Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is a major problem throughout the developed world. Although current antihypertensive treatment regimens reduce morbidity and mortality, patients are often noncompliant, and medications may not completely normalize blood pressure. As a result, current therapy frequently does not prevent or reverse the cardiovascular remodeling that often occurs when blood pressure is chronically elevated. Blockade of the renin-angiotensin system (RAS) is effective in controlling hypertension and treating congestive heart failure. Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) inhibit the activity of the RAS, but these two classes of antihypertensive medications have different mechanisms of action and different pharmacologic profiles. Angiotensin-converting enzyme inhibitors block a single pathway in the production of angiotensin II (Ang II). In addition, angiotensin I is not the only substrate for ACE. The ACE inhibitors also block the degradation of bradykinin that may have potential benefits in cardiovascular disease. Bradykinin is, however, the presumed cause of cough associated with ACE inhibitor therapy. Data from clinical trials on ACE inhibitors serve to support the involvement of the RAS in the development of cardiovascular disease. Angiotensin receptor blockers act distally in the RAS to block the Ang II type 1 (AT1) receptor selectively. Thus, ARBs are more specific agents and avoid many side effects. Experimental and clinical trials have documented the efficacy of ARBs in preserving target-organ function and reversing cardiovascular remodeling. In some instances, maximal benefit may be obtained with Ang II blockade using both ARBs and ACE inhibitors. This review describes clinical trials that document the efficacy of ARBs in protecting the myocardium, blood vessels, and renal vasculature.
 ...
PMID:Angiotensin receptor blockers: evidence for preserving target organs. 1128 62

Angiotensin II(AII) accelerates the progress of cardiovascular diseases. This was proved by the fact that the blockade of renin-angiotensin system provided clinical benefits for patients with cardiovascular diseases. This review focuses on the differences between AT1-receptor antagonist and ACE inhibitor in basic and clinical aspects. Beside decreased AII concentration, increased tissue bradykinin concentration may contribute to the beneficial effect of ACE inhibitor, on the other hand, this increases the rate of cough to decrease the compliance. Increased AII concentration by AII receptor antagonist may antagonize the binding of the drug as well as stimulate AT2 receptor subtype. ACE inhibitor can not block the effect of non-ACE AII formation, but AII receptor does. These differences should be considered for their clinical use.
 ...
PMID:[Comparison between AngII receptor antagonist and ACE inhibitor]. 1139 5

In both diabetic and nondiabetic renal disease, reducing blood pressure with antihypertensive therapy has beneficial effects on renal function. The key role of the renin-angiotensin system in blood pressure and volume homeostasis has long been established, but its importance for the overall normal functioning of the kidney itself is also increasingly being recognized. Angiotensin-converting enzyme (ACE) inhibitors, widely and successfully used in the treatment of hypertension, may also provide renal protection independent of blood pressure reduction; however, their relatively nonspecific mode of action in blocking an early metabolic step entails major clinical disadvantages, such as accumulation of bradykinin and substance P, that may cause the characteristic ACE-inhibitor side effects of persistent dry cough and, more rarely, angioneurotic edema. Angiotensin II antagonists or receptor blockers, a new class of antihypertensive agent, selectively antagonize the AT1 receptor subtype and, because of greater specificity, do not give rise to the side effects associated with ACE inhibitors. More important, these new drugs may have mechanistic advantages over other antihypertensives, including ACE inhibitors.
 ...
PMID:Valsartan and the kidney: review of preclinical and clinical data. 1144 69

Angiotensin Converting Enzyme (ACE) inhibitors represent a major advance in the treatment of: hypertension, and generally speaking, in cardiovascular prevention; myocardial infarction; cardiac failure. They have a cardio and vascular protective action by tending to correct hypertension, left ventricular hypertrophy and remodelling, endothelial dysfunction, arterial smooth muscle proliferation and thrombotic phenomena. However, besides the cough that this therapeutic class engenders, a major question remains unanswered: is there resistance to this family of drugs? In other words, does left ventricular remodelling and arterial smooth muscle proliferation continue with regular treatment at the prescribed dosages? The synthesis of angiotensin II does not only depend on the angiotensin converting enzyme but also on the quality of angiotensin I and the presence of other enzymes such as chymase. A secondary increase of angiotensin II with ACE inhibitor therapy may reflect insufficient blockade of the renin-angiotensin system or a synthesis of angiotensin II by an alternative pathway to the converting enzyme. In vivo measurement of ACE inhibition shows that blockade of the renin-angiotensin system is automatically limited due to the very accurate regulation of angiotensin II concentrations.
 ...
PMID:[Resistance to ACE inhibitors. Myth or reality?]. 1160 63

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.
 ...
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.
 ...
PMID:Perindopril: in congestive heart failure. 1207 91

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.
 ...
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.
 ...
PMID:Eprosartan for the treatment of hypertension. 1251 47

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.
 ...
PMID:Clinical profile of eprosartan. 1276 89

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.
 ...
PMID:Advances in angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). 1287 Nov 64


<< Previous 1 2 3 4 5 6 Next >>