Overview
This lecture reviews the drug class of alpha blockers, focusing on their mechanisms, uses, side effects, and clinical considerations in blood pressure management and other indications.
Centrally Acting Alpha-2 Agonists
- Centrally acting alpha-2 agonists (e.g., clonidine, guanfacine, methyldopa) reduce sympathetic outflow by activating alpha-2 receptors in the brain.
- These drugs must cross the blood-brain barrier to act at presynaptic terminals, decreasing norepinephrine release.
- Resulting effects include reduced heart rate (negative chronotropy), decreased cardiac contractility (negative inotropy), and vasodilation, leading to lower blood pressure.
- Indirectly lower renin release by reducing sympathetic stimulation of the kidneys.
- Side effects include sedation, depression, sexual dysfunction, and risk of rebound hypertension if abruptly stopped (notably with clonidine).
- Methyldopa requires metabolic activation and may cause hemolytic anemia (positive Coombs test).
- Clonidine and guanfacine are also used for ADHD and withdrawal syndromes; clonidine is available as a patch for better compliance.
- Dexmedetomidine (Precedex), another alpha-2 agonist, is used for sedation in ICU settings without suppressing respiratory drive.
Alpha-1 Blockers
- Alpha-1 blockers (e.g., prazosin, doxazosin, terazosin) induce peripheral vasodilation by blocking smooth muscle contraction in blood vessels.
- Main use is hypertension and sometimes benign prostatic hyperplasia (BPH), but agents specific to Alpha-1A are preferred for BPH symptoms.
- Vasodilation decreases afterload and may cause reflex tachycardia; risk of orthostatic hypotension, especially in elderly or volume-depleted patients.
- Monotherapy may activate the renin-angiotensin-aldosterone system (RAAS), potentially reducing long-term effectiveness and increasing fluid retention.
- First-dose phenomenon: significant orthostasis can occur with the initial dose, especially if combined with diuretics or negative chronotropes.
Non-Selective Alpha Blockers
- Phentolamine and phenoxybenzamine block both alpha-1 and alpha-2 receptors.
- Primary uses include preoperative management of pheochromocytoma (adrenal tumor causing hypertension) and treatment of catecholamine extravasation.
- Phenoxybenzamine is available orally, phentolamine is parenteral and can be injected locally for tissue protection after extravasation.
Key Terms & Definitions
- Alpha-2 agonist — drug that stimulates alpha-2 receptors to reduce sympathetic nervous system outflow.
- Alpha-1 blocker — drug that blocks alpha-1 receptors on vasculature, causing vasodilation.
- RAAS (Renin-Angiotensin-Aldosterone System) — hormonal system regulating blood pressure and fluid balance.
- Reflex tachycardia — compensatory increase in heart rate in response to blood pressure drop.
- First-dose phenomenon — marked orthostatic hypotension seen after the initial dose of alpha-1 blockers.
- Coombs test — lab test for hemolytic anemia, can be positive with methyldopa.
Action Items / Next Steps
- Review mechanisms, uses, and side effects of alpha blockers.
- Remember specific clinical indications (e.g., clonidine for withdrawal, dexmedetomidine for ICU sedation, alpha-blocker selection in BPH).
- Note the risk of rebound hypertension with abrupt discontinuation of clonidine.
- Study adverse effect profiles, especially in elderly, pregnant, or non-compliant patients.