Adrenergic Antagonists

Alpha Blockers - Alpha's Off Switch

• Mechanism: Block $\alpha_1$ &/or $\alpha_2$ receptors.
  • $\alpha_1$ block: Vasodilation (↓BP), relaxation of prostate & bladder neck.
• Types & Key Drugs:
  • Non-selective ($\alpha_1 + \alpha_2$):
    • Phenoxybenzamine (Irreversible; Pheochromocytoma pre-op)
    • Phentolamine (Reversible; Pheochromocytoma, hypertensive crisis)
  • Selective $\alpha_1$ (suffix "-zosin"): Prazosin, Terazosin, Doxazosin (Hypertension, BPH); Tamsulosin, Alfuzosin, Silodosin (BPH - more uroselective).
  • Selective $\alpha_2$: Yohimbine (used for orthostatic hypotension).
• Main Uses:
  • Hypertension (esp. with BPH)
  • Benign Prostatic Hyperplasia (BPH)
  • Pheochromocytoma
• Key Side Effects:
  • First-dose hypotension (postural) - esp. Prazosin.
  • Reflex tachycardia.
  • Nasal congestion.
  • Retrograde ejaculation (Tamsulosin). 📌 "-ZOSIN" drugs are $\alpha_1$ selective blockers.

⭐ Phenoxybenzamine is an irreversible alpha-blocker, crucial for pre-operative blood pressure control in pheochromocytoma. oka

Beta Blockers (NS/B1) - Heart's Chill Pill

• MoA: Block $\beta$-receptors.
  • $\beta_1$ (heart): ↓HR, ↓contractility, ↓AV conduction, ↓renin.
  • $\beta_2$ (NSBBs): Bronchoconstriction, vasoconstriction.
• Types & Examples:
  • Non-Selective (NS: $\beta_1 + \beta_2$): Propranolol, Timolol, Nadolol, Sotalol (K+ ch. block).
  • Cardioselective ($\beta_1$ > $\beta_2$): E.g., Metoprolol, Atenolol, Nebivolol (+NO). (📌 BEMBA: Bisoprolol, Esmolol, Metoprolol, Betaxolol, Atenolol, Acebutolol, Nebivolol).
  • With ISA (Partial Agonists): Pindolol, Acebutolol (less bradycardia).
• Key Uses: HTN, Angina, Post-MI, Arrhythmias, CHF (stable). Glaucoma (Timolol), Hyperthyroidism (symptoms), Migraine prophylaxis.
• Side Effects: Bradycardia, AV block, hypotension. Bronchospasm (NSBBs). Fatigue, sexual dysfunction. Masks hypoglycemia (except sweating) ⚠️. Rebound on withdrawal.

⭐ Beta blockers are contraindicated in cocaine-induced MI due to risk of unopposed alpha-stimulation, worsening coronary vasoconstriction.

Beta Blockers (Special) & Mixed - The Dual Agents

• With Intrinsic Sympathomimetic Activity (ISA):
  • Pindolol, Acebutolol (Partial $\beta$-agonists).
  • Mechanism: Act as partial agonists at $\beta$-receptors.
  • Effects: Less bradycardia, less adverse lipid profile changes. Preferred for bradycardia/mild asthma (use with caution).
  • 📌 Mnemonic: "Pindolol & Acebutolol are Partial Agonists".
• Mixed $\alpha_1$ & $\beta$ Blockers (Dual Action):
  • Labetalol, Carvedilol.
  • Mechanism: Blocks $\beta_1, \beta_2$ & $\alpha_1$ receptors → vasodilation + $\beta$-blockade.
  • Labetalol:
    • $\beta:\alpha$ blockade ratio: approx. 3:1 (oral), 7:1 (IV).
    • Uses: HTN in pregnancy (DOC), hypertensive emergencies, pheochromocytoma.
  • Carvedilol:
    • Non-selective $\beta$-blocker + $\alpha_1$ blocker.
    • Additional properties: Antioxidant, anti-proliferative.
    • Uses: CHF (↓mortality/morbidity), hypertension.

    ⭐ Carvedilol shows mortality benefit in CHF due to combined $\beta + \alpha_1$ blockade & antioxidant properties.

• Third-Generation $\beta$-Blockers (Vasodilatory via NO):
  • Nebivolol.
  • Highest $\beta_1$ selectivity among all $\beta$-blockers.
  • Mechanism: Stimulates endothelial NO synthase → ↑NO release → vasodilation.
  • Uses: Hypertension, Chronic Heart Failure.

Blocker Blueprint - Uses & Warnings

• α-Blockers (e.g., Prazosin, Tamsulosin, Phenoxybenzamine):
  • Uses: Hypertension (α1), BPH (α1A), Pheochromocytoma (non-sel.).
  • Warnings: First-dose hypotension ⚠️, reflex tachycardia, nasal congestion.
• β-Blockers (e.g., Propranolol, Atenolol, Carvedilol):
  • Uses: HTN, Angina, Post-MI, Arrhythmias, CHF (specific ones), Glaucoma, Hyperthyroidism symptoms, Migraine prophylaxis.
  • Warnings: Bronchoconstriction (Asthma/COPD ⚠️), bradycardia, AV block, fatigue. Mask hypoglycemia symptoms. Avoid abrupt withdrawal (rebound HTN/angina).

  ⭐ Beta-blockers (esp. non-selective) can mask hypoglycemia symptoms like tremors & palpitations, but not sweating; critical for diabetics on insulin. oka

High‑Yield Points - ⚡ Biggest Takeaways

• Alpha-1 blockers (e.g., Prazosin) treat hypertension & BPH; risk of first-dose hypotension. Tamsulosin is uroselective for BPH.
• Non-selective alpha-blockers (e.g., Phentolamine) are used for pheochromocytoma management.
• Non-selective beta-blockers (e.g., Propranolol) block β1 & β2 receptors; contraindicated in asthma/COPD.
• Cardioselective beta-blockers (e.g., Metoprolol, Atenolol) primarily target β1; safer in asthma (use cautiously).
• Beta-blockers are key for hypertension, angina, MI, heart failure, arrhythmias.
• Labetalol & Carvedilol are mixed α & β blockers, used in hypertensive emergencies & heart failure.
• Common β-blocker side effects: bradycardia, fatigue, bronchospasm (non-selective), masking of hypoglycemia symptoms.