Calcium channel blockers interactions

Calcium channel blockers interact with cardiac glycosides. The main mechanism is inhibition of digoxin renal tubular secretion by inhibition of P glycoprotein. In a review of the interactions of calcium channel blockers with digoxin, in which their clinical relevance was assessed, it was concluded that serious consequences can be prevented by careful monitoring, especially in patients whose serum digoxin concentration is already near the upper end of the therapeutic range (174). 

Kostic, D. et al. (1995). Intestinal absorption, serum clearance, and interactions between lutein and beta-carotene when administered to human adults in separate or combined oral doses. Am. J. Clin. Nutr. 62 604—610. Kuo, S. M. et al. (2001). Dihydropyridine calcium channel blockers inhibit ascorbic acid accumulation in human intestinal Caco-2 cells. Life Sci. 68(15) 1751-1760. 

Batra S (1990) Interaction of antiestrogens with binding sites for muscarinic cholinergic drugs and calcium channel blockers in cell membranes. Cancer Chemother Pharmacol 26 310-312... 

Ma, B., Prueksaritanont, T. and Lin, J.H. (2000) Drug interactions with calcium channel blockers possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metabolism and Disposition, 28 (2), 125-130. 

Drugs that can significantly interact adversely with calcium-channel blockers include ... 

Drugs that may interact with nitrates include alcohol, alteplase, aspirin, beta-blockers, calcium channel blockers, dihydroergotamine, heparin, nondepolarizing muscle relaxants, phenothiazines, phosphodiesterase inhibitors (eg, sildenafil, tadalafil, vardenafil), and vasodilators. 

Drugs that may affect amiodarone include hydantoins, cholestyramine, fluoroquinolones, rifamycins, ritonavir, and cimetidine. Drugs that may be affected by amiodarone include anticoagulants, beta-blockers, calcium channel blockers, cyclosporine, dextromethorphan, digoxin, disopyramide, fentanyl, flecainide, hydantoins, lidocaine, methotrexate, procainamide, quinidine, and theophylline. Drug/Lab test interactions Amiodarone alters the results of thyroid function tests, causing an increase in serum T4 and serum reverse T3 levels and a decline in... 

The following drug classes may have a potential drug interaction with nevirapine Antiarrhythmics, anticonvulsants, antifungals, calcium channel blockers, cancer chemotherapy (cyclophosphamide), ergot alkaloids, immunosuppressants, motility agents, opiate agonists. 

Available evidence suggests that a single unifying mechanism does not exist but rather that various vasodilators may act at different places in the series of processes that couple excitation of vascular smooth muscle cells with contraction. For example, the vasodilators known as calcium channel antagonists block or limit the entry of calcium through voltage-dependent channels in the membrane of vascular smooth muscle cells. In this way, the calcium channel blockers limit the amount of free intracellular calcium available to interact with smooth muscle contractile proteins (see Chapter 14). 

Mibefradil, a calcium channel blocker, is not toxic when used alone for cardiovascular treatment but on the market it was found to interact with at least 25 other drugs, resulting in increased plasma concentrations and consequently, toxicity. This example was one that increased regulatory focus on drug-drug interactions but only common interactions can be researched premarketing and the commonality of multiple polytherapy, for example in the elderly, cannot be fully legislated. 

Important differences between the available calcium channel blockers arise from the details of their interactions with cardiac ion channels and, as noted above, differences in their relative smooth muscle versus cardiac effects. Sodium channel block is modest with verapamil, and still less marked with diltiazem. It is negligible with nifedipine and other dihydropyridines. Verapamil and diltiazem interact kinetically with the calcium channel receptor in a different manner than the dihydropyridines they block tachycardias in calcium-dependent cells, eg, the atrioventricular node, more selectively than do the dihydropyridines. (See Chapter 14 for additional details.) On the other hand, the dihydropyridines appear to block smooth muscle calcium channels at concentrations below those required for significant cardiac effects they are therefore less depressant on the heart than verapamil or diltiazem. 

Drug interactions NSAIDs Salicylates Sulfonamides Chloramphenicol Probenecid Coumarins MAO inhibitors Beta-blockers Thiazides and other diuretics Corticosteroids Phenothiazines Thyroid products Estrogens Oral contraceptives Phenytoin Nicotinic acid Sympathomimetic Calcium channel blockers Isoniazid Miconazole... 

Lehmann, K.A., Kriegel, R., Ueki, M. Clinical relevance of drug interactions between opiates and calcium channel blockers, Anaesthesist 1989, 38, 110-115. 

In a retrospective case-control study, a primary diagnosis of hypoglycemia was identified in 413 patients registered as diabetic in 1993 (164). Five controls of the same age and sex, without hypoglycemia, were selected for each case from the same cohort. The relative risks of hypoglycemia with ACE inhibitors, beta-blockers, calcium antagonists, and salicylates were determined. There was an association between enalapril and sulfonylureas. However, other ACE inhibitors could not be identified as a risk factor. There was no interaction with beta-blockers, calcium channel blockers, or salicylates. 

In a meta-analysis of megatrials of simvastatin, the overall incidence of myopathy was 0.025% the same proportion of those with myositis had used calcium channel blockers as the proportion overall, suggesting that there is no important interaction between these two groups of drugs (32). 

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