Lecture #39: Pharmacology: Adrenergic Antagonists

What is the primary pharmacologic action of adrenergic antagonists?

They block adrenergic receptors and prevent norepinephrine and epinephrine from activating target tissues

What are the two major classes of adrenergic antagonists?

Alpha-adrenergic antagonists (alpha blockers) and beta-adrenergic antagonists (beta blockers)

How do alpha blockers lower blood pressure?

By relaxing arterial and venous smooth muscle, decreasing peripheral vascular resistance and venous return

What receptors are blocked by nonselective alpha blockers?

Both α1 and α2 adrenergic receptors

What are examples of nonselective alpha blockers?

Phenoxybenzamine and phentolamine

How does phenoxybenzamine differ mechanistically from phentolamine?

Phenoxybenzamine is an irreversible alpha antagonist, while phentolamine is a reversible competitive antagonist

What is the primary clinical use of phenoxybenzamine?

Presurgical management of hypertension and sweating in pheochromocytoma

Why do nonselective alpha blockers cause marked tachycardia?

Alpha2 blockade increases norepinephrine release and vasodilation triggers reflex sympathetic activation

What is epinephrine reversal?

Alpha blockade converts epinephrin’s pressor response into a depressor response due to unopposed β2-mediated vasodilation

Why does phenylephrine not show epinephrine reversal?

It lacks β2 activity so its pressor effect is suppressed but not reversed

What are selectiveα1blockers commonly used for?

Add-on treatment of hypertension and relief of urinary symptoms due to benign prostatic hyperplasia

What drugs are quinazoline α1 blockers?

Prazosin, terazosin, and doxazosin

What is the first-dose effect associated with α1 blockers?

Severe orthostatic hypotension, syncope, dizziness, and tachycardia

Why are α1 blockers recommended to be taken at bedtime initially?

To reduce the risk of orthostatic hypotension during the first doses

Which α1 blockers are selective for α1A receptors in the prostate?

Tamsulosin, silodosin, and alfuzosin

Why are α1A-selective blockers preferred for BPH?

They improve urinary flow with less effect on systemic blood pressure

What is intraoperative floppy iris syndrome and what causes it?

Poor iris dilation during cataract surgery caused by α1 blockade of the iris dilator muscle

What is yohimbine and how does it act?

A competitive α2 antagonist that increases sympathetic outflow

Why does yohimbine increase blood pressure and heart rate?

Blockade of presynaptic α2 receptors increases norepinephrine release

What defines beta blockers pharmacologically?

They antagonize β-adrenergic receptors and inhibit sympathetic cardiac effects

What receptors are blocked by nonselective beta blockers?

Both β1 and β2 adrenergic receptors

What are the primary cardiovascular effects of beta blockers?

Decreased heart rate,decreased contractility, slowed AV conduction, and reduced cardiac output

How do beta blockers lower blood pressure chronically?

By reducing cardiac output and suppressing renin release from the kidney

Why can beta blockers cause bronchoconstriction?

β2 blockade increases airway resistance, especially in asthma and COPD

How do beta blockers affect hypoglycemia awareness?

They mask adrenergic warning signs such as tremor and tachycardia

What is the major risk of abrupt beta blocker withdrawal?

Rebound hypertension, angina, myocardial infarction, and arrhythmias

What beta blocker properties may provide additional benefits?

Partial agonism, α1 blockade, nitric oxide production, calcium channel blockade, and antioxidant effects

What are common therapeutic uses of beta blockers?

Hypertension, angina, myocardial infarction, heart failure, arrhythmias, migraine prophylaxis, and performance anxiety

Which beta blocker is commonly used in pregnancy-related hypertension?

Labetalol

Why are lipophilic beta blockers associated with CNS effects?

They cross the blood-brain barrier and can cause fatigue, depression, and insomnia

What is the unifying mechanism behind beta blocker therapeutic effects?

Inhibition of sympathetic nervous system stimulation of β-adrenergic receptors