CLINICAL Pharm Antihypertensives

7/23/2019 CLINICAL Pharm Antihypertensives

1/33

Clinical Pharmacology ofClinical Pharmacology of

Drugs for ControllingDrugs for Controlling

Vascular Tone.Vascular Tone.

ANTIHYPERTENSIVEANTIHYPERTENSIVEDRUGSDRUGS


2/33

ANTIHYPERTENSIVE DRUGSANTIHYPERTENSIVE DRUGS

I. DIURETICSI. DIURETICS

Bumetanide, furosemide, hydrochlorthiaide, s!ironolactone, triamtereneBumetanide, furosemide, hydrochlorthiaide, s!ironolactone, triamtereneII.II. "B#$C%ERS"B#$C%ERS

&tenolol, la'etalol, meto!rolol, !ro!ranolol, timolol&tenolol, la'etalol, meto!rolol, !ro!ranolol, timolol

III. &CE I()IBIT$RSIII. &CE I()IBIT$RS

Ca!to!ril, 'enae!ril, enala!ril, fosino!ril, lisino!ril, moe*i!ril, +uina!ril,Ca!to!ril, 'enae!ril, enala!ril, fosino!ril, lisino!ril, moe*i!ril, +uina!ril,

rami!rilrami!ril

IV. &(I$TE(SI( II &(T&$(ISTIV. &(I$TE(SI( II &(T&$(IST

#osartan#osartan

V. Ca--C)&((E# B#$C%ERSV. Ca--C)&((E# B#$C%ERS

&mlodi!ine, diltiaem, felodi!ine, isradi!ine, nicardi!ine, nifedi!ine,&mlodi!ine, diltiaem, felodi!ine, isradi!ine, nicardi!ine, nifedi!ine,

nisoldi!ine, era!amilnisoldi!ine, era!amil

VI.VI. "B#$C%ERS"B#$C%ERS

Do*aosin, !raosin, teraosinDo*aosin, !raosin, teraosin

VII. $T)ERVII. $T)ERClonidine, diao*ide, hydralaine,Clonidine, diao*ide, hydralaine, "methyldo!a, mino*idil, sodium"methyldo!a, mino*idil, sodium

nitro!russidenitro!russide


3/33

TREATMENT STRATEGIESTREATMENT STRATEGIES

Mild hypertension can often be controlled with aMild hypertension can often be controlled with asingle drug. More severe hypertension aysingle drug. More severe hypertension ayre!uire treatent with several drugs that arere!uire treatent with several drugs that areselected to inii"e adverse effects of theselected to inii"e adverse effects of thecobined regien. Treatent is initiated withcobined regien. Treatent is initiated with

any of four drugs depending on the individualany of four drugs depending on the individualpatient# a diuretic$ apatient# a diuretic$ a %bloc&er$ an A'E inhibitor$%bloc&er$ an A'E inhibitor$or a calciu channel bloc&er. If blood pressureor a calciu channel bloc&er. If blood pressureis inade!uately controlled$ a second drug isis inade!uately controlled$ a second drug isadded. Aadded. A %bloc&er is usually added if the initial%bloc&er is usually added if the initial

drug was a diuretic$ or a diuretic is added if thedrug was a diuretic$ or a diuretic is added if thefirst drug was afirst drug was a %bloc&er. A vasodilator can be%bloc&er. A vasodilator can beadded as a third step for those patients who stilladded as a third step for those patients who stillfail to respond.fail to respond.


4/33


5/33

Treatment of arterial hy!ertensionTreatment of arterial hy!ertensionDrugs of first rowDru

gs of first row

--diureticsdiuretics((furosemid, dichlothiazide, spironolactonfurosemid, dichlothiazide, spironolacton))

--inhibitors of ACEinhibitors of ACE((captopril, enalapril, ramiprilcaptopril, enalapril, ramipril))

--antagonists of angiotesine II receptorsantagonists of angiotesine II receptors(( !!) !!) (losartan)(losartan)

-"--"-adrenobloc#ersadrenobloc#ers((anaprilinanaprilin,, atenololatenolol,, th$mololth$molol))

-%-, "--%-, "-adrenobloc#ersadrenobloc#ers((labetolol, car&edilollabetolol, car&edilol))

--Ca ions antagonistsCa ions antagonists((niphedipine, amlodipine, &erapamilniphedipine, amlodipine, &erapamil))

Drugs of second rowDru

gs of second row''-%--%-adrenobloc#ersadrenobloc#ers((prasosine, terasosineprasosine, terasosine))

--agonists ofagonists of %%adrenoreceptors of central actionadrenoreceptors of central action((clophelineclopheline,,

meth$ldopameth$ldopa))

--s$mpathol$ticss$mpathol$tics ((reserpin, octadinreserpin, octadin))--direct &asodilatorsdirect &asodilators((molsidominmolsidomin,, h$dralasinh$dralasin))

*ew drugs*ew dru

gs''

--imidasolinesimidasolines((mo+onidine, rilmenidinemo+onidine, rilmenidine))

--serotonin receptors bloc#ersserotonin receptors bloc#ers((#etanserin#etanserin))

--monaterilmonateril((calcium antagonistcalcium antagonist, %, %--adrenobloc#eradrenobloc#er))


6/33

Mechanism of action of thiaside diuretics

in case of arterial hypertension

D$chlothiaside

(h$pothiaside)

+odolin

(chlortalidon, h$groton)

hiaside

diuretics

.olding sodium and

water

/olume of circulating

blood

Cardiac output

0eripheral &ascular

resistance

Decreasing of arterial

pressure


7/33

(ydrochlorothia"ide)*osartan(ydrochlorothia"ide)*osartan


8/33

Thia"ide diuretics.Thia"ide diuretics.Adverse effectsAdverse effects##

Thia"ide diuretics induce hypo&aleia andThia"ide diuretics induce hypo&aleia andhyperuriceia in +, - of patients$ and hyperglyceia inhyperuriceia in +, - of patients$ and hyperglyceia in, - of patients. Seru potassiu levels should be, - of patients. Seru potassiu levels should beonitored closely on patients who are predisposed toonitored closely on patients who are predisposed to

cardiac arrhythias /with left ventricular hypertrophy$cardiac arrhythias /with left ventricular hypertrophy$ischeic heart disease$ or chronic congestive heartischeic heart disease$ or chronic congestive heartfailure0 /to prevent developent of fatigue$ craps$ andfailure0 /to prevent developent of fatigue$ craps$ andarrhythias0 and who are concurrently being treated witharrhythias0 and who are concurrently being treated withboth thia"ide diuretics and digitalis glycosides. 1iureticsboth thia"ide diuretics and digitalis glycosides. 1iuretics

should be avoided in the treatent of hypertensiveshould be avoided in the treatent of hypertensivediabetics or patients with hyperlipideiadiabetics or patients with hyperlipideia


9/33

*oop diuretics*oop diuretics

TheThe loop diureticsloop diureticsact proptly$ even inact proptly$ even in

patients who have poor renal function orpatients who have poor renal function or

who have not responded to thia"ides orwho have not responded to thia"ides or

other diuretics.other diuretics.


10/33

Mechanism of action of beta-adrenoblockers

(anaprilin, atenolol, methoprolol etc.)in case of arterial hypertension

"-

drenobloc#ers

acti&ation of

"1-adrenoreceptors

of heart

Cardiac

output

Angiotensine 22 enin

Aldosterone

.olding sodium

and water

0eripheral resist-

ance of &essels

/olume of

blood

Decreasing of

blood pressure


11/33

%bloc&ers. Therapeutic uses%bloc&ers. Therapeutic uses

TheThe %bloc&ers are ore effective for%bloc&ers are ore effective fortreating hypertension in white youngtreating hypertension in white youngpatients. They are useful in treatingpatients. They are useful in treating

conditions that ay coe2ist withconditions that ay coe2ist withhypertension$ such ashypertension$ such as

supraventricular tachyarrhythia$supraventricular tachyarrhythia$

previous yocardial infarction$previous yocardial infarction$angina pectoris$angina pectoris$

glaucoa$ andglaucoa$ and

igraine headache.igraine headache.


12/33

//"adreno'loc0ers"adreno'loc0ers

Used for mostly mild to moderate cases of &)Used for mostly mild to moderate cases of &)1fre+uently in com'inations 2ith other drugs31fre+uently in com'inations 2ith other drugs3

Sta'le hy!otensie res!onse deelo!s oerSta'le hy!otensie res!onse deelo!s oer4"5 2ee0s4"5 2ee0s

Titration the effectie dose.Titration the effectie dose. TheThe %bloc&ers ay%bloc&ers ayta&e several wee&s to develop their full effectsta&e several wee&s to develop their full effects

&ntihy!ertensie action is maintained oer&ntihy!ertensie action is maintained oer67 hr after single daily dose67 hr after single daily dose

ContraindicationsContraindications8 'ronchial asthma,8 'ronchial asthma,!eri!heral ascular disease, dia'etes!eri!heral ascular disease, dia'etes


13/33

&CE"I()IBIT$RS&CE"I()IBIT$RS

The angiotensin%converting en"ye /A'E0The angiotensin%converting en"ye /A'E0

inhibitors /inhibitors /captopril, enalapril, lisinopril,captopril, enalapril, lisinopril,

perindopril)perindopril) are recoended when theare recoended when the

preferred first%line agents /diuretics orpreferred first%line agents /diuretics or %%

bloc&ers0 are contraindicated orbloc&ers0 are contraindicated or

ineffective.ineffective.


14/33

9EC)&(IS9 $: &CTI$( $:I&CE

Decrease of

arterial

pressure

s$mpathetic

tone

peripheral

&essels tone

retention of

*a3 and .

bradicinine

A*4IE*5I*4E*

A*4IE*5I*

(inacti&e)

IACE

Decrease

angiotensine II

production

Decrease

aldosterone

production

-

ACE

enin (#idne$s)


15/33


16/33

Therapeutic usesTherapeutic uses

*i&e*i&e %bloc&ers$ A'E inhibitors are ost%bloc&ers$ A'E inhibitors are osteffectiveeffective in hypertensive patientsin hypertensive patientswho arewho are

white and youngwhite and young..

(owever$ when used in cobination with a(owever$ when used in cobination with adiuretic$ the effectiveness of A'E inhibitors isdiuretic$ the effectiveness of A'E inhibitors issiilar in white and blac& hypertensive patients.siilar in white and blac& hypertensive patients.

A'E inhibitors are effectiveA'E inhibitors are effective in the managementin the managementof patients with chronic congestive heartof patients with chronic congestive heart

failurefailure..A'E inhibitors are now a standard in the care ofA'E inhibitors are now a standard in the care ofa patient followinga patient following a myocardial infarctiona myocardial infarction..Therapy is started 34 hours after the end of theTherapy is started 34 hours after the end of the

infarction.infarction.


17/33

A'E inhibitorsA'E inhibitors adverse effectsadverse effects

'oon side effects include'oon side effects includedry cough$ rashes$ fever$ altered taste$dry cough$ rashes$ fever$ altered taste$hypotension$ and hyper&aleia.hypotension$ and hyper&aleia.

5otassiu levels ust be onitored$ and5otassiu levels ust be onitored$ and

potassiu suppleents or spironolactone arepotassiu suppleents or spironolactone arecontraindicated.contraindicated.

6ecause of the ris& of angioedea and first6ecause of the ris& of angioedea and firstdose syncope$ A'E inhibitors are firstdose syncope$ A'E inhibitors are firstadinistered in the physician7s office with closeadinistered in the physician7s office with close

observation.observation.Reversible renal failure can occur in patientsReversible renal failure can occur in patientswith severe renal artery stenosis.with severe renal artery stenosis.

A'E inhibitors are fetoto2ic andA'E inhibitors are fetoto2ic and should not beshould not be

used in pregnant woen.used in pregnant woen.


18/33

&(I$TE(SI( II &(T&$(ISTS&(I$TE(SI( II &(T&$(ISTS#osartan 1Coaar;3, Valsartan 1Dioan;3,#osartan 1Coaar;3, Valsartan 1Dioan;3,

Ir'esartan 1&a!ro;3, CandesartanIr'esartan 1&a!ro;3, Candesartan

1&tacand;3.1&tacand;3.The nanopeptideThe nanopeptide losartanlosartan$ a highly$ a highly

selective angiotensin II receptor bloc&er$selective angiotensin II receptor bloc&er$has recently been approved forhas recently been approved for

antihypertensive therapy. Itsantihypertensive therapy. Its

pharacologic effects are siilar to A'Epharacologic effects are siilar to A'E

inhibitors in that it produces vasodilationinhibitors in that it produces vasodilation

and bloc&s aldosterone secretion. Itsand bloc&s aldosterone secretion. Its

adverse effects is iproved over the A'Eadverse effects is iproved over the A'E

inhibitors$ although it isinhibitors$ although it is fetoto2icfetoto2ic..


19/33

&(I$TE(SI( II &(T&$(ISTS&(I$TE(SI( II &(T&$(ISTS


20/33

CCIU9 C)&((E# B#$C%ERSCCIU9 C)&((E# B#$C%ERS

8 'alciu channel bloc&ers are recoended when'alciu channel bloc&ers are recoended whenthe preferred first%line agents are contraindicated orthe preferred first%line agents are contraindicated orineffective.ineffective.

8 'alciu channel antagonists bloc& the inward'alciu channel antagonists bloc& the inward

oveent of calciu by binding to *%tipe calciuoveent of calciu by binding to *%tipe calciuchannels in the heart and in the sooth%uscle of thechannels in the heart and in the sooth%uscle of thecoronary and peripheral vasculature. This causescoronary and peripheral vasculature. This causesvascular sooth uscle to rela2$ dilating ainlyvascular sooth uscle to rela2$ dilating ainlyarterioles.arterioles.

8 'alciu channel bloc&ers have an intrinsic natriuretic'alciu channel bloc&ers have an intrinsic natriureticeffecteffect9 therefore$ they do not usually re!uire the9 therefore$ they do not usually re!uire theaddition of a diuretic.addition of a diuretic.


21/33

ArterialArterial

h$pertensionh$pertension

VerapamilVerapamil DilthiasemDilthiasem NiphedipinNiphedipin FelodipinFelodipin mlodipinmlodipin

IschemicIschemicheart diseaseheart disease

DilthiasemDilthiasem NiphedipinNiphedipin mlodipinmlodipinVerapamilVerapamil

5upra&entricule5upra&entricule

tachicardiatachicardia

VerapamilVerapamil DilthiasemDilthiasem

0ossibilit$ to0ossibilit$ tocombine withcombine withbeta-bloc#ersbeta-bloc#ers

DilthiasemDilthiasem

!"#$%&'!"#$%&'

NiphedipinNiphedipin mlodipinmlodipin

recommended drug to use carefull$

diseases DRUGS

FelodipinFelodipin

Calcium channels bloc#ersCalcium channels bloc#ers

administrationadministration


22/33

"&DRE(ERIC B#$C%I( &E(TS"&DRE(ERIC B#$C%I( &E(TS

Prazosin,Prazosin,doxazosindoxazosin andandterazosinterazosinproduce aproduce a

copetitive bloc& ofcopetitive bloc& of adrenoreceptors. They decrease adrenoreceptors. They decreaseperipheral vascular resistance and lower arterial bloodperipheral vascular resistance and lower arterial blood

pressure by causing the rela2ation of both arterial andpressure by causing the rela2ation of both arterial and

venous sooth uscle. These drugs cause only inialvenous sooth uscle. These drugs cause only inial

changes in cardiac output$ renal blood flow$ andchanges in cardiac output$ renal blood flow$ and

gloerular filtration rate. 5ostural hypotension aygloerular filtration rate. 5ostural hypotension ay

occur in soe individuals. 5ra"osin is used to treatoccur in soe individuals. 5ra"osin is used to treat

ild to oderate hypertension and is prescribed inild to oderate hypertension and is prescribed in

cobination with propranolol or a diuretic for additivecobination with propranolol or a diuretic for additive

effectseffects


23/33

PrasosinePrasosine//::88adrenobloc&eradrenobloc&er00


24/33

CE(TR#


25/33

CE(TR#


26/33

CE(TR#


27/33

V&S$DI#&T$RSV&S$DI#&T$RS

The direct%acting sooth uscle rela2ants$ suchThe direct%acting sooth uscle rela2ants$ such

asas hydralazinehydralazineandand minoxidilminoxidil$ have traditionally$ have traditionally

not been used as priary drugs to treatnot been used as priary drugs to treat

hypertension. They act by producing rela2ationhypertension. They act by producing rela2ationof vascular sooth uscle$ which decreasesof vascular sooth uscle$ which decreases

resistance and therefore decreases bloodresistance and therefore decreases blood

pressure. These agents produce refle2pressure. These agents produce refle2

stiulation of the heart. They ay proptstiulation of the heart. They ay proptangina pectoris$ yocardial infarction$ or cardiacangina pectoris$ yocardial infarction$ or cardiac

failure in predisposed individuals.failure in predisposed individuals.


28/33

V&S$DI#&T$RSV&S$DI#&T$RS


29/33

PRINCIPLES OF THERAPYPRINCIPLES OF THERAPY

Therapeutic RegimensTherapeutic Regimens

$nce the diagnosis of hy!ertension is esta'lished, a$nce the diagnosis of hy!ertension is esta'lished, athera!eutic regimen must 'e designed andthera!eutic regimen must 'e designed and

im!lemented. The goal of management for mostim!lemented. The goal of management for most

clients is to achiee and maintain normal 'loodclients is to achiee and maintain normal 'lood

!ressure range 1'elo2 47=>?= mm )g3. If this goal!ressure range 1'elo2 47=>?= mm )g3. If this goal

cannot 'e achieed, lo2ering 'lood !ressure to anycannot 'e achieed, lo2ering 'lood !ressure to anye*tent is still considered 'eneficial in decreasing thee*tent is still considered 'eneficial in decreasing the

incidence of coronary artery disease and stro0e.incidence of coronary artery disease and stro0e.


30/33

PRINCIPLES OF THERAPYPRINCIPLES OF THERAPY

c!nt"#$c!nt"#$

If the initial drug 1and dose3 does not !roduce the desiredIf the initial drug 1and dose3 does not !roduce the desired

'lood !ressure, o!tions for further management include'lood !ressure, o!tions for further management include

increasing the drug dose, su'stituting another drug, orincreasing the drug dose, su'stituting another drug, or

adding a second drug from a different grou!. If theadding a second drug from a different grou!. If the

res!onse is still inade+uate, a second or third drug mayres!onse is still inade+uate, a second or third drug may'e added, including a diuretic if not !reiously'e added, including a diuretic if not !reiously

!rescri'ed. @hen current management is ineffectie,!rescri'ed. @hen current management is ineffectie,

reassess the clientAs com!liance 2ith lifestylereassess the clientAs com!liance 2ith lifestyle

modifications and drug thera!y. In addition, reie2 othermodifications and drug thera!y. In addition, reie2 other

factors that may decrease the thera!eutic res!onse,suchfactors that may decrease the thera!eutic res!onse,suchas oer"the"counter a!!etite su!!ressants, dietary oras oer"the"counter a!!etite su!!ressants, dietary or

her'al su!!lements, or nasal decongestants, 2hich raiseher'al su!!lements, or nasal decongestants, 2hich raise

'lood !ressure.'lood !ressure.


31/33

HYPERTENSIVE EMERGENCYHYPERTENSIVE EMERGENCY

88 is a life%threatening situation in which theis a life%threatening situation in which thediastolic blood pressure is either over ;,diastolic blood pressure is either over ;, (g /with systolic blood pressure (g /with systolic blood pressure

greater than 3, (g0 in an otherwisegreater than 3, (g0 in an otherwisehealthy person$ or


32/33

9&(&E9E(T $: ) = *aCI*aCI

solution slowl$solution slowl$))

6-:66-:6 minmin 'radicardia'radicardia

9agnesium9agnesiumsulfassulfas

7-16-67-16-6 mlml 7 =7 = solutionsolution ((i? &? &er$i? &? &er$

slowl$ or droppl$)slowl$ or droppl$)17-617-6 minmin redness of s#inredness of s#in

#a'etololum#a'etololum 6-@66-@6 mgmg ((slowl$ 16 minslowl$ 16 min)) oror mgmg88#g#g

((droppl$droppl$)) the whole dosethe whole dose 76-:66 76-:66 mgmg

7-167-16 minmin nauseanausea,, &omiting&omiting,,,, h$potension,h$potension,

dizzenessdizzeness


33/33

RE=EREN'ESRE=EREN'ES

http#>>www.escardio.orghttp#>>www.escardio.org

http#>>www.cardiosart.orghttp#>>www.cardiosart.org

http#>>www.edscape.co>cardiologyhttp#>>www.edscape.co>cardiology
http://www.escardio.org/http://www.escardio.org/http://www.cardiosmart.org/http://www.cardiosmart.org/http://www.medscape.com/cardiologyhttp://www.medscape.com/cardiologyhttp://www.medscape.com/cardiologyhttp://www.cardiosmart.org/http://www.escardio.org/

Documents

CLINICAL Pharm Antihypertensives