13.Adrenergic antagonists

What is the "First-Dose Phenomenon" associated with alpha-blockers?

A sudden, severe drop in blood pressure and orthostatic hypotension occurring at the start of therapy.

Why do non-selective \alpha-blockers (like Phentolamine) cause more severe tachycardia than \alpha_1-selective blockers?

They block prejunctional \alpha_2 receptors, which increases Norepinephrine release. This extra NE stimulates cardiac \beta_1 receptors, causing reflex tachycardia and increased renin secretion.

Compare the binding mechanisms of Phenoxybenzamine vs. Phentolamine.

Phenoxybenzamine: Irreversible (covalent/insurmountable) antagonist; long duration of action.

​Phentolamine: Reversible competitive antagonist; shorter action.

Which \alpha-blockers are preferred for Benign Prostatic Hyperplasia (BPH) to minimize blood pressure side effects?

Tamsulosin and Silodosin, because they are relatively selective for the \alpha_{1A} receptor subtype dominating the prostate.

What are the metabolic effects of alpha-receptor blockade?

Inhibition of liver glycogenolysis (\alpha_1 effect).

​Stimulation of insulin secretion (\alpha_2 effect).

​Improvement of lipid profile (decreased LDL, increased HDL) with Prazosin congeners.

What is Intrinsic Sympathomimetic Activity (ISA) in beta blockers?

It refers to drugs that act as partial agonists (e.g., Pindolol, Acebutolol). They provide low-level receptor stimulation, protecting against extreme bradycardia, but are less effective in heart failure or post-MI.

Why must beta-blocker therapy be tapered gradually rather than stopped abruptly?

Long-term use causes \beta_1 receptor upregulation. Sudden withdrawal can lead to a "rebound effect" featuring dangerous tachycardia, arrhythmias, and angina.

List the three negative cardiac "tropic" effects of \beta_1 blockade.

1. Negative Chronotropic: Decreased heart rate.

2. Negative Inotropic: Decreased contractility.

3. Negative Dromotropic: Decreased AV conduction velocity.

Which beta blockers are specifically used for Congestive Heart Failure?

Metoprolol, Bisoprolol, and Carvedilol. They inhibit long-term cardiac remodeling.

Why are non-selective beta blockers risky for diabetic patients?

They inhibit glycogenolysis (causing hypoglycemia) and mask the warning symptoms of hypoglycemia, such as tachycardia and tremors.

Which beta blockers provide vasodilation via \alpha_1 blockade?

Labetalol and Carvedilol.

How does Nebivolol achieve vasodilation?

It is \beta_1-selective but also increases the release of Nitric Oxide (NO) from the endothelium via \beta_3 agonism.

What is the unique clinical use for Esmolol?

It is given only i.v. for emergency control of supraventricular tachycardia or perioperative tachycardia due to its ultra-short half-life (~10 mins).

Why is Propranolol used in hyperthyroidism?

It blocks \beta receptors and specifically inhibits the peripheral conversion of T4 to T3.

What is the primary contraindication for all Ergot alkaloids?

Pregnancy, as they can act as uterotonics and cause abortion.

Match the Ergot derivative to its use: Ergotamine, Ergometrine, Bromocriptine.

Ergotamine: Migraine attacks.

​Ergometrine: Uterotonic (postpartum hemorrhage).

​Bromocriptine: Parkinson’s disease and prolactinoma (D2 agonist).

What are the symptoms of "Ergotism" (Ergot poisoning)?

Gangrenous ergotism (severe vasoconstriction/gangrene) and convulsive ergotism (skeletal muscle cramps).

What are the dual mechanisms of Urapidil?

It acts as an \alpha_1-receptor antagonist and a 5-HT_{1A}receptor partial agonist (central sympatholytic effect).

Why is Urapidil used in hypertensive crises?

It is administered i.v. to lower blood pressure rapidly without causing tachycardia.

Which \alpha_1 antagonist causes apoptosis in prostate cells independently of receptor blockade?

Terazosin and Doxazosin.

What is the theoretical vs. actual effect of \alpha_2 receptor inhibition on blood pressure?

Theoretically, vascular \alpha_2 block causes vasodilation, but it is overcompensated by increased Norepinephrine release (via prejunctional block), which stimulates \beta_1 and \alpha_1 receptors to increase blood pressure.

Name two antidepressants that function as \alpha_2 receptor antagonists.

Mianserin and Mirtazapine

Which beta blockers are hydrophilic and primarily renally excreted?

Atenolol, Nadolol, and Sotalol. (Note: They penetrate the CNS poorly, leading to fewer central side effects).

Which enzyme primarily metabolizes lipophilic beta blockers like Propranolol and Metoprolol?

CYP2D6. (Note: Genetic polymorphism in this enzyme causes variable plasma levels).

What is the half-life and administration route of Esmolol?

It is given only i.v. and has a very short half-life of ~10 minutes due to rapid hydrolysis by erythrocyte esterases.

Which beta blocker is eliminated through both renal and biliary excretion in an unchanged form?

Celiprolol

List the absolute cardiac contraindications for beta blockers.

Bradycardia

​AV-block

​Severe heart failure

​Hypotension

Why are beta blockers contraindicated in Asthma and COPD?

Blockade of \beta_2 receptors in the lungs can trigger life-threatening bronchospasms.

Which calcium channel blockers should be avoided when taking beta blockers due to the risk of severe cardiodepression?

Verapamil and Diltiazem

What are the CNS-related adverse effects of lipophilic beta blockers?

Dizziness, sleep disorders, nightmares, hallucinations, and depression.

What is the "Dumping syndrome" and which drug is used for it?

It is a condition treated with Methysergide (a 5-HT_{2A/2C} antagonist).

What is the major long-term risk of Methysergide therapy?

Retroperitoneal and mediastinal fibrosis (therapy must be limited to a maximum of 6 months).

What is Dihydroergotoxin?

A mixture of three hydrogenated ergot alkaloids with predominantly \alpha-antagonistic effects.

Which Ergot derivative is a partial agonist at 5-HT_{2A} and acts as a hallucinogen?

LSD (Lysergic acid diethylamide)