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IntroductiontoPharmacologyOverviewTheaimofdrugtherapyDrugtargettissueAbsorptionDistributionMetabolismEliminationTherouteofadministrationisdeterminedbythepropertiesofthedrugandbythetherapeuticobjectives.Enteralandparenteral

enteralOral:themostcommonrouteSublingual:allowsthedrugtodiffuseintothecapillarynetworkRectal:FiftypercentofthedrainageoftherectalregionbypassesportalcirculationparenteralIntravascular:IVinjectionisthemostcommonrouteusedfordrugsthatarenotabsorbedorally.Intramuscular:canbeaqueoussolutionsorspecializeddepotpreparationsSubcutaneous:slowerthantheIVrouteandminimizestherisksassociatedwithIV.OtherInhalation:providestherapiddeliveryacrossthesurfaceareaofthemucousmembranesoftherespiratorytract.Intranasal:desmopressininthetreatmentofdiabetesinsipidus.Intrathecal/intraventricular:tointroducedrugsdirectlyintotheCSF.Topical:theapplicationisusedwhenalocaleffectofthedrugisdesired.AbsorptionofdrugsAbsorptionisthetransferofadrugfromitssiteofadministrationtothebloodstream.Therateandefficiencyofabsorptiondependontherouteofadministration.TransportofdrugfromtheGItractPassivediffusion:movesfromaregionofhighconcentrationtooneoflowerconcentration.Activetransport:involvesspecificcarrierproteins.Energy-dependent.Againstaconcentrationgradient.EffectofpHondrugabsorptionWeakacidsorweakbasesHAH++A+

BHB+H+

theeffectiveconcentrationofthepermeableformofeachdrugatitsabsorptionsiteisdeterminedbytherelativeconcentrationsofthechargedandunchargedforms.PhysicalfactorsinfluencingabsorptionBloodflowtotheabsorptionsiteTotalsurfaceareaavailableforabsorptionContacttimeattheabsorptionsurfaceBioavailabilityBioavailabilityisthefractionofadministereddrugthatreachesthesystemiccirculation.Bioavailabilityisdeterminedbycomparingplasmalevelsofadrugafteraparticularrouteof

administrationwithplasmadruglevelsachievedbyIVinjectionFactorsthatinfluencebioavailabilityFirst-passhepaticmetabolismSolubilityofdrugChemicalinstabilityNatureofthedrugformulationDrugdistributionDrugdistributionistheprocessbywhichadrugreversiblyleavesthebloodstreamandentersthecellsofthetissues.DependsonBloodflowCapillarypermeability

capillarystructuredrugstructureBindingofdrugstoproteinsVolumeofdistributionThevolumeofdistribution(Vd)isahypotheticalvolumeoffluidintowhichthedrugisdisseminated.A.watercompartmentsinthebody

1.Plasmacompartment2.Extracellularfluid3.Totalbodywater4.othersitesB.theapparentvolumeofdistributionDeterminationofVdDistributionofdrugintheabsenceofeliminationDistributionofdrugwheneliminationispresentCalculationofdrugconcentrationifdistributionwereinstantaneousBindingofdrugstoplasmaproteinsBindingcapacityofalbuminCompetitionforbindingbetweendrugsDrugmetabolismKineticsofmetabolism

First-orderkineticszero-orderkineticsReactionofdrugmetabolismPhaseI:PhaseIreactionfunctiontoconvertlipophilicmoleculesintomorepolarmoleculesbyintroducingorunmaskingapolarfunctionalgroupPhaseII:Thisphaseconsistsofconjugationreaction.PharmacokineticsQuantitative,timedependentKineticsofintravenousinfusion

Withcontinousintravenousinfusion,therateofdrugentryintothebodyisconstant.

Steady-statedruglevelsinbloodInfluenceoftherateofdruginfusiononthesteady-stateTimerequiredtoreachthesteadystatedrugconcentration

ExponentialapproachtosteadystateThesoledeterminantoftheratethatadrugapproachessteadystateisthet1/2Kineticsoffixed-dose,fixedtimeintervalregimensSingleintravenousinjectionMultipleintravenousinjectionDose-responsequantitationDrugreceptorGradeddose-resposeAnagonistEfficacymaximalresponseED50=drugdosethatshows50%ofmaximalresponsePotenc

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