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)

Blockade of the renin-angiotensin system has proved an important principle in the pharmacotherapy of cardiovascular diseases. There is now overwhelming documentation on the beneficial effect of angiotensin converting enzyme inhibitors (ACE inhibitors) on mortality and morbidity in patients with cardiovascular risk factors. Such documentation is still lacking for the angiotensin II receptor antagonists which, in 1999, sold for 77% of the amount spent on ACE inhibitors in Denmark. This review assesses the therapeutic effects of angiotensin II antagonists compared with the ACE inhibitors in patients with uncomplicated essential hypertension. From 21 comparative studies with a duration of up to one year, it can be concluded that the lowering of the blood pressure with the two classes is similar. Both showed relatively few side effects, the only difference being a higher incidence of cough after ACE inhibitors. Until larger comparative long-term studies on mortality and morbidity have been conducted, angiotensin II antagonists should only be used in hypertensive patients experiencing unacceptable side effects with ACE inhibitors.
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PMID:[Angiotensin II antagonists versus ACE inhibitors in the treatment of raised blood pressure]. 1179 33

Because many antihypertensive drugs can affect airway function, the treatment of hypertension in patients with airway dysfunction is complex. For example, the worsening or precipitation of asthma by beta-adrenoceptor antagonists is well-recognized, but beta(1)-adrenoceptor blockers that exert mild beta(2)-agonist effects, and those that modulate the endogenous production of nitric oxide, affect airway function to a lesser extent. Therapy with selective alpha(1)-blockers is not contraindicated in cases of chronic airway obstruction. Conversely, alpha(2)-agonists must not be given to asthmatic subjects because they can adversely affect the bronchi. Calcium channel blockers do not exert severe side effects on the airways. Angiotensin-converting enzyme inhibitors may cause cough and exacerbate or even induce asthma; however, angiotensin II type I (AT(1)) antagonists do not cause cough. 5-Hydroxytryptamine modifiers such as urapidil are a treatment option for patients with chronic airway obstruction. In patients with airway dysfunction, we suggest treatment with thiazide diuretics as the initial drug choice, and calcium channel blockers if the response is poor. In the case of no response, calcium channel blockers alone must be used. However, there is no strict rule because individual patients may respond differently to individual drugs and drug combinations. Consequently, it is important to adopt a flexible approach. For patients who are unresponsive to the aforementioned drugs, AT(1) receptor antagonists, newer beta(1)-adrenoceptor-blocking agents with ancillary properties (eg, celiprolol or nebivolol), and/or vasodilators can be considered.
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PMID:The pharmacologic treatment of uncomplicated arterial hypertension in patients with airway dysfunction. 1179 56

Angiotensin II receptor antagonists (AAIIs) are the most specific inhibitors of the renin-angiotensin-aldosterone system. There are two types of angiotensin II (Ang II) receptors, the AT(1) receptor, which is responsible for all the classical physiological properties of Ang II, and the AT(2) receptor, whose function in humans remains unclear. The different AAIIs used in clinical practice vary depending on their pharmacodynamic and pharmacokinetic properties, and, for some of them, depending on their metabolism in vivo into an active metabolite. AAIIs are relatively well tolerated, and, unlike angiotensin-converting enzyme inhibitors (ACEIs), do not induce cough. AAIIs are indicated in mild, moderate and severe essential hypertension, where their efficacy has been proven in many studies. The maximal antihypertensive effect is obtained in a few days or weeks, and is somewhat retarded when compared with ACEIs. Their effect is independent of age and sex, but does depend to a certain extent on ethnic origin, since Afro-American patients are less sensitive to AAIIs than Caucasians. In general, the antihypertensive and haemodynamic response to blockers of the renin-angiotensin system is potentiated in presence of a negative salt balance and attenuated in case of a positive salt balance. This means that AAII efficiency is improved by salt depletion induced by a salt-free diet or thiazide diuretics. AAIIs induce short-term improvement of haemodynamic parameters in cardiac insufficiency. Several ongoing clinical trials have been designed to compare their efficacy in cardiac insufficiency and myocardial infarction with those of reference treatments. Valsartan has been recently shown to improve morbimortality in patients with cardiac insufficiency and receiving a conventional treatment including an ACEI. It has been convincingly shown that blockade of the renin-aldosterone system by ACEIs decreases proteinuria and slows down the progression of renal insufficiency, especially in type 2 diabetic nephropathy. Recent trials have shown that AAIIs share the same properties as ACEIs in these indications. It appears that the beneficial effect of AAIIs and ACEIs is not entirely explained by the blood pressure lowering effect of these drugs. AAII administration increases renin release and Ang II production, which may overcome Ang II blockade. On this basis, the combination of an AAII and an ACEI has been proposed to achieve a maximal renin-angiotensin system blockade. Several experimental studies in animals and preliminary clinical studies all indicate that the combination of the two drugs may be more beneficial than either drug used alone in hypertension, cardiac insufficiency and post-myocardial infarction. Clinical trials are necessary to further document the putative advantages of such a combined therapy. The future of AAIIs depends on the following: progress made in the understanding of the molecular and cellular activities of angiotensin (angiotensin receptor signalling, receptor dimerisation, presence of other angiotensin receptor subtypes, role of AT(2) receptor, etc.);a comprehensive view of the role of the local renin system in various organs (local generation and effect of Ang II on cellular proliferation, fibrosis, inflammation, angiogenesis, etc.);predictability of the response to AAII treatment (genetic predisposition to AAII treatment, in conjunction with environmental factors); andresults of the ongoing clinical trials designed to assess the long-term effects of AAIIs in cardiovascular mortality and morbidity, in comparison with reference treatments.
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PMID:[Angiotensin II receptor blockers: current status and future prospects]. 1203 89

Perindopril is a long-acting ACE inhibitor, acting through its only active metabolite perindoprilat. It inhibits the renin-angiotensin system by preventing both the conversion of angiotensin I to angiotensin II and the degradation of bradykinin, thereby reducing the vasoconstriction and left ventricular remodelling characteristic of heart failure. Perindopril 4mg significantly improved a range of haemodynamic parameters in single-dose and long-term (8 weeks and 3 months) studies involving patients with congestive heart failure (CHF), with little or no effect on blood pressure or heart rate. In randomised, double-blind, placebo-controlled clinical trials conducted over 3 months and a large noncomparative study (up to 30 months), perindopril 4mg once daily significantly increased exercise tolerance and reduced symptoms of heart failure in patients with mild to moderate CHF. Perindopril 4mg once daily is generally well tolerated in patients with mild to moderate CHF. In a large noncomparative study the most commonly reported adverse clinical event was cough, which led to 2.8% of patients discontinuing treatment. In short-term comparative trials there was a significantly lower incidence of first-dose hypotension following the recommended starting dose of perindopril 2mg than after the equivalent starting doses of captopril, enalapril and lisinopril.
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PMID:Perindopril: in congestive heart failure. 1207 91

Bradykinin (BK) and related kinins are autocoid peptides that play integral roles in many pathophysiological processes such as cough. In this study, the inhibitory effect of noscapine, the antitussive opioid alkaloid, on BK receptors, was tested in the guinea-pig ileum. Contractions of the isolated ileum of the guinea-pig in response to BK were inhibited by noscapine (10-1,000 nM) in a concentration-dependent manner. Concentration-response curves (CRCs) to BK were slightly shifted to the right with a concomitant decrease in the maximum effect. A pA2 value of 6.68 was calculated for noscapine. The slope of the Schild plot of the antagonism was found to be 0.56. Noscapine had no effect on contractions induced by KCl, acetylcholine, histamine, 5-hydroxy tryptamine or angiotensin II. In conclusion, noscapine has a specific antagonistic effect on BK receptors and the mode of inhibition was found to be non-competitive.
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PMID:Efffect of noscapine, the antitussive opioid alkaloid, on bradykinin-induced smooth muscle contraction in the isolated ileum of the guinea-pig. 1216 81

Angiotensin II receptor antagonists block angiotensin II type 1 (AT1) receptors and reduce the pressor effects of angiotensin in the vasculature. By this mechanism, they induce similar pharmacological effects to angiotensin-converting enzyme (ACE) inhibitors, resulting in a lowering of blood pressure (BP). However, AT1 antagonists differ from ACE inhibitors with respect to side effects, and induce less cough, which is related to bradykinin activation. Within the class of angiotensin II antagonists, eprosartan differs from other currently clinically available agents in terms of its chemical structure and its dual pharmacological mode of action. Eprosartan acts not only at vascular AT1 receptors but also at presynaptic AT1 receptors, causing inhibition of sympathetically stimulated noradrenaline release. Eprosartan is not metabolized by cytochrome P450 enzymes and therefore has a low potential for metabolic drug interactions, which may be of importance when treating the elderly and patients on multiple drugs. In clinical trials eprosartan has proven to be at least as effective as the ACE inhibitor enalapril in reducing BP, but with a significantly lower incidence of side effects. Eprosartan is safe, effective and well tolerated in long-term treatment, either as monotherapy or in combination with other antihypertensive drugs such as hydrochlorothiazide.
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PMID:The clinical profile of the angiotensin II receptor blocker eprosartan. 1218 62

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

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

The use of angiotensin-converting enzyme (ACE) inhibitors to treat hypertension has recently increased. However, their use is associated with a persistent dry cough in a significant percentage of such patients. The present study was designed to assess the contribution of polymorphisms as a genetic marker of ACE-inhibitor-related cough in a Japanese hypertensive population. Genotyping was carried out in 190 patients, 70 with cough and 120 without cough, who had been treated with ACE inhibitors. Polymorphisms of ACE insertion/deletion (I/D), angiotensin II type 1 receptor (1166A/C), type 2 receptor (3123C/A), and bradykinin B2 receptor (-58T/C, exon 1, I/D), were analyzed in these subjects. The TT genotype and T allele of bradykinin B2 receptor (-58T/C) were identified at a significantly higher frequency in the cough (+) patients than in the cough (-) patients. This difference was even more pronounced in women. However, there was no significant relationship between polymorphisms of ACE, angiotensin II receptors, or bradykinin B2 receptor exon 1, and occurrence of ACE-inhibitor-related cough. The transcriptional activity of the bradykinin B2 receptor promoter is involved in the occurrence of cough, and this new marker may provide a valuable tool to detect patients at risk of developing this side effect of ACE inhibitors. In conclusion, Susceptibility to develop cough is associated with a genetic variant of the bradykinin B2 receptor promoter; thus, it may be possible to identify those patients who will develop this adverse reaction to ACE inhibitors in advance.
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PMID:Association of polymorphisms of the renin-angiotensin system and bradykinin B2 receptor with ACE-inhibitor-related cough. 1252 67

Hypertension remains one of the most unmet medical needs of this century. While many drugs are available for treating hypertension, efforts are still insufficient to find potent therapeutic agents since cause for hypertension in all patients is not the same. Angiotensin-converting enzyme inhibitors (ACEIs) have emerged as an important class of drugs in the treatment of hypertension, congestive heart failure (CHF), protenuric renal disease, myocardial infarction and stroke. This class of drugs blocks the conversion of angiotensin I to angiotensin II and prevents bradykinin breakdown. However, the lack of specificity of ACEIs leads to the frequent side effects like cough and angio-oedema. Recently developed, specific non-peptide and orally active angiotensin receptor blockers (ARBs) have become the prime therapeutics as they alone or co-administration with ACE inhibitors can control the renin angiotensin disorders. This review explores recent developments in the design, synthesis, and structural modifications of ACE inhibitors as well as angiotensin receptor blockers.
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PMID:Advances in angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). 1287 Nov 64


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