ANTIHYPERTENSIVE Rx
MED PHARM 2010
Headlines of the St Louis Post-Dispatch
April 13,1945
Messerli F. N Engl J Med 1995;332:1038-1039
Diastolic and Systolic Arterial Pressure of Franklin D. Roosevelt
Messerli F. N Engl J Med 1995;332:1038-1039
Risk Factors for Hypertension
Chobanian A. N Engl J Med 2009;361:878-887
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 SmoothMuscle Tone by an Excess of Sodium and a Deficit of Potassium in Primary Hypertension
Adrogue H and Madias N. N Engl J Med 2007;356:1966-1978
DRUGS FOR HYPERTENSION
DIURETICS
Thiazide – Type
Hydrochlorothiazide
Chlorthalidone
LOOP
Furosemide
DIRECT VASODILATORS
Hydralazine
Minoxidil
Nitroprusside
CENTRAL ALPHA-ADRENERGIC
AGONISTS
Clonidine
POTASSIUM – SPARING
Triamterene
CALCIUM CHANNEL BLOCKERS
Verapamil
Diltiazem
Amlodopine
DRUGS FOR HYPERTENSION
ALPHA-ADRENERGIC
BLOCKERS
Prazosin
ALPHA –BETA BLOCKERS
Carvedilol
Labetalol
ACE-Inhibitors
Benazepril
BETA-ADRENERGIC
BLOCKERS
Propranolol
Metoprolol
ANGIOTENSIN RECEPTOR
ANTAGONISTS
Losartan
RENIN ANTAGONISTS
Aliskiren
DIURETICS for HYPERTENSION
Chlorthalidone
Hydrochlorthiazide
ADVERSE EFFECTS
Fluid & electrolyte imbalance
Hypokalemia
Dysglycemia
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
Ernst M and Moser M. N Engl J Med 2009;361:2153-2164
Regulation of Vascular Smooth-Muscle Tone
Landry D and Oliver J. N Engl J Med 2001;345:588-595
CENTRALLY ACTING
ANTIHYPERTENSIVE
DRUGS
CLONIDINE
CLONIDINE
• Central a2 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
• Metoprolol
non-selective
cardioselective, b block
1
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
Bad dreams
Depression
Cardiovascular
Aggravation of severe CHF
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
MINOXIDIL
ACTION: Direct acting peripheral
vasodilator for resistant
hypertension
HEMODYNAMIC ACTIONS:
Decrease in systemic
vascular resistance
ADVERSE EFFECTS:
Fluid retention, Tachycardia,
Angina, Pericardial effusion,
Hirsutism, EKG changes
Regulation of the Relaxation of Vascular Smooth Muscle by Nitric Oxide
Griffiths, M. J.D. et al. N Engl J Med 2005;353:2683-2695
Regulation of Vascular Smooth-Muscle Tone
Landry D and Oliver J. N Engl J Med 2001;345:588-595
SODIUM NITROPRUSSIDE
ACTION
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
The angiotension II types 1 (AT 1 ) and 2 (AT 2 ) receptors have generally
opposing effects
Oparil, S. et. al. Ann Intern Med 2003;139:761-776
Actions of Angiotensin II
Goodfriend, T. L. et al. N Engl J Med 1996;334:1649-1655
BENAZEPRIL
A Long-acting Inhibitor of
Angiotensin Converting Enzyme
BENAZEPRIL
ACTION:
HEMODYNAMIC EFFECT:
ADVERSE EFFECTS:
Inhibits angiotensin converting enzyme, to
reduce formation of angiotensin II and
aldosterone, inhibits lysis of bradykinin,
may alter prostaglandin metabolism
and sympathetic transmission.
Decreases total peripheral resistance
Heart 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 & CNS
2nd half oligohydramnios
growth retardation
pulmonary hypoplasia
renal failure
hypotension
death
:
ANGIOTENSIN RECEPTOR
ANTAGONISTS ( ARBs)
LOSARTAN
OTHERS
Signal Transduction by Angiotensin AT1 Receptors
Goodfriend T et al. N Engl J Med 1996;334:1649-1655
The angiotension II types 1 (AT 1 ) and 2 (AT 2 ) receptors have generally
opposing effects
Oparil, S. et. al. Ann Intern Med 2003;139:761-776
RAAS
RENIN 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 ANTAGONISTS
ADVERSE EFFECTS
Hypotension
Headache
Constipation
Heart failure
AV Block
Peripheral edema
DRUG INTERACTIONS:
Digoxin or Beta blockers to cause A-V
block
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 (19762004)
Chobanian A. N Engl J Med 2009;361:878-887
Comparative Drug Trials in Patients with Hypertension
Chobanian A. N Engl J Med 2009;361:878-887
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 THERAPY
FIRST-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