NR 565 - advanced pharmacology FINAL -
vb vb vb vb vb vb
Chamberlain Practice EXAM
vb vb vb
NR565 ADVANCED PHARMACOLOGY
FUNDAMENTALS WEEK 1
DrugvbDevelopmentvbProcessvb-vbanswer--Pre-clincialvbStagevb(Animalvbtesting)vbofvbR&D
INDClinicalvb(Safetyvbandvbeffectiveness)
R&DFinalvbProductvbDevelopment
Post-marketing
Variationsvbinvbdrugvbdevelopmentvbprocess
PreclinicalvbstagevbofvbR&Dvb-vbanswer--1.vbDrugvbdiscovery
2.vbBiologicalvbcharacterizationvb(drugvbaction/vbfate)
3.vbPre-formulationvbstudies
4.vbInitialvbformulations
5.vbManufacturingvbandvbcontrols
6.vbPackagevblabelvbandvbdesign
ClinicalvbStagevb-vbanswer--Phasevb1:vbBiologicalvbeffects,vbsafevbdosage
Phasevb2:vbNewvbdrugvbtreatsvbsmallvbamountvbofvbpatients
Phasevb3:vbLargervbsize,vbmustvbbevbasvbgoodvbasvborvbbettervbthanvbothers.
DrugvbDiscoveryvb-vbanswer--1.vbtargetvbidentificationvbandvbvalidation
2.vbhitvbidentificationvbandvbscreening
3.vbleadvbidentificationvbandvboptimization
4.vbcandidatevbpreclinicalvbandvbclinicalvbdrugvbdevelopment
Gradedvbdosevbresponsevb-vbanswer--
Drugvbresponsevbisvbcontinuousvbandvbgradual.vbThevbconcentrationvbincreases,vbthevbmagnitudevbofvbthevbeffectvbincre
es
TypesvbofvbDrugvbResponsevb-vbanswer---Gradedvb-
vbresponsesvbthatvbcanvbbevbmeasuredvb(BP,vbHR,vbDiuresis,vbBronchodilation,vbPainvbscale,vbComavbScore)
-QuantalvbEffects-vbmayvborvbmayvbnotvboccurvb(convulsions,vbpregnancy,vbrash,vbsleep,vbdeath)
Receptorsvbexistvbinvbwhatvbtwovbstates?vb-vbanswer--
1)vbInactivevb(R)2)vbActivevb(R*)Equilibriumvbfavorsvbinactivevbstatevb(R)
Fourvbmajorvbreceptorvbfamilies-
vbreceptorsvbarevbproteinsvbthatvbtransducevbextracellularvbsignalsvbtovbintracellularvbresponsesvb-vbanswer--1)vbLigand-
gatedvbionvbchannel
2)vbGvbprotein-coupledvbreceptors
3)vbEnzyme-linkedvbreceptors
4)vbIntracellularvbreceptorsvbregulatingvbgenevbexpression
1vb/vb8
, NR 565 - advanced pharmacology FINAL -
vb vb vb vb vb vb
Chamberlain Practice EXAM
vb vb vb
IonvbChannelvbReceptorsvb/vbGatedvbionvbchannelsvb-vbanswer---
vbRapidvbonsetvbandvbshortvbdurationvb(musclevbcontraction)
Transmitvbsignalsvbacrossvbthevbcellvbmembranevbbyvbincreasingvbthevbflowvbofvbionsvbandvbalteringvbthevbelectricalvbpote
alvborvbseparationvbofvbchargedvbionsvbacrossvbthevbmembrane
GatedvbIonvbChannelvbReceptors:
Openvborvbclosevbchannelsvbtovballowvbcertainvbionsvbtovbpassvbthroughvbcellvbmembrane.
vbAvbgatedvbchannelvbforvbavbspecificvbion.vbThevbopeningvborvbclosingvbofvbsuchvbchannelsvbmayvbaltervbavbcell'svbmembra
evbpotential.
Gvbprotein-coupledvbreceptorsvb(Guaninevbnucleotidevbregulatoryvbproteins)vb-vbanswer---Foundvbinvbcellvbmembrane
-Madevbupvbofvb3vbmajorvbsubunitsvb(alphavbα,vbbetavbβ,vbgammavbγ)vbandvbcanvbhavevbisotopesvb(variations)
Generatevbintracellularvbsecondvbmessengersvbthatvbtriggervbavbchangevbinvbcellvbfunction
Transmembranevbreceptorsvb-vbanswer---Extracellularvbhormone-bindingvbdomain
-Intracellularvbenzymevbdomain
-combinationsvbcausevb2vbreceptorsvbtovbbindvbtovbeachvbother.
(Insulin,vbandvbplatelet)
Havevbitsvbligand-bindingvbdomainvbonvbthevbcell'svbsurface.Keyvbfeature:vbdown-
regulationvbofvbreceptorsvb(decreasevbinvbnumbervbofvbreceptorsvbavailablevbforvbresponse)
Intracellularvbreceptorsvb-vbanswer--
lipidvbsolublevbdrugsvbattachvbtovbintracellularvbreceptorsvbandvbinitiatevbdirectvbchangesvbinvbthevbcellvbbyvbaffectingvbDNA
ranscription
Intracellularvbreceptorsvbarevbdifferentvbreceptorsvbinvbwhatvbway?vb-vbanswer--
Entirelyvbintracellularvbsovbligandvbmustvbdiffusevbintovbcellvbtovbinteractvbwithvbreceptor.vbMustvbbevblipidvbsolublevbtovbbev
ansportedvbattachedvbtovbplasmavbproteinvbsuchvbasvbalbumin.vbDNA,vbRNAvbtranscriptionvbintovbproteins.vb(i.e.vbAntine
asticvbagents)vb
Eg:vbCorticosteroids,vbmineralocorticoids,vbsexvbsteroids,vbvitaminvbD,vbandvbthyroidvbhormones...producingvbmorevbsu
ainedvbresponses.
Enzymesvb-vbanswer--Biologicalvbmoleculesvbthatvbencouragevbspecificvbchemicalvbreactions.
SixvbwaysvbgenevbexpressionvbcanvbbevbregulatedvbbetweenvbDNAvb+vbproteinvb-vbanswer--1.vbTranscriptionvb-->vbwhen/
howvboften
2.vbControllingvbmRNAvbsplicingvborvbprocessing
3.vbSelectingvbwhichvbmRNAvbarevbexportedvbtovbcytosol
4.vbSelectivelyvbdegradingvbsomevbmRNAs
5.vbSelectingvbwhichvbmRNAsvbarevbtranslatedvbbyvbthevbribosomes
6.vbSelectivelyvbactivatingvborvbinactivatingvbproteinsvboncevbmade.
Drugvbactionvbatvbreceptorsvb-vbanswer---agonists
-antagonists
-partialvbagonists
agonistsvb-vbanswer--
Agonists,vborvbfullvbagonists,vbarevbdrugsvbthatvbproducevbreceptorvbstimulationvbandvbavbconformationalvbchangevbevery
mevbtheyvbbind.vbFullvbagonistsvbdovbnotvbneedvballvbofvbthevbavailablevbreceptorsvbtovbproducevbavbmaximumvbresponse.
-Lessvbthanvb10%vbneededvbforvbmaximumvbresponse.
2vb/vb8
vb vb vb vb vb vb
Chamberlain Practice EXAM
vb vb vb
NR565 ADVANCED PHARMACOLOGY
FUNDAMENTALS WEEK 1
DrugvbDevelopmentvbProcessvb-vbanswer--Pre-clincialvbStagevb(Animalvbtesting)vbofvbR&D
INDClinicalvb(Safetyvbandvbeffectiveness)
R&DFinalvbProductvbDevelopment
Post-marketing
Variationsvbinvbdrugvbdevelopmentvbprocess
PreclinicalvbstagevbofvbR&Dvb-vbanswer--1.vbDrugvbdiscovery
2.vbBiologicalvbcharacterizationvb(drugvbaction/vbfate)
3.vbPre-formulationvbstudies
4.vbInitialvbformulations
5.vbManufacturingvbandvbcontrols
6.vbPackagevblabelvbandvbdesign
ClinicalvbStagevb-vbanswer--Phasevb1:vbBiologicalvbeffects,vbsafevbdosage
Phasevb2:vbNewvbdrugvbtreatsvbsmallvbamountvbofvbpatients
Phasevb3:vbLargervbsize,vbmustvbbevbasvbgoodvbasvborvbbettervbthanvbothers.
DrugvbDiscoveryvb-vbanswer--1.vbtargetvbidentificationvbandvbvalidation
2.vbhitvbidentificationvbandvbscreening
3.vbleadvbidentificationvbandvboptimization
4.vbcandidatevbpreclinicalvbandvbclinicalvbdrugvbdevelopment
Gradedvbdosevbresponsevb-vbanswer--
Drugvbresponsevbisvbcontinuousvbandvbgradual.vbThevbconcentrationvbincreases,vbthevbmagnitudevbofvbthevbeffectvbincre
es
TypesvbofvbDrugvbResponsevb-vbanswer---Gradedvb-
vbresponsesvbthatvbcanvbbevbmeasuredvb(BP,vbHR,vbDiuresis,vbBronchodilation,vbPainvbscale,vbComavbScore)
-QuantalvbEffects-vbmayvborvbmayvbnotvboccurvb(convulsions,vbpregnancy,vbrash,vbsleep,vbdeath)
Receptorsvbexistvbinvbwhatvbtwovbstates?vb-vbanswer--
1)vbInactivevb(R)2)vbActivevb(R*)Equilibriumvbfavorsvbinactivevbstatevb(R)
Fourvbmajorvbreceptorvbfamilies-
vbreceptorsvbarevbproteinsvbthatvbtransducevbextracellularvbsignalsvbtovbintracellularvbresponsesvb-vbanswer--1)vbLigand-
gatedvbionvbchannel
2)vbGvbprotein-coupledvbreceptors
3)vbEnzyme-linkedvbreceptors
4)vbIntracellularvbreceptorsvbregulatingvbgenevbexpression
1vb/vb8
, NR 565 - advanced pharmacology FINAL -
vb vb vb vb vb vb
Chamberlain Practice EXAM
vb vb vb
IonvbChannelvbReceptorsvb/vbGatedvbionvbchannelsvb-vbanswer---
vbRapidvbonsetvbandvbshortvbdurationvb(musclevbcontraction)
Transmitvbsignalsvbacrossvbthevbcellvbmembranevbbyvbincreasingvbthevbflowvbofvbionsvbandvbalteringvbthevbelectricalvbpote
alvborvbseparationvbofvbchargedvbionsvbacrossvbthevbmembrane
GatedvbIonvbChannelvbReceptors:
Openvborvbclosevbchannelsvbtovballowvbcertainvbionsvbtovbpassvbthroughvbcellvbmembrane.
vbAvbgatedvbchannelvbforvbavbspecificvbion.vbThevbopeningvborvbclosingvbofvbsuchvbchannelsvbmayvbaltervbavbcell'svbmembra
evbpotential.
Gvbprotein-coupledvbreceptorsvb(Guaninevbnucleotidevbregulatoryvbproteins)vb-vbanswer---Foundvbinvbcellvbmembrane
-Madevbupvbofvb3vbmajorvbsubunitsvb(alphavbα,vbbetavbβ,vbgammavbγ)vbandvbcanvbhavevbisotopesvb(variations)
Generatevbintracellularvbsecondvbmessengersvbthatvbtriggervbavbchangevbinvbcellvbfunction
Transmembranevbreceptorsvb-vbanswer---Extracellularvbhormone-bindingvbdomain
-Intracellularvbenzymevbdomain
-combinationsvbcausevb2vbreceptorsvbtovbbindvbtovbeachvbother.
(Insulin,vbandvbplatelet)
Havevbitsvbligand-bindingvbdomainvbonvbthevbcell'svbsurface.Keyvbfeature:vbdown-
regulationvbofvbreceptorsvb(decreasevbinvbnumbervbofvbreceptorsvbavailablevbforvbresponse)
Intracellularvbreceptorsvb-vbanswer--
lipidvbsolublevbdrugsvbattachvbtovbintracellularvbreceptorsvbandvbinitiatevbdirectvbchangesvbinvbthevbcellvbbyvbaffectingvbDNA
ranscription
Intracellularvbreceptorsvbarevbdifferentvbreceptorsvbinvbwhatvbway?vb-vbanswer--
Entirelyvbintracellularvbsovbligandvbmustvbdiffusevbintovbcellvbtovbinteractvbwithvbreceptor.vbMustvbbevblipidvbsolublevbtovbbev
ansportedvbattachedvbtovbplasmavbproteinvbsuchvbasvbalbumin.vbDNA,vbRNAvbtranscriptionvbintovbproteins.vb(i.e.vbAntine
asticvbagents)vb
Eg:vbCorticosteroids,vbmineralocorticoids,vbsexvbsteroids,vbvitaminvbD,vbandvbthyroidvbhormones...producingvbmorevbsu
ainedvbresponses.
Enzymesvb-vbanswer--Biologicalvbmoleculesvbthatvbencouragevbspecificvbchemicalvbreactions.
SixvbwaysvbgenevbexpressionvbcanvbbevbregulatedvbbetweenvbDNAvb+vbproteinvb-vbanswer--1.vbTranscriptionvb-->vbwhen/
howvboften
2.vbControllingvbmRNAvbsplicingvborvbprocessing
3.vbSelectingvbwhichvbmRNAvbarevbexportedvbtovbcytosol
4.vbSelectivelyvbdegradingvbsomevbmRNAs
5.vbSelectingvbwhichvbmRNAsvbarevbtranslatedvbbyvbthevbribosomes
6.vbSelectivelyvbactivatingvborvbinactivatingvbproteinsvboncevbmade.
Drugvbactionvbatvbreceptorsvb-vbanswer---agonists
-antagonists
-partialvbagonists
agonistsvb-vbanswer--
Agonists,vborvbfullvbagonists,vbarevbdrugsvbthatvbproducevbreceptorvbstimulationvbandvbavbconformationalvbchangevbevery
mevbtheyvbbind.vbFullvbagonistsvbdovbnotvbneedvballvbofvbthevbavailablevbreceptorsvbtovbproducevbavbmaximumvbresponse.
-Lessvbthanvb10%vbneededvbforvbmaximumvbresponse.
2vb/vb8
