BETA-

ADRENOCEPTOR-
BLOCKING
AGENTS
PROPRANOLOL

• was the first B blocker shown to be effective in

hypertension and ischemic heart disease.
• has now been largely replaced by cardioselective B
blockers such as metoprolol and atenolol.
PROPRANOLOL
• All B-adrenoceptor-blocking agents are useful for lowering
blood pressure in mild to moderate hypertension.
• In severe hypertension, B blockers are especially useful in
preventing the reflex tachycardia that often results from
treatment with direct vasodilators.
• Beta blockers have been shown to reduce mortality after a
myocardial infarction and some also reduce mortality in patients
with heart failure; they are particularly advantageous for treating
hypertension in patients with these conditions.
PROPRANOLOL
A. Mechanism and Sites of Action
• decreases blood pressure primarily as a result of a decrease in cardiac
output.
**Other B blockers may decrease cardiac output or decrease
peripheral vascular resistance to various degrees, depending on cardio
selectivity and partial agonist activities.
• inhibits the stimulation of renin production by catecholamines (mediated by
B1 receptors).
**Propranolol’s effect is due in part to depression of the renin-
angiotensin-aldosterone system.
PROPRANOLOL
• reduces blood pressure in hypertensive patients with normal or
even low renin activity.
**Beta blockers might also act on peripheral presynaptic B
adrenoceptors to reduce sympathetic vasoconstrictor nerve
activity.
• produces a significant reduction in blood pressure without
prominent postural hypotension in mild to moderate
hypertension
PROPRANOLOL
B. Pharmacokinetics and Dosage
• indicators of propranolol’s B-blocking effect:
 Resting bradycardia
 reduction in the heart rate during exercise
• Propranolol can be administered twice daily, and slow release
once-daily preparations are also available.
PROPRANOLOL
C. Toxicity
• discontinued after prolonged regular use, some patients
experiences:
withdrawal syndrome
Nervousness
Tachycardia
increased intensity of angina, and;
increase of blood pressure
• Myocardial infarction has been reported in a few patients.
• The incidence of these complications is probably low, thus B
blockers should not be discontinued abruptly.
• The withdrawal syndrome may involve upregulation or
supersensitivity of B adrenoceptors.
METOPROLOL & ATENOLOL

• They are cardioselective.

• The most widely used B blockers in the treatment of
hypertension.
METOPROLOL
• approximately equipotent to propranolol in inhibiting stimulation of B1
adrenoceptors such as those in the heart but 50- to 100-fold less potent
than propranolol in blocking B2 receptors.
• Relative cardioselectivity is advantageous in treating hypertensive patients
who also suffer from asthma, diabetes, or peripheral vascular disease.
• Causes less bronchial constriction than propranolol at doses that produce
equal inhibition of B1-adrenoceptor responses.
• extensively metabolized by CYP2D6 with high firstpass metabolism.
• has a relatively short half-life of 4–6 hours, but the extended-release
preparation can be dosed once daily.
• Sustained-release metoprolol is effective in reducing mortality from heart
failure and is particularly useful in patients with hypertension and heart
failure.
ATENOLOL
• Not extensively metabolized
• Excreted primarily in the urine with a half-life of 6 hours;
• It is usually dosed once daily.
• Less effective than metoprolol in preventing the complications
of hypertension.
**A possible reason for this difference is that once-daily
dosing does not maintain adequate blood levels of atenolol. The
usual dosage is 50–100 mg/d.
• Patients with reduced renal function should receive lower
doses.
PROPRANOLOL