principles of antihypertensive therapy-resume

8/9/2019 Principles of Antihypertensive Therapy-resume

http://slidepdf.com/reader/full/principles-of-antihypertensive-therapy-resume 1/4

Principles of Antihypertensive Therapy. Nonpharmacological therapy is an important

component of treatment of all patients with hypertension. In some stage 1 hypertensives,

blood pressure may be adequately controlled by a combination of weight loss (inoverweight individuals), restricting sodium intake, increasing aerobic eercise, and

moderating consumption of alcohol. !hese lifestyle changes, though difficult for many to

implement, may facilitate pharmacological control of blood pressure in patients whoseresponses to lifestyle changes alone are insufficient.

"rterial pressure is the product of cardiac output and peripheral vascular resistance.

#rugs lower blood pressure by actions on peripheral resistance, cardiac output, or both.

#rugs may reduce the cardiac output by inhibiting myocardial contractility or by

decreasing ventricular filling pressure. $eduction in ventricular filling pressure may beachieved by actions on the venous tone or on blood volume via renal effects. #rugs can

reduce peripheral resistance by acting on smooth muscle to cause relaation of resistance

vessels or by interfering with the activity of systems that produce constriction of

resistance vessels (e.g., the sympathetic nervous system). In patients with isolatedsystolic hypertension, comple hemodynamics in a rigid arterial system contribute to

increased blood pressure% drug effects may be mediated by changes in peripheralresistance but also via effects on large artery stiffness (&ranklin, '). "ntihypertensive

drugs can be classified according to their sites or mechanisms of action

lassification of "ntihypertensive #rugs by !heir *rimary +ite or

echanism of "ction

Diuretics (hapter '-)

1. !hiaides and related agents (hydrochlorothiaide,chlorthalidone, etc.)

2. /oop diuretics (furosemide, bumetanide, torsemide, ethacrynicacid)

3. 0 2sparing diuretics (amiloride, triamterene, spironolactone)

Sympatholytic drugs (hapters 3, 1, and 44)

1. b "drenergic antagonists (metoprolol, atenolol, etc.)

2. a "drenergic antagonists (praosin, teraosin, doaosin, phenoybenamine, phentolamine)

3. ied adrenergic antagonists (labetalol, carvedilol)

4. entrally acting agents (methyldopa, clonidine, guanaben,

guanfacine)

5. "drenergic neuron blocking agents (guanadrel, reserpine)

Ca2+ channel blockers (hapters 41, 4', 44, and 45) (verapamil,

diltiaem, nimodipine, felodipine, nicardipine, isradipine,

amlodipine)

Angiotensin converting enzyme inhibitors (hapters 4 and 41),



(captopril, enalapril, lisinopril, quinapril, ramipril, benaepril,

fosinopril, moeipril, perindopril, trandolapril)

Angiotensin IIreceptor antagonists (hapters 4 and 44) (losartan,candesartan, irbesartan, valsartan, telmisartan, eprosartan)

!asodilators (hapter 44)

1. "rterial (hydralaine, minoidil, diaoide, fenoldopam)

2. "rterial and venous (nitroprusside)

JNC7 guidelines recommend thiazide-type diuretics wheneverpossible as frst-line therapy or most patients.1 igure 1!"#displays the algorithm or the treatment o hypertension. $his recommendationis specifcally or those without compelling indicationsand is based on the best available evidence demonstrating reductionsin morbidity and mortality. %owever& diuretics are also useul agentsin hypertensive patients with compelling indications& but they are not

always the frst agent recommended based on the compelling indicationpresent. $hree landmar' placebo-controlled clinical trials have establishedthe benefts o both hypertension treatment and diuretic therapy. $he (ystolic %ypertension in the )lderly *rogram +(%)*,&1#

the (wedish $rial in ld *atients with %ypertension +($*%ypertension,&1! and the edical /esearch Council +/C, trial10

showed signifcant reductions in stro'e& myocardial inarction& andall-cause cardiovascular disease and mortality with thiazide diuretic"based therapy versus placebo. $hese trials allowed or β-bloc'ers asadd-on therapy or * control. Newer agents +i.e.& 2C) inhibitors&angiotensin 33 receptor bloc'ers 42/s5& and calcium channel bloc'ers4CCs5, were not available at the time o these studies. %owever&subse6uent clinical trials have compared these newer antihypertensiveagents +2C) inhibitors& 2/s& and CCs, to diuretics.0!08

$hese data show similar e9ects& but most trials used a prospective&open-label& blinded end point +*/), study methodology that isnot double-blinded and limited their ability to prove e6uivalence o newer drugs to diuretics.

: The ALLHAT Study0;

$he results o the 2ntihypertensive and <ipid-<owering $reatmentto *revent %eart 2ttac' $rial +2<<%2$, was the deciding evidencethat the JNC7 used to =ustiy thiazide diuretics as frst-linetherapy.0; 3t was designed to test the hypothesis that newer antihypertensiveagents +an α-bloc'er& 2C) inhibitor& and dihydropyridineCC, would be superior to thiazide diuretic therapy. $he primaryob=ective was to compare the combined end point o atal coronaryheart disease and nonatal myocardial inarction. ther hypertensionrelatedcomplications +e.g.& heart ailure and stro'e, were evaluated

as secondary end points. $his was the largest hypertension trial everconducted and included 0#&018 patients aged >> years and olderwith hypertension and one additional cardiovascular ris' actor. $hisprospective& double-blind trial randomized patients to chlorthalidone+a thiazide diuretic,& amlodipine +dihydropyridine CC,& do?azosin+α-bloc'er,& or lisinopril +2C) inhibitor, or a mean ollow-up o 0.@ years. $he do?azosin arm was terminated early when a signifcantlyhigher ris' o heart ailure compared with chlorthalidone wasobserved.0@ $he other arms were continued as scheduled& and no



signifcant di9erences in the primary end point were seen betweenchlorthalidone and either lisinopril or amlodipine. %owever& chlorthalidonehad statistically ewer secondary end points than amlodipine+heart ailure, and lisinopril +combined cardiovascular disease& heartailure& and stro'e,. $he study conclusions were that chlorthalidonewas superior in preventing one or more ma=or orms o cardiovasculardisease and was less e?pensive than amlodipine and lisinopril.

$he 2<<%2$ was double-blinded and provided the most scientifcrigor when compared with other comparative trials that wereopen label. Ahile the JNC7 recommendations ollow the 2<<%2$results& the #BB! )uropean (ociety o %ypertension)uropean (ocietyo Cardiology guidelines or the management o arterial hypertensiondo not support thiazide diuretics over other primary antihypertensiveclasses.>B $hese guidelines are ounded on the principle thattarget-organ disease and cardiovascular ris' reduction are unctionso * control that are largely independent o specifc drug+s,.>B $heseguidelines criticize the 2<<%2$& stating limitations such as lower *values +1 to 0 mm %g, with chlorthalidone versus other agents& especiallyin 2rican-2mericansD β-bloc'ers& clonidine& and reserpineas unrealistic add-on therapiesD and an overreliance on the end pointo heart ailure that was not systematically evaluated throughout thestudy.

2<<%2$ was designed as a superiority study with the hypothesisthat amlodipine& do?azosin& and lisinopril would be better thanchlorthalidone.>1 3t did not prove this hypothesis because the primaryend point was not di9erent among chlorthalidone& amlodipine& andlisinopril. $hereore& thiazides remain unsurpassed in their ability toreduce hypertension-related morbidity and mortality.2meta-analysisin #BB! supports this statement. 3n this analysis o 0# clinical trialsrepresenting 1@#&078 patients& low-dose diuretics were ound tobe the most e9ective frst-line agent or preventing cardiovascularmortality.># $he preponderance o evidence supports the JNC7 recommendationo using a thiazide-type diuretic in most patients unlessthere are contraindications or a compelling indication or anotheragent is present. (ince most patients re6uire two or more agents tocontrol *& a thiazide diuretic should be one o these agents unless

contraindicated.

6emodynamic 7ffects of /ong2!erm "dministration of "ntihypertensive "gents 67"$! $"!7 "$#I"

89!*9!

!8!"/

*7$I*67$"/$7+I+!"N7

*/"+"

:8/97

*/"+"

$7NIN"!I:I!;

#iuretics < < = 2= >

+ympatholytic agents

entrally acting 2= 2= = 2> 2=



"drenergic neuron

blockers

2= = = > 2>

? "drenergic antagonists 2> 2> = 2> <

@ "drenergic antagonists

No I+"A = = 2= 2> =

I+" < < = 2> 2=

"rteriolar vasodilators > > = > >

a' channel blockers = or > = or > = 2> 2>

"7 inhibitors < < = < >

"!12receptor antagonists < < = < >

hanges are indicated as followsB >, increased% =, decreased% 2>, increased or no change% 2=,

decreased or no change% <, unchanged.AI+", intrinsic sympathomimetic activity. "7, angiotensin converting enyme% "!1, the type1 receptor for angiotensin II.

principles of antihypertensive therapy-resume

Documents