Hemodynamic effects of intravenous diltiazem in patients treated chronically with propranolol

The effects of two bolus injections (0.2 mg kg-1) and two infusion rates (0.2 mg min-1 and 0.4 mg min-1) of diltiazem on global and regional left (LV) and right ventricular (RV) performance (ultrasonic dimension technique), on coronary (electromagnetic flow meters) and systemic haemodynamics, and on electrophysiology (PR, QRS, QTc intervals) were studied in eight open-chest dogs anaesthetized with droperidol and fentanyl. The two bolus injections of diltiazem resulted in plasma concentrations of 688 +/- 115 and 650 +/- 85 ng ml-1 (means +/- SE), respectively, and caused substantial decreases in systemic and coronary vascular resistances, and in aortic pressure, and increases in LV segment shortening, stroke volume and aortic flow. Electrophysiological variables were little affected. At the low infusion rate (plasma concentration 140 +/- 23 ng ml-1) coronary and systemic vasodilatation occurred, but global and regional RV and LV performance were little affected. PR interval increased by 15%. At the higher infusion rate (plasma concentration 282 +/- 33 ng ml-1) coronary and systemic vasodilatation were maintained. Aortic pressure decreased slightly. Whereas LV end-diastolic and end-systolic dimensions remained unchanged, they increased in the RV. In addition, the PR interval increased by 35%, and three animals developed atrioventricular block type I. The data indicate that diltiazem is a potent coronary and systemic vasodilator with little effect on global RV and LV performance. However, at a higher infusion rate RV dimensions clearly tend to increase, and conduction abnormalities develop.

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“…In contrast, diltiazem did not alter PVR and PAP. Similar results have been reported previously [9,[23][24][25].…”

Section: Effects Of Diltiazem On Systemic and Pulmonary Circulationssupporting

confidence: 93%

Cardiovascular Effects of Diltiazem in the Dog

Skarvan

Priebe

1988

British Journal of Anaesthesia

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“…The coadministration of verapamil at a dose of 360 to 480 mg/ day and propranolol at a dose of 120 to 320 mg/ day has been generally well tolerated, and was associated with a significant improvement in exercise capacity in patients with stable angina pectoris (Leon et al 1981;Subramanian et al 1982). Similar results have been obtained for combined treatment with diltiazem and (j-adrenoceptor antagonists (Hung et al 1983;Rocha et al 1986). However, because of the negative inotropic and dromotropic effects of both calcium antagonists and (j-adrenoceptor antagonists, the likelihood of a pharmacodynamic drug interaction exists when the drugs are administered concomitantly.…”

Section: 3-adrenoceptor Antagonistsmentioning

confidence: 58%

Clinical Pharmacokinetics of Verapamil, Nifedipine and Diltiazem

Echizen

Eichelbaum

1986

Clinical Pharmacokinetics

181

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The calcium antagonists diltiazem, nifedipine and verapamil are widely used in the treatment of coronary heart disease, arterial hypertension, certain supraventricular tachyarrhythmias and obstructive hypertrophic cardiomyopathy. During recent years their pharmacokinetic properties and metabolism have been studied in more detail. Although these 3 calcium antagonists exhibit great diversity in chemical structure, they exhibit common pharmacokinetic properties. These drugs are extensively metabolised and only traces of unchanged drugs are eliminated in urine. Their systemic plasma clearances are high and dependent on liver blood flow. Therefore, their bioavailabilities (diltiazem 40 to 50%; nifedipine 40 to 50%; verapamil 10 to 30%) are low despite almost complete absorption following oral administration. During long term treatment, oral clearance decreases and bioavailability increases due to saturation of hepatic first-pass metabolism. Pronounced intra- and inter-individual variations in clearance and bioavailability are observed. In patients with liver cirrhosis the various pharmacokinetic parameters are grossly altered. Clearance decreases, elimination half-life is substantially prolonged, and bioavailability more than doubles. In addition, the volume of distribution increases. Whereas renal disease has no impact on the pharmacokinetics of diltiazem and verapamil, elimination half-life of nifedipine increases in relation to the degree of renal impairment due to an increase in volume of distribution. Systemic clearance, however, remains unchanged. The data so far available indicate that the plasma concentrations of these drugs correlate with both their electrophysiological and haemodynamic effects. However, no effective therapeutic plasma concentration range has been firmly established. As reliable clinical end-points are available for dose titration of calcium antagonists, it is doubtful whether therapeutic drug monitoring will be of great value. Calcium antagonists are often administered in combination with a variety of other drugs. Thus, the potential for both pharmacodynamic and pharmacokinetic drug interaction exists. The interaction between digoxin and these drugs is of clinical importance. Verapamil and diltiazem cause a significant increase in plasma digoxin concentrations. In contrast, nifedipine does not lead to a significant increase in the plasma digoxin concentration. The mechanism responsible for this interaction is inhibition of both renal and non-renal digoxin clearance.(ABSTRACT TRUNCATED AT 400 WORDS)

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Combined Treatment of Stable Effort-Induced Angina and Mixed Angina

Egstrup

1990

Pathophysiology and Rational Pharmacotherapy of Myocardial Ischemia

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Hemodynamic effects of intravenous diltiazem in patients treated chronically with propranolol

Cited by 16 publications

References 23 publications

Cardiovascular Effects of Diltiazem in the Dog

Cardiovascular Effects of Diltiazem in the Dog

Clinical Pharmacokinetics of Verapamil, Nifedipine and Diltiazem

Combined Treatment of Stable Effort-Induced Angina and Mixed Angina

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