Drug interactions with calcium antagonists

Kirch, Wilhelm; Kleinbloesem, C. H.; Belz, G. G.

doi:10.1016/0163-7258(90)90011-p

Cited by 27 publications

(21 citation statements)

References 131 publications

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“…The data of the present study are in agreement with literature data (24) and have also been shown for other dihydropyridine derivatives (25). Furthermore, drugs which induce or inhibit hepatic metabolism are known to alter kinetics of dihydropyridines, like nifedipine (26). Finally, there was a slight, but insignificant, increase of nifedipine AUCoo in renal failure -a result which is exactly in accordance with literature data for nifedipine (27) and also for nitrendipine (28,29), and that can be partially explained by a reduced protein binding of nifedipine in renal failure (30).…”

Section: Discussionsupporting

confidence: 82%

Clinical pharmacokinetics of the nifedipine/co-dergocrine combination in impaired liver and renal function

Kirch

Nokhodian

Halabi

et al. 1992

European Journal of Drug Metabolism and Pharmacokinetics

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Following a single oral dose of 20 mg nifedipine combined with 2 mg co-dergocrine to 24 subjects, the pharmacokinetics of this drug were studied. 8 normotensive subjects had normal renal and hepatic function, 8 patients had chronic renal insufficiency (creatinine clearance less than 30 ml.min-1) and 8 patients had liver cirrhosis which was confirmed by liver biopsy. The area under the plasma level time curve (AUC infinity) of co-dergocrine increased from 0.59 +/- 0.41 ng.ml-1. (mean +/- SD) in the normals to 1.24 +/- 0.95 ng.ml-1.h in liver cirrhosis (P less than 0.05) and to 1.81 +/- 0.9 ng.ml-1.h in renal failure (P less than 0.05 compared with the control group). Corresponding values for the nifedipine AUC infinity were 564.5 +/- 268 ng.ml-1.h, 1547.5 +/- 1134 (P less than 0.05) and 929 +/- 533 ng.ml-1.h (P less than 0.05; gas chromatographic method). The incidence of adverse effects was lower in patients with renal failure than in subjects with normal renal and liver function as well as in those with liver cirrhosis.

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Section: Discussionsupporting

confidence: 82%

Clinical pharmacokinetics of the nifedipine/co-dergocrine combination in impaired liver and renal function

Kirch

Nokhodian

Halabi

et al. 1992

European Journal of Drug Metabolism and Pharmacokinetics

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“…Although verapamil may elevate serum concentrations of propranolol (McGourty et al 1988) and increase gastrointestinal absorption and decrease renal clearance of atenolol, no clinically relevant pharmacokinetic interaction has been demonstrated between calcium antagonists and ~-blockers (Kirch et al 1990). However, significant pharmacodynamic effects are common during combination therapy with ~-blockers and calcium entry blockers, particularly verapamil (Carruthers et al 1989;Packer et al 1982;Wayne 1983).…”

Section: ~-Blockersmentioning

confidence: 99%

“…Some calcium antagonists, most notably verapamil, increase serum digoxin concentrations (Kirch et al 1990). In single-and multiple-dose verapamil studies in patients on digoxin, serum concentrations of digoxin increased by 70% as a result of considerably reduced digoxin clearance, both renal and nonrenal (Klein et al 1982;Pedersen et al 1981).…”

Section: Digoxinmentioning

confidence: 99%

Poisoning Due to Calcium Antagonists

Pearigen

Benowitz

1991

Drug Safety

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The calcium antagonists are a heterogeneous class of drugs which block the inward movement of calcium into cells through 'slow channels' from extracellular sites. By inhibiting phase 0 depolarisation in cardiac pacemaker cells and phase 2 plateau in myocardium, and by depressing calcium ion flux in smooth muscle cells of blood vessels, these agents may exert profound effects on the cardiovascular system, particularly in susceptible individuals or in overdose. Sinus node depression, impaired atrioventricular (AV) conduction, depressed myocardial contractility, and peripheral vasodilatation may result. Pharmacokinetic features of calcium antagonists include rapid and complete absorption from the gastrointestinal tract, with extensive first-pass hepatic metabolism yielding generally low bioavailability. The volume of distribution is generally large and protein binding is high. Elimination is almost entirely by the liver. Impaired renal function does not affect pharmacokinetics. Verapamil is the most potent inhibitor of cardiac conduction and contractility, with diltiazem also showing such effects. Nifedipine is the most potent vasodilator, but only occasionally impairs the sinus node or AV conduction. Significant pharmacodynamic effects are common during combination therapy with calcium antagonists, especially verapamil and beta-blockers. Verapamil may significantly elevate serum digoxin concentrations and may exert additive negative effects on chronotropism and dromotropism when this combination is used. Overdoses of calcium entry blockers are becoming more frequent and reflect an extension of the known pharmacodynamic profile of these agents. Typical features include confusion or lethargy, hypotension, sinus node depression and cardiac conduction defects. Onset of symptoms may be delayed if a sustained release preparation is ingested. Management of calcium antagonist overdose includes gut decontamination with lavage and activated charcoal. All symptomatic patients and patients with a history of ingesting a sustained release preparation should be admitted for ECG monitoring. If bradycardia and/or conduction defects contribute to hypotension, atropine or isoprenaline (isoproterenol) may accelerate the ventricular rate. Transvenous pacing may be required. Depressed myocardial contractility usually responds well to calcium chloride or calcium gluconate administration, but further inotropic support may be required. Peripheral vasodilation should be managed with intravenous fluids and a pressor agent such as dopamine or norepinephrine (noradrenaline).

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“…the extent to which a drug is absorbed systemically, needs to be assessed at an early stage. Failure to recognize it has invalidated a number of clinical trials [17,18]. To give an example, nifedipine, the calcium antagonist drug, has a bioavailability of only about 15% in normal healthy volunteers, but in epileptic patients receiving enzyme-inducing drugs it is further reduced to perhaps 5%.…”

Section: Alan Richensmentioning

confidence: 99%

New Drug Treatments in Epilepsy

Küntzer

1994

Eur Neurol

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With New Drug Treatments in Epilepsy Dr Kuntzer and I are happy to introduce the new section Emerging Therapies in Neurology. We expect to publish 3 a year, and we are open to suggestions by the readers. Epilepsy is one of the neurologic diseases in which drug therapy has evolved the most during the last few years. Actually, a series of new drugs has lately been marketed in several countries, after years of pharmacological research and clinical trials. This leaves the patients and doctors with more possibilities for treatment, but also with more difficulty in choosing and adapting each individual drug regimen. Loiseau, Richens, Sanders and O’Donoghue address the progresses and problems linked to these recent developments in antiepileptic drugs. Among unanswered questions, one could be applied to neurology as a whole. Given the rapid expansion of disease classification and of treatment varieties, will there be a limit when non-ultraspecialists will not be allowed by reinbursement parties to prescribe newly available treatments?

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Drug interactions with calcium antagonists

Cited by 27 publications

References 131 publications

Clinical pharmacokinetics of the nifedipine/co-dergocrine combination in impaired liver and renal function

Clinical pharmacokinetics of the nifedipine/co-dergocrine combination in impaired liver and renal function

Poisoning Due to Calcium Antagonists

New Drug Treatments in Epilepsy

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