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Messerli F. N Engl J Med 1995;332:1038-1039
Diastolic and Systolic Arterial Pressure of Franklin D. Roosevelt
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
aPotential Complications of DiureticAAAAs nd Their Associated Mechanisms
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)
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
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
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
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
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
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
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)
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)