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 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cadralazine is a peripheral arteriolar vasodilator which, unlike hydralazine or dihydralazine, has a protected hydrazino group. In hypertensive patients the optimal effect, based on the antihypertensive efficacy to tolerability ratio, is seen after a 15 mg dose when the drug is administered as monotherapy. When administered in combination with other antihypertensive agents, a 10 mg daily dosage seems appropriate. Noncomparative trials have shown that, in patients who had failed to respond adequately to a beta-blocker and/or diuretic, the addition of cadralazine 10 to 30 mg once daily reduced systolic/diastolic blood pressure by 11 to 19%/13 to 22%. This antihypertensive effect becomes evident over a 2- to 6-week period of therapy and persists during longer term administration. Comparative studies have shown that cadralazine is superior to placebo, and has a similar blood pressure lowering effect to hydralazine, dihydralazine and prazosin in patients not controlled by beta-blocker and/or diuretic but who continued to receive these treatments. Similarly, cadralazine and chlorthalidone were equally effective in reducing blood pressure in resting hypertensive patients but cadralazine shows an advantage in reducing the pressor response in exercising patients. Cadralazine is well tolerated when administered with a beta-blocker or diuretic. Most adverse effects become less frequent and severe with continued use, occur more frequently at dosages of 20 mg/day or more, and do not generally require withdrawal of therapy. Manifestations of the drug's vasodilating properties such as headache, asthenia, dizziness, palpitations and flushing are the most commonly reported symptoms during cadralazine monotherapy, but these may be reduced during combination therapy. The drug does not appear to induce a systemic lupus-like erythematosus syndrome, as may occur with hydralazine, but additional clinical experience is required to completely exclude this possibility. In conclusion, because of its efficacy as a second- or third-line antihypertensive agent, its simple once daily dosage regimen and favourable risk: benefit ratio, cadralazine may have a useful role, particularly in those hypertensive patients who do not respond adequately to established antihypertensive treatments. However, the therapeutic potential of cadralazine cannot be clearly established until the present limited clinical base is expanded to include comparisons with other classes of vasodilating drugs (ACE inhibitors and calcium antagonists), and its utility in the management of other indications such as severe hypertension during pregnancy has been adequately explored.
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PMID:Cadralazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension. 208 13

Dilevalol, the RR-stereoisomer of labetalol, is a non-cardioselective beta-adrenoceptor antagonist with substantial partial beta 2-agonist and negligible alpha 1-blocking activity. Reduction in blood pressure during dilevalol administration is associated with peripheral vasodilatation, and heart rate remains essentially unchanged. Following oral administration, dilevalol is completely absorbed. Once-daily administration is possible, due to a long elimination half-life. Large well-controlled trials reveal that dilevalol is equivalent in antihypertensive efficacy to metoprolol, the ACE inhibitors captopril and enalapril, and the calcium antagonist nifedipine. Smaller noncomparative and comparative trials demonstrate the blood pressure-lowering effects of dilevalol and suggest an efficacy at least equivalent to that of the 'pure' beta-blockers atenolol and propranolol and the alpha 1-blockers urapidil and doxazosin. Dilevalol appears to be well tolerated, the most frequent adverse effects being dizziness, headache and diarrhoea in only about 7% of patients each. Unlike alpha 1-blockers and labetalol, dilevalol is not commonly associated with orthostatic hypotension. Thus, data suggest that dilevalol, with its distinctive pharmacological profile, is likely to be a useful addition to the options currently available for treating patients with mild to moderate essential hypertension.
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PMID:Dilevalol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in hypertension. 218 2

The present single-blind, randomised, cross-over, placebo-controlled study was set up to compare the first-dose effects upon blood pressure (BP) and cerebral blood flow (CBF, measured by Xenon inhalation) of a single oral dose of atenolol 50 mg and enalapril 5 mg in ten hypertensive patients receiving a thiazide diuretic. It was found that a) the timing and degree of fall in BP after the first dose of atenolol and enalapril on a diuretic background were similar and generally not associated with symptoms or a fall in CBF, and b) dizziness, which is sometimes associated with the first-dose effect of ACE inhibitors in hypertensives on diuretics, can occasionally occur accompanied by a substantial fall (43%) in CBF in the absence of marked falls in systolic blood pressure. It is suggested that the latter event may be linked to a disturbance of cerebral autoregulation in part dependent on localised renin-angiotensin systems.
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PMID:First-dose effects of enalapril and atenolol upon blood pressure and cerebral blood flow in patients with mild hypertension on diuretic therapy. 219 32

Various antihypertensive drugs reduce blood pressure by different mechanisms. In some instances, adverse reactions occur because of specific hemodynamic effects. Examples include syncope with alpha-blockade or vasodilator therapy; fatigue or exercise intolerance with the reduction in cardiac output following the use of beta-adrenergic inhibitors; edema, headaches, or dizziness with the use of vasodilators such as calcium entry blockers; renal failure in patients with renal artery stenosis or renal insufficiency following the use of ACE inhibitors; and marked hyponatremia with volume depletion following the use of diuretics, especially in elderly patients. In the majority of patients, however, blood pressure lowering can be achieved without significant adverse effects. Combining small doses of different agents with different hemodynamic actions often results in good blood pressure control and minimal reactions. Examples of these include diuretics and beta-adrenergic inhibitors, diuretics and ACE inhibitors, and beta-blockers and vasodilators.
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PMID:Do different hemodynamic effects of antihypertensive drugs translate into different safety profiles? 220 Jun 92

The safety and tolerability of lisinopril (1.25-160 mg daily) were assessed in 3,270 patients (2,688 hypertensives and 582 patients with congestive heart failure (CHF] and 280 healthy subjects. The duration of therapy ranged from a single dose to 43 months; 438 patients received lisinopril for at least 12 months (mean 20 months). In the hypertensive population, the most frequent adverse events reported were headache, dizziness, cough, nausea, diarrhoea and fatigue, although not all of these events were thought to be related to lisinopril; 6.1% discontinued lisinopril due to adverse clinical events, most commonly cough and nausea. Twelve hypertensive patients died (0.45%), but most of these were not receiving lisinopril at the time of death and none was considered to be drug-related. In CHF patients, the most frequently reported adverse events were dizziness, dyspnoea, diarrhoea, hypotension and fatigue. Again, not all of these reports were considered to be drug-related. Therapy was withdrawn in 9.6% of patients--hypotension, dizziness, diarrhoea and rash being the most frequent reasons. Fifty-three CHF patients died (9.1%) and in three cases death was considered to be related to lisinopril therapy. Hypotension, orthostatic effects or dizziness following the initial dose of lisinopril occurred infrequently (in 1.3% of the hypertensive group, including those receiving hydrochlorothiazide, and in 4.8% of CHF patients). Changes in laboratory parameters were generally minor and seldom resulted in discontinuation of therapy. Long-term treatment of hypertension and CHF with lisinopril for at least 3 years confirms that the drug is well tolerated. Overall, the side-effect profile is very similar to that of other ACE inhibitors with regard to class-specific effects. However, taste disturbance was rarely observed.
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PMID:Clinical experience with lisinopril. Observations on safety and tolerability. 255 Jun 41

Pharmacotherapy of hypertension in the aged does not differ qualitatively but only quantitatively from that in use for younger patients. Adjusted, usually lower doses of diuretics, beta-blocking agents, ACE-inhibitors and calcium-channel blockers are the basic drugs. Individual aging processes and concomitant diseases determine the choice of drugs in the elderly (individualized therapy). All substances are initially prescribed at very low dose. The increasing infirmity of the aged often associated with tiredness, dyspnea and dizziness even without treatment requires careful instruction of the patient about effects and side effects of the prescribed medication. The old WHO-guidelines (systolic BP greater than or equal to 160, diastolic BP greater than or equal to 95 mm mercury) should be maintained for diagnosis and treatment of hypertension. However antihypertensive therapy in patients over 80 years of age and in those with marginally elevated diastolic or solely elevated systolic pressure is controversial today.
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PMID:[Hypertension and old age]. 268 25

The efficacy, tolerability and impact on quality of life of the ACE inhibitor lisinopril were evaluated in a 12-week open, multicenter post-marketing surveillance study. 233 patients, 45 years and over with diastolic blood pressure (DBP) 95-105 mm Hg were followed after a washout period of 7 days. 22 withdrew due either to adverse reactions, mainly cough (4.3%) and dizziness (3%), or noncompliance. DBP of 90 mm Hg or less was achieved in 50.7% with once-a-day 10 mg lisinopril, in 26.1% with 20 mg and in 16.1% with 20 mg plus addition of hydrochlorothiazide, 12.5 mg; in only 7.1% was BP not controlled. Adverse reactions other than cough or dizziness were experienced by fewer than 1%. Dartmouth COOP Functional Health Assessment Charts/WONCA were used to evaluate quality of life and were found useful in the study. Compared to baseline assessments, all functional status indicators (physical fitness, feelings, daily activities, social activities, change in health and overall health) scored significantly better in all treated patients after 12 weeks. Thus, in more than 90% of patients lisinopril was well-tolerated, highly effective in lowering blood pressure and possibly (no control group) improved the quality of life of all patients.
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PMID:[A multicenter study of lisinopril in the treatment of mild to moderate hypertension]. 755 4

A 50-year-old very obese man had suffered from hypertension for more than 20 years and had undergone various treatment regimens, the last being with an ACE inhibitor. Since his hypertension had nevertheless increased, and he developed dizziness and headaches, a combination of ACE-inhibitor and calcium antagonist was now tried, followed--when this treatment proved unsuccessful--by the fixed-combination preparation containing enalapril plus hydrochlorothiazide. This at last led to a reduction in his blood pressure to approaching normal values, and his subjective symptoms cleared up.
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PMID:[Lowering blood pressure in an obese patient with long-term hypertension. Using a fixed combination of enalapril/hydrochlorothiazide]. 760 92

The pharmacokinetics and pharmacodynamics of the ACE inhibitor quinaprilat have been studied in six chronic haemodialysis (HD) patients and in six patients undergoing continuous ambulatory peritoneal dialysis (CAPD) after a single oral dose of 2.5 mg quinapril. Mean tmax and Cmax values (SEM) for quinaprilat in interdialytic HD patients were 4.0 (0) h and 84 (8.4) ng.ml-1 respectively, and they did not differ significantly from those in CAPD patients (4.7 (0.7) h and 64 (5.7) ng.ml-1). Elimination half lives were 30 (10.1) h (HD) and 34 (7.3) h (CAPD). Cmax, tmax, t1/2, and AUC were increased and CL was decreased compared to data reported previously after giving 2.5 mg to healthy subjects. Peritoneal clearance was calculated as 0.1 (0.1) ml.min-1, thus less than 0.5% of the dose were removed within 24 h by CAPD. ACE activity was suppressed by more than 93% between 4 and 24 h postdose (P < 0.001). It decreased in both groups with increasing plasma quinaprilat levels. Angiotensin II concentration compared to baseline was significantly decreased at 4 hours (-30.4 +/- 10%) and 24 h (-30 +/- 9.9%) (P < 0.05, n = 11), while active plasma renin concentration was still significantly increased at 48 h postdose (+ 60.2 +/- 14.5%, P < 0.01). Mean arterial pressure 24 h postdose was significantly (P < 0.05) decreased in HD (-12 mmHg) and CAPD patients (-20 mm Hg). Only two patients reported unwanted effects (fatigue, dizziness, nausea, and weakness). In conclusion, due to its long lasting effect on ACE activity and on blood pressure in terminal renal failure a starting dose of quinapril 2.5 mg o.d. may be used in hypertensive HD and CAPD patients.
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PMID:Pharmacokinetics and pharmacodynamics of quinaprilat after low dose quinapril in patients with terminal renal failure. 838 27

Losartan potassium is an orally active, nonpeptide angiotensin II (AII) receptor antagonist. It is the first of a new class of drugs to be introduced for clinical use in hypertension. This novel agent binds competitively and selectively to the AII subtype 1 (AT(1)) receptor, thereby blocking AII-induced physiological effects. An active metabolite, E3174, contributes substantially to its antihypertensive effect, which persists throughout 24 hours after once-daily administration. In patients with mild to moderate hypertension, losartan potassium 50 to 100mg once daily as monotherapy lowers blood pressure to a similar degree to enalapril, atenolol and felodipine extended release (ER). Losartan potassium combined with hydrochlorothiazide reduces blood pressure further than either drug given separately. About one-third of patients with severe hypertension have responded to the combination product. Losartan potassium appears to be effective in elderly patients. Losartan potassium is very well tolerated. In clinical trials, dizziness was the only drug-related event reported more frequently with losartan potassium monotherapy than with placebo. First-dose hypotension is uncommon. An aspect of the drug's tolerability profile which may prove to be particularly advantageous is that it is associated with a similar incidence of cough to placebo in patients with a history of ACE inhibitor-related cough. Additionally, clinically relevant adverse metabolic effects or laboratory abnormalities have not been documented during losartan potassium therapy and renal function is preserved in patients with or without renal insufficiency. The adverse effect profile of the losartan potassium-hydrochlorothiazide combination resembles those for losartan potassium monotherapy and placebo. Long term tolerability data are limited (<2 years) but support the very good tolerability profile in shorter studies. Elements of the drug's profile yet to be assessed or reported fully in the literature include long term efficacy; potential to favourably influence cardiovascular and renovascular systems (and ultimately mortality) in patients with hypertension and, lastly, cost effectiveness and influence on quality of life. In summary, losartan potassium is the first AT(1)+ receptor antagonist to become available for the management of hypertension and, as such, it is an important new antihypertensive agent. Pending long term data as outlined above, it is likely to find initial use in patients with mild to severe hypertension who are unresponsive to, or intolerant of their current therapy. However, with its novel mechanism of action, good efficacy and favourable tolerability profile, losartan potassium is well placed to claim a prominent position in the management of patients with essential hypertension in the future.
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PMID:Losartan potassium: a review of its pharmacology, clinical efficacy and tolerability in the management of hypertension. 886 49


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