Alpha adrenergic blocking agents
Alpha blockers are a chemically heterogeneous group of drugs that act by blocking alpha-adrenergic receptors.
Classification
- Non-selective: Phenoxybenzamine, Phentolamine, Dihydroergotamine
- Selective: Prazosin, Doxazosin, Terazosin, Alfuzosin, Yohimbine (α2)
Pharmacodynamics
Alpha blockers inhibit the action of norepinephrine and epinephrine on alpha-adrenergic receptors, leading to vasodilation and decreased blood pressure.
- Non-selective alpha blockers (e.g., phentolamine) block both α1 and α2 receptors, reducing peripheral vascular resistance. However, they can also cause reflex tachycardia due to increased cardiac output.
- Selective alpha-1 blockers (e.g., prazosin) specifically block α1 receptors in vascular smooth muscle, causing vasodilation without significant reflex tachycardia.
- Alpha-1 blockers also reduce smooth muscle tone in the bladder neck and prostate, improving urinary flow in benign prostatic hyperplasia (BPH) patients.
- Both non-selective and selective alpha blockers effectively lower blood pressure and relieve BPH symptoms.
Pharmacokinetics
- Non-selective alpha blockers (e.g., phentolamine)
- Administered intravenously → rapid onset, short duration
- Used for acute hypertensive crises and pheochromocytoma management
- Metabolized in the liver, excreted in urine
- Short half-life → requires frequent administration
- Selective alpha-1 blockers (e.g., prazosin)
- Administered orally → well-absorbed from the gastrointestinal tract
- Undergo significant first-pass metabolism in the liver
- Moderate half-life, allowing once or twice-daily dosing
- Highly protein-bound, affecting distribution and duration of action
- Metabolized in the liver, excreted in urine
Side Effects
- Non-selective alpha blockers (e.g., Phentolamine):
- Hypotension, reflex tachycardia, nasal congestion, gastrointestinal disturbances
- Selective alpha-1 blockers (e.g., Prazosin):
- Dizziness, orthostatic hypotension, headache, fatigue, nasal congestion
Drug Interactions
- Antihypertensives, diuretics, nitrates → Increased hypotensive effect
- NSAIDs → Reduced efficacy of alpha blockers
- PDE-5 inhibitors (e.g., sildenafil) → Enhanced hypotension
- Beta-blockers → Exacerbate reflex tachycardia
- Alcohol → Additive hypotensive effects
- Sympathomimetics → Counteract alpha blocker effects
- CYP enzyme inhibitors/inducers → Altered metabolism of alpha blockers
Therapeutic Use
- Hypertension → Lowers blood pressure by vasodilation
- Benign prostatic hyperplasia (BPH) → Improves urinary flow and relieves symptoms
- Pheochromocytoma → Manages hypertension and prevents catecholamine-induced crises
- Raynaud’s disease → Reduces vasospasm and improves blood flow to extremities
- Peripheral vascular disease → Enhances blood flow to affected areas
Contraindications
- Pregnancy → Risk of hypotension and reduced placental perfusion; use only if necessary
- Lactation → Limited safety data; potential adverse effects on infant; caution advised
Recap Questions
- What is the main difference between non-selective and selective alpha blockers?
- Why do non-selective alpha blockers cause reflex tachycardia while selective alpha-1 blockers do not?
- Which alpha blocker is used to treat BPH, and how does it help with urinary symptoms?