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6/5/13

Prazosin

Prazosin [PRAY-zoe-sin], terazosin [ter-AY-zoe-sin], doxazosin [dox-AY-zoe-sin], and tamsulosin [tam-SUE-loh-sin] are selective competitive blockers of the α1 receptor. In contrast to phenoxybenzamine and phentolamine the first three drugs are useful in the treatment of hypertension. Tamsulosin and alfuzosin [al-FYOO-zoe-sin] are indicated for the treatment of benign prostatic hypertrophy (also known as benign prostatic hyperplasia or BPH). Metabolism leads to inactive products that are excreted in the urine except for those of doxazosin, which appear in the feces. Doxazosin is the longest acting of these drugs

1. Cardiovascular effects: All of these agents decrease peripheral vascular resistance and lower arterial blood pressure by causing the relaxation of both arterial and venous smooth muscle. Tamsulosin has the least effect on blood pressure. These drugs, unlike phenoxybenzamine and phentolamine, cause minimal changes in cardiac output, renal blood flow, and the glomerular filtration rate.

 2. Therapeutic uses: Individuals with elevated blood pressure who have been treated with one of these drugs do not become tolerant to its action. However, the first dose of these drugs produces an exaggerated orthostatic hypotensive response that can result in syncope (fainting). This action, termed a “first-dose” effect, may be minimized by adjusting the first dose to one-third or one-fourth of the normal dose and by giving the drug at bedtime. An increase in the risk of congestive heart failure has been reported when α1-receptor blockers have been used as monotherapy in hypertension. The α1-receptor antagonists have been used as an alternative to surgery in patients with symptomatic BPH. Blockade of the α receptors decreases tone in the smooth muscle of the bladder neck and prostate and improves urine flow. Tamsulosin is a more potent inhibitor of the α1A receptors found on the smooth muscle of the prostate. This selectivity accounts for tamsulosin's minimal effect on blood pressure. [Note: Finasteride and dutasteride inhibit 5α-reductase, preventing the conversion of testosterone to dihydrotestosterone. These drugs are approved for the treatment of BPH by reducing prostate volume in selected patients ]

3. Adverse effects: α1 Blockers may cause dizziness, a lack of energy, nasal congestion, headache, drowsiness, and orthostatic hypotension (although to a lesser degree than that observed with phenoxybenzamine and phentolamine). An additive antihypertensive effect occurs when prazosin is given with either a diuretic or a β-blocker, thereby necessitating a reduction in its dose. Due to a tendency to retain sodium and fluid, prazosin is frequently used along with a diuretic. Male sexual function is not as severely affected by these drugs as it is by phenoxybenzamine and phentolamine; however, by blocking a receptors in the ejaculatory ducts and impairing smooth muscle contraction, inhibition of ejaculation and retrograde ejaculation have been reported. Figure below summarizes some adverse effects observed with αblockers.


Figure : Some adverse effects commonly observed with nonselective α- adrenergic blocking agents.



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