Prazosin adverse effects

Prazosin, oxazosin and terazosin (see p. 73) produce a competitive block of oci adrenoceptors. They decrease peripheral vascular resistance and lower arterial blood pressure by causing the relaxation of both arterial and venous smooth muscle. These drugs cause only minimal changes in cardiac output, renal blood flow, and glomerular filtration rate. Therefore, long-term tachycardia and increased renin release do not occur. Postural hypotension may occur in some individuals. Prazosin is used to treat mild to moderate hypertension and is prescribed in combination with propranolol or a diuretic for additive effects. Reflex tachycardia and first dose syncope are almost universal adverse effects. Concomitant use of a p-blocker may be necessary to blunt the short-term effect of reflex tachycardia. 

The postsjmaptic alpha-adrenoceptor antagonists, indor-amin, prazosin, and related quinazoline derivatives, block alphai-adrenoceptor-mediated vasoconstriction of peripheral blood vessels (both arterial and venous) and are effectively peripheral vasodilators (1,2). Qualitatively and quantitatively common adverse effects are generally similar, although indoramin has additional effects on other neurotransmitter systems and therefore tends to be considered separately. Their use in benign prostatic hyperplasia has been reviewed (3,4). 

Indoramin penetrates the nervous system significantly and is reported to have a relatively high incidence of adverse effects, including sedation, dizziness, depression, headache, palpitation, dry mouth, and constipation (2). In a comparison with prazosin, prazosin produced a lower incidence of sedation, which is the most common adverse effect of indoramin, usually transient, in about 19% of cases (1). Other adverse effects that have sometimes led to withdrawal of indoramin have been dry mouth, dizziness, and failure of ejaculation. These adverse effects can be reduced by starting therapy with small doses and titrating gradually. 

The alphai-adrenoceptor antagonist terazosin has similar adverse effects to those of prazosin. The long-term efficacy and safety of terazosin have been reviewed, in both monotherapy and combination therapy in whites and blacks (1,2). 

Prazosin, terazosin, doxazosin, tamsulosin, and alfuzosin have been studied extensively and used widely in patients with benign prostatic hyperplasia. With the exception of tamsulosin, the comparative efficacies of each of these drugs, especially in comparison with relative adverse effects such as postural hypotension, appear similar, although direct comparisons are limited. Tamsulosin at the recommended dose of 0.4 mg daily is less likely to cause orthostatic hypotension than the other drugs. There is growing evidence that the predominant a,-receptor subtype expressed in the human prostate is the a,-receptor. Developments in this area will provide the basis for the selection of Ct receptor antagonists with specificity for the relevant subtype of aj-receptor. However, the possibility remains that some of the symptoms of BPH are due to aj-receptors in other sites, such as bladder, spinal cord, or brain. 

An adverse effect of prazosin and its congeners is the first-dose effect marked postural hypotension and syncope may occur 30-90 minutes after the initial dose. The mechanisms responsible for exaggerated hypotensive response and the subsequent development of tolerance to the effect are not clear an action in the CNS to reduce sympathetic outflow may contribute. Risk of the first-dose phenomenon is minimized by limiting the initial dose (e.g., 1 mg at bedtime), by increasing the dosage slowly, and by introducing additional antihypertensive drugs cautiously. Since orthostatic... 

E. Adrenoceptor Blockers Alpha -selective agents (eg, prazosin) and beta-blockers (eg, propranolol) are effective antihypertensive drugs. Alpha-blockers reduce vascular resistance and venous return. The nonselective alpha-blockers (phentolamine, phenoxybenzamine) are of no value in chronic hypertension because of excessive compensatory responses, especially tachycardia. Alpha,-selective adrenoceptor blockers are relatively free of the severe adverse effects of the nonselective alpha-blockers and postganglionic nerve terminal sympathoplegic agents. 

Communication with the profession was at first maintained by continuing (until January 1985) the Adverse Reaction Series leaflets started by CSD, and later by a regularly published bulletin on Current Problems . The first issue of Current Problems in September 1975 led with the adverse oculo-cutaneous effects and sclerosing peritonitis associated with p-adrenergic receptor blocking agents and also included items on loss of consciousness associated with prazosin and on the risks of anti-inflammatory agents and asthma. 

Prazosin blocks postsynaptic ttj-receptors but not presynaptic a -autoreceptors. It has a curious adverse first-dose effect within 2h of the first (rarely after another) dose there may be a brisk hypotension sufficient to cause loss of consciousness. Hence the first dose should be small (0.5 mg) and given before going to bed. This side effect together with a rather short duration of action (tj 3 h) has meant that newer longer-acting drugs have largely replaced it. 

Effective antihypertensive therapy should include agents that do not adversely affect carbohydrate metabolic abnormalities. Commonly used antihypertensive agents, such as thiazide, thiazide-like diuretics and /3-blockers, are associated with glucose intolerance and increased insulin resistance (Sowers, 1991). In contrast, calcium antagonists and peripheral a-blockers (such as prazosin and terazosin) do not adversely affect glucose tolerance or insulin sensitivity. 

Direct information seems to be limited to this study but what occurred is consistent with the way indometacin reduces the effects of many other different antihypertensives (e.g. see ACE inhibitors + NSAIDs , p.28, and Beta blockers + Aspirin or NSAIDs , p.835). It apparently does not affect every patient. If indometacin is added to established treatment with prazosin, be alert for a reduced antihypertensive response. It is not known exactly what happens in patients taking both drugs long-term, but note that with other interactions between antihypertensives and NSAIDs the effects seem to be modest. The manufacturers say that prazosin has been given with indometacin (and also aspirin and phenylbutazone) without any adverse interaction in clinical experience to date. Other manufacturers also... 

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