaredrugsthatformcovalentbondswithcationicmetals.
` Antibiotics showing Conc. dependant
flouroquinolones,carbapenems.

killing

involve

aminoglycosides,

` While those showing time dependant killing involve lactams, macrolides,

clindamycin.
` NarrowSpectrum:Coveringsingleorlimitedgroupofmicrobes.e.gIsoniazid.
` Extended Spectrum: Covering gram +ve and also significant gram ve bacteria. e.g
Ampicillin
` Broad Spectrum: Covering a wie variety of microbes; also the beneficial microbes
causingCandidaalbicans.e.gTetracyclines,Chloramphenicol.
` AnginaPectoris:Itisacharacteristicsudden,severe,pressingchestpainradiatingto
theneck,jaw,back,andarms.Itiscausedbycoronarybloodflowthatisinsufficient
tomeettheoxygendemandsofthemyocardium,leadingtoischemia.
` StableAngina(Typical):Itischaracterizedbyaburning,heavy,orsqueezingfeeling
in the chest. It is caused by the reduction of coronary perfusion due to a fixed
obstructionproducedbycoronaryatherosclerosis.
` UnstableAngina:Inunstableangina,chestpainsoccurwithincreasedfrequencyand
areprecipitatedbyprogressivelylesseffort.(liesb/wAnginaandMI)
` Prinzmetal/Variant/Vasopastic Angina: It is an uncommon pattern of episodic
anginathatoccursatrestandisduetocoronaryarteryspasm.Symptomsarecaused
bydecreasedbloodflowtotheheartmuscleduetospasmofthecoronaryartery.
` Mixed Angina: Patients with advanced coronary artery disease may present with
angina episodes during effort as well as at rest, suggesting the presence of a fixed
obstructionassociatedwithendothelialdysfunction.
` Angiodema: AngioedemaorQuincke's edemais the rapid swelling (edema) of
thedermis,subcutaneous tissue, mucosaand submucosal tissues. Also known as
angioneuroticoedema.Duetoincreasedbradykinin(vasodilator)levelswhichoccurs
inACEIstreatment.
` HydralazinecausesLupusLikeSyndrome.
` Hypothyroidism&AntidepressantscausesWeightGain.
` LowDensityLipoproteinsLPLsactasCarriersofcholesterolinPlasma.
` HDLscauseatherosclerosis.
` Sites of Antibiotics: Cell wall synthesis(Blactams); metabolism(sulfonamides);
protein synthesis(macrolides); nucleic acid function or synthesis(cipro); cell
membranefunction(isoniazid).

` DrugsAffectingOtherOrgans
` RespiratorySystem:
a.Asthma:
2Adrenergic Agonists, Corticosteroids, Montelukast(Cysteinyl leukotriene antagonist),
Theophylline,Omalizumab.
b.AllergicRhinitis:
AdrenergicAgonists,Antihistamines,Corticosteroids,Cromolyn.
c.COPD:AdrenergicAgonists,Corticosteroids,Ipratropium.
d.Cough:Dextromethorphan,Opiates.

` GITDrugs:
Parietal cell is acted upon by Acetylcholine, Gastrin, Histamine & Prostaglandin. PG has
inhibitoryeffectwhileothersincreaseacidrelease.
a.AntiMicrobials:
Amoxycillin,Clarithromycin,Tetracycline,Metronidazole.
b.H2ReceptorAntagonist:
They are competitive antagonists of histamine and are fully reversible. These agents
completelyinhibitgastricacidsecretioninducedbyhistamineorgastrin.
Cimetidine,Ranitidine,Famotidine.
c.PPIs:
TheybindtotheH+/K+ATPaseenzymesystem(protonpump)oftheparietalcell,thereby
suppressing secretion of hydrogen ions into the gastric lumen. The membranebound
protonpumpisthefinalstepinthesecretionofgastricacid
Esomeprazole,Omeprazole,Lansoprazole.
d.Prostaglandins:
ProstaglandinE2,producedbythegastricmucosa,inhibitssecretionofHClandstimulates
secretionofmucusandbicarbonate.
Misoprostol(ProstaglandinE2analog).
e.Antacids:
AluminiumHydroxide,MagnesiumHydroxide.
f.MucosalProtectiveAgents:
Sucralfate.

` AntiEmetics:
a.Phenothiazines:
Prochlorperazine(Blockdopaminereceptors)
b.5HT3receptorblocker:
Theyselectivelyblock5HT3receptorsintheperiphery(visceralvagalafferentfibers)andin
thebrain.
Ondansetron,Granisetron,Dolasetron.
c.Butyrophenones:
Droperidol,Haloperidol(BlockDopaminereceptors).
d,SubstanceP/NeurokininIBlocker:
Aprepitant (It targets the neurokinin receptor in the brain and blocks the actions of the
naturalsubstance)

` Antidiarrheals:
a.Antimotilityagents:
Both are analogs of meperidine and have opioidlike actions on the gut, activating
presynapticopioidreceptorsintheentericnervoussystemtoinhibitacetylcholinerelease
anddecreaseperistalsis.Attheusualdoses,theylackanalgesiceffects.
Diphenoxylate,Loperamide.
b.Adsorbents:
Bismuthsubsalicylate,Methylcellulose,Aluminumhydroxide.
c.Agentsthatmodifyfluidandelectrolytetransport:
Bismuthsubsalicylate.(Travellersdiarrhea)

` Laxatives:
a.Irritants&Stimulants:
Senna,Bisacodyl.
b.BulkLaxatives:
They form gels in the large intestine, causing water retention and intestinal distension,
therebyincreasingperistalticactivity.
Methylcellulose,Psylliumseeds,Bran.
c.Stoolsofteners:(Emollientlaxatives/Surfactants)
Docusatesodium,Docusatecalcium,Docusatepotassium.
d.LubricantLaxatives:
Mineraloil&Glycerinsuppositories.(Facilitatethepassageofhardstools)

` OtherTherapies
` ErectileDysfunction(PDE5Inhibitors):
Sildenafil,Vardenafil.
` Osteoporosis:
Alendronate,Ibandronate,Calcitonin,ZoledronicAcid.
` Obesity:
Orlistat(lipaseinhibitor),Sibutramine(anorexiant),Phentermine(anorexiant).

` AdrenalHormones
` Structure: Inner part Medulla secreting Epinehprine. Outer part cortex. Cortex is
further divided into three parts. Inner most of cortex is Reticularis which secretes
Adrenal androgens; Middle part called Fasciculata secreting Glucocorticoids and
outermostistheGlomerulosawhichsecretesMineralocorticoids.
` Physiology:
Hypothalamus

APituitary

AdrenalGland

` Glucocorticoids&MineralocorticoidsarecollectivelyknownasCorticosteroids.
` Cortisol also acts as a feedback mechanism and inhibits both processes from
hypothalamustoanteriorpituitaryandpituitarytoadrenalglands.
` Glucocorticoids:
a. ShortActing(112hrs):Hydrocortisone,Cortisone.
b. IntermediateActing(1236hrs):Prednisone,Prednisolone,Methylprednisolone.
c. LongActing(3655hrs):Betamethasone,Dexamethasone.
` Mineralocorticoids:Deoxycorticosterone,Fludrocortisone.
` GlucocorticoidsactasantiinflammatorybyinhibitingPGsandLeukotrienes&also
redistributeWBCstootherbodysites;alsoreducehistaminereleasefrommastcells
and basophils; decrease ability of macrophages and leukocytes to antigens and
mitogens.
` Also used in Treatment of Allergies and Diagnosis of Cushings disease
(Overproductionofglucocoricoids)

` BiopharmConcepts
` Metabolismcanhappenintwophases.
` Phase I reactions involve hydrolysis, oxidation and reduction (results in low
hydrophilicity).
` Phase II reactions involve glucoronidation, sulfonation, acetylation, methylation,
conjugationwithglutathioneoraminoacids(causehighhydrophilicity).
` PhaseImayormaynotprecedePhaseII.
` Clearanceisthevolumeofplasmaclearedoffdrugperunittime.Itsunitisml/min.
` Pharmacokinetics involves the movement of drug or its metabolites into or out of
thebodyandalsoevaluatesitsmetabolismrates.
` Zero order kinetics is independent of drug concentrations; usually seen when
reactionsystemissaturated.e.gMetabolismofPhenytoin,ConstantrateIVInfusion.
` In First order kinetics rate of drug elimination at particular time is directly
proportionaltotheamountofdruginthebodyatthattime;SemiLogarithmicplot
ofPlasmaDrugConcvstimeisastraightline.
` Eliminationrateconstant,Vd,clearanceandhalflifeareindependentofthedoseof
thedrug.
` First order kinetics is also known as monoexponential kinetics; in which rate of
reactionisdirectlyproportionaltothedrugconcentrationinthereaction.
` MixedOrderKineticsdependsonthedoseofthedrugandarethusknownasDose
Dependant or NonLinear Kinetics. Generally described by Michelis Menten
Equation.
` BiopharmConcepts
` PharmacokineticModelsareimaginarycompartments.
` CentralCompartmentrepresentsplasmaandtissueswhichrapidlyequilibratewith
drugs.
` PeripheralCompartmentsrepresentstissuesororganswhichequilibrateslowly.
` Number and site of compartments is determined by the blood perfusion capacity
anddrugphysicochemicalproperties.
` MichelisMentenEquation:
dc=VmaxxC
dtKm+C
` Plasmaalbuminhas4bindingsites.i.eWarfarin,Diazepam,Tamoxifen,Digoxin.
` Totalbodytissuecomprises40%ofthetotalbody.

` PharmaceuticalEquivalents:Iftwodrugscontainsameamountofactiveingredient
insamedosageform.Theymaycontaindifferentexcipients.
` Pharmaceutical Alternatives: If two drugs contain same drug molecule but in
differentchemicalforme.gdifferentsaltorstrength.
` Bioavailability: Rate and extent to which a drug is absorbed from the site of
administrationandbecomeavailableatthesiteofaction.
` Bioeuivalence:Drugsshowingsamebioavailabilityaresaidtobebioequivalent.
` EssentiallySimilarProduct:AcopyoftheresearchorInnovatorProduct.(ME2)
` BiopharmConcepts
` Therapeutic Equivalents: If two drugs provide the same desired therapeutic effect
withsamesafetyandefficacy.
` Cmax:MaximumDrugPlasmaconcentrationpartlydependsontherateofreleaseof
drugfromtheformulation.
` Tmax: Time required to reach maximum Plasma drug concentration; also dependant
onrateofdrugrelease.
` T1/2:Eliminationhalflife.
` Mean Residence Time (MRT): Time a drug molecule spends in the body before it
getsexcretedout.
` MetabolismreactionsarealsosaidtobeBioactivationreactions.
` Metabolismisbasicallyinvolvedinconvertingadrugmorehydrophilictofacilitateits
excretionfromthebody.