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)

The successful introduction of angiotensin converting enzyme (ACE) inhibitors in the treatment of patients with essential hypertension or heart failure has increased interest in the (patho)physiological role of the renin-angiotensin system (RAS). ACE is not only involved in the formation of angiotensin II from angiotensin I, but also inactivates vasoactive substances such as bradykinin and substance P. Accumulation of these substances during treatment with ACE inhibitors may contribute to both their therapeutic action and certain adverse effects associated with their use, such as cough and angioneurotic oedema. Renin inhibitors offer an alternative approach to inhibit the RAS. The major advantage of these, still experimental, drugs is their high specificity for the RAS since angiotensinogen is the only known substrate of renin. The currently available renin inhibitors are pseudopeptides that are rapidly taken up by the liver and excreted in the bile. Consequently, these drugs are subjected to a considerable first pass effect which limits their oral bioavailability. Additionally, plasma elimination half-life times are short and the duration of action is limited. Despite these shortcomings, single oral or intravenous administration results in a 80 to 90% inhibition of plasma renin activity and a slight reduction in blood pressure in patients with hypertension. The extent of blood pressure reduction is dependent on the patient's salt balance. After 1 week of oral treatment with the renin inhibitor remikiren, the antihypertensive effect was reduced in salt-repleted hypertensive patients. Subsequent intravenous administration of the drug did not further affect blood pressure, indicating that it was not the first pass effect that was limiting the efficacy of remikiren.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical pharmacokinetics and efficacy of renin inhibitors. 758 99

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

Left ventricular systolic dysfunction is associated with neurohormonal activation which contributes to progressive ventricular remodeling and worsening clinical heart failure. Renin-angiotensin-aldosterone and sympathetic nervous systems are activated, not only in patients with clinically overt heart failure, but also in patients with asymptomatic or minimally symptomatic left ventricular systolic dysfunction. Activation of the angiotensin and adrenergic systems produces deleterious effects on systemic and coronary hemodynamics, promotes myocyte hypertrophy and fibroblast growth, and myocyte necrosis and apoptosis. Thus, therapy of heart failure should consist of pharmacologic agents not only to relieve symptoms but also to prevent and attenuate ventricular remodeling and progressive heart failure, thereby improving prognosis. In patients who are symptomatic, ACE inhibitors along with digitalis and diuretics as initial therapy (triple therapy) have the greater potential to improve exercise tolerance and decrease the incidence of treatment failure compared with diuretics alone or a combination of diuretics and digitalis. Diuretics alone should not be considered for long-term therapy as plasma renin activity, angiotensin II, aldosterone, norepinephrine and vasopressin levels may increase. ACE inhibitors decrease mortality in patients with heart failure resulting from left ventricular systolic dysfunction. The results of presently available studies indicate that angiotensin II receptor blockers (ARBs) do not provide any advantage over ACE inhibitors regarding survival benefit but may be better tolerated. Long-term adrenergic inhibition with the use of ss-adrenoceptor antagonists added to ACE inhibitors is associated with attenuation of ventricular remodeling, improvement in ventricular function and clinical class and survival of patients with symptomatic systolic left ventricular failure. Thus, initial pharmacotherapy for systolic heart failure should consist of: maximal tolerated dosages of ACE inhibitors;ARBs if ACE inhibitors are not tolerated because of intractable cough or angioedema;adequate dosages of hydralazine and isosorbide dinitrate if ACE inhibitors or ARBs are not tolerated; relatively low dosages of digoxin (serum concentrations of < or = 1.0 ng/dl) if not contraindicated; and diuretics to relieve congestive symptoms. Addition of spironolactone to ACE inhibitors can result in a significant reduction in the risk of sudden death in patients with symptomatic severe heart failure. Myocardial infarction resulting from ischemic heart disease is the most common cause of systolic left ventricular failure and the therapeutic modalities with potential to reduce the risks of myocardial infraction, such as risk factor modification, adequate control of diabetes and hypertension, antiplatelet agents and lipid-lowering agents, should also be included in the initial therapy.
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PMID:Congestive heart failure: what should be the initial therapy and why? 1472 93

Targeting the renin-angiotensin-aldosterone system (RAAS), specifically the effector peptide angiotensin II (Ang II), represents a major opportunity for slowing the progression of cardiovascular disease (CVD) and, in turn, reducing the risk of morbidity and mortality. Inhibition of angiotensin-converting enzyme (ACE) and selective blockade of Ang II AT1 receptors are two approaches through which the pathophysiological effects of Ang II can be targeted. Numerous clinical studies have established the benefits of ACE inhibitors (ACE-Is) in lessening the morbidity and mortality burden of CVD. There are, however, tolerability concerns associated with ACE-Is, such as angioedema and dry cough. By blocking Ang II at the AT1 receptor level, Ang II receptor blockers (ARBs) provide a more specific and complete blockade of the deleterious effects of Ang II and tend to have more favourable tolerability. A number of clinical trials have shown that ARBs are not only associated with positive outcomes across the CVD continuum but mat also have a role in the prevention or delay of diabetes (a major cardiovascular risk factor). Ongoing trials are aiming to define the place of such agents in lessening morbidity and mortality from CVD.
J Renin Angiotensin Aldosterone Syst 2006 Jun
PMID:Clinical evidence for the cardiovascular benefits of angiotensin receptor blockers. 1696 48

Left ventricular (LV) dysfunction and/or heart failure (HF) are frequent complications of hypertension and myocardial infarction (MI), placing affected patients at increased risk of significant morbidity and premature death. Given that the renin-angiotensin-aldosterone system (RAAS) is activated and of pathophysiological importance in such patients, a strong therapeutic rationale exists to target the main effector mechanism (that is, angiotensin II [Ang II]) in order to lessen the associated morbidity and mortality burden. Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce mortality and LV dysfunction and to slow disease progression in patients with HF, including high-risk, post-MI patients. However, ACE inhibitors (ACE-Is) may not provide optimal long-term RAAS blockade (a finding that is associated with a worse prognosis) and many patients are unable to tolerate such therapy (because of troublesome dry cough, for example). In contrast, Ang II receptor blockers (ARBs) may block the RAAS more completely than ACE-Is and appear to be better tolerated. Several large-scale trials gave evaluated the efficacy of ARBs in patients with LV dysfunction and/or HF (including high-risk, post-MI patients), and have confirmed their utility as an efficacious and well-tolerated alternative to ACE-Is in this setting.
J Renin Angiotensin Aldosterone Syst 2006 Jun
PMID:Use of valsartan in post-myocardial infarction and heart failure patients. 1698 31

Angiotensin-converting enzyme (ACE) inhibitors improve the prognosis in mild, moderate and severe heart failure, as well as preventing the onset of heart failure in patients with chronic asymptomatic left-ventricular dysfunction and in those with reduced ejection fraction after myocardial infarction (MI). Imidapril is a long-acting ACE inhibitor that is rapidly converted in the liver to its active metabolite, imidaprilat. Maximum plasma concentrations of imidapril and imidaprilat are achieved after 2 and 5-6 hours, respectively, with corresponding elimination half-lives of 1.1-2.5 and 10-19 hours. Imidapril is used in the treatment of hypertension, chronic heart failure, acute MI and diabetic nephropathy. In patients with mild-to-moderate chronic heart failure, imidapril 10 mg once-daily increased exercise time and physical working capacity, decreased plasma atrial natriuretic peptide and brain natriuretic peptide levels and reduced blood pressure. It also improved left ventricular ejection fraction, being significantly more effective than bisoprolol, in patients with acute MI. Imidapril is well tolerated and preliminary studies suggest it has an advantage over captopril and enalapril in terms of a lower incidence of cough. In conclusion, imidapril is a well-investigated versatile ACE inhibitor for the treatment of a range of cardiovascular diseases.
J Renin Angiotensin Aldosterone Syst 2006 Sep
PMID:Imidapril in heart failure. 1709 51

The renin angiotensin system (RAS) plays an important role in regulation of blood pressure and fluid-electrolyte homeostasis. The renin-angiotensin system consists of a cascade of enzymatic reactions producing angiotensin II (Ang II). Ang II is a vasoconstrictive peptide hormone that exerts a wide variety of physiological actions on cardiovascular, renal, endocrine and central nervous systems. The RAS can be inhibited at various points to control pathogenesis of hypertension. Renin inhibitors and angiotensin-converting enzyme (ACE) inhibitors were the earliest RAS blocking agents. A relatively new class of compounds known as Ang II receptor antagonists (SARTANs) is developed for the treatment of hypertension. They exert their action by blocking the binding of Ang II on AT(1) receptor. Angiotensin converting enzyme (ACE) inhibitors are associated with incident of side effects such as cough and angioedema while clinical trials with Ang II receptor antagonists have confirmed that these drugs are safe and efficacious for the treatment of hypertension. Based upon the understanding of molecular interaction of Ang II receptor antagonists with AT(1) receptor some of the common structural features have been identified, such as a heterocyclic (nitrogen atom) ring system, an alkyl side chain and an acidic tetrazole group. Research efforts for development of new molecules with similar structural features have led to the discovery of various non-peptidic Ang II receptor antagonists with different substituted heterocyclic such as imidazole (losartan) and benzimidazole (candesartan and telmisartan). In this study we have critically reviewed various benzimidazole substituted compounds as Ang II-AT(1) receptor antagonists and explored other potential clinical uses for this class of compounds.
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PMID:Substituted benzimidazole derivatives as angiotensin II-AT1 receptor antagonist: a review. 2093 29

The present study examined whether (1) the cough associated with angiotensin converting enzyme inhibitor therapy is attenuated by oral intake of iron and anti-oxidants, and (2) nitric oxide (NO) has any role in this attenuation. Of the 100 patients under investigation, cough occurred in 28 of them with preponderance in females. All the 28 patients were followed up for six weeks: the first two weeks were the observation period and the remaining four weeks the experimentation period. After the observation period, 11 patients received a single oral dose of ferrous sulphate (200 mg), eight received vitamin E (200 mg, o.d.) and vitamin C (150 mg, o.d.) and nine were given placebo during the experimentation period. Cough scoring, serum NO and malondialdehyde (MDA) levels were determined during both the periods. While there were significant decreases in cough scores, NO and MDA levels between these two periods in the iron group, cough scores and MDA level decreased significantly in the anti-oxidant group. None of these parameters changed in the control group. NO level was found to be increased significantly in patients who developed cough (n = 28) compared with those who did not cough (n = 72). These results suggest that iron supplementation suppresses cough in patients on ACE-I therapy through its effect on NO generation.
J Renin Angiotensin Aldosterone Syst 2011 Dec
PMID:Attenuation of angiotensin converting enzyme inhibitor induced cough by iron supplementation: role of nitric oxide. 2142 58

New approaches to the definition and treatment of hypertension have increased emphasis on reducing overall cardiovascular risk and on targeting the underlying mechanisms of cardiovascular disease. During the past several decades, renin-angiotensin-aldosterone system (RAAS) activation has emerged as an important factor in the pathophysiology of endothelial dysfunction and cardiovascular disease (CVD). Angiotensin-converting enzyme inhibitors (ACEIs) have well-established efficacy for treating CVD, but their use may be limited by intolerable side effects, such as cough and angioedema. Angiotensin II receptor blockers (ARBs), a different class of RAAS inhibitors, are considered a viable alternative to ACEIs. Clinical trials have further elucidated the role of ARBs in CVD. This article reviews the mechanism of action of ARBs and selected clinical trials of ARBs in CVD.
J Renin Angiotensin Aldosterone Syst 2012 Sep
PMID:The role of angiotensin receptor blockers in reducing the risk of cardiovascular disease. 2261 Sep 16