Selection of Antihypertensive Drug. ACE Inhibitor AT 1 Antagonist AT 1 Antagonist Diuretic Ca ++...

Selection ofAntihypertensive Drug

ACE ACE InhibitorInhibitor

ATAT11AntagonistAntagonist

DiureticDiureticCaCa++++ Antagonist Antagonist

BetaBeta BlockerBlocker

Alpha BlockerAlpha Blocker

Drug of choiceDrug of choice

Dr. RxDr. RxRationaRationall

GanglionicGanglionic blockersblockers

- agonists- agonists

VasodilatorsVasodilators

Selection of Antihypertensive Drug

Level of blood pressureLevel of blood pressure

++ Presence of other risk factors for CVDPresence of other risk factors for CVD

& target organ damage& target organ damage

++Coexisting diseasesCoexisting diseases

Antihypertensive TherapyAntihypertensive Therapy

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22

33

Selection of Antihypertensive Drug

Pharmacotherapy of Hypertension

Target organ damage/clinical CVDTarget organ damage/clinical CVD

• LVH - Heart failure - Angina - Prior MI LVH - Heart failure - Angina - Prior MI or revascularization or revascularization

• Stroke or TIAStroke or TIA

• NephropathyNephropathy

• Retinopathy Retinopathy

• Peripheral vascular diseasePeripheral vascular disease


Blood Pressure Classification

SBP DBPSBP DBP mm Hgmm Hg mmHg mmHg

• Normal

• Prehypertensive • Stage 1 Hypertension

• Stage 2 Hypertension

<120 and <80

120-139 or 80-89 140-159 or 90-99

> 160 or > 100

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Goal Blood Pressure

SBP DBPSBP DBP mm Hgmm Hg mmHg mmHg

• Most patients

• Diabetes • Chronic Renal Disease

< 140 < 90

< 130 < 80 < 130 < 80

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Lifestyle Modifications

Approximate SBP ReductionApproximate SBP Reduction mmHgmmHg

•Weight reduction

• DASH eating plan

• Reduced Sodium Intake • Physical activity

•Moderation of alcohol consumption

5 – 20

8 – 14

2 – 8

4 – 9

2 – 4

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Algorithm for Treatment of Hypertension

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LifestyleLifestyleModificationsModifications

Not at Goal Blood Pressure

Initial Drug Initial Drug ChoicesChoices


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““Excellent clinical trial outcome data prove that lowering BP with several classes of drug,

including ACE inhibitors, angiotensin receptors blockers (ARBs),”beta-blockers”, calcium channel

blockers (CCBs) and thiazide-type diureticswill reduce the complications of hypertension.” .”


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WithoutWithoutCompelling Compelling

Indication (s) Indication (s)

WithWithCompelling Compelling

Indication (s) Indication (s)


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Initial Drug ChoicesInitial Drug Choices

Stage 1- Hypertension 140-159 / 90-99 mmHg Without Compelling Indication

Thiazide-like diuretics for most,Thiazide-like diuretics for most,ACEI, ARB, BB or CCB ACEI, ARB, BB or CCB

May consider combinationMay consider combination


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Stage 2 - Hypertension >160 / > 100 mmHg Without Compelling Indication

2-drug combination for most2-drug combination for mostUsually thiazide-like diuretic plus ACEI, Usually thiazide-like diuretic plus ACEI,

or ARB, or BB or CCBor ARB, or BB or CCB


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WithoutWithoutCompelling Indication (s)Compelling Indication (s)

WithWithCompelling Indication (s) Compelling Indication (s)

Not at Goal Blood PressureNot at Goal Blood Pressure

Optimize dosage or add additional Optimize dosage or add additional drug until goal BP is achieved. Considerdrug until goal BP is achieved. Consider

consultation with HNT specialistconsultation with HNT specialist

Compelling Compelling Indication*Indication* Diuretic BB ACEI ARB CCB ALD & ANT

Heart failure ● ● ● ● ●

Postmyocardial infarction ● ● ●

High coronary disease risk ● ● ● ●

Diabetes ● ● ● ● ●

Chronic kidney disease ● ●

Recurrent stroke prevention

● ●

Clinical trial and guideline basis for compelling indications for individual drug classes

Class Drug (Trade Name) Usual Dose

Range in

mg/Day

Usual Daily

mg/Day

Frequency*

Thiazide diuretics

chlorothiazide

chlorthalidone

hydrochlorothiazide

polythiazide

indapamide

metolazone

metolazone

125–500

12.5–25

12.5–50

2–4

1.25–2.5

0.5–1.0

2.5–5

1–2

1

1

1

1

1

1

Loop

diuretics

bumetanide

furosemide

torsemide

0.5–2

20–80

2.5–10

2

2

1

Potassium-sparing diuretics

amiloride

triamterene

5–10

50–100

1–2

1–2

Aldosterone receptor blockers

eplerenone

Spironolactone

50–100

25–50

1

1


Range in

mg/Day

Usual Daily

mg/Day

Frequency*

BBs Atenolol

Propranolol

propranolol long-acting

25–100

40-160

60-180

1

2

1

Combined

alpha- and

BBs

Carvedilol

labetalol

12.5–50

200–800

2

2

ACEIs enalapril

ramipril

5-40

2.5-20

1-2

1

Angiotensin II antagonists

losartan 25-100 1-2

CCBs—nondihydropyridines

diltiazem extended release

diltiazem extended release

verapamil immediate release

verapamil long acting

Verapamil

180-420

120-540

80-320

120-480

120-360

1

1

2

1-2

1


Range in

mg/Day

Usual Daily

mg/Day

Frequency*

CCBs-dihydropyridines

amlodipine

nifedipine long-acting

2.5-10

30-60

1

1

Alpha-1

blockers

doxazosin

prazosin

terazosin

1-16

2-20

1-20

1

2-3

1-2

Central alpha-2 agonists and other

centrally acting drugs

clonidine

clonidine patch

methyldopa

reserpine

guanfacine

0.1-0.8

0.1-0.3

250-1000

0.1-0.25

0.5-2

2

1 wkly

2

1

1

Direct vasodilators

hydralazine

minoxidil

25-100

2.5-80

2

1-2

Hypertension in Elderly

Pharmacological treatment: - Lower initial doses (1/2 dose than in younger patients)

- The reduction in BP should be gradual - Greater caution in patients with co-existing diseases or

orthostatic hypotension.

Choice of therapy: - Thiazide diuretic (hydrochlorothiazide, HCTZ 12.5 mg) - STOP-Hypertension trial: ACE inhibitors, long-acting calcium antagonist and beta- blockers may provide

the same protection as diuretics.

Choice of therapy: special considerations

A diuretic should be used for heart failure or edema

A beta-blocker should be used for patient with coronary

heart disease, tachyarrhitmias or migraine

An ACE inhibitors in patients with heart failure

Calcium antagonist should be used in patients with

angina pectoris,and peripheral vascular disease

Alpha-blocker in patient with benign prostatic hyperplasia

Hypertension in Elderly

Treatment:Treatment:• Early treatmentEarly treatment to prevent cardiovascular disease to prevent cardiovascular disease

and minimize progression of renal and retinal disease. and minimize progression of renal and retinal disease.

• The benefits ofThe benefits of tight blood pressure controltight blood pressure control in in diabetics may be as great or greater than benefits of diabetics may be as great or greater than benefits of strict glycemic control.strict glycemic control.

• Initial therapy should includeInitial therapy should include non-pharmacological non-pharmacological methodsmethods. .

• ACE Inhibitors, ARBs, C++ Channel Blockers,ACE Inhibitors, ARBs, C++ Channel Blockers,

Hypertension and DiabetesHypertension and Diabetes

Hypertension and DiabetesHypertension and Diabetes

Pathogenesis:Pathogenesis:

• Kidneys in diabetic patients are more sensitive Kidneys in diabetic patients are more sensitive to any increase in blood pressureto any increase in blood pressure

• Proteinuria is not only the marker of renal Proteinuria is not only the marker of renal damage, damage, but also risk factor for progression of renal but also risk factor for progression of renal diseasedisease

Asthma COPD and Hypertension

• Beta-blockersBeta-blockers (i) increase bronchial obstruction, (i) increase bronchial obstruction, (ii) increase in airways reactivity, and (iii) inhibit the (ii) increase in airways reactivity, and (iii) inhibit the bronchodilatatory effects of beta agonist bronchodilatatory effects of beta agonist

• Cardioselective, beta-blockers none should be considered Cardioselective, beta-blockers none should be considered safe.Even topical administration for the treatment of safe.Even topical administration for the treatment of glaucoma may led to asthmatic exacerbations.glaucoma may led to asthmatic exacerbations.

• ACE inhibitorsACE inhibitors are not contraindicated and may be used; are not contraindicated and may be used; very rarely worsen airflow obstruction; produce persistent very rarely worsen airflow obstruction; produce persistent dry cough and are not first line drug for hypertensive dry cough and are not first line drug for hypertensive patients with asthma or COPD. patients with asthma or COPD.

• Diuretics: Diuretics: can be effectively used but there is an can be effectively used but there is an increased risk of increased risk of hypokalemiahypokalemia (inhaled (inhaled -2 agonist drive -2 agonist drive potassium into cell and orally administered potassium into cell and orally administered corticosteroids mildly increase urinary potassium corticosteroids mildly increase urinary potassium excretion). excretion).

• Only low dose (12.5-25 mg) of thiaizides to be used. Only low dose (12.5-25 mg) of thiaizides to be used.

• In patients with COPD and chronic hypercapnia, In patients with COPD and chronic hypercapnia, diuretics-induced metabolic alkalosis may suppress the diuretics-induced metabolic alkalosis may suppress the ventilatory drive and exacerbates the hypoxia. ventilatory drive and exacerbates the hypoxia.

Asthma COPD and Hypertension

Asthma, COPD and Hypertension

Calcium channel blockersCalcium channel blockers (CCB) are (CCB) are preferred for preferred for treatmenttreatment of hypertension in astma & COPD. May of hypertension in astma & COPD. May be combined with diureticsbe combined with diuretics

Short-acting CCB (niphedipine) should not be used Short-acting CCB (niphedipine) should not be used because they increase CV risk. because they increase CV risk.

Only long-acting CCB or slow-release niphedipine Only long-acting CCB or slow-release niphedipine formulation should be used.formulation should be used.

Ischemic Heart Disease and Hypertension

• IHD is the most common form of target-organ damage associated with hypertension.

• Beta blockers and long acting Ca++ channel blockers are the first choice in HTN patient with stable angina pectoris.

• HTN patients with unstable angina or MI should be treated with beta blocker or ACE inhibitor.

• In patients with post-myocardial infarction, ACE inhibitors, beta blockers and aldosterone antagonists; all reduce progression of left ventricular dysfunction and mortality.

– ACE inhibitors and beta blockers are recommended for HTN patients with asymptomatic ventricular dysfunction

– In HTN patients with symptomatic ventricular dysfunction (NYHA III and IV) in addition to ACE inhibitors and beta blockers, treatment with diuretics, Ang II receptor antagonists and aldosterone antagonists.

– In hypertensive HF patient, if volume depleted, ACE inhibitors may induce hypotension and acute renal failure. Beta blockers may induce initial/transient worsening of HF.

Hart Failure and Hypertension

-Pregnancy : Methyl Dopa, HydralazinePregnancy : Methyl Dopa, Hydralazine

- Gout & Dyslipidemia: Avoid diureticsGout & Dyslipidemia: Avoid diuretics

- Benign prostatic hypertrophy: Alfa-1 adrenergicBenign prostatic hypertrophy: Alfa-1 adrenergic blockers blockers


ACE ACE InhibitorInhibitor

ATAT11AntagonistAntagonist

DiureticDiureticCaCa++++ Antagonist Antagonist

BetaBeta BlockerBlocker

Alpha BlockerAlpha Blocker

Drug of Drug of choicechoice

Dr. RxDr. RxRationaRationall

GanglionicGanglionic blockersblockers

- agonists- agonists

VasodilatorsVasodilators


Selection of Antihypertensive Drug. ACE Inhibitor AT 1 Antagonist AT 1 Antagonist Diuretic Ca ++...

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Transcript of Selection of Antihypertensive Drug. ACE Inhibitor AT 1 Antagonist AT 1 Antagonist Diuretic Ca ++...