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)

Theoretical considerations and experimental data suggest that AT1-antagonists can offer the same advantages as ACE-inhibitors in the treatment of hypertensive patients without causing side effects such as angioedema and cough. The pharmacokinetic properties of these drugs suggest that AT1-antagonists can be given once-daily. Preliminary data obtained with losartan indicate that this drug, given once daily, significantly reduced blood pressure with a favourable trough to peak ratio. Moreover the hypotensive effect of this drug was similar to that exerted by other hypotensive drugs currently employed in the treatment of hypertensive patients. Losartan can be usefully combined with a thiazide diuretic inducing an additive antihypertensive effect. No negative effect on lipid and glucose profiles was recorded. Furthermore, losartan exerted an uricosuric action, thus reducing serum uric acid. Preliminary data suggest that the incidence of cough in patients treated with losartan was similar to that observed in patients receiving placebo or a thiazide diuretic. Although these data need to be confirmed by ongoing and future studies, it is tempting to hypothesize that this new class of antihypertensive drugs can offer a further useful tool in the treatment of hypertensive patients.
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PMID:[Clinical experience with angiotensin II antagonists in arterial hypertension]. 763 5

Angiotensin-converting enzyme inhibitors (ACE-I) have been proven to be effective in reducing morbidity and mortality in patients with heart failure or post-myocardial infarction left ventricular dysfunction. Despite evidence from several large-scale randomized trials, the use of ACE-I in patients with heart failure remains relatively low. In part, the failure to achieve more widespread use of ACE-I in patients with heart failure may be due to physician's perceptions of the side effects associated with ACE-I, such as angioedema, renal dysfunction, cough, and hypotension. Many of these side effects are thought to be due to ACE-I-induced bradykinin accumulation. It is possible to inhibit the effect of angiotensin II without increasing bradykinin levels using an angiotensin II type I blocking agent such as losartan. How effective losartan is compared with an ACE-I is uncertain, however. Some of the beneficial effects of ACE-I have been attributed to bradykinin accumulation, and therefore ACE-I might have an advantage compared with an angiotensin II type I receptor antagonist such as losartan. On the other hand, angiotensin II may be produced by non-ACE-I-dependent mechanisms, which would suggest that an angiotensin II type I receptor blocking agent would be advantageous. To determine the relative safety and efficacy of an ACE-I, which results in bradykinin accumulation and inhibitors of angiotensin II, versus an angiotensin II type I receptor blocking agent, which does not result in bradykinin accumulation, we have begun the Evaluation of Losartan In The Elderly (ELITE) trial, which will compare the safety and efficacy of captopril and losartan in elderly patients with heart failure.
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PMID:Angiotensin II receptor antagonists in heart failure: rationale and design of the evaluation of losartan in the elderly (ELITE) trial. 857 52

Losartan is an orally active angiotensin II antangonist that selectively blocks effects mediated by the stimulation of the AT1 subtype of the angiotensin II receptor. This agent, at doses of 50-150mg/day, is as effective at lowering blood pressure as chronic angiotensin converting enzyme (ACE) inhibitors. Losartan is generally well tolerated and has an incidence of adverse effects very similar, in double-blind controlled trials, to that of placebo. It does not cause coughing, the most common side-effect of the ACE inhibitors, most probably because angiotensin II antagonism has no impact on ACE, an enzyme known to process bradykinin and other cough-inducing peptides. Losartan is a promising antihypertensive agent with the potential to become a first-line option for the treatment of patients with high blood pressure.
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PMID:Angiotensin II antagonists: a new class of antihypertensive agent. 879 3

Despite the availability of safe and efficacious antihypertensive agents, hypertension continues to be a major source of morbidity and mortality in the United States. Losartan, the first of a new class of agents, the angiotensin II receptor antagonists, can be administered as monotherapy in the treatment of hypertension or to complement existing therapy. The angiotensin II receptor antagonists block the effects of angiotensin II through preferential binding to angiotensin II receptor subtype AT1 on the cell membrane. Compared with angiotensin-converting enzyme inhibitors, they may provide more complete blockade of the renin-angiotensin system and be associated with a lower frequency of cough as a side effect.
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PMID:A new class of antihypertensive therapy: angiotensin II receptor antagonists. 888 79

The clinical efficacy and tolerability of losartan were studied in clinical trials in Japanese patients with essential hypertension. In a short-term trial, losartan (25 to 100 mg once daily) provided good control of blood pressure for 24 h without affecting the patient's own diurnal blood pressure profile. In a double-blind study, the efficacy and tolerability of losartan (25 to 50 mg once daily) were compared to enalapril (5 to 10 mg) in Japanese patients with mild to moderate essential hypertension. Losartan, 25 to 50 mg given once daily, produced an antihypertensive effect comparable to enalapril, 5 to 10 mg, in these patients. The incidence of adverse reactions in the losartan group was 9.0% (13/144), which was lower than that observed in the enalapril group, 20.3% (29/143). The incidence of cough in the losartan group (0.7%) was lower than that of the enalapril group (13.3%). No discontinuation due to cough was observed in the losartan group: however, seven patients were discontinued from the enalapril group. Losartan exhibited antihypertensive efficacy comparable to enalapril and a tolerability profile superior to enalapril in this study. The efficacy and tolerability of losartan were also investigated in 29 hypertensive patients with renal impairment. When losartan (25 to 100 mg) once daily was used, blood pressure was controlled in 62.1% (18/29) of patients. The rate of cases assessed as "useful" was 58.3% when the pretreatment serum creatinine level was less than 3.0 mg/dL. No cases, however, were assessed as "useful" in patients in which the level was 3.0 mg/dL or higher. In a trial with hypertensive diabetic patients, losartan did not adversely affect glucose tolerance and lipid metabolism. Losartan was associated with a decreased total cholesterol (p < 0.01) and LDL cholesterol (p < 0.01) without significantly changing HDL cholesterol in patients with total serum cholesterol of > 220 mg/dL. In summary, losartan, the first angiotensin II antagonist, is an effective antihypertensive agent with an excellent tolerability profile.
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PMID:The clinical efficacy and tolerability of the angiotensin II-receptor antagonist losartan in Japanese patients with hypertension. 891 45

Angiotensin receptor antagonists represent a new class of drugs for the treatment of patients with hypertension. Reduction of blood pressure in patients with essential hypertension requires increased activity of the renin-angiotensin system. Losartan, the first orally active, nonpeptide angiotensin antagonist, specifically competes with angiotensin II (Ang II) for the AT1 receptor and reversibly alters the receptor. Maximum blood pressure reductions occur after doses of approximately 50 mg, although some patients will require 100 mg; the parent compound and a metabolite are responsible for a smooth 24-hour effect on blood pressure. Once-daily dosing with losartan has been documented to be safe. The drug's safety has been evaluated in 4,058 patients; of these patients, more than 1,200 were treated for longer than 6 months and more than 800 were treated for longer than 1 year with doses of 10 mg to 150 mg. Overall, no hypertensive patients were withdrawn from treatment because of elevated serum creatinine or potassium levels, and there were no reports of angioedema. In addition, some reductions in plasma uric acid levels were noted. Cough occurred significantly less often in patients treated with losartan than in those treated with hydrochlorothiazide or lisinopril. In contrast to angiotensin-converting enzyme (ACE) inhibitors, losartan does not activate bradykinin-nitric oxide-prostanoid vasodilation.
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PMID:Losartan: first of a new class of angiotensin antagonists for the management of hypertension. 893 38

Raised blood pressure in the elderly is not a normal consequences of aging, but is a major risk factor for cardiovascular disease. Cardiac and cerebrovascular disease account for > 50% of deaths among people aged > 65 years. Because the percentage of elderly people in most populations is rising, blood pressure control in this group is becoming increasingly important. Several large intervention studies in the elderly have demonstrated that antihypertensive medication reduces cardiovascular morbidity and mortality. In addition, the absolute benefits of blood pressure reduction are higher in elderly compared with younger patients. ACE inhibitors are effective and well tolerated in the treatment of hypertension in the elderly. Their success led to interest in alternative ways of blocking the renin angiotensin system, and the subsequent development of angiotensin II (AII) receptor antagonists. Losartan was the first drug in this class to become commercially available. Since then, valsartan has been launched in some markets and others are likely to be launched in the near future. Losartan is effective in the treatment of essential hypertension and has a low incidence of adverse effects. First-dose hypotension is very uncommon and, at the present time, cough does not appear to be an adverse effect of these drugs, although long term tolerability studies are needed to confirm this. Angioedema, a rare but life-threatening adverse effect of ACE inhibitors, has also been associated with losartan. Current data suggest that All receptor antagonists are effective in elderly hypertensive patients, although further data are needed to confirm these findings. At present, All receptor antagonists are likely to be used in hypertensive patients who are intolerant of ACE inhibitors, although this may change with the availability of long term tolerability and clinical outcomes data.
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PMID:Angiotensin II receptor antagonists. Potential in elderly patients with cardiovascular disease. 920 48

ACE inhibitors have been shown to be effective in reducing the morbidity and mortality of patients with left ventricular systolic dysfunction, but their application to clinical practice in this situation is still limited. In part, the failure to prescribe an ACE inhibitor to a patient with left ventricular systolic dysfunction is due to perceptions regarding their side effects, such as cough and renal dysfunction. Relatively few patients with left ventricular systolic dysfunction and a serum creatinine > or = 2 mg/dl receive an ACE inhibitor in clinical practice. In this situation one should consider an agent such as fosinopril, which is metabolized by the liver as well as secreted by the kidney. In patients with moderate renal dysfunction, fosinopril has been well tolerated without an increase in serum creatinine. In patients who develop cough due to an ACE inhibitor, consideration should be given to an angiotensin II type 1 receptor blocking agent, such as losartan. The relative safety and efficacy of an ACE inhibitor compared with an angiotensin II type 1 receptor blocking agent is being explored in a prospective randomized trial (Evaluation of Losartan In The Elderly [ELITE]), as well as the safety and pharmacological effectiveness of adding an angiotensin II receptor antagonist to an ACE inhibitor (Randomized Angiotensin receptor antagonists-ACE-inhibitor Study [RAAS]). There may also be a role for the combination of an aldosterone receptor antagonists and an ACE inhibitor in patients with left ventricular systolic dysfunction. Once an ACE inhibitor is administered to a patient with left ventricular systolic dysfunction it should be continued indefinitely. ACE inhibitors may be of value not only in preventing the progression of heart failure but also in reversing endothelial dysfunction and preventing the development of atherosclerosis and its consequences, such as myocardial infarction.
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PMID:ACE inhibitors in heart failure: prospects and limitations. 921 Oct 22

Losartan is a novel orally active nonpeptidal antihypertensive agent that specifically blocks the angiotensin II type 1 receptor. This paper compares the short- and long-term safety and tolerability of losartan with those of placebo. Approximately 3800 patients with mild-to-severe essential hypertension were enrolled in 16 double-masked and 4 open clinical trials worldwide. Of these, approximately 2900 were treated with losartan either alone or in combination with other antihypertensive drugs. These trials included patients with diabetes mellitus (n = 133). An additional 5 trials enrolled hypertensive patients with compromised renal function (n = 115) or heart failure (n = 220). Losartan dosages primarily ranged from 10 to 150 mg once daily, with most patients receiving 50 to 100 mg per day. Hypertension trials generally lasted 12 weeks. The most frequently reported adverse events were headache, upper respiratory tract infection, dizziness, and asthenia/fatigue, but only dizziness occurred more frequently (> or = 1%) in the losartan-treated groups. Cough occurred in 3.1% of patients treated with losartan and 2.6% of patients treated with placebo. The overall incidence of clinical and laboratory adverse events in the losartan- and placebo-treated groups was similar among patients with hypertension and either diabetes mellitus, renal impairment, or heart failure. The data suggest that losartan can be safely administered in hypertensive patients with concomitant illnesses. It can be considered for first-line therapy and is suitable as an alternative therapy in patients already experiencing side effects with other agents.
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PMID:Clinical safety and tolerability of losartan. 937 6

Angiotensin II type 1 (AT1) receptor antagonists inhibit the renin-angiotensin system more completely than ACE inhibitors, and do not increase bradykinin levels as ACE inhibitors do. ACE inhibitors have been proven to increase survival and improve quality of life in patients with congestive heart failure (CHF). At the 48-week follow-up of the Evaluation of Losartan in the Elderly (ELITE) Study, the AT1 receptor antagonist losartan (at a dosage of 50 mg/day) was found to be superior to captopril 50 mg 3 times daily in terms of its effects on total mortality, total mortality and/or hospitalisation for CHF, and hospitalisation for any reason. Hospitalisation for CHF was the same for both drugs. Adverse effects occurred in 12 and 21% of those receiving losartan and captopril, respectively. Cough, rash, angioedema or taste disturbances/reduced appetite prompted the cessation of drug treatment in 0 and 7% of those receiving losartan and captopril, respectively. Until additional data are available, this author recommends that elderly patients with CHF and an abnormal or normal left ventricular ejection fraction, and who are unable to tolerate ACE inhibitors, should receive losartan 50 mg/day.
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PMID:The ELITE Study. What are its implications for the drug treatment of heart failure? Evaluation of Losartan in the Elderly Study. 963 91


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