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)

Dry cough is a troublesome side-effect associated with certain antihypertensive agents that act by modulating aspects of the renin-angiotensin-aldosterone system. The incidence of dry cough associated with two of these therapies, the novel All receptor antagonist telmisartan and the ACE inhibitor lisinopril, was assessed in a multicentre, randomised, parallel-group, double-blind, placebo-controlled, 8-week study of 88 patients with mild to moderate hypertension who previously demonstrated ACE inhibitor-related cough. Patients received either telmisartan 80 mg, lisinopril 20 mg, or placebo once daily. Cough incidence, measured at each visit by a self-administered symptom assessment questionnaire, was significantly higher with lisinopril (60%) than with telmisartan (15.6%) or placebo (9.7%). A visual analogue scale demonstrated a similar trend for cough frequency. Thus the incidence of cough with telmisartan 80 mg is significantly less than that seen with lisinopril 20 mg and is comparable to placebo.
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PMID:The incidence of cough: a comparison of lisinopril, placebo and telmisartan, a novel angiotensin II antagonist. Telmisartan Cough Study Group. 1034 43

In this review angiotensin II receptor antagonists (Angiotensin antagonists are discussed on the efficacy and safety in the treatment of essential hypertension. Angiotensin antagonists are more complete renin angiotensin system blockade, and are potent as ACE inhibitors, but they have rarely troublesome dry cough specific to ACE inhibitors. Angiotensin antagonists have demonstrated an excellent tolerability profile. Angiotensin antagonists will have potentially greater protection from end-organ damage, since they have provided end-organ protection in animal experiments. These agents will be considered for first-line therapies in very near future.
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PMID:[Comparison with other antihypertensive drugs, especially with ACEI]. 1036 54

Losartan is the first orally active angiotensin II receptor type 1 antagonist for a new class of cardiovascular therapeutic agent. Losartan is converted to an active metabolite (E3174) after oral administration in humans and rats. Both losartan and E3174 contribute to the net angiotensin II receptor blockade and produce anti-hypertensive effect. Losartan not only blocks the vasoconstrictive effect of angiotensin II but also inhibits its mitogenic effect; thus losartan is expected to protect against end-organ-damage-related hypertension and chronic heart failure. Unlike angiotensin-coverting-enzyme inhibitor, losartan does not elicit adverse effects of cough and angioneurotic edema by its blockade of angiotensin II receptor. It is also expected to reduce proteinuria in nephropathy. In addition to its blockade of angiotensin II receptor, losartan blocks thromboxane A2 receptor and facilitates excretion of uric acid, although therapeutic importance of these effects are under investigation. In summary, losartan, an angiotensin II type 1 receptor antagonist is a new class of antihypertensive agent and its therapeutic potentials are not merely reduction of blood pressure but total protection from end-organ damage resulting from activation of both the systemic and local renin-angiotensin system.
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PMID:[Pharmacological characteristics and clinical application of losartan, an orally active AT1 angiotensin II receptor antagonist]. 1052 59

The renin-angiotensin system plays a central role in the regulation of blood pressure through its primary effector hormone angiotensin II. Studies conducted nearly 30 years ago with peptidic angiotensin II receptor blockers (ARB) suggested that disruption of the renin-angiotensin system offered considerable promise for the treatment of hypertension as well as heart failure. This promise was initially realized with the advent of angiotensin converting enzyme inhibitors, and more recently with nonpeptidic ARB that selectively antagonize the AT1-angiotensin receptor subtype. The potent and long-acting agent candesartan cilexetil illustrates how these new ARB fulfill the promises suggested by the early studies. Candesartan cilexetil provides a clinically relevant, dose-dependent reduction in diastolic and systolic blood pressure at doses of 4 to 16 mg once daily in patients with mild to moderate hypertension. Recent studies suggest that further blood pressure lowering is obtained with a 32-mg once daily dose. In comparative clinical trials, 8 mg of candesartan cilexetil and 10 to 20 mg of enalapril provided comparable antihypertensive effects. The safety and tolerability profile of candesartan cilexetil is comparable to placebo. Notably, this agent does not produce the dry, nonproductive cough that often limits use of angiotensin converting enzyme inhibitors, nor does it cause side effects that limit other antihypertensive drug classes. On the basis of the results of initial clinical studies, ARB also possess cardioprotective and renoprotective properties that promise to expand the role that these new agents will play in treating cardiovascular disorders.
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PMID:Update on the clinical pharmacology of candesartan cilexetil. 1067 85

Information from clinical and pharmacokinetic studies of angiotensin-converting enzyme inhibitors (ACEIs) has come from subjects who are mostly male and Caucasian, but the use of ACEIs extends to populations worldwide. Significant differences between Chinese in general and male Caucasians have been demonstrated in the pharmacokinetics/dynamics of other drug classes that could have implications for the use of ACEIs in the Chinese population. These include: significant Chinese/Caucasian genetic variation in the renin-angiotensin system based on an insertion/deletion (O/D) polymorphism of the ACE gene; the genetic determination of plasma ACE activity in the Chinese population; and genetic factors involving the disease substrate which may also influence the response to treatment. Oral and IV pharmacokinetic data from various studies of Chinese and Caucasian subjects are available for cilazapril, fosinopril, and perindopril, and pharmacodynamic data are available for eight different ACEIs. Based on these data, there are few differences among the pharmacokinetics of ACEIs between Chinese and Caucasians. Most ACEIs showed good blood pressure lowering efficacy in Chinese (benazepril, enalapril, fosinopril and spirapril), with perhaps less blood pressure lowering with cilazapril or a relatively shorter-term effect with cilazapril or perindopril compared to Caucasions. Chinese experience more cough from ACEIs (captopril and enalapril) than Caucasians. Data suggest that fosinopril may not induce cough in as many subjects as other ACEIs, and this seems to be true of Chinese as well. The mechanism, currently unknown, could involve fosinopril's dual elimination pathway (hepatic and renal). Pharmacokinetic data also support the use of fosinopril in congestive heart failure where elimination pathways may be impaired. In conclusion, ethnic differences between Chinese and Caucasians with respect to ACE and AGT gene polymorphism, which might be expected to differentially affect the action of ACEIs in these two ethnic groups, do not, in fact, have such an effect. Rather, differences among the ACEIs appear to be more important. Journal of Human Hypertension (2000) 14, 163-170.
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PMID:Does Chinese ethnicity affect the pharmacokinetics and pharmacodynamics of angiotensin-converting enzyme inhibitors? 1069 29

The effective treatment of hypertension is an extremely important consideration in patients with end-stage renal disease (ESRD). Virtually any drug class--with the possible exception of diuretics--can be used to treat hypertension in the patient with ESRD. Despite there being such a wide range of treatment options, drugs which interrupt the renin-angiotensin axis are generally suggested as agents of choice in this population, even though the evidence in support of their preferential use is quite scanty. ACE inhibitors, and more recently angiotensin antagonists, are the 2 drug classes most commonly employed to alter renin-angiotensin axis activity and therefore produce blood pressure control. ACE inhibitor use in patients with ESRD can sometimes prove an exacting proposition. ACE inhibitors are variably dialysed, with compounds such as catopril, enalapril, lisinopril and perindopril undergoing substantial cross-dialyser clearance during a standard dialysis session. This phenomenon makes the selection of a dose and the timing of administration for an ACE inhibitor a complex issue in patients with ESRD. Furthermore, ACE inhibitors are recognised as having a range of nonpressor effects that are pertinent to patients with ESRD. Such effects include their ability to decrease thirst drive and to decrease erythropoiesis. In addition, ACE inhibitors have a unique adverse effect profile. As is the case with their use in patients without renal failure, use of ACE inhibitors in patients with ESRD can be accompanied by cough and less frequently by angioneurotic oedema. In the ESRD population, ACE inhibitor use is also accompanied by so-called anaphylactoid dialyser reactions. Angiotensin antagonists are similar to ACE inhibitors in their mechanism of blood pressure lowering. Angiotensin antagonists are not dialysable and therefore can be distinguished from a number of the ACE inhibitors. In addition, the adverse effect profile for angiotensin antagonists is remarkably bland, with cough and angioneurotic oedema rarely, if ever, occurring. In patients with ESRD, angiotensin antagonists are also not associated with the anaphylactoid dialyser reactions which occur with ACE inhibitors. The nonpressor effects of angiotensin antagonists--such as an influence on thirst drive and erythropoiesis--have not been explored in nearly the depth, as they have been with ACE inhibitors. Although ACE inhibitors have not been compared directly to angiotensin antagonists in patients with ESRD, angiotensin antagonists possess a number of pharmacokinetic and adverse effect characteristics, which would favour their use in this population.
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PMID:Risk-benefit ratio of angiotensin antagonists versus ACE inhibitors in end-stage renal disease. 1083 Feb 52

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

Two independent pharmacologic methods of specifically interfering with the renin-angiotensin-aldosterone system have been brought to the marketplace: angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). These agents have the potential not only to be very widely used for a broad variety of clinical indications but also to compete against each other as treatments for hypertension, heart failure, renal impairment, and other conditions. Many short-term comparative studies of these two classes of drugs have now been completed. Most have focused on surrogate endpoints, such as blood pressure, renal function, or cough. These studies have generally concluded that ARBs are better tolerated but that the two drug classes otherwise have similar efficacy. The largest clinical trial comparing ARBs and ACE inhibitors thus far completed, Evaluation of Losartan in the Elderly (ELITE 2), failed to confirm the results of a smaller study; it did not demonstrate a significant improvement in outcomes (death or hospitalization for heart failure) with an ARB used alone, despite better tolerability. Many longer-term outcome studies with survival endpoints are under way, but most will compare the combination against an ACE inhibitor alone. These studies will define the optimal use of these agents in medicine for decades to come.
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PMID:Therapeutic trials comparing angiotensin converting enzyme inhibitors and angiotensin II receptor blockers. 1098 Nov 76

The pharmacology of angiotensin-converting-enzyme (ACE) inhibitors and their role in the renin-angiotensin system (RAS) are described, and pharmacokinetic properties and common adverse events are presented. ACE inhibitors play a vital role in the RAS by regulating the potent vasoconstrictor angiotensin II. All ACE inhibitors share the same basic structure; however, they can be separated on the basis of their functional (binding) group: carboxyl, sulfhydryl, or phosphinyl. These functional groups are, in part, responsible for differences in the pharmacokinetic and safety profiles of these agents. Captopril and lisinopril are the only ACE inhibitors that are not prodrugs requiring activation through hepatic biotransformation. Differences among the ACE inhibitors in lipophilicity are described; fosinopril has the greatest lipophilicity and lisinopril the least. ACE is found in numerous tissues, and there is increasing evidence of differences among ACE inhibitors in their ability to inhibit tissue ACE. Most ACE inhibitors are eliminated mainly by the kidneys and to a lesser extent through the liver. Lisinopril is the only ACE inhibitor that does not require hepatic metabolism. In the selection of an ACE inhibitor for once-daily use to treat hypertension, differences in trough-peak ratios are clinically relevant. Fosinopril, ramipril, and trandolapril have minimum trough-peak ratios of 50% or greater. ACE inhibitors are generally well tolerated, with hypotension, cough, and hyperkalemia being the most frequently reported adverse effects for the entire class. Drug interactions across the ACE inhibitor class as well as agent-specific interactions are described. Factors to be considered in the selection of an ACE inhibitor include differences in potency, affinity for ACE, pharmacokinetics, and toxicity that are related to structural properties of the drug; whether the trough-peak ratio enables use of a once-daily dose; and potential adverse effects related to a drug's functional (binding) group.
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PMID:Overview of the angiotensin-converting-enzyme inhibitors. 1103 16


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