Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tolerability and not efficacy is the limiting factor for long-term successful antihypertensive treatment. Since the discontinuation rate of first line antihypertensives may be as high as 50-60% over six months, it is important to develop new agents with an improved efficacy/tolerability ratio. Candesartan cilexetil is particularly promising in this respect. Candesartan is a potent and selective angiotensin II type 1 (AT1) receptor blocker that binds selectively and tightly (insumontable binding) to the receptor. Candesartan is not associated with any increased risk of cough or angiodema. It is an orally effective vasodilator that does not cause reflex tachycardia or first dose hypotension or orthostatic hypotension. In the dose range from 4-16 mg, once daily candesartan cilexetil is not associated with any dose-dependent adverse events and it is equally well tolerated in men and women and by older (> 65 years) and younger (< 65 years) patients. Furthermore, the drug has no adverse effect on glucose homeostasis or plasma lipid profile. In a double-blind comparison with losartan 50 mg od, candesartan cilexetil 16 mg once daily was significantly more effective in lowering the diastolic blood pressure at the end of the 24 h dose interval but was equally well tolerated. In meta-analyses of clinical trials, candesartan cilexetil showed a tolerability profile comparable to that of placebo therapy.
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PMID:Tolerability of a modern antihypertensive agent: candesartan cilexetil. 983 64

Clinical trials of candesartan cilexetil conducted in Japan are reviewed. Candesartan cilexetil inhibited the pressor response to intravenous angiotensin II in healthy volunteers, with peak effects observed at 4 or 8 h after oral dosing; suppressing effects persisted up to 24 h. In 14 multicentre studies with 928 hypertensive patients treated for 8 to 12 weeks, candesartan cilexetil had an efficacy rate (reduction of systolic/diastolic blood pressure > or = 20/10 mm Hg and/or mean blood pressure > or = 13 mm Hg) of 72% and 63%, and an adverse effect rate of 9.9% and 7.3%, in patients with mild-to-moderate essential hypertension and those with impaired renal function, respectively. When data for elderly patients were analysed, there was no difference in efficacy and tolerability compared to non-elderly patients. In a double-blind comparative study, candesartan cilexetil was superior to enalapril in hypertensive patients: efficacy rate, 74% vs 66% (NS); adverse symptom rate, 10.4% vs 27.3% (P < 0.01); incidence of cough, 1.5% vs 14.8% (P < 0.01). Treatment with 2-8 mg of candesartan cilexetil once daily for 8 to 12 weeks reduced the left ventricular mass index without deterioration of cardiac function. In conclusion, 4-12 mg of candesartan cilexetil once daily is effective and well tolerated in patients with essential hypertension, including elderly patients, those with severe hypertension, and hypertensive patients with renal insufficiency. Its improved tolerability profile over angiotensin-converting enzyme inhibitors, as well as its end-organ protective effects, suggest that candesartan cilexetil is useful as a first-line antihypertensive drug.
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PMID:Clinical efficacy and tolerability of candesartan cilexetil. Candesartan Study Groups in Japan. 1007 18

The renin-angiotensin system plays a central role in the regulation of blood pressure through its primary effector hormone angiotensin II. Studies conducted nearly 30 years ago with peptidic angiotensin II receptor blockers (ARB) suggested that disruption of the renin-angiotensin system offered considerable promise for the treatment of hypertension as well as heart failure. This promise was initially realized with the advent of angiotensin converting enzyme inhibitors, and more recently with nonpeptidic ARB that selectively antagonize the AT1-angiotensin receptor subtype. The potent and long-acting agent candesartan cilexetil illustrates how these new ARB fulfill the promises suggested by the early studies. Candesartan cilexetil provides a clinically relevant, dose-dependent reduction in diastolic and systolic blood pressure at doses of 4 to 16 mg once daily in patients with mild to moderate hypertension. Recent studies suggest that further blood pressure lowering is obtained with a 32-mg once daily dose. In comparative clinical trials, 8 mg of candesartan cilexetil and 10 to 20 mg of enalapril provided comparable antihypertensive effects. The safety and tolerability profile of candesartan cilexetil is comparable to placebo. Notably, this agent does not produce the dry, nonproductive cough that often limits use of angiotensin converting enzyme inhibitors, nor does it cause side effects that limit other antihypertensive drug classes. On the basis of the results of initial clinical studies, ARB also possess cardioprotective and renoprotective properties that promise to expand the role that these new agents will play in treating cardiovascular disorders.
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PMID:Update on the clinical pharmacology of candesartan cilexetil. 1067 85

The mechanism of action, pharmacokinetics, pharmacodynamics, clinical efficacy, and adverse effects of candesartan cilexetil are reviewed. Candesartan is an angiotensin II-receptor blocker (ARB). It is administered as a pro-drug that undergoes activation during gastrointestinal absorption. The agent is excreted mostly unchanged and has a terminal half-life of about nine hours (slightly longer in the elderly). Candesartan differs from other agents in its class in that it is tightly bound to angiotensin II type 1 receptors, allowing prolonged activity. In clinical trials, candesartan cilexetil has produced a dose-dependent effect when given in dosages of 2-32 mg/day. Observed trough-to-peak blood pressure ratios support a once-daily dosage regimen. The antihypertensive effect of candesartan cilexetil 4-16 mg/day was as great as that of enalapril 10-20 mg/day and amlodipine 5 mg/day and larger than that of losartan potassium 50 mg/day. Adding candesartan cilexetil to hydrochlorothiazide 12.5-25 mg/day and amlodipine 5 mg/day led to enhanced blood-pressure reductions and was well tolerated. It appears that candesartan can decrease renal perfusion without adversely affecting renal blood flow and may mediate a decrease in albuminuria in hypertensive patients with type 2 diabetes. No clinically important drug interactions have been reported. Adverse effects include headache, dizziness, nausea, diarrhea, and transient elevations in liver transaminases. The frequency of cough is similar to that seen with placebo. Candesartan cilexetil is an effective antihypertensive agent that can be used alone or in combination with other antihypertensive drugs. It is generally well tolerated and may be an option for patients who cannot tolerate angiotensin-converting-enzyme inhibitors because of cough.
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PMID:Candesartan cilexetil: an angiotensin II-receptor blocker. 1078 59

The aim of this large, randomized, double-blind, parallel-group study in hypertensive women was to compare the antihypertensive efficacy and effects on subjective symptoms and quality of life of the new angiotensin II type 1 (AT1) receptor blocker candesartan cilexetil, the angiotensin-converting enzyme inhibitor enalapril, and the diuretic hydrochlorothiazide (HCTZ). Women, aged 40 to 69 years, with a seated diastolic blood pressure (DBP) of 95 to 115 mm Hg, were randomized to candesartan cilexetil, 8 to 16 mg (n = 140), enalapril, 10 to 20 mg (n = 146), or HCTZ, 12.5 to 25 mg (n = 143), for 12 weeks; the higher doses were used if DBP was greater than 90 mm Hg after 6 weeks. Candesartan cilexetil lowered seated blood pressure by 17/11 and 19/11 mm Hg after 6 and 12 weeks of treatment, respectively. This reduction was greater (P < .01) than with enalapril (12/8 and 13/9 mm Hg) or HCTZ (12/7 and 13/8 mm Hg). The proportions of patients with controlled DBP (< 90 mm Hg) after 12 weeks of treatment with candesartan cilexetil, enalapril, or HCTZ were 60%, 51%, and 43%, respectively. Patients experienced less dry cough (P < 0.001) with candesartan cilexetil or HCTZ than with enalapril. No treatment differences were found in the incidence of dizziness and quality of life was well maintained in all groups. Compared with candesartan cilexetil and enalapril, HCTZ increased uric acid and decreased serum potassium (P < .001). In conclusion, candesartan cilexetil reduced blood pressure more effectively and was better tolerated than enalapril or HCTZ in women with mild to moderate hypertension.
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PMID:Angiotensin II type 1 (AT1) receptor blockade in hypertensive women: benefits of candesartan cilexetil versus enalapril or hydrochlorothiazide. 1082 1

Hypertension is a major cardiovascular risk factor, but most patients remain asymptomatic for many years. Successful therapy not only needs to be effective, it also needs to be well tolerated. Angiotensin receptor blockers have emerged as a major therapeutic class because they meet both of these requirements. Numerous studies indicate that all approved angiotensin receptor blockers are highly selective for angiotensin-1 receptors, lower blood pressure as monotherapies, and work well in combination with other drugs - particularly diuretics. The side-effect profile of angiotensin receptor blockers is similar to that of placebo and they have not been associated with known side effects of angiotensin-converting enzyme inhibitors such as cough and angioneurotic edema. Candesartan cilexetil is an angiotensin receptor blocker with insurmountable binding properties to the angiotensin-1 receptor, long duration of action and improved efficacy. In patients with hypertension, candesartan monotherapy has been shown to be safe and effective. Comparative data have shown similar or better results to other monotherapies in blood-pressure control, and in combination with hydrochlorothiazide it has been shown to have additive or synergistic effects. More recent data demonstrate that candesartan cilexetil is useful in the treatment of patients with heart failure and may protect against diabetic nephropathy. Studies have also shown protection from stroke, particularly in patients with isolated systolic hypertension.
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PMID:Candesartan cilexetil in cardiovascular disease. 1550 Apr 28

Candesartan cilexetil is the prodrug of candesartan, an angiotensin II receptor antagonist. Candesartan binds selectively and non-competitively to the angiotensin II receptor type 1, thus preventing the actions of angiotensin II. Clinical trials have demonstrated its efficacy at a dose range of 2 to 32 mg once daily in hypertension of all grades, heart failure, in reducing urinary albumin excretion in diabetes mellitus and in coexisting hypertension and renal failure. Pharmacokinetic properties of candesartan cilexetil in elderly patients are not significantly different from those in younger individuals. Hepatic impairment does not change pharmacokinetics of candesartan cilexetil at doses up to 12 mg/day. No dose adjustment is necessary in patients with mild or moderate renal impairment. Tolerability of candesartan cilexetil is not much different from that of placebo. All adverse events are usually of mild to moderate severity and not dose-related. The most common adverse events were headache, upper respiratory tract infection, back pain, and dizziness. The incidence of these adverse effects, as well as of cough, was similar in patients treated with candesartan cilexetil or placebo. The incidence of adverse events in long-term trials was not different from that in short-term trials. Tolerability of candesartan cilexetil does not differ with either age or gender.
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PMID:Candesartan. 1559 74

Treatment with angiotensin-converting enzyme (ACE) inhibitors is frequently associated with persistent dry cough. This side effect is thought to be due to the non-specific action of ACE inhibitors, which, in addition to suppressing the renin-angiotensin system (RAS), leads to the accumulation of kinins, encephalins and other biologically active peptides. Candesartan cilexetil is a new, long-acting angiotensin II type 1 (AT 1 ) receptor blocker, which offers a more specific means of suppressing the RAS than can be achieved with ACE inhibitors. In this study, we compared the incidence and severity of cough during treatment with candesartan cilexetil, enalapril and placebo in patients with hypertension and enalapril-induced cough. Men and women, aged 20-80 years, with a history of medically treated primary hypertension and ACE-inhibitor-related cough were enrolled. The presence of cough was confirmed during a 4-week challenge period with enalapril, 10 mg, which abated during a subsequent 4-week washout period with placebo. Patients with confirmed ACE-inhibitor-related cough were then randomized to double-blind treatment with candesartan cilexetil, 8 mg once daily ( n = 62), enalapril, 10 mg once daily ( n = 66), or placebo ( n = 26). Baseline blood pressure was similar in all groups. Although blood pressure was recorded during the study, this was for safety monitoring, and the measurements were not standardized in relation to study drug intake or time of day. The frequency of dry cough was recorded on a visual analogue scale (VAS). For each assessment, patients marked a cross on a straight horizontal 100 mm line, rating cough frequency from 'none of the time( at one end of the line to 'all of the time( at the other end. The impact of treatment on quality of life was also studied, using the Symptom Assessment (SA) questionnaire and the Minor Symptom Evaluation (MSE) profile. The SA questionnaire assessed the severity of nine symptoms, including dry cough, by means of a five-graded Likert scale (not at all, a little, moderately, quite a bit, extremely). Changes in the three dimensions of the MSE profile - contentment, vitality and sleep - were recorded using a VAS. Candesartan cilexetil was superior to enalapril regarding the change in frequency ( p = 0.001) and severity ( p < 0.001) of dry cough. After 8 weeks of treatment, the proportions of patients with cough were 26.9% for placebo, 35.5% for candesartan cilexetil and 68.2% for enalapril ( p < 0.001, candesartan cilexetil versus enalapril; p > 0.20, candesartan cilexetil versus placebo). Treatment with candesartan cilexetil did not compromise patients' well-being. Compared with placebo, candesartan cilexetil was superior in terms of its effect on contentment; similar trends were noted for vitality and sleep, although the differences were not significant. When all adverse events were considered, candesartan cilexetil was very well tolerated. No serious adverse events occurred in the candesartan cilexetil or placebo groups, while three patients in the enalapril group reported serious adverse events (chest pain, agranulocytosis, accidental fracture). No treatment-related changes of clinical relevance could be found with regard to laboratory variables, ECG or vital signs/physical findings, except the anticipated blood pressure reduction in the active treatment groups. In conclusion, candesartan cilexetil is not associated with cough in hypertensive patients with previous ACE-inhibitor-induced cough. The incidence of dry cough in patients treated with candesartan cilexetil was similar to that of placebo and lower than that of enalapril.
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PMID:Candesartan Cilexetil is not Associated with Cough in Patients with Enalapril-induced Cough. 2842