Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this article is to review the pharmacokinetics of perindopril and its active metabolite perindoprilat in high-risk populations in comparison with their basic features in healthy volunteers. As it has been shown that the kinetics of perindoprilat are mainly affected by renal insufficiency, a dosage reduction is therefore recommended on initiation of treatment in elderly patients and in those with renal failure according to the degree of renal failure. In patients with chronic heart failure, the kinetics of both perindopril and perindoprilat were shown to have been altered, also indicating the need for an initial dosage reduction in such patients. Hepatic impairment had no significant effect on the kinetics of either the prodrug or the active metabolite.
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PMID:Pharmacokinetics of perindopril in high-risk populations. 172 3

Drug interactions common to all angiotensin-converting enzyme (ACE) inhibitors include those with thiazide diuretics and other antihypertensive agents. Interactions involving specific ACE inhibitors include captopril-digoxin, resulting in decreased clearance of digoxin from plasma in patients with heart failure, and captopril-probenecid, causing a decrease in captopril clearance. Tissue kinins, such as bradykinin, are metabolised by ACE inhibitors. Interactions involving bradykinin include captopril-indomethacin, in which an attenuation of the antihypertensive effects of captopril is manifest. Interestingly, neither enalapril nor lisinopril appear to show this interaction with indomethacin. Kinin-based interactions may also be important in the genesis of ACE inhibitor-induced cough and skin rash. Renal dysfunction affects the pharmacokinetics and pharmacodynamics of all ACE inhibitors, necessitating dosage reduction. Hepatic impairment is of less clinical importance, causing a delay in the onset of action of enalapril with initial doses, but probably having little relevance to long-term therapy.
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PMID:Drug interactions with ACE inhibitors. 267 38

Hepatic impairment can alter the pharmacokinetic profiles of cardiovascular drugs, which can lead to unwanted toxicity. In the presence of cirrhosis, portosystemic shunting occurs and cytochrome P450 activity is reduced. Impaired oxygen uptake caused by changes in the liver's sinusoids, as proposed by the oxygen limitation theory, may also explain the alteration of drug metabolism seen in cirrhosis. With congestive heart failure, sinusoidal congestion and hypoperfusion of the liver are seen. Similar to cirrhosis, the common pathway for hepatic damage in congestive heart failure seems to be liver hypoxia, which may explain the disease's effect on drug metabolism. Since routine hepatic function tests do not always relate to the liver's ability to eliminate drugs, existing guidelines for dosing cardiovascular drugs in patients with hepatic impairment are limited. This article provides guidance for dosing cardiovascular drugs in cirrhotic and heart failure patients based on available research data. Altered drug metabolism, especially in congestive heart failure, tends to be overlooked or not realized in clinical practice. Therefore, further research is needed in congestive heart failure to better elucidate safe prescribing patterns.
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PMID:Cardiovascular drug therapy in patients with hepatic diseases and patients with congestive heart failure. 1063 18

Candesartan cilexetil is the prodrug of candesartan, an angiotensin II receptor antagonist. Candesartan binds selectively and non-competitively to the angiotensin II receptor type 1, thus preventing the actions of angiotensin II. Clinical trials have demonstrated its efficacy at a dose range of 2 to 32 mg once daily in hypertension of all grades, heart failure, in reducing urinary albumin excretion in diabetes mellitus and in coexisting hypertension and renal failure. Pharmacokinetic properties of candesartan cilexetil in elderly patients are not significantly different from those in younger individuals. Hepatic impairment does not change pharmacokinetics of candesartan cilexetil at doses up to 12 mg/day. No dose adjustment is necessary in patients with mild or moderate renal impairment. Tolerability of candesartan cilexetil is not much different from that of placebo. All adverse events are usually of mild to moderate severity and not dose-related. The most common adverse events were headache, upper respiratory tract infection, back pain, and dizziness. The incidence of these adverse effects, as well as of cough, was similar in patients treated with candesartan cilexetil or placebo. The incidence of adverse events in long-term trials was not different from that in short-term trials. Tolerability of candesartan cilexetil does not differ with either age or gender.
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PMID:Candesartan. 1559 74