ANTIHYPERTENSIVE Rx

MED PHARM 2010

Messerli F. N Engl J Med 1995;332:1038-1039

Headlines of the St Louis Post-DispatchApril 13,1945

Messerli F. N Engl J Med 1995;332:1038-1039

Diastolic and Systolic Arterial Pressure of Franklin D. Roosevelt

Chobanian A. N Engl J Med 2009;361:878-887

Risk Factors for Hypertension

Adrogue H and Madias N. N Engl J Med 2007;356:1966-1978

Interaction of the Modern Western Diet and the Kidneys in the Pathogenesis of Primary Hypertension

Adrogue H and Madias N. N Engl J Med 2007;356:1966-1978

Molecular Pathways Implicated in the Generation of Increased Arterial and Arteriolar Smooth-Muscle Tone by an Excess of Sodium and a Deficit of Potassium in Primary Hypertension

DRUGS FOR HYPERTENSION

DIURETICS DIRECT VASODILATORS

Thiazide – Type Hydralazine

Hydrochlorothiazide Minoxidil

Chlorthalidone Nitroprusside

LOOP CENTRAL ALPHA-ADRENERGIC

Furosemide AGONISTS

Clonidine

POTASSIUM – SPARING

Triamterene CALCIUM CHANNEL BLOCKERS Verapamil

Diltiazem

Amlodopine

DRUGS FOR HYPERTENSION

ALPHA-ADRENERGIC BETA-ADRENERGIC

BLOCKERS BLOCKERS

Prazosin Propranolol

Metoprolol

ALPHA –BETA BLOCKERS ANGIOTENSIN RECEPTOR

Carvedilol ANTAGONISTS

Labetalol Losartan

ACE-Inhibitors RENIN ANTAGONISTS

Benazepril Aliskiren

DIURETICS for HYPERTENSION

Chlorthalidone

Hydrochlorthiazide

ADVERSE EFFECTS

Fluid & electrolyte imbalance

Hypokalemia

Dysglycemia

Ernst M and Moser M. N Engl J Med 2009;361:2153-2164

Sites of Diuretic Action in the Nephron

Ernst M and Moser M. N Engl J Med 2009;361:2153-2164

aPotential Complications of DiureticAAAAs nd Their Associated Mechanisms

Landry D and Oliver J. N Engl J Med 2001;345:588-595

Regulation of Vascular Smooth-Muscle Tone

CENTRALLY ACTING

ANTIHYPERTENSIVE

DRUGS

CLONIDINE

CLONIDINE

• Central agonist

• Hemodynamics

Decrease in :

Cardiac output

Systemic vascular resistance

ALPHA- ADRENERGIC ANTAGONISTS

PRAZOSIN

Hemodynamics

Decrease in systemic vascular

resistance

ADVERSE RESPONSE

first dose hypotension

BETA ADRENERGIC ANTAGONISTS

• Propranolol non-selective

• Metoprolol cardioselective, block

Beta blockers are not as effective as the other 4 classes of drugs in reducing stroke, particularly in the elderly

BETA BOCKERS – ADVERSE EFFECTS

CNS Cardiovascular

Bad dreams Aggravation of severe CHF

Depression Aggravation of occlusive arterial disease

Slow A-V conduction

Pulmonary

Bronchospasm in Asthmatics

Drug interactions

Drugs that impair A-V conduction (digoxin and some calcium channel blockers)

VASODILATORS FOR HYPERTENSION

HYDRALAZINE

MINOXIDIL

SODIUM NITROPRUSSIDE

HYDRALAZINE

A direct acting vasodilator

May prevent oxidation of NO

Hemodynamics- Decrease in systemic vascular resistance

HYDRALAZINE

Adverse Effects

Fluid retention

Lupus-like syndrome in slow

acetylators

Reflex tachycardia

MINOXIDILACTION:

HEMODYNAMIC ACTIONS:

ADVERSE EFFECTS:

Direct acting peripheral vasodilator for resistant hypertension

Decrease in systemic vascular resistance

Fluid retention, Tachycardia,

Angina, Pericardial effusion,

Hirsutism, EKG changes

Griffiths, M. J.D. et al. N Engl J Med 2005;353:2683-2695

Regulation of the Relaxation of Vascular Smooth Muscle by Nitric Oxide

Landry D and Oliver J. N Engl J Med 2001;345:588-595

Regulation of Vascular Smooth-Muscle Tone

SODIUM NITROPRUSSIDEACTION

Direct relaxation of all vascular smooth muscle

Balanced arteriolar and venous dilation

Decrease in systemic vascular resistance

Intravenous administration

USES

Hypertensive crisis

Heart failure

RAAS

ANGIOTENSIN II FORMATION

A II ACTIONS

Oparil, S. et. al. Ann Intern Med 2003;139:761-776

The angiotension II types 1 (AT 1 ) and 2 (AT 2 ) receptors have generally opposing effects

Goodfriend, T. L. et al. N Engl J Med 1996;334:1649-1655

Actions of Angiotensin II

BENAZEPRIL

A Long-acting Inhibitor of Angiotensin Converting Enzyme

BENAZEPRIL

ACTION:

HEMODYNAMIC EFFECT:

ADVERSE EFFECTS:

Inhibits angiotensin converting enzyme, toreduce formation of angiotensin II and aldosterone, inhibits lysis of bradykinin, may alter prostaglandin metabolismand sympathetic transmission.

Decreases total peripheral resistanceHeart rate and cardiac output unchanged

Cough, angioedema, teratogenic,neutropenia, agranulocytosis, loss of taste, skin rash,& hypotension

ACEI & ARB TERATOGENICITY

1st half ~2.7X increase in malformations CV & CNS2nd half oligohydramnios growth retardation pulmonary hypoplasia renal failure hypotension death

:

ANGIOTENSIN RECEPTOR ANTAGONISTS ( ARBs)

LOSARTAN

OTHERS

Goodfriend T et al. N Engl J Med 1996;334:1649-1655

Signal Transduction by Angiotensin AT1 Receptors

Oparil, S. et. al. Ann Intern Med 2003;139:761-776

The angiotension II types 1 (AT 1 ) and 2 (AT 2 ) receptors have generally opposing effects

RAASRENIN ANTAGONIST

• ANGIOTENSIN II FORMATION

ALISKIREN

Renin inhibitor

Lowers blood pressure

Outcome studies-none

CALCIUM CHANNEL BLOCKERS

Verapamil

Diltiazem

Amlododipine

CALCIUM CHANNEL BLOCKERS ON THE HEART

CALCIUM CHANNEL ANTAGONISTSADVERSE EFFECTS

Hypotension Heart failure

Headache AV Block

Constipation Peripheral edema

DRUG INTERACTIONS:

Digoxin or Beta blockers to cause A-V block

Chobanian A. N Engl J Med 2009;361:878-887

Advances in the Treatment of Hypertension

Chobanian A. N Engl J Med 2009;361:878-887

Changes in the Prevalence and Control of Hypertension in the United States (1988-2004)

Chobanian A. N Engl J Med 2009;361:878-887

Rates of Awareness, Treatment, and Control of High Blood Pressure in the United States (1976-2004)

Chobanian A. N Engl J Med 2009;361:878-887

Comparative Drug Trials in Patients with Hypertension

HYPERTENSION & CV DISEASE

Hypertension:

Increased risk SCD & LVH 3X

Risk increases with sbp

Independently predisposes to CAD

Increases risk of silent MI

63% of coronary events occur in:

HTN+ at least 2 other risk factors

ANTIHYPERTENSIVE THERAPYFIRST-LINE DRUGS

• DIURETICS: THIAZIDE or THIAZIDE

TYPE

• ACE INHIBITOR : LONG ACTING

• ARB :

• CCB : LONG ACTING

• BETA BLOCKERS : NO, absent a compelling indication ( Post - MI, HF,angina)

Algorithm for Management of Hypertension