Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urapidil has been approved as sustained-release capsules containing 30, 60 and 90 mg, respectively, and as ampules containing 25 and 50 mg for treatment of all grades of hypertension, in several countries in Europe, South America, as well as in Japan and other Asian regions. In general, the treatment should start with 60 mg twice daily, 1 capsule in the morning and 1 in the evening. This schedule may be adapted according to the therapeutic needs. During the last few years, urapidil has been investigated extensively in comparison with several types of established antihypertensive drugs. Urapidil given orally has been tested in comparative trials against placebo, acebutolol, metoprolol, captopril, nifedipine and nitrendipine with responder rates of 40 to 70%. These responder rates are to be expected for a variety of antihypertensive drugs in monotherapy. Further studies with clonidine, prazosin and alpha-methyldopa showed similar responder rates as established for the other antihypertensive drugs studied. Adverse reactions include dizziness, headache and nausea and occasionally tiredness, orthostatic dysregulation and gastric disorders. These symptoms were transient, mostly occurring during the early phases of therapy and disappearing as treatment continued. Adverse effects are considered to be mainly due to blood pressure reduction. Intravenous comparative trials have been performed with urapidil against placebo, diazoxide and sodium nitroprusside. Adverse effects of parenterally applied urapidil are similar to those observed during oral treatment. Specific contraindications for urapidil are unknown. However, as for other vasodilating drugs, intravenous urapidil should not be administered to patients with stenosis of the aortic isthmus or with aortic valve insufficiency.
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PMID:Overview of clinical trials with urapidil. 266 12

Urapidil is a postsynaptic alpha 1-adrenoceptor antagonist with a pharmacodynamic profile similar to prazosin. Unlike prazosin, however, urapidil also has some central activity which may explain the apparent improved tolerability of urapidil, including the absence of first-dose syncope. In clinical trials urapidil therapy resulted in significant reductions in blood pressure in patients with mild to severe essential hypertension, with little influence on heart rate. It is an effective antihypertensive when administered as monotherapy or in combination with beta-blockers and thiazide diuretics. In the few patients with cardiac dysfunction who have been studied to date, urapidil has improved myocardial oxygen consumption, systemic vascular resistance, left ventricular function, cardiac output and pulmonary capillary wedge pressure; however, further study is needed to assess the full therapeutic potential of urapidil in these patients. Urapidil has also been used successfully in the treatment of hypertensive emergencies, including eclampsia and pre-eclampsia, hypertensive crisis and hypertension occurring during general and cardiac surgery, rapidly lowering blood pressure without altering heart rate. Urapidil does not affect lipid or glucose metabolism, nor does it impair renal function. In addition, urapidil may be beneficial to patients with pulmonary hypertension, in whom it dilates pulmonary vascular beds to a greater extent than systemic vasculature, although therapeutic trials have not examined this effect. The most common adverse effects associated with urapidil therapy are dizziness, nausea, headache, fatigue and palpitations; however, these tend to be mild and transient and usually do not require discontinuation of treatment. Thus, urapidil offers a useful alternative to currently available drugs for the treatment of mild to severe hypertension, either as monotherapy or in combination with other antihypertensive drugs.
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PMID:Urapidil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension. 269 46

Urapidil is an alpha 1-adrenoceptor antagonist which also has a central antihypertensive effect, the mechanism of which has yet to be conclusively defined. A number of open and comparative studies have produced evidence for the efficacy and safety of urapidil. A study recently completed by the author produced a dose-dependent antihypertensive effect of urapidil which, however, failed to achieve statistical significance, probably due to a large variance of the data and an unexpectedly large placebo effect. Adverse reactions are those expected from an alpha 1-blocker, particularly dizziness, as well as nausea and fatigue. Urapidil is potentially an important new antihypertensive agent; further variable dose and combination (with other antihypertensive agents) studies would help further define its therapeutic niche.
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PMID:Urapidil in the treatment of hypertension. 304 58

The study was designed to follow the haemodynamic effects and pharmacokinetics under steady-state conditions of three different doses of urapidil infused continuously. Nine male hypertensive patients received three randomly assigned intravenous infusions of 32.5, 65 and 130 mg urapidil, over 14 h during 6 consecutive days, in a change-over fashion. Blood pressure and heart rate were measured over a period of 28 h after the infusion began and were compared with a reference profile obtained prior to the treatment periods. Urapidil and its main metabolite, parahydroxylated urapidil, were also determined for 28 h after the infusion began using HPLC. The 32.5 mg dose of urapidil caused a maximum decrease in systolic blood pressure of 33 +/- 8 mmHg, the 65 mg dose a maximum decrease of 39 +/- mmHg and the 130 mg dose a maximum decrease of 50 +/- 12 mmHg. The 32.5 and 65 mg doses resulted in similar serum urapidil concentrations, with maximum levels in the 100 to 200 ng/ml range, and the 130 mg dose caused a maximum level approximately four times that achieved with the 32.5 mg dose. The serum concentration of parahydroxy urapidil was proportional to the corresponding dose of urapidil. Four patients reported mild headache, fatigue, weakness, pressure in the head, perspiration and orthostatic dysregulation. The side-effects were probably drug related but required no specific therapy. In summary, the 32.5 mg dose of urapidil resulted in a pronounced decrease in blood pressure. The average pressure reduction over the 14-h infusion period showed further dose-dependent increases after the 65 and 130 mg doses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacodynamics and pharmacokinetics of three different doses of urapidil infused in hypertensive patients. 375 42