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)

This report presents data on the safety and tolerability of losartan potassium (losartan), a selective antagonist of the angiotensin II AT-1 receptor, in approximately 2,900 hypertensive patients treated in double-blind clinical trials. In these studies, headache (14.1%), upper respiratory infection (6.5%), dizziness (14.1%), asthenia/fatigue (3.8%), and cough (3.1%) were the clinical adverse experiences most often reported in patients treated with losartan. These adverse experiences were also frequently reported in patients receiving placebo: 17.2%, 5.6%, 2.4%, 3.9%, and 2.6%, respectively. Dry cough as an adverse event was reported in 8.8% of patients treated with angiotensin-converting enzyme inhibitors, and in 3.1% and 2.6% of patients treated with losartan or placebo, respectively. Only dizziness was considered "drug-related" more often in losartan-treated (2.4%) than placebo-treated (1.3%) patients. In controlled clinical trials, losartan was better tolerated than other antihypertensive agents as determined by the incidence of patients reporting any drug-related adverse experiences. Rates of discontinuation due to clinical adverse experiences in patients who received losartan monotherapy or losartan+hydrochlorothiazide were 2.3% and 2.8%, respectively, compared with placebo (3.7%). No laboratory adverse experiences were unexpected or of clinical importance. First-dose hypotension rarely occurred with losartan or with losartan plus hydrochlorothiazide, and withdrawal effects such as rebound hypertension were not observed in clinical trials. There were no clinically important differences in the clinical or laboratory safety profiles in the demographic subgroups for age, gender, or race. In controlled clinical trials, losartan demonstrated an excellent tolerability profile.
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PMID:Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension. 771 81

While the bulk of the existing data are in diabetic renal disease, there are some animal and clinical studies that compare the effects of angiotensin I (AT-1) receptor antagonists to angiotensin converting enzyme (ACE) inhibitors in renal disease of nondiabetic origin. Based on these data, preservation of renal function and morphology occurs with AT-1 receptor antagonists in animal models where renal injury is hemodynamically mediated such as in the remnant kidney. Conversely, in non-hemodynamically mediated renal injury such as in puromycin nephrosis, AT-1 receptor antagonists have not consistently protected against declines in glomerular filtration rate or development of interstitial fibrosis. This may, however, be related to dosage, since high doses of AT-1 receptor antagonists show some protection against progression in these models. It is too early, however, to make judgments regarding the clinical impact of the AT-1 receptor antagonists on progression of nondiabetic renal disease. The result of the ELITE trial support the concept that progression of renal dysfunction associated with heart failure is ameliorated to a similar extent between ACE inhibitors and the AT-1 receptor antagonist, losartan. The AT-1 receptor antagonist group also had fewer side effects including the absence of cough as well as a lower, albeit not statistically significant, incidence of hyperkalemia. Thus, the emerging database supports the concept that AT-1 receptor antagonists have an efficacy similar to ACE inhibitors for preserving renal function and morphology in hemodynamically mediated renal injury. It is unclear, however, whether this drug class will reduce immunologically-mediated renal injury.
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PMID:Angiotensin II receptor blockade and progression of nondiabetic-mediated renal disease. 940 25

Angiotensin II receptor antagonists (AT-1) represent a new group of orally active antihypertensive agents. Activation on AT-1 receptor leads to vasoconstriction, stimulation of the release of catecholamines and antidiuretic hormone with production of thirst, and promote growth of vascular and cardiac muscle; these effects are blocked by AT-1 antagonist agents. The first chemically useful, orally active AT-1 receptor antagonist was losartan, followed by other agents currently in clinical use, such as: valsartan, eprosartan, irbesartan, telmisartan, candesartan, and many others under investigation. AT-1 receptor antagonists are effective in reducing high blood pressure in hypertensive patients. Monotherapy in mild to moderate hypertension controls blood pressure in 40 to 50% of these patients; when a low dose of a thiazide diuretic is added, 60 to 70% of patients are controlled. The efficacy is similar to angiotensin-converting enzyme inhibitors, diuretics, calcium antagonists and beta-blocking agents. Tolerability has been reported to be very good. AT-1 receptor antagonists would be a drug of choice in otherwise well-controlled hypertensive patients treated with angiotensin-converting enzyme inhibitors who developed cough or angioedema. The final position in the antihypertensive therapy in this special population and other clinical situations, such as left ventricular hypertrophy, heart failure, diabetes mellitus and renal disease, has to be determined in large prospective clinical trials, some of which are now being conducted.
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PMID:Angiotensin II receptor antagonists in arterial hypertension. 1085 84

Both angiotensin-converting enzyme (ACE) inhibitors and AT-1 receptor antagonists reduce the effects of angiotensin II, however they may have different clinical effects. This is because the ACE inhibitors, but not the AT-1 receptor antagonists, increase the levels of substance P, bradykinin and tissue plasminogen activator. The AT-1 receptor antagonists, but not the ACE inhibitors, are capable of inhibiting the effects of angiotensin II produced by enzymes other than ACE. On the basis of the present clinical trial evidence, AT-1 receptor antagonists, rather than the ACE inhibitors, should be used to treat hypertension associated with left ventricular (LV) hypertrophy. Both groups of drugs are useful when hypertension is not complicated by LV hypertrophy, and in diabetes. In the treatment of diabetes with or without hypertension, there is good clinical support for the use of either an ACE inhibitor or an AT-1 receptor antagonist. ACE inhibitors are recommended in the treatment of renal disease that is not associated with diabetes, after myocardial infarction when left ventricular dysfunction is present, and in heart failure. As the incidence of cough is much lower with the AT-1 receptor antagonists, these can be substituted for ACE inhibitors in patients with hypertension or heart failure who have persistent cough. Preliminary studies suggest that combining an AT-1 receptor antagonist with an ACE inhibitor may be more effective than an ACE inhibitor alone in the treatment of hypertension, diabetes with hypertension, renal disease without diabetes and heart failure. However, further trials are required before combination therapy can be recommended in these conditions.
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PMID:Angiotensin AT-1 receptor antagonism: complementary or alternative to ACE inhibition in cardiovascular and renal disease? 1243 89