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 (AT1) receptor antagonists inhibit the renin-angiotensin system more completely than ACE inhibitors, and do not increase bradykinin levels as ACE inhibitors do. ACE inhibitors have been proven to increase survival and improve quality of life in patients with congestive heart failure (CHF). At the 48-week follow-up of the Evaluation of Losartan in the Elderly (ELITE) Study, the AT1 receptor antagonist losartan (at a dosage of 50 mg/day) was found to be superior to captopril 50 mg 3 times daily in terms of its effects on total mortality, total mortality and/or hospitalisation for CHF, and hospitalisation for any reason. Hospitalisation for CHF was the same for both drugs. Adverse effects occurred in 12 and 21% of those receiving losartan and captopril, respectively. Cough, rash, angioedema or taste disturbances/reduced appetite prompted the cessation of drug treatment in 0 and 7% of those receiving losartan and captopril, respectively. Until additional data are available, this author recommends that elderly patients with CHF and an abnormal or normal left ventricular ejection fraction, and who are unable to tolerate ACE inhibitors, should receive losartan 50 mg/day.
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PMID:The ELITE Study. What are its implications for the drug treatment of heart failure? Evaluation of Losartan in the Elderly Study. 963 91

Most antihypertensives have advantages and disadvantages. The ideal antihypertensive drug should be effective in lowering blood pressure, well tolerated, safe in the long term, and easy to use. Ideally, it should be relatively inexpensive. Most importantly it should reduce the risk of the adverse effects of high blood pressure, such as myocardial infarction, sudden death, stroke, heart failure, renal damage, and retinal changes. Most antihypertensive drugs effectively reduce blood pressure, are available as once daily preparations, and are safe long-term. Unfortunately, most antihypertensive drugs cause adverse effects in some patients and for few drugs is there good evidence that they protect the heart, the brain, the kidney, and the eye? Reducing the effects of Angiotensin II (using an ACE inhibitor) has been shown to reduce the incidence of coronary events, sudden death, heart failure, renal damage, and fundal changes. AT1 blocking drugs offer the same pharmacological advantages but also very good tolerability, in particular no cough. Therefore, they have the potential to meet all the criteria for an ideal antihypertensive drug.
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PMID:Therapeutic advantages of AT1 blockers in hypertension. 983 62

One possible intervention to interrupt the deleterious effects of the renin-angiotensin system is suppression of angiotensin II (Ang II) formation by inhibition of angiotensin-converting enzyme (ACE). However, ACE inhibition incompletely suppresses Ang II formation and also leads to accumulation of bradykinin. Angiotensin II type 1 (AT1) receptors are believed to promote the known deleterious effects of Ang II. Therefore, AT1 receptor antagonists have been recently introduced into therapy for hypertension and congestive heart failure (CHF). Although there are significant differences between the effects of AT1 receptor antagonists and ACE inhibitors including the unopposed stimulation of angiotensin II type 2 (AT2) receptors by AT1 receptor antagonists, the discussion of whether ACE inhibitors, AT1 receptor antagonists or the combination of both are superior in the pharmacotherapy of CHF is still largely theoretical. Accordingly, AT1 receptor antagonists are still investigational. Angiotensin-converting enzyme inhibitors remain first line therapy in patients with CHF due to systolic dysfunction. However, in patients not able to tolerate ACE inhibitor induced side effects, in particular cough, AT1 receptor antagonism is a good alternative. In clinical practice, emphasis should be placed on increasing the utilization of ACE inhibitors, as more than 50% of patients with CHF do not receive ACE inhibitors. In addition, the majority of those on ACE inhibitors receive doses lower than the dosage used in the large clinical trials. Although not yet completely proved, it is likely that high doses of ACE inhibition are superior to low doses with respect to prognosis and symptoms.
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PMID:Recent insight into therapy of congestive heart failure: focus on ACE inhibition and angiotensin-II antagonism. 1019 12

Angiotensin II (AT-II)-receptor antagonists are reviewed. Research focused on blocking the renin-angiotensin system (RAS) led to the discovery of angiotensin-converting-enzyme (ACE) inhibitors, which are effective in the treatment of hypertension but are associated with a high frequency of cough and other adverse effects. AT-II-receptor antagonists were developed as agents that would more completely block the RAS and thus decrease the adverse effects seen with ACE inhibitors. AT-II-receptor antagonists include losartan, valsartan, irbesartan, candesartan, eprosartan, telmisartan, and tasosartan. Several clinical trials have demonstrated that AT-II-receptor antagonists are as effective as calcium-channel blockers, beta-blockers, and ACE inhibitors in the treatment of hypertension and induce fewer adverse effects. The adverse effects of AT-II-receptor antagonists--dizziness, headache, upper-respiratory-tract infection, cough, and gastrointestinal disturbances--occur at about the same rate as with placebo. [corrected]. All available AT-II-receptor antagonists seem to be equally effective in reducing both systolic and diastolic blood pressure, and they are comparable in cost. Currently, AT-II-receptor antagonists are used either as monotherapy in patients who cannot tolerate ACE inhibitors or in combination with other antihypertensive agents. Angiotensin II-receptor antagonists are well tolerated and are as effective as ACE inhibitors in decreasing blood pressure.
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PMID:Angiotensin II-receptor antagonists: an overview. 1090 66

The renin-angiotensin system (RAS) plays an important role in regulating blood pressure, and maintaining fluid and electrolyte balance. Angiotensin II is the principal mediator of the RAS and has been implicated in the development of hypertension as well as other forms of cardiovascular and renal disease. Angiotensin II-receptor antagonists are a new class of drugs that inhibit the RAS by selectively blocking the AT(1) receptor. These compounds therefore provide more specific and thorough blockade of the RAS by inhibiting the deleterious actions of angiotensin II at the receptor level, irrespective of how this peptide is formed. The increased specificity of action of angiotensin II-receptor antagonists may also circumvent unwanted side-effects normally associated with angiotensin-converting enzyme (ACE) inhibitors (eg, cough and angioedema) as these agents do not interfere with the metabolism of other peptides (eg, bradykinin, substance P, etc.). There is still some concern with angiotensin II-receptor antagonists and the long-term effects of hyper-stimulation of the unopposed AT(2) receptor that is caused by elevated levels of angiotensin II. However, it appears that stimulation of the AT(2) receptor may actually contribute to the beneficial effects of angiotensin II-receptor antagonists by counteracting the effects mediated by the AT(1) receptor. Angiotensin II-receptor antagonists display great therapeutic promise in the field of cardiovascular medicine and are currently being exploited as new antihypertensive agents. These drugs have demonstrated safety, efficacy, and tolerability; however, morbidity and mortality data are still lacking. Nonetheless, it is likely that angiotensin II-receptor antagonists will become part of the medical arsenal against cardiovascular and renal disease, thus consideration should be given to their future use as first-line antihypertensive agents.
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PMID:Spectrum of use for the angiotensin-receptor blocking drugs. 1098 Oct 96

Suppression of the renin-angiotensin system (RAS) with angiotensin-converting enzyme (ACE) inhibitors is an established method for controlling blood pressure and reducing the risk of cardiovascular disease. In addition to reducing blood pressure, suppression of the RAS is able to protect against the target-organ damage that results from hypertension. Unfortunately, despite the use of ACE inhibitors and agents from the other classes of conventional antihypertensives, effective control of blood pressure remains poor. A major contribution to this failure to control blood pressure appears to be lack of compliance with the prescribed medication, arising from the presence of unacceptable side effects. Angiotensin II type 1 (AT1) receptor blockers, such as candesartan, are the latest class of antihypertensive agent to be developed. They target the AT1-receptor - the final common pathway for all the known negative cardiovascular effects of angiotensin II - and provide pronounced antihypertensive efficacy without the side effects of cough and angioneurotic oedema that are associated with the use of ACE inhibitors.
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PMID:The renin-angiotensin system and cardiovascular disease. 1105 28

Angiotensin II type 1 (AT1) receptor blockers, such as candesartan, are attractive alternatives to ACE inhibitors in the treatment of hypertension and cardiovascular disease. Although angiotensin-converting enzyme (ACE) inhibitors are able to suppress the renin-angiotensin system (RAS), their mechanism of action may limit their clinical utility in the treatment of hypertension. For example, they act as competitive inhibitors of ACE. This means that their effects can be overcome by high levels of angiotensin I, which occur after ACE inhibition due to removal of the negative feedback effect of angiotensin II on renal renin release. ACE inhibitors are also unable to block the production of angiotensin II by non-ACE-mediated pathways. Furthermore, ACE is not a specific enzyme. Its inhibition therefore has effects on other substances, such as bradykinin, leading to the class-specific side effects associated with ACE inhibitors. Candesartan, on the other hand, binds insurmountably to the AT1-receptor, thereby providing more complete blockade of the negative cardiovascular effects of angiotensin II than is possible with ACE inhibitors. The specificity of AT1-receptor blockade also ensures that efficacy is achieved without inducing the side effect of cough that results from the non-specific consequences of ACE inhibition. Preclinical and early clinical studies demonstrate that AT1-receptor blockers produce at least the same degree of target-organ protection as has been demonstrated for ACE inhibitors. Additional benefits of AT1-receptor blockers may arise from the fact that, unlike ACE inhibitors, they do not prevent the activity of angiotensin II on AT2-receptors in the heart, which is thought to reduce cardiac remodelling. From a mechanistic perspective, therefore, AT1-receptor blockers appear to have advantages over ACE inhibitors, in terms of a more complete blockade of angiotensin II effects, while also avoiding the specific side effects associated with ACE inhibition.
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PMID:Angiotensin II type 1 receptor blockade: a novel therapeutic concept. 1105 29

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.
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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.
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PMID:Valsartan and the kidney: review of preclinical and clinical data. 1144 69

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


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