Alpha-Blockers

Alpha-Blockers

Drug	Clinical Applications	Toxicity
Nonselective α-Blockers
Phenoxybenzamine (irreversible, preferred)	• Pheochromocytoma  • High catecholamine states	• Orthostatic hypotension • Reflex tachycardia
Phentolamine (reversible)
Selective α1-blockers (-zosin)
Prazosin	• Hypertension • Urinary retention in benign prostatic hyperplasia (tamulosin is the most specific for urinary symptoms)	• First dose orthostatic hypotension  • Headache and dizziness
Doxazosin
Terazosin
Tamulosin
Selective α2 blockers
Mirtazapine	• Depression	• Sedation • Xerostomia • ↑ serum cholesterol • ↑ appetite
Yohimbine	• Male erectile dysfunction • Hypotension	• Anxiety

α-Blockers + Sympathomimetics effects

• Epi + α-blocker 
  • before non selective α-blocker is given, epi’s net effect is to increase heart rate, contractility, and vasoconstriction leading a net pressor effect on blood pressure
  • after α-blocker is given, epi’s α response is blocked while its β₂ response remains leading to net depressor effect on blood pressure (top of image)
    • β₂ is Gs coupled, increases cAMP, causes vasodilation
    • α is Gq coupled, increases calcium causes vasoconstriction
• Epi + β-blocker
  • before nonselective α-blocker is given, epi’s net effect is to increase heart rate, contractility, and vasoconstriction leading a net pressor effect on blood pressure
  • after β-blocker given, epi’s β response is blocked, while α response remains leading to net pressor effect (bottom of image)
• Phenylephrine + α-blocker 
  • phenylephrine (α₁ > α₂ agonist) leads to a net pressor effect on blood pressure
  • administration of a nonselective α-blocker leads a net zero effect on blood pressure

Overview

Alpha-blockers are a class of medications that primarily act by blocking the alpha-adrenergic receptors in the sympathetic nervous system. These receptors are found in various tissues throughout the body, including blood vessels and smooth muscles.

Alpha-blockers work by inhibiting the action of norepinephrine, a neurotransmitter that binds to alpha receptors. By blocking these receptors, alpha-blockers cause the relaxation of smooth muscles in the walls of blood vessels and other structures, leading to vasodilation (widening of blood vessels) and a decrease in peripheral vascular resistance.

Alpha-blockers are commonly prescribed for various medical conditions, including:

1. Hypertension: By relaxing blood vessels, alpha-blockers help lower blood pressure. They are often used as a second-line treatment for hypertension or in combination with other antihypertensive medications.
2. Benign prostatic hyperplasia (BPH): Alpha-blockers can relieve the symptoms associated with an enlarged prostate gland, such as urinary hesitancy, frequent urination, and weak urine flow. They relax the smooth muscle in the prostate and bladder neck, allowing for easier urination.
3. Raynaud’s disease: Alpha-blockers can be used to treat Raynaud’s disease, a condition characterized by episodes of reduced blood flow to the extremities (fingers and toes), leading to color changes, numbness, and pain. By dilating blood vessels, alpha-blockers can improve blood circulation.
4. Phaeochromocytoma: Alpha-blockers may be prescribed in the management of phaeochromocytoma, a rare tumor that secretes excessive amounts of adrenaline and noradrenaline. These medications help control blood pressure fluctuations caused by the excessive release of catecholamines.
5. Erectile dysfunction: Some alpha-blockers, such as tamsulosin, are used to treat erectile dysfunction by relaxing the smooth muscle in the prostate and bladder neck, allowing for improved blood flow to the erectile tissues.

Commonly prescribed alpha-blockers include doxazosin, prazosin, terazosin, alfuzosin, and tamsulosin. These medications can have side effects, including dizziness, low blood pressure, nasal congestion, and sexual dysfunction. It is important to follow the prescribed dosage and consult a healthcare professional for guidance and monitoring while taking alpha-blockers.

Studies

Alpha-blockers have been extensively studied for their efficacy and safety in various medical conditions. Here are some notable studies and findings related to alpha-blocker use:

1. Hypertension:
   • The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) compared the effectiveness of different antihypertensive medications, including alpha-blockers. The study found that diuretics and calcium channel blockers were more effective in reducing cardiovascular events compared to alpha-blockers.
   • The European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) trial evaluated the use of the alpha-blocker doxazosin in patients with stable coronary artery disease. The study found no significant benefit of doxazosin in reducing cardiovascular events compared to placebo.
2. Benign Prostatic Hyperplasia (BPH):
   • The Medical Therapy of Prostatic Symptoms (MTOPS) trial compared the effectiveness of several medications, including the alpha-blocker doxazosin, finasteride (a 5-alpha-reductase inhibitor), and a combination of both, in the treatment of BPH. The study showed that doxazosin and finasteride reduced the risk of BPH progression, but the combination therapy was most effective.
   • A study published in The New England Journal of Medicine compared the efficacy and safety of different alpha-blockers (doxazosin, terazosin, and tamsulosin) in the treatment of BPH. The study found that all three medications improved urinary symptoms, but tamsulosin had a lower risk of cardiovascular side effects.
3. Raynaud’s Disease:
   • A systematic review published in the Journal of the American Academy of Dermatology examined the use of alpha-blockers in the treatment of Raynaud’s disease. The review concluded that alpha-blockers, particularly prazosin and doxazosin, were effective in reducing the frequency and severity of Raynaud’s attacks.
4. Phaeochromocytoma:
   • Studies have shown the efficacy of alpha-blockers, such as phenoxybenzamine and prazosin, in controlling blood pressure and preventing hypertensive crises in patients with phaeochromocytoma. These medications are often used as part of the preoperative management to stabilize blood pressure before tumor removal.
5. Erectile Dysfunction:
   • Alpha-blockers, particularly tamsulosin, have been studied for their use in improving erectile dysfunction in men with BPH. Research has shown that tamsulosin can enhance erectile function by improving blood flow to the erectile tissues.

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