Terazosin
Tóm tắt
Terazosin selectively antagonises α1-adrenoceptor-mediated contraction of the prostate, prostatic capsule, proximal urethra and bladder base, and consequently reduces urethral pressure, bladder outlet resistance and urinary symptoms associated with symptomatic benign prostatic hyperplasia. The efficacy of terazosin is reflected in increases in peak urinary flow rate, and reductions in obstructive and irritative symptom scores compared with placebo, and reductions in residual urinary volume from baseline. Clinical improvements begin to occur within 2 weeks and have been sustained for up to 2 years. The most marked treatment effects tend to occur in patients with more severe pretreatment urinary flow abnormalities. The relatively long duration of action of terazosin, allowing once-daily administration, offers a potential clinical advantage over other α1-adrenoceptor antagonists although formal compliance studies have not been reported. Terazosin is generally well tolerated, but caution is recommended at treatment initiation and when dosage adjustments are made due to an increased risk of postural hypotension and related adverse effects at these times; such a risk has also been observed with several other α1-adrenoceptor antagonists. Although publication of clinical trial results with terazosin is still evolving, this drug shows promise in the treatment of patients with mild to moderate symptomatic benign prostatic hyperplasia for whom surgery is not absolutely indicated. Terazosin also shows promise as a nonsurgical treatment alternative in patients with severe symptoms who are unfit for surgery and also in those who are on long waiting lists for surgery. Terazosin has high in vitro affinity for postjunctional α
1-adrenoceptors; its affinity for α
1-adrenoceptors (in prostatic tissue) is 400-fold greater than for α
2-adrenoceptors, and its affinity for α
1-adrenoceptors (in rat liver homogenates) is one-third that of prazosin. Terazosin has 4-fold greater selectivity for α
1-adrenoceptors than doxazosin. The dose-contractile response curves to phenylephrine and norepinephrine (noradrenaline) are displaced in parallel to the right by terazosin, demonstrating competitive binding at the α
1-adrenoceptor. Terazosin significantly increases peak urinary flow rate compared with placebo, and reduces residual urinary volume from baseline in patients with benign prostatic hyperplasia. Terazosin has similar affinity for α
1-adrenoceptors in genitourinary and vascular tissue. Minimal, but statistically significant, reductions in blood pressure (4.6/3.7mm Hg) in patients with benign prostatic hyperplasia receiving oral terazosin 1 to 20 mg/day have been observed. Terazosin has a favourable effect on the lipid profile. Oral terazosin is almost completely absorbed, with a bioavailability of approximately 90% and time to peak plasma concentration of 1 to 2 hours. Coadministration with food appears to reduce the rate but not the extent of absorption. The apparent volume of distribution is 18 to 30L and terazosin is 90 to 94% protein bound. Terazosin is extensively metabolised by the liver, and the biliary tract is the major route of elimination; the drug is also excreted in the urine. The relatively long terminal phase plasma elimination half-life (8 to 13h) of terazosin allows once-daily administration. The overall pharmacokinetic profile of terazosin is not affected by increasing age, renal impairment or heart failure, and dosage adjustments do not appear necessary in these patient groups. The effects of liver impairment on the pharmacokinetics of terazosin have not been reported. Although published clinical data of terazosin in benign prostatic hyperplasia are still relatively limited, oral terazosin 1 to 20mg once daily decreases obstructive, irritative and total symptom scores and increases peak urinary flow rate compared with placebo in patients with symptomatic benign prostatic hyperplasia. Terazosin also reduces residual urinary volume from baseline. Improvements begin to occur within 2 weeks and have been sustained for up to 2 years. The greatest improvements occur in patients with more severe obstruction (pretreatment peak urinary flow rates ⩽ 8.5 ml/sec). Symptom and urinary flow improvements do not appear to be correlated with age. Oral terazosin 1 to 20 mg/day is generally well tolerated in the short (⩽ 6 months) and longer term (up to 2 years) in patients with benign prostatic hyperplasia. In placebo-controlled trials, the most common adverse effects were asthenia (7.4%) and dizziness (9.1%), and were generally mild to moderate, reversible and of minimal clinical significance. Withdrawal rates were not significantly different between terazosin- and placebo-treated patients. The incidence of adverse effects, particularly dizziness, postural hypotension, asthenia, nausea and somnolence is greatest 1 to 3 days after dosage initiation or adjustment; caution is recommended at these times. Postural hypotension, syncope, dizziness and related adverse effects are more common in elderly (> 65 years) than in younger (< 65 years) patients. The recommended dosage of terazosin in patients with benign prostatic hyperplasia is 5 to 10mg once daily, titrated up to this level after initial doses of l mg at bedtime. Caution is recommended at dose initiation, dosage change, and treatment reinitiation after a period of drug withdrawal, especially in the elderly. Concomitant administration of terazosin and an angiotensin-converting enzyme inhibitor or diuretic should be closely monitored as dizziness or dizziness-related adverse effects may be enhanced.
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