Alpha-adrenergic antagonists

Mechanism of Action - The Alpha Blockade

• Alpha-adrenergic antagonists competitively or non-competitively block α-adrenergic receptors on effector tissues.
• This prevents the binding of endogenous catecholamines like norepinephrine (NE) and epinephrine (Epi).

• α1 Receptor Blockade:
  • Primary mechanism for clinical effects.
  • Inhibits vasoconstriction in arterioles and veins.
  • Leads to ↓ peripheral vascular resistance and ↓ blood pressure.
  • Also causes relaxation of smooth muscle in the prostate and bladder neck.

⭐ Epinephrine Reversal: In the presence of an alpha-blocker, epinephrine administration causes a paradoxical fall in blood pressure. The α1-mediated vasoconstriction is blocked, unmasking the β2-mediated vasodilation.

Drug Roster - Selective vs. Non-Selective

• Non-selective α-antagonists (block α1 & α2)

  • Phenoxybenzamine: Irreversible, long-acting. Covalently binds.
  • Phentolamine: Reversible, competitive, short-acting.

• Selective α1-antagonists (-osin suffix)

  • Prazosin, Terazosin, Doxazosin: Treat hypertension & BPH.
  • Tamsulosin, Alfuzosin: Uroselective for α1A subtype in prostate/bladder; minimal BP effect.
  • Key Side Effect: First-dose orthostatic hypotension (less with uroselective agents).
  • 📌 The "-osins" help the urine "flow-sin" in BPH.

⭐ Phentolamine is used to diagnose and manage hypertensive crises, especially from pheochromocytoma or tyramine toxicity with MAOIs. It's also an antidote for norepinephrine extravasation.

Clinical Uses - Alpha Blockers at Work

• Benign Prostatic Hyperplasia (BPH): Selective α1A-blockers (e.g., tamsulosin) are preferred. They relax smooth muscle in the bladder neck and prostate, improving urinary stream with minimal impact on blood pressure.
• Hypertension: Prazosin, doxazosin, terazosin. Used as second-line therapy. Major side effect is first-dose orthostatic hypotension.
• Pheochromocytoma: Phenoxybenzamine (irreversible non-selective) is crucial for pre-operative BP management to prevent intraoperative hypertensive crises.
• Pressor Extravasation: Phentolamine is infiltrated locally to antagonize vasoconstriction from extravasated vasopressors like norepinephrine.

⭐ For pheochromocytoma, remember the sequence: Alpha-blockade first, then beta-blockade. Giving a beta-blocker alone can lead to unopposed α1-receptor stimulation, causing a catastrophic rise in blood pressure.

Adverse Effects - The Blockade's Backfire

• Cardiovascular:
  • Orthostatic hypotension (postural dizziness/syncope), especially after the first dose.
  • Reflex tachycardia (due to ↓ blood pressure activating baroreceptors).
  • Fluid retention/edema.
• CNS:
  • Dizziness, lethargy, headache.
• Other:
  • Nasal congestion and stuffiness.
  • Miosis (pupillary constriction).
  • Inhibition of ejaculation.

⭐ First-Dose Effect: Severe postural hypotension and syncope can occur 30-90 minutes after the initial dose of prazosin or with a rapid dose increase. Advise patients to take the first dose at bedtime.

High‑Yield Points - ⚡ Biggest Takeaways

• Phentolamine is a reversible, non-selective α-blocker used for pheochromocytoma and MAOI hypertensive crisis.
• Phenoxybenzamine is an irreversible, non-selective α-blocker, primarily for preoperative management of pheochromocytoma.
• The "-osins" (prazosin, terazosin) are selective α1 blockers for hypertension and BPH.
• Watch for first-dose orthostatic hypotension as a major side effect across the class.
• Tamsulosin is uroselective for BPH, targeting α1A/D receptors with minimal BP effects.
• Reflex tachycardia is a common adverse effect due to the drop in blood pressure.