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)

Angiotensin II type 1 receptor blockers belong to a novel class of cardiovascular agents that is characterized by excellent tolerance. The overall rate of their side effects is similar to that of placebo. Specific nonproductive cough is much less common during treatment with angiotensin II blockers compared with angiotensin converting enzyme inhibitors. Nevertheless serious side effects very rarely occur with angiotensin II blockers and include cough, angioneurotic edema, anemia, liver damage, renal failure, aggravation of angina and migraine. The data of current literature concerning adverse effects of angiotensin II in different clinical situations are extensively reviewed. Angiotensin II type 1 receptor blockers are not considered to be safe in pregnancy, bilateral renal artery stenosis and severe renal or hepatic impairment.
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PMID:[Adverse effects of angiotensin II type 1 receptor blockers ]. 1249 95

Antihypertensive agents are proven to reduce the cardiovascular risk of stroke, coronary heart disease and cardiac failure. The ideal antihypertensive agent should control all grades of hypertension and have a placebo-like side effect profile. Angiotensin II (AII) receptor antagonists are a relatively new class of antihypertensive agent that block AII Type 1 (AT(1)) receptors, and reduce the pressor effects of AII in the vasculature. By this mechanism, they induce similar pharmacological effects compared with angiotensin-converting enzyme (ACE) inhibitors, resulting in a lowering of blood pressure. However, AII receptor blockers differ from ACE inhibitors with respect to side effects, and induce less cough, a side effect which may be related to bradykinin or other mediators such as substance P. Within the class of AII blockers, eprosartan differs from other currently available agents in terms of chemical structure, as it is a non-biphenyl, non-tetrazole, non-peptide antagonist with a dual pharmacological mode of action. Eprosartan acts at vascular AT(1) receptors (postsynaptically) and at presynaptic AT(1) receptors, where it inhibits sympathetically stimulated noradrenaline release. Its lack of metabolism by cytochrome P450 enzymes confers a low potential for metabolic drug interactions and may be of importance when treating elderly patients and those on multiple drugs. In clinical trials, eprosartan has been demonstrated to be at least as effective in reducing blood pressure as the ACE inhibitor enalapril, and has significantly lower side effects. Eprosartan is safe, effective and well-tolerated in long-term treatment, either as a monotherapy or in combination with other antihypertensive drugs such as hydrochlorothiazide.
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PMID:Eprosartan for the treatment of hypertension. 1251 47

Angiotensin-converting enzyme (ACE) inhibitors and more recently angiotensin-receptor blockers (ARBs) have become popular therapies in the end-stage renal disease (ESRD) patient. The ability of either of these drug classes to reduce blood pressure in the ESRD patient is well accepted; however, there is considerably less information available to guide the clinician in the safe and effective use of these drugs in the ESRD patient with congestive heart failure and/or coronary artery disease. Head-to-head studies in the ESRD patient are lacking for both drug classes. Several pharmacokinetic factors can influence the selection of these drugs, including dialysability and the propensity for systemic accumulation. ACE inhibitors (ACE-Is) and ARBs are recognised as having a range of nonpressor effects that are pertinent to patients with ESRD. Such effects include their ability to decrease both thirst drive and erythropoiesis. These drug classes, though, are distinguishable by the unique adverse effect profile for ACE-Is. As is the case in patients without renal failure, ESRD patients can experience cough and, less frequently, angioneurotic oedema with ACE-Is. In the ESRD population, so-called anaphylactoid dialyser reactions can occur in conjunction with ACE-I use. The use of a drug from within the ARB class carries both less risk and permits a compound with a preferred pharmacokinetic profile limited dialysability and minimal systemic accumulation to be administered. These attributes would favour the increased use of ARBs in this population.
J Renin Angiotensin Aldosterone Syst 2002 Dec
PMID:The pharmacokinetics and pharmacodynamics of angiotensin-receptor blockers in end-stage renal disease. 1258 68

Angiotensin receptor blockers (ARBs) have gained widespread use in clinical medicine during the past decade. Several large, prospective and randomized multi-center trials have led us to reconsider the role of ARBs in the treatment of hypertension. Firstly, in view of the favorable safety and side effect profile of ARBs, we recommend their use in hypertensive subjects in whom ACE inhibitors are indicated but are unable to tolerate agents of this type due to intractable cough. Secondly, in light of the results of the RENAAL and IDNT studies, we consider ARBs as the drug of choice in diabetic subjects with hypertension and proteinuria (> 300 mg/L). Thirdly, we view ACE inhibitors and ARBs as equally adequate for the treatment of diabetic patients with hypertension and microalbuminuria and recommend the use of the maximal allowable doses of these drugs in such patients. Finally, older hypertensive individuals with left ventricular hypertrophy should receive either ACE inhibitors or ARBs, as these drug classes presently appear to provide better overall protection than beta blockers or calcium channel blockers in this particular subgroup of patients.
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PMID:[Standpoint on the use of angiotensin receptor blockers in the treatment of hypertension]. 1275 85

Angiotensin II (AII) receptor blockers offer an alternative means of blocking the renin-angiotensin-aldosterone system (RAAS) to angiotensin converting enzyme (ACE) inhibitors. Being highly selective for the AII receptor subtype AT(1), AII receptor blockers may avoid side-effects associated with ACE inhibitor treatment, such as cough. Eprosartan is a non-biphenyl, non-tetrazole competitive blocker that is chemically distinct from other AII receptor blockers, which may account for differences in its pharmacological properties. It induces dual blockade of AT(1) receptors both presynaptically and postsynaptically, reducing sympathetic nerve activity to a significantly greater degree than other AT(1) receptor blockers. At the recommended dose of 600 mg once daily, eprosartan effectively lowers blood pressure (BP) in hypertensive patients to a similar degree as seen with other AII receptor blockers and ACE inhibitors. However, a greater proportion of patients achieved adequate BP control compared with enalapril. When eprosartan is given in combination with hydrochlorothiazide (HCTZ), it provides a significantly greater BP reduction compared with eprosartan alone. Eprosartan has a side-effect profile that is similar to placebo and to other AII receptor blockers, but is better than that of enalapril because it lacks the propensity to cause dry cough. Eprosartan is not metabolized by the cytochrome P450 enzyme system, and so has no interaction with drugs that affect this system. Eprosartan completely reverses renal vasoconstriction induced by AII and may, therefore, have further applications in situations where stimulation of the RAAS is a problem. In summary, eprosartan, alone or in combination with HCTZ, provides an effective and well-tolerated approach to lowering BP in patients with all grades of hypertension. Further development of eprosartan may offer therapeutic opportunities that go far beyond the current recommendations.
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PMID:Clinical profile of eprosartan. 1276 89

Angiotensin Converting Enzyme Inhibitors (ACEI) like captopril and enalapril, can induce persistant cough in man. Noscapine, an antitussive alkaloid, can be used to suppress ACEI-induced cough. Some workers have suggested a role for bradykinin in precipitation of ACE-induced cough. Work carried out in our laboratory has shown noscapine to be a non-competitive inhibitor of bradykinin in guinea pig ileum. It is therefore possible that noscapine suppresses cough by blocking the effect of bradykinin receptor activation in the airways. Guinea pigs were placed in a cough-chamber connected to an air pump and a pressure transducer. Capsaicin was sprayed into the chamber and cough was recorded as a distinctive change in air pressure inside the cough-chamber. Animals treated with 1 mg/kg captopril and enalapril for 7 days, showed increased cough response. Ten microgram/kg FR190997, a non-peptide agonist of the bradykinin B2 receptor, also increased the cough response. Noscapine at 0.5, 1 and 2 mg/kg was able to reverse the effects of ACEI and FR190997. Naloxone, a specific opioid receptor inhibitor, did not block the antitussive effects of noscapine in enalapril or FR190997 treated guinea pigs. This antitussive effect of noscapine is not mediated via the mu, kappa or delta opioid receptors. It is therefore possible that noscapine exerts its antitussive action by interfering with the bradykinin cough mediation.
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PMID:Interaction of noscapine with the bradykinin mediation of the cough response. 1290 13

The development of drugs which block the renin-angiotensin system (RAS) has been proven a major advance in cardiovascular medicine. Angiotensin converting enzyme (ACE) inhibitors, which block the formation of angiotensin II from the inactive angiotensin I, are widely used as first line treatment in hypertension, heart failure and diabetic nephropathy. More recently, selective antagonists of the angiotensin type-1 receptor (AT1R) have become available for clinical use. Accumulating evidence suggests that AT1R antagonists have similar effects to ACE inhibitors in hypertension, heart failure and diabetic nephropathy. Although ACE inhibitors and AT1R antagonists block the same system, experimental evidence suggest that their mechanisms of action differ in several respects, such as increased bradykinin and angiotensin 1-7 levels with ACE inhibitors and AT2R activation with AT1R antagonists. Nevertheless, the clinical significance of these differences remains largely unknown and, in practice, the only clear advantage of AT1R antagonists over ACE inhibitors is the absence of cough as a side effect. Recent clinical data suggest that combined ACE inhibition and AT1R antagonism offer additive effects in reducing blood pressure in hypertension, in reducing proteinuria in nephropathy and in improving prognosis in heart failure. Further evidence suggests that some hypertensive patients may have a good antihypertensive response with ACE inhibition but not with AT1R antagonism, or the reverse. These data suggest that these two drug classes have important similarities, because they act on the same system, but they also appear to have important differences, which are not only of theoretical but also of clinical importance.
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PMID:Renin-angiotensin system blockade at the level of the angiotensin converting enzyme or the angiotensin type-1 receptor: similarities and differences. 1496 13

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

Angiotensin-converting enzyme inhibitors are widely-prescribed drugs for hypertension and are supported by clinical trials in which they reduce cardiovascular events. In the high-risk patients in the Heart Outcomes Prevention Evaluation, the Perindopril Protection Against Recurrent Stroke Study, and European Trial of Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease, ramipril and perindopril showed impressive benefits. One reason trandolapril did somewhat less well in the Prevention of Events With Angiotensin-Converting Enzyme Inhibition trial may be that its patients were very well treated with other effective modalities. In the Antihypertensive and Lipid Lowering to Prevent Heart Attack Trial, lisinopril-treated patients had a slightly lower incidence of myocardial infarction, despite much poorer control of blood pressure, perhaps because a second-line diuretic was prohibited by protocol. Although angiotensin-converting enzyme inhibitors can cause cough and angioedema (more common among blacks), angiotensin receptor blockers are currently more expensive and have fewer outcome trials to support their use.
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PMID:Cardiovascular events in hypertension trials of Angiotensin-converting enzyme inhibitors. 1610 30

Angiotensin II plays a central role in the pathogenesis and progression of proteinuric nephropathies and related cardiovascular complications. Losartan is a selective non-peptide angiotensin Type 1-receptor blocker (ARB) with unique uricosuric effect, not shared by other ARBs. Losartan has demonstrated renoprotective effects in animals and humans with diabetic and non-diabetic renal diseases similar to those of angiotensin-converting enzyme inhibitors, with a lower incidence of dry cough and angioneurotic oedema. A reduced incidence of cerebrovascular events and diabetes has been reported in hypertensive patients with left ventricular hypertrophy on losartan therapy compared with patients treated with atenolol. Whether ARBs have superior cardioprotective effects, compared with other blood pressure medications, is still unknown. Combined angiotensin-converting enzyme inhibitor and ARB therapy improves renal outcomes in non-diabetic nephropathies more than single drug renin-angiotensin system inhibition. Whether this also applies to diabetic nephropathy and related cardiovascular outcomes is still unknown.
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PMID:Inhibition of the renin-angiotensin system and cardio-renal protection: focus on losartan and angiotensin receptor blockade. 1614 12


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