Normalcontrol

PosturalBaroreflex

RenalresponsetoBP

DrugClass DrugExamples MOA ClinicalIndications AdverseEffects Contraindications DrugInteractions/Comorbidities

Cardioselectiveagents1selective:Atenolol,Metoprolol

block1A.R.onheart,kidneyHR(negavechronotrope)contraclity(negaveinotrope)COrenalreninsecreon

treatsHTNcthefollowingcomorbidities:Ischemicheartdisease,nondecomensatedheartfailure,dissectingthoracicaneurysm(notaseffectiveforelderlyorAA)insevereHTN,usefultopreventreflextachythatresultsfromdirectvasodilators

Vasodilatingagents:Carvedilol,Labetalol,Nebivolol

carevilolandlabetalolblockand;nebivololcoupledcNO(release)andonly

htncarvedilolandlabetalol:pheochromocytoma,HTNemergencies,andclonidinewithdrawalsyndrome

AgentscISA:Pindolol,Acebutolol,penbutolol

arepartialagonists(blockcsomeintrinsicsympathomimeticactivity):BPbyPVR

note:HRandCOlessthanotherbetablockers(greateragonsitthanantagonistactivityat2)preferredforpaentscbradyarrhythmiasorPVD

EsmololBeta1selectiveblockerthatisrapidlymetabolizedviahydrolysisbyRBC

shorthalflifemakesitpreferredforintraoperativeandpostoperativeHTN,andHTNemergenicesassociatedctachycardia

1and2blockers(phenoxybenzamine,phentolamine)

relaxvascularsmoothmusclesbypreventingNEfrominteractingc1receptorsandblocks2onpresynapticsympatheticautrecptors

Phenoxybenazomine/phentolamine:dxandtxpheochromocytomaPhentolamine:addpropranololtotxclonidinewithdrawalsyndrome

reflextachycardia(blocks,1stdosehypotension,posturalhypotension,urinaryincontinence

note:ex:doxazosinhaslong1/2life(1012hrs)

1selectiveblocker(prazosin,doxazosin,terazosin)

relaxvascularsmoothmusclesbypreventingNEfrominteractingc1receptors

Prazosin:uselimitedbysevereposturalhypotension,usefulonlyasaddontotreatresistanthypertensionDoxazosin:sxofbladderoulowtractobstructionandBPH

1stdosehypotension,posturalhypotension,urinaryincontinence

Methyldopa

takenupintoadrenergicnerveconvertedtomethylNEinCNSwhere2receptorsarestimulatedtosympathecoulowtoperiphery

DOCduringpregnancyusefulinpatientswhocan'ttolerateotherdrugsPVR(variableinHRandCO)

note:advantageiscausesreduconinrenalvascularresistance

Clonidine(partialagonist)

BPbyCO2*HRandrelaxaonofcapacitancevessels,TPR;alsorenalvascularresistanceandmaintenanceofrenalbloodflowbindstoimidazolinereceptorNEreleasecentrally

HRandCOmorethanmethyldopa

drymouthandsedationDONOTstopsuddenlywillcauselifethreateningHTNcrisis2*symphactivity

ptsatriskfordepression,concomitantcTCAs

causesshortBP(directsmofperipheralreceptors)prolongedhypotension(adrenoceptorsinmedulla)

IndirectlydrugmetabolismbyCOhepacbloodflow(egdrugschighhepaticextractionratio:lidocaine,morphine,sodiumpentothal,ASA,propranolol)Additiveeffectscverapamil,lidocaine,&othernegativeinotropes(ifverapamilandBblockergiventogether:canbefatal)

decompensatedheartfailureasthma

adrenergicblockers(systemic)

PharmacologyAntiHypertensives

Sympatholytics

kidneysresponsibleforlongtermBPcontrol,renalperfusionpressurecausesintrarenalredistribuonofbloodflowandreabsorponofsaltandwaterreninproduconangiotensinIIproducon;angiotensinIIcauses1)directconstrictionsofresistancevessels,2)stimulationofaldosteronesynthesisinadrenalcortex(renalNaabsorponandintravascularbloodvolume);vasopressinreleasedfromposteriorpituitaryregulateswaterreabsorptionbykidneys

NormalregulationofBP

BPmaintainedbyregofCOandPVR(atarterioles,postcapillaryvenules(capacitancevessels),andheart),kidneyregulatesintravascularfluidvolume,localreleaseofvasoactivesubstancesfromvascularendothelium(i.e.endothelin1constricts,NOdilates);baroreceptors(controlledbyautonomicsandreninsystem)coordinateoverallfunctiontomaintainnmlBP;cHTNthesystemis"set"forahigherpressure

baroreceptorsresponsibleforrapidadjustmentsinBP,sympatheticneuronsinmedullaaretonicallyactive,carotidbaroreceptorsarestimulatedbystretchofthevesselwall2*to BP,baroreceptorsmulaoninhibitscentralsympatheticdischarge(oppositeisalsotrue);whensomeonestands,baroreceptorssensethereductioninBPfrompoolingofbloodintheveins>sympatheticdischargeisdisinhibited sympatheticoutflowtoPVR(constrictsarterioles)andCO(directsmofheartandconstriconofcapacitancevessels)

Blockers

TGsandHDLbronchospasm:useccautioninCOPDfatigue,coldextremities,canworsenRaynaud's,vividdreams,impotence,hyperglycemiapropranolol(nonselective):willmaskhypoglycemiainDM

Centrallyacting2adrenergicagonist

MCsedation(atonsetoftx)depression,hepatitis,immunehemolyticanemia(positiveCoomb'stest),fever,nightmares,lactation;longtermtx:persistentmentallassitudeandimpairedconcentration

ACEinhibitors(angiotensin

convertingenzyme)

longactingdrugs:trandolapril,ramipril=qddosing"pril"

competitiveinhibitorofACEinhibitsynthesisofangiotensinIIandaccumulationofbradykinincirculanglevelsofaldosterone

preferredfor:whiteyoungorAsianhypertensivepatient,plasmareninmortalityin:acuteMI,CHF,riskofCVdiseaserenalprotectiveinchronickidneydiseaseandchypertensiveptscdiabeticneuropathy

1stdosehypotension,drycough&angioedema(bradykinin),dysgeusia,anemia(EPO),serumK+,hypoglycemia,fxnalrenalfailurechxofrenalstenosis

pregnancy(devdefectsifgivenin2nd,3rd)b/lrenalarterystenosis,renalfailure,angioedema

beneficialdruginteractions:K+wastingdiuretic(loopdiuretic,thiazidediuretics)badinteractions:K+supplements,allK+sparingdiuretics,NSAIDs,ARBs

AngiotensinReceptorBlockers(ARBs)

allendin"sartan"losartan,candesartan,eprosartan,irbesartan,olmesartan,telmisartan,valsartan

inhibitsangiotensin2receptors(AT1,AT2)aldosteronelevelsplasmavolumeandTPRnoeffectonbradykinin

riskofcough/angioedemaofACEsameasabove,effectiveafteracuteMI,heartfailure

1stdosehypotension(lisinopril)givenighttimedoseserumK+(M)

Hydralazineunclear,directvasodilatoractiononvascularsmoothmuscle;usuallycombinedwithotherdrugs

severehypertensionduringpregnancy(nifedipineispreferredbysome)

HA,flushing,tachycardia,fluidretentionlongtermtherapycdosesmycauseSLElikesxinsomepts

Fenoldopam

AlcoholCigaretteSmoking

WeightRegularExerciseDietarychoicesRelaxation

Diuretics(thiazides) betablockers

Thiazides

ACEinhibitors ARBs CCBs(nondihydropyridine) thiazide ACEinhibitorsdiuretics ACEI CCBs

aerobicexerciseuseful,HRandconcentraoncirculangcatecholamine's,HDL,ANPreleasecaloricrestrictionandfruitsandvegetablesuseful

LifestyleChronicalcoholintakecorrelatescHTN,consumptionresistancetoanhypertensivemedssecondarytobioavailabilityofanhypertensivedrugstransientinBP2*toeectofniconeonautonomicganglia,riskfordevelopingsustainedhypertension,atherogenic

CalciumChannelBlockers(CCB)

briefhere,morelater

effectiveinelderlypts,AA,CaribbeanriskofMIandstrokeinptscHTNatrialflutter(combinedcquinine)angina

generallywelltoleratedshortacting(nifedipinecapsules):flushing,HA,anginapedaledemaverapamil:exacerbateheartfailure,constipation

IVverapamil:cancausecirculatorycollapsecconcurrentblockers

VisceralobesitycorrelatescHTN,if10%idealweightthen10kgweightloss520mmHgdropinsystolicBP,waisttohipraoimportantindex

1stlineforuncomplicatedHTN

Diabetes

Elderly

BestUse(inorderLefttoRight)

Reninangiotensinaldosteronesystemantagonists

PeripheralvasodilatorsworkbestincombowithdrugthatwillopposecompensatoryCVresponsecautionwithischemicheartdisease2*toreflextachycardia

Oralvasodilators

parenteralvasodilators

arteriolesonly,notveins

Generalorderofuse

Peripheralneuropathynoalphaorbetablockers

stresshormones(cortisol,NE,epi)arereleaseandcouldBP,relaxaonstateusefultoBP

diuretics CCBbetablockers ACEIbetablockers orCCB(notboth!)CCBMethyldopa NifedipineorHydralazine ifpreeclampsia:labetalolalphablockers ACEI(ARBs) CCBs IndapamideACEI(unlessb/lstenosis)betablockers nondihydropyridineCCBsalpha1selectiveblockersbetablockers ACEIACEI(ARB) diuretics aldosterone betablockersGout:thiazides Asthma:betablockers

DrugClass DrugExamples MOA ClinicalIndications AdverseEffects Contraindications DrugInteractions

GeneraleecveinAAandelderly(saltsensitive)

LoopDiuretics(Highceiling)

Furosemide(lasix),Ethacynicacid,Toresmide,Bumetanide

inhibitsNa/K/2Cltransporter(TALthickascendinglimb)reabsorponofdivalentcaons(Mg,Ca)SignificantKwasting

Acutepulmonaryedema,edemaofnephroticsyndrome,HTN(2*tothiazidesinsufficiency),CHF,severehypercalcemia(combinecisotonicsaline),urineflowindrugoverdose

hypokalemia,hypomagnesaemia(riskforarrhythmias);hypochloremicmetabolicalkalosis(H+,K+depletion)hyperuricemiagoutaacksototoxicity(highdosesalterendolymph)

postmenopausalosteopenicwomen

note:generallytoopotentandshortlivedforuseasantihypertensiveagents;butusefulinptscrenalinsufficiencywhodonotrespondtootherdiuretics

ThiazidesHydrochlorothiazide(HCTZ),chlorothiazide,chlorthlidone,indapmide

inhibitsNaClsymportintheDCTonlythiazideshavesignificanteffectonthissymport

bestinitialtherapyforuncomplicatedHTN,heartfailure,hepaticcirrhosis,nephroticsyndrome,chronicliverfailure,acuteglomerulonephritis,nephrogenicdiabetesinsipidus,calciumnephrolithiasisandosteoporosis

hypokalemicmetabolicalkalosisandhyperuricemia,hyperlipidemia(totalcholesterolandLDL),impairedcarbohydratetolerance,quinidineinducestorsadesdepointes

mostcommonlyuseddiureticinHTN

amiloridetriameterene

lumennegavetransepithelialvoltageexcreonrateofK+,H+,Ca,MgantikaliureticactiontooffsettheexcretionofK+andH+byK+wastingdiureticslowimpactonNa+excretion

UsedincombinationwithotherdiureticstocurtailK+lossduringtreatmentofedemaassociatedwithCHFand/orhypertensionAmilorideblocksLi+transportinthecollectingtubulesandisthereforeusedtotreatlithiuminducednephrogenicdiabetes

commonforboth:N/Vamiloride:diarrhea,HAtriameterne:legcrampsanddizzinessriskoflifethreatening:contraindicatedinptscrenalfailureortakingACEI,otherK+sparingdiuretic,K+supplement,pentamidine,trimethoprimTriamtereneisaweakfolicacidantagonistandcanexacerbatemegaloblastosis

AmilorideisexcretedintactintheurineTriamtereneundergoesextensivehepatictransformationcautioninbothhepaticandrenalinsufficiency

Aldosteroneantagonists:Eplerenone(Inspra)andSpironolactone(Aldactone)

Inhibitsmineralocorticoidreceptor(MR)inepithelialcellsoftheDCTandCTConservepotassiumattheexpenseofsodium

Spironolactone:diureticofchoiceinptschepaticcirrhosis,PrimaryAldosteronism,Refractoryedemaassociatedwithsecondaryhyperaldosteronism

Hyperkalemia,Impotence,decreaselibido,hirsutism,gynecomastia,deepeningofthevoiceandmenstrualirregularities;diarrhea,gastritis,gastricbleedingandpepticulcers;SpironolactonemaycauseskinrashanditsCNSeffectsmayincludedrowsiness,ataxia,lethargy,confusionandHA

patientswithgastriculcers

Osmoticdiuretic Mannitolwaterexcreoninpreferencetosodiumexcretion;majoreffectinPCTanddescendinglimbofHenle

intracranialhypertension

Diuretics(Naexcreon,rateofurineflow)

youngwhiteexertionalangina

Pregnancy

priorMI

AfricanAmerican

heartfailure

prinzmetal'svariant

dyslipidemiachronickidney

BPHMigrainecephalgia

Avoids Depression:Centralalphaagonists,betablockers

circulatoryvolume,CO,andmeanarterialpressure;mosteecveinpaentscmildtomoderateHTNwhohavenormalrenalfxn,1015mmHg

K+sparingdiuretics