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Side Effects — Overdosage — Contraindications — Drug Interactions

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Calcium Antagonists

Abstract

Calcium antagonists are generally judged to be well tolerated drugs. Although, depending on substance and dosage, between 5% and 50% of all patients experience side effects (Table 31), the latter are frequently only minor and recede during the course of treatment. Severe side effects which lead to discontinuation of calcium antagonist therapy are relatively rare, the incidence stated in the literature lying between 1% and 5%, depending on the substance employed (Bleifeld and Spokojny 1983; Bussmann and Hopf 1985; see also Table 31). Thus, calcium antagonists can be considered, like β-receptor blockers, well-tolerated drugs (review by Lydtin and Lohmöller 1980), which is of particular significance since these drugs are often employed in long-term treatment, e.g. in stable angina pectoris or arterial hypertension.

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References

  • Agnoli A, Nappi G (1986) Useless Drugs? Lancet 2: 1217

    Google Scholar 

  • Ahmad S (1984 a) Nifedipine-induced acute psychosis J Am Geriatr Soc 32: 408

    Google Scholar 

  • Ahmad S (1984 b) Nifidipine-phenytoin interaction J Am Coll Cardinol 3:1582

    Google Scholar 

  • Alemany ML, (1986) Parkinsonism as late toxic effect of dihydropyridines? Lancet 1: 737

    Google Scholar 

  • Arzneimittelkommission der deutschen Ärzteschaft (1986) Zentralnervöse Reaktionen auf Flunarizin Dtsch Ärztebl 83: 1954

    Google Scholar 

  • Arznei-Telegramm (1981) Zerebrale Mangeldurchblutung als Folge der Anwendung des Kalziumantagonisten Nifedipin (Adalat) Arzneitelegramm 11: 99

    Google Scholar 

  • Arznei-Telegramm (1986) Gynäkomastie und Nifedipin Arzneitelegramm 4: 32

    Google Scholar 

  • Arznei-Telegramm (1986) Nifedipin und Zahnfleischhyperplasie Arzneitelegramm 7: 68

    Google Scholar 

  • Beiz GG, Doering W, Munkes R, Aust PE, Beiz G (1981 a) Effects of various calcium-antagonists on blood level and renal clearance of digoxin Circulation 64 (Suppl 4 ): IV - 24

    Google Scholar 

  • Belz GG, Aust PE, Munkes R (1981 b) Digoxin plasma concentrations and nifedipine Lancet 1; 844–845

    Google Scholar 

  • Belz GG, Doering W, Munkes R, Matthews J (1983) Interaction between digoxin and calcium antagonists and antiarrhytmic drugs Clin Pharmacol Ther 33: 410–417

    CAS  Google Scholar 

  • Benvenuti F, Baroni A, Bandinelli S, Sommazzi P, Corradetti R, Pantaleo T (1986) Side effects of flunarazine Lancet 2: 464

    Google Scholar 

  • Berman JL (1985) Dysomia, Dysgeusia and Diltiazem Ann Intern Med 102: 717

    CAS  Google Scholar 

  • Bleifeld W, Spokojny A (1983) Therapie der koronaren Herzkrankheit mit Kalziumantagonisten in Klinik und Praxis Med Welt 34: 1335–1339

    CAS  Google Scholar 

  • Boden WE, More G, Sharma A, Bough EW, Korr KS, Young PM, Shulman RS (1986) No increase in serum digoxin concentration with high-dose diltiazem Am J Med 81: 425–428

    CAS  Google Scholar 

  • Bosch X, Campistol JM, Botey A, Cases A, Revert LL (1986) Nifedipine-induced parotitis Lancet 2: 467

    CAS  Google Scholar 

  • Bosso JV, Gazzara PC, Rosati M (1986) Tetany associated with nifedipine N Engl Med 315: 584–585

    CAS  Google Scholar 

  • Bourbigot B, Guiserix J, Airiau J, Bressollette L, Morin JF, Cledes J (1986) Nicardipine increases cyclosporin blood levels Lancet 1: 1447

    CAS  Google Scholar 

  • Brink DD (1984) Diltiazem and hyperactivity Ann Intern Med 100: 459–460

    CAS  Google Scholar 

  • Brodmerkel GJ (1983) Nifedipine and erythromelalgia Ann Intern Med 99: 415

    Google Scholar 

  • Brodsky SJ, Cutler SS, Weiner DA, Klein MD (1981) Hepatotoxicity due to treatment with verapamil Ann Intern Med 94: 490–491

    CAS  Google Scholar 

  • Bussmann WD, Hopf R (1985) Kalziumantagonisten in der Therapie der koronaren Herzerkrankung Inn Med 12: 255–258

    Google Scholar 

  • Capewell S, Freestone S, Critchley JAJH, Pottage A, Prescott LF (1988) Reduced felodipine bioavailability in patients taking anticonvulsants Lancet 2: 480–482

    CAS  Google Scholar 

  • Chaffman M, Brogden RN (1985) Diltiazem-a review of its pharmacological properties and therpeutic efficacy Drugs 29: 387–454

    CAS  Google Scholar 

  • Chouza C, Caamano JL, Aljanati R, Scaramelli A, De Medina O, Romero S (1986) Parkinsonism, tardive dyskinesia, akathisia and depression induced by flunarazine Lancet 1: 1303–1304

    CAS  Google Scholar 

  • D’Allessandro R, Benassi G, Morganti G (1986) Side-effects of flunarazine Lancet 2: 463

    Google Scholar 

  • De Cesaris R, Ranieri G, Chiarappa R, Balestrazzi M (1984) Interaktionen einiger Kalziumantagonisten mit der Wirksamkeit von Digitalis Biol Med 6: 169–177

    Google Scholar 

  • De Medina A, Biasini O, Rivera A, Sampera A (1986) Nifedipine and myoclonic dystonia Ann Intern Med 104: 125

    Google Scholar 

  • Diamond JR, Cheung JY, Fang LST (1984) Nifedipine-induced renal dysfunction Am J Med 77: 905–909

    CAS  Google Scholar 

  • Ebner F, Dünschede HB (1976) Haemodynamics, therapeutic mechanism of action and clinical findings of Adalat use based on worldwide clinical trials In: Jatene AD, Lichtlen PR (eds) 3rd International Adalat Symposium Excerpta Medica Amsterdam pp 284–300

    Google Scholar 

  • Ebner F (1977) Wirkung und Verträglichkeit von Adalat bei Kombination mit verschiedenen Medikamenten Münch Med Wschr 119 (Suppl 1): 69

    Google Scholar 

  • Ebner F, Leisten L, Lejeune P, Donath M, Rämsch KD (1983) Administration of nifedipine to patients with digitalisglycosides, anti-diabetic agents and beta-blockers In: Kaltenbach M, Neufeld HN (eds) 5th International Adalat Symposium Excerpta Medica Amsterdam pp 328–338

    Google Scholar 

  • Eichstädt H (1984) Calcium-Antagonisten In: Roskamm H (ed) Handbuch der inneren Medizin Vol 9β: Koronarerkrankungen Springer Berlin pp 1069–1113

    Google Scholar 

  • Elkayam U, Parikh K, Torkan B, Weber L, Cohen JL, Rahimtoola SH (1985) Absence of effect of diltiazem on digoxin serum concentration and renal clearance in patients with cardiac disease J Am Coll Cardiol 5: 419 (abstract)

    Google Scholar 

  • Etoh A, Kohno K, Shimizu T (1983) Studies on the drug interaction of diltiazem. II. Effect of co-administered diltiazem on the bioavailability of propranolol J Pharmaceutical Soc Jap 103: 434–441

    Google Scholar 

  • Farringer JA, Green JA, O’Rourke RA, Linn WA, Clement WA (1984) Nifedipine-induced alterations in serum quinidine concentration. Am Heart J 108: 1570–1572

    Article  PubMed  CAS  Google Scholar 

  • Fisher JR, Padnick MB, Olstem S (1983) Nifedipine and erythromelalgia Ann Intern Med 98: 671–672

    CAS  Google Scholar 

  • Fraser AG, Ikram S (19 86) Torsade de pointes with prenylamine: do we still need the drug? Lancet 2: 572

    Google Scholar 

  • Grayson HA, Kennedy JD (1982) Torsades de pointes and nifedipine Ann Intern Med 97: 144

    CAS  Google Scholar 

  • Grino JM, Sabate I, Castelao AM, Alsina J (1986) Influence of diltiazem on cyclosporin clearance Lancet 1: 1387

    CAS  Google Scholar 

  • Hare DL, Horowitz JD (1986) Verapamil hepatotoxicity: a hypersensitivity reaction Am Heart J 111: 610–611

    CAS  Google Scholar 

  • Harrod CS (1987) Theophylline toxicity and nifedipine Ann Intern Med 106: 480

    CAS  Google Scholar 

  • Hedner T (1986) Calcium channel blockers: spectrum of side effects and drug interactions Acta Pharmacol Toxicol 58 (Suppl 2): 119–130

    CAS  Google Scholar 

  • Herrington DM, Insley BM, Weinmann GG (1986) Nifedipine overdose Am J Med 81: 344–346

    CAS  Google Scholar 

  • Hicks CB, Abraham K (1985) Verapamil and myoclonic dystonia Ann Intern Med 103: 154

    CAS  Google Scholar 

  • Holmes B, Brogden RN, Heel RC, Speight TM, Avery GS (1984) Flunarazine-a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use Drugs 27: 6–44

    CAS  Google Scholar 

  • Hopf R, Becker HJ, Kober G, Dowinsky S, Kaltenbach M (1982) Therapie der Angina pectoris mit Calcium-Antagonisten Herz 7: 221–234

    CAS  Google Scholar 

  • Ishikawa T, Imamura T, Koiwaya Y, Tanaka K (1983) Atrioventricular dissociation and sinus arrest induced by oral diltiazem N Engl J Med 309: 1124–1125

    CAS  Google Scholar 

  • Jacobs MB (1983) Diltiazem and akathisia Ann Intern Med 99: 794–795

    CAS  Google Scholar 

  • Jee LD, Opie LH (1984) Nifedipine for hypertension and angina pectoris: interactions during combination therapy In: Opie LH (ed) Calcium antagonists and cardiovascular disease Raven Press New York pp 339–346

    Google Scholar 

  • Kahn JK (1986) Nifedipine-associated acute psychosis Am J Med 81: 705–706

    CAS  Google Scholar 

  • Kewitz H, Nitz M, Gaus V (1986) Aspirin and cataract Lancet 2: 689

    Article  CAS  Google Scholar 

  • Kimbel KH (1983) Unerwünschte Wirkungen von Kalziumantagonisten In: Magometschnigg D (ed) Kalziumantagonisten in der Therapie der arteriellen und pulmonalen Hypertonie Uhlen Wien pp 135–140

    Google Scholar 

  • Kirch W, Janisch HD, Heidemann H, Rämsch K, Ohnhaus EE (1983) Einfluß von Cimetidin und Ranitidin auf Pharmakokinetik und antihypertensiven Effekt von Nifedipin Dtsch Med Wschr 108: 1757–1761

    CAS  Google Scholar 

  • Kirch W, Hütt HJ, Heidemann H, Rämsch K, Janisch HD, Ohnhaus EE (1984) Drug interactions with nifedipine J Cardiovasc Pharmacol 6: 982–985

    Google Scholar 

  • Klein HO, Lang R, Weiss E, DiSegni E, Libhaber C, Guerrero J, Kaplinsky E (1982) The influence of verapamil on serum digoxin concentration Circulation 65: 998–1003

    CAS  Google Scholar 

  • Kozeny GA, Ragona BP, Bansal VK, Hurley RM, Dixon DW, Vertuno LL, Hano JE (1986) Myocardial infarction with normal results of coronary angiography following diltiazem withdrawal Am J Med 80: 1184–1186

    CAS  Google Scholar 

  • Krämer B, Kübler W (1983) Calcium-Antagonisten bei koronarer Herzerkrankung: Wirkungsmechanismen und therapeutische Möglichkeiten Dtsch Ärztebl 80: 21–30

    Google Scholar 

  • Kroemer IX (1986) Calciumantagonisten erhöhen Neurotoxität von Carbamazepin Arzneimitteltherapie 4: 163–164

    Google Scholar 

  • Kuhlmann J (1985) Effects of verapamil, diltiazem, and nifedipine on plasma levels and renal excretion of digitoxin Clin Pharmacol Ther 38: 667–670

    CAS  Google Scholar 

  • Laporte JR, Capella D (1986) Useless drugs are not placebos: lessons from flunarazine and cinnarizine Lancet 2: 853–854

    PubMed  CAS  Google Scholar 

  • Levenson JL, Kennedy K (1985) Dysomia, dysgeusia and nifedipine Ann Intern Med 102: 135–136

    CAS  Google Scholar 

  • Lindholm A, Henricsson S (1987) Verapamil inhibits cyclosporin metabolism Lancet 1: 1262–1263

    CAS  Google Scholar 

  • Luderschmidt C (1987) Nebenwirkungen von Calciumantagonisten Dtsch Med Wschr 112: 279

    CAS  Google Scholar 

  • Lydtin H, Lohmöller G (1977) Beta-Rezeptorenblocker Aesopus Lugano pp 152–160

    Google Scholar 

  • Macphee GJA, Mclnnes GT, Thompson GG, Brodie MJ (1986) Verapamil potentiates carbamazepine neurotoxicity: a clinically important inhibitory interaction Lancet 1: 700–703

    CAS  Google Scholar 

  • Maisel AS, Motulsky HJ, Insel PA (1985) Hypotension after quinidine plus verapamil-possible additive competition at alpha-adrenergic receptors N Engl J Med 312: 167–170

    CAS  Google Scholar 

  • Mayer U, Buhl N, Sachs H, Sigel H (1985) Tödliche Vergiftung mit Verapamil in Retard-Form Dtsch Med Wschr 110: 1293–1296

    CAS  Google Scholar 

  • McLean AJ, Knight R, Harrison PM, Harper RW (1985) Clearance-based oral drug interaction between verapamil and metoprolol and comparison with atenolol Am J Cardiol 55: 1628–1629

    CAS  Google Scholar 

  • Micheli FE, Fernandez Pardal MM, Giannaula R, Gatto M, Casas Parera I, Paradiso G, Torres M, Pikielny R, Fernandez Pardez J (1989) Movement disorders and depression due to flunarizine and cinnarizine Movement Disorders 4: 139–146

    Google Scholar 

  • Okada M, Inoue H, Nakamura Y, Kishimoto M, Suzuki T (1985) Excretion of diltiazem in human milk N Engl J Med 312: 992–993

    CAS  Google Scholar 

  • Opie LH (1980) Drugs and the heart: III. Calcium antagonists Lancet 1: 806–810

    CAS  Google Scholar 

  • Opie LH, Jee LD (1984) Nifedipine: expanding indications in hypertension In: Opie LH (ed) Calcium antagonists and cardiovascular disease Raven press New York pp 333–337

    Google Scholar 

  • Opie LH (1986) Fluid retention with nifedipine in antihypertensive therapy Lancet 2: 1456

    CAS  Google Scholar 

  • Parisi AF, Strauss WE, Mclntyre KM, Sasahara AA (1982) Considerations in evaluating new antiangial drugs Circulation 65: I 38–142

    Google Scholar 

  • Pharmaprofil Verapamil (1986) Klinikarzt 15: 959–562

    Google Scholar 

  • Pieper JA (1984) Serum protein binding interactions between propranolol and calcium channel blockers Drug Intelligence and Clinical Pharmacy 18: 492

    Google Scholar 

  • Piepho RW, Culbertson YL, Rhodes RS (1987) Drug interaction with the calcium-entry blockers Circulation 75 (Suppl V): 181–194

    Google Scholar 

  • Pochet JM, Pirson Y (1986) Cyclosporin-diltiazem interaction Lancet 1: 979

    CAS  Google Scholar 

  • Rahn KH, Mooy J, Böhm R, Vet AVD (1985) Reduction of bioavailability of verapamil by rifampin. N Engl J Med 312: 920–921

    PubMed  CAS  Google Scholar 

  • Rodger JC, Torrance TC (1983) Can nifedipine provoke menorrhagia? Lancet 2: 460

    Article  PubMed  CAS  Google Scholar 

  • Ross JL, Mackenzie TB, Hanson DR, Charles CR (1987) Diltiazem for tardive dyskinesia Lancet 1: 268

    Article  CAS  Google Scholar 

  • Roundtable (1981): The current role of calcium antagonists in cardiac arrhytmias In: Zanchetti A, Krikler DM (eds) Calcium antagonism in cardiovascular therapy: experience with verapamil Excerpta Medica Amsterdam pp 405–417

    Google Scholar 

  • Schrör K (1985) Kalziumantagonisten-Physiologische Grundlagen, allgemeine und spezielle Pharmakologie und Prinzipien der klinischen Anwendung unter besonderer Berücksichtigung des Gefaßsystems In: Hossmann V, Grötz J, Schrör K (eds) Kalziumantagonisten und zerebrale Erkrankungen Springer Berlin pp 1–39

    Google Scholar 

  • Scolnick B, Brinberg D (1985) Diltiazem and generalized lymphadenopathy Ann Intern Med 102: 558

    CAS  Google Scholar 

  • Singh G, Kaul R, Khan W, Malaviya AN (1983) Can nifedipine provoke menorrhagia? Lancet 2: 1022

    Article  PubMed  CAS  Google Scholar 

  • Smith MS, Benyunes MC, Bjornsson TD, Shand DG, Pritchett ECC (1984) Influence of Cimetidine on verapamil kinetics and dynamics Clin Pharmacol Ther 36: 551–554

    CAS  Google Scholar 

  • Smith WM, Gallagher JJ “Les torsades de pointes”: an unusual ventricular arrhythmia Ann Intern Med 93: 578–584

    Google Scholar 

  • Subramanian VB, Bowles MJ, Khurmi NS, Davies AB, O’Hara MJ, Raftery EB (1983) Calcium antagonist withdrawal syndroms: objective demonstration with frequency-modulated ambulatory ST-segment monitoring Br Med J 286: 520–521

    CAS  Google Scholar 

  • Ter Wee PM, Rosmann JB, van der Geest S (1984) Acute renal failure due to diltiazem Lancet 2: 1337–1338

    Google Scholar 

  • Traber J, Hoffmeister F, Kuhlmann J (1986) Dihydropyridines and parkinsonism Lancet 2: 292 Valdiserri EV: A possible interaction between lithium and diltiazem: case report J Clin Psychiat 46: 540 Van

    Google Scholar 

  • Heyningen R, Harding JJ (1986) Do aspirin-like analgesics protect against cataract? Lancet 1: 1111–1113

    Article  PubMed  Google Scholar 

  • Voth AJ, Turner RH (1983) Nifedipine and agranulocytosis Ann Intern Med 99: 882

    CAS  Google Scholar 

  • Walker WS (1983) Atrioventricular junctional rhythm in patients receiving oral verapamil therapy JAMA 249: 389–396

    CAS  Google Scholar 

  • Williams, Donaldson RM (1986) Nifedipine and nocturia Lancet 1: 738

    Article  CAS  Google Scholar 

  • Winship LC, McKenney JM, Wright JT, Wood JH, Goodman RP (1985) The effect of ranitidine 238 and Cimetidine on single-dose diltiazem pharmacokinetics. Pharmacotherapy 5: 16

    PubMed  CAS  Google Scholar 

  • Winters SL, Schweitzer P, Kupersmith J, Gomes JA (1985) Verapamil-induced polymorphous ventricular tachycardia J Am Coll Cardiol 6: 257

    CAS  Google Scholar 

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Lydtin, H., Trenkwalder, P. (1990). Side Effects — Overdosage — Contraindications — Drug Interactions. In: Calcium Antagonists. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74887-5_5

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  • DOI: https://doi.org/10.1007/978-3-642-74887-5_5

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