Drug Safety

, Volume 15, Issue 2, pp 91–106 | Cite as

A Comparative Review of the Adverse Effects of Calcium Antagonists

  • Hamish T. Dougall
  • James McLay
Review Article Drug Experience

Summary

A large number of drugs within the 3 currently available classes of calcium antagonists are in common medical use for the treatment of hypertension and ischaemic heart disease. The reported adverse effect profile for each of these drugs varies, but tends to hold true to drug class and are typified by the adverse reactions reported for nifedipine and amlodipine (dihydropyridines), diltiazem (benzothiazepines) and verapamil (phenylalkylamines). Minor adverse effects such as flushing, headache, ankle oedema, palpitations and constipation are not uncommon and frequently require the cessation of treatment. Of greater concern affecting the wide and common first-line use of calcium antagonists is the as-yet unresolved issue of a reportedly greater risk of myocardial infarction and death following the use of short-acting nifedipine in patients with a history of hypertension, myocardial infarction or angina. Until this issue is fully resolved, it would seem prudent to limit the use of this agent in ‘at-risk’ patients and to await the results of further prospective studies before a final conclusion can be made.

Keywords

Adis International Limited Verapamil Nifedipine Diltiazem Calcium Antagonist 

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References

  1. 1.
    Fleckenstein A. History of calcium antagonists. Circ Res 1983 Feb; 52 (2 Pt 2): 13–6Google Scholar
  2. 2.
    Fisher M, Grotta J. New uses for calcium channel blockers. Drugs 1993; 46(6): 961–75PubMedGoogle Scholar
  3. 3.
    Amery WK. Flunarizine, a calcium channel blocker: a new prophylactic drug in migraine. Headache 1983; 23: 70–4PubMedGoogle Scholar
  4. 4.
    Ferrari R, Cucchini F, Bolognesi R. How do calcium antagonists differ in clinical practice? Cardiovasc Drugs Ther 1994; 8 Suppl. 3: 565–75PubMedGoogle Scholar
  5. 5.
    Reid JL, Meredith PA, Donnelly R, et al. Pharmacokinetics of calcium antagonists. J Cardiovasc Pharmacol 1988; 12 Suppl. 7: S22–6PubMedGoogle Scholar
  6. 6.
    Myers MG. Dihydropyridine calcium antagonists and the trough: peak ratio: focus on adverse effects. J Hypertens 1994 Nov Suppl.; 12(8): S73–7Google Scholar
  7. 7.
    Hosie J, Bremner AD, Fell PJ, et al. Side effects of dihydropyridine therapy: comparison of amlodipine and nifedipine retard. J Cardiovasc Pharmacol 1993; 22 Suppl. A: S9–12PubMedGoogle Scholar
  8. 8.
    Eichelbaum M, Mikus G, Vogelgesang B. Pharmacokinetics of (+)-, (−)-and (+/−)-verapamil after intravenous administration. Br J Clin Pharmacol 1984; 17: 453–8PubMedGoogle Scholar
  9. 9.
    Sorkin EM, Clissold SP, Brogden RN. Nifedipine: a review of it’s pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in ischaemic heart disease, hypertension and related cardiovascular disorders. Drugs 1985; 30: 182–274PubMedGoogle Scholar
  10. 10.
    Zanchetti A. Why a new calcium antagonist? J Cardiovasc Pharmacol 1991; 17 Suppl. 4: v–viiPubMedGoogle Scholar
  11. 11.
    Blecker D. Antihypertensive therapy with isradipine in patients with special safety concerns. Angiology 1994 Dec; 45(12): 997–1008PubMedGoogle Scholar
  12. 12.
    Weiss RJ. A large, prospective, open-label study of isradipine in patients with essential hypertension. The Isradipine Investigators Group. Clin Ther 1994 Jul–Aug; 16(4): 647–52PubMedGoogle Scholar
  13. 13.
    Van Zwieten PA, Pfaffendorf M. Pharmacology of the dihydropyridine calcium antagonists: relationship between lipophilicity and pharmacodynamic responses. J Hypertens 1993 Dec; 11 Suppl. 6: S3–8Google Scholar
  14. 14.
    Psaty BM, Heckbert SR, Koepsell TD, et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA 1995; 274(8): 620–5PubMedGoogle Scholar
  15. 15.
    Pahor M, Guralnick JM, Corti M-C, et al. Long-term survival and use of antihypertensive medications in older persons. J Am Geriatr Soc 1995; 43: 1309–10Google Scholar
  16. 16.
    Furberg CD, Psaty BM, Meyer JV. Nifedipine: dose-related increase in mortality in patients with coronary heart disease. Circulation 1995; 92: 1326–31PubMedGoogle Scholar
  17. 17.
    Yusuf S, Held P, Furberg C. Update of effects of calcium antagonists in myocardial infarction or angina in light of the second Danish Verapamil Infarction Trial (DAVIT-II) and other recent studies. Am J Cardiol 1991; 67: 1295–7PubMedGoogle Scholar
  18. 18.
    Lichtlen PR, Hugenhoitz PG, Rafflenbeul W, et al. Retardation of angiographic progression of coronary artery disease by nifedipine: results of the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT). Lancet 1990; 335: 1109–13PubMedGoogle Scholar
  19. 19.
    Cleland JGF. Clinical perspective. ACE inhibitors for myocardial infarction: how should they be used? Eur Heart J 1995; 16: 153–9Google Scholar
  20. 20.
    Lichtlen PR. Risks and benefits of calcium antagonists [letter]. Lancet 1995; 346: 962PubMedGoogle Scholar
  21. 21.
    NationalInstitute of Health, Public Health Service, US Department of Health and Human Services. New analyses regarding the safety of calcium channel blockers: a statement for health professionals from the National Heart, Lung and Blood Institute. 1995 Sep.Google Scholar
  22. 22.
    Martsevich SY, Koutishenko N, Metelitsa VI. Withdrawal phenomenon after abrupt cessation of nifedipine in stable angina pectoris. Int J Cardiol 1993 Dec 31; 42(3): 298–301PubMedGoogle Scholar
  23. 23.
    Waller PC, Inman WHW. Diltiazem and heart block [letter]. Lancet 1989; I: 617Google Scholar
  24. 24.
    Nattel S, Talajic M, Goldstein RE, et al. Determinants and significance of diltiazem plasma concentrations after acute myocardial infarction. Am J Cardiol 1990; 66: 1422–8PubMedGoogle Scholar
  25. 25.
    Choopra DA, Maxwell RT. Complete heart block with low dose nifedipine [letter]. BMJ 1984; 288: 760Google Scholar
  26. 26.
    O’Mailia JJ, Sander GE, Giles TD. Nifedipine-associated myocardial ischaemia or infarction in the treatment of hypertensive urgencies. Ann Intern Med 1987; 107: 185–6PubMedGoogle Scholar
  27. 27.
    Leavitt AD, Zweifler AJ. Nifedipine, hypotension, and myocardial injury. Ann Intern Med 1988; 108: 305–6Google Scholar
  28. 28.
    Sia STB, MacDonald PS, Triester B, et al. Aggravation of myocardial ischaemia by nifedipine. Med J Aust 1985; 142: 48–50PubMedGoogle Scholar
  29. 29.
    Boden WE, Korr KS, Bough EW. Nifedipine-induced hypotension and myocardial ischaemia in refractory angina pectoris. JAMA 1985; 253: 1131–5PubMedGoogle Scholar
  30. 30.
    The SOLVD investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure. N Engl J Med 1991; 325: 293–302Google Scholar
  31. 31.
    Josephson MA, Singh BH. Use of calcium antagonists in ventricular dysfunction. Am J Cardiology 1985; 55: 81B–8BGoogle Scholar
  32. 32.
    Goldstein RE, Boccuzzi SJ, Cruess D, et al. Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. Circulation 1991; 83: 52–60PubMedGoogle Scholar
  33. 33.
    Elkayam U, Amin J, Mehra A. A prospective, randomised, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure. Circulation 1990; 82: 1954–61PubMedGoogle Scholar
  34. 34.
    Packer M. Calcium channel blockers in chronic heart failure: the risks of ‘physiological rationale’ therapy. Circulation 1990; 82: 2254–7PubMedGoogle Scholar
  35. 35.
    Ferrari R. Calcium antagonists and left ventricular dysfunction. Am J Cardiol 1995; 75: 71E–6EPubMedGoogle Scholar
  36. 36.
    Bohm M, Schwinger RHG, Eddmann E. Different cardio-depressant potency of various calcium antagonists in human myocardium. Am J Cardiol 1990; 65: 1039–41PubMedGoogle Scholar
  37. 37.
    Dunselman PHJ, Van Der Mark TW, Kuntze CEE, et al. Different results in cardiopulmonary exercise tests after long-term treatment with felodipine and enalapril in patients with congestive heart failure due to ischaemic heart disease. Eur Heart J 1990; 11: 200–6PubMedGoogle Scholar
  38. 38.
    Ghoerghiade M, Hall V, Goldberg D, et al. Long-term clinical and neurohumoral effects of nicardipine in patients with severe heart failure on maintenance therapy with angiotensin converting enzyme inhibitors [abstract]. J Am Coll Cardiol 1991; 17 Suppl. A: 274AGoogle Scholar
  39. 39.
    Conti R. Use of calcium antagonists to treat heart failure. Clin Cardiol 1994; 17: 101–2PubMedGoogle Scholar
  40. 40.
    Hammond JJ, Cutler SA. A comparison of isradipine and felodipine in Australian patients with hypertension: focus on ankle oedema. The Physician’s Study Group. Blood Press 1993 Sep; 2(3): 205–11PubMedGoogle Scholar
  41. 41.
    MacLean D, MacConnachie AM. Selected side effects: 1. Peripheral oedema with dihydropyridine calcium antagonists. PrescrJ 1991; 31: 4–6Google Scholar
  42. 42.
    Benjamin N, Vallance P. Local control of human peripheral vascular tone: implications for drug therapy. Clin Sci 1991; 80: 183–90PubMedGoogle Scholar
  43. 43.
    Olszewski WL, Engeset A. Lymphatic contractions [letter]. N Engl J Med 1979; 300: 316PubMedGoogle Scholar
  44. 44.
    McHale NG, Allen JM. The effects of external Ca2+ concentrations on the contractility of bovine mesenteric lymphatics. Microvasc Res 1983; 26: 182–92PubMedGoogle Scholar
  45. 45.
    Elliott H. Ca antagonists: treating angina and hypertension —clinical pharmacology and side-effects. Prescriber 1994 March 5: 37–42Google Scholar
  46. 46.
    Webster J. Ca antagonists: treating angina and hypertension —choosing the best drug for each condition. Prescriber 1994 March 5: 42–56Google Scholar
  47. 47.
    Aderka D, Pinkhas J. Pulmonary oedema precipitated by nifedipine. BMJ 1984; 289: 1272Google Scholar
  48. 48.
    Gillmar DJ, Kark P. Pulmonary oedema precipitated by nifedipine. BMJ 1980; 280: 1420–1Google Scholar
  49. 49.
    Kalra L, Bone MF. Nifedipine and impaired oxygenation in patients with chronic bronchitis and cor pulmonale. Lancet 1989; I: 1135–6Google Scholar
  50. 50.
    Diamond JR, Cheung, JY, Fang LS. Nifedipine-induced renal dysfunction: alterations in renal hemodynamics. Am J Med 1984; 77: 905–9PubMedGoogle Scholar
  51. 51.
    Antonelli D, Koltun B. Excessive nifedipine diuretic effect [letter]. BMJ 1984; 288: 760Google Scholar
  52. 52.
    Williams G, Donaldson RM. Nifedipine and nocturia [letter]. Lancet 1986; I: 738Google Scholar
  53. 53.
    ter Wee PM, Rosman JB, van der Geest S. Acute renal failure due to diltiazem. Lancet 1984; II: 1337–8Google Scholar
  54. 54.
    Achenbach V, Rafelt M, Wagner K, et al. Acute renal failure due to diltiazem [letter]. Lancet 1985; I: 176Google Scholar
  55. 55.
    Leonetti G, Rappelli A. Are there differences in the renal effects of calcium antagonists? J Hypertens 1993 Mar; 11(1): S45–8Google Scholar
  56. 56.
    Demarie BK, Bakris GL. Effects of different calcium channel antagonists on proteinuria associated with diabetes mellitus. Ann Intern Med 1990; 113: 987–8PubMedGoogle Scholar
  57. 57.
    Bakris GL. Effects of diltiazem or lisinopril on massive proteinuria associated with diabetes mellitus. Ann Intern Med 1990; 112: 707–8PubMedGoogle Scholar
  58. 58.
    Anderson S, Clarey LE, Riley SL, et al. Acute infusion of calcium channel blockers reduces glomerular capillary pressure in rats with reduced renal mass [abstract]. Kidney Int 1988; 33: 370AGoogle Scholar
  59. 59.
    Zatz R, Dunn BR, Meyer TW, et al. Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest 1986; 77: 1925–30PubMedGoogle Scholar
  60. 60.
    Ramon Y, Behar S, Kishon Y, et al. Gingival hyperplasia caused by nifedipine —a preliminary report. Int J Cardiol 1984; 5: 195–204PubMedGoogle Scholar
  61. 61.
    Shaftic AA, Widdup LL, Abate MA, et al. Nifedipine-induced gingival hyperplasia. Drug Intell Clin Pharm 1986; 20: 602–5PubMedGoogle Scholar
  62. 62.
    Seymour RA. Calcium channel blockers and gingival overgrowth. Br Dent J 1991; 170: 376–9PubMedGoogle Scholar
  63. 63.
    Steele RM, Schuna AA, Schreiber RT. Calcium antagonist-induced gingival hyperplasia. Ann Intern Med 1994; 120: 663–4PubMedGoogle Scholar
  64. 64.
    Miller CS, Damm DD. Incidence of verapamil-induced gingival hyperplasia in a dental population. J Periodontol 1992 May; 63(5): 453–6PubMedGoogle Scholar
  65. 65.
    Fattore L, Stablein M, Bredfeldt G, et al. Gingival hyperplasia: a side effect of nifedipine and diltiazem. Spec Care Dentist 1991; 11: 107–9PubMedGoogle Scholar
  66. 66.
    Endersby CA, Brown EG, Perelman MS. Safety profile of lacidipine: a review of clinical data. J Cardiovasc Pharmacol 1991; 17 Suppl. 4: S45–7PubMedGoogle Scholar
  67. 67.
    Lombardi T, Fiore-Donno G, Belser U, et al. Felodipine-induced gingival hyperplasia: a clinical and histologic study. J Oral Pathol Med 1991 Feb; 20(2): 89–92PubMedGoogle Scholar
  68. 68.
    Seymour RA, Ellis JS, Thomason JM, et al. Amlodipine-induced gingival overgrowth. J Clin Periodontol 1994 Apr; 21(4): 281–3PubMedGoogle Scholar
  69. 69.
    Lawrence DB, Weart W, Laro JJ, et al. Calcium channel blocker-induced gingival hyperplasia: case report and review of this iatrogenic disease. J Fam Pract 1994 Nov; 39: 483–8PubMedGoogle Scholar
  70. 70.
    Brown RS, Sein P, Corio R, et al. Nitrendipine-induced gingival hyperplasia. First case report. Oral Surg Oral Med Oral Pathol 1990 Nov; 70(5): 593–6PubMedGoogle Scholar
  71. 71.
    Brown RS, Beaver WT, Bottomly WK. On the mechanism of drug-induced gingival hyperplasia. J Oral Pathol Med 1991; 20: 201–9PubMedGoogle Scholar
  72. 72.
    Bosch X, Campistol JM, Botey A, et al. Nifedipine-induced parotitis [letter]. Lancet 1986; II: 467Google Scholar
  73. 73.
    Bosch X, Sobrino J, Lopez-Soto A, et al. Parotitis due to nicardipine [letter]. BMJ 1992 Apr 4; 304: 882PubMedGoogle Scholar
  74. 74.
    Guttenberg SA. Chemical injury of the oral mucosa from verapamil [letter]. N Engl J Med 1990; 323: 615PubMedGoogle Scholar
  75. 75.
    Levenson JL, Kennedy K. Dysomia, dysgeusia, and nifedipine. Ann Intern Med 1985; 102: 135–6PubMedGoogle Scholar
  76. 76.
    Coulter DM. Eye pain with nifedipine and disturbance of taste with captopril: a mutually controlled study showing a method of postmarketing surveillance. BMJ 1988; 296: 1086–8PubMedGoogle Scholar
  77. 77.
    Ward DJ, Wark JW, Griffo W, et al. Intravenous calcium for fecal impaction secondary to verapamil. N Engl J Med 1982; 307: 1709–10PubMedGoogle Scholar
  78. 78.
    Krebs R. Adverse reactions with calcium antagonists. Hypertension 1983; 5 Suppl. II: 125–9Google Scholar
  79. 79.
    Rolachon A, Bichard P, Kezachian G. Chronic diarrhea caused by isradipine. Gastroenterol Clin Biol 1993; 17(4): 310–1PubMedGoogle Scholar
  80. 80.
    Castell DO. Calcium channel blockers for gastrointestinal diseases. Am J Cardiol 1985; 55: 201–2Google Scholar
  81. 81.
    Blackwell JN, Holt S, Heading RC. Effect of nifedipine on oesophageal motility and gastric emptying. Digestion 1981; 21: 50–6PubMedGoogle Scholar
  82. 82.
    Hund E, Aschoff A, Tronnier V, et al. Nimodipine: evidence for clinically significant gastrointestinal side-effects. Acta Neurochir Wien 1990; 102: 73–5PubMedGoogle Scholar
  83. 83.
    Torrealba G, Sharp A, Soto B. Nimodipine-treated subarachnoid hemorrhage associated with acute pseudo-obstruction of the colon. Surg Neurol 1987; 28: 150–2PubMedGoogle Scholar
  84. 84.
    Mantzoros CS, Prabhu AS, Sowers JR. Paralytic ileus as a result of diltiazem treatment. J Internal Med 1994; 235: 613–4PubMedGoogle Scholar
  85. 85.
    Lamaison D, Abrieu V, Fialip J, et al. Occlusion intestinale aigue et antagonistes calciques [in French]. Therapie 1989; 44: 201–2PubMedGoogle Scholar
  86. 86.
    Pahor M, Gurainik JM, Furberg CD, et al. Risk of gastrointestinal haemorrhage with calcium antagonists in hypertensive persons over 67 years old. Lancet 1996; 347: 1061–5PubMedGoogle Scholar
  87. 87.
    Greenstein DB, Wilcox CM, Frontin K, et al. Nifedipine (Procardia XL) as a cause of false-positive results on barium enema study. South Med J 1994 Aug; 87(8): 808–10PubMedGoogle Scholar
  88. 88.
    Babany G, Uzzan F, Larrey D, et al. Alcoholic-like liver lesions induced by nifedipine. J Hepatol 1989 Sep; 9(2): 252–5PubMedGoogle Scholar
  89. 89.
    Abramson M, Littlejohn GO. Hepatic reactions to nifedipine. Med J Aust 1985; 142: 47–8PubMedGoogle Scholar
  90. 90.
    Shaw DR, Misan GM, Johnson RD. Nifedipine hepatitis. Aust N Z J Med 1987; 17: 447–8PubMedGoogle Scholar
  91. 91.
    Brodsky SJ, Cutler SS, Weiner DA, et al. Hepatotoxicity due to treatment with verapamil. Ann Intern Med 1981; 94: 490–1PubMedGoogle Scholar
  92. 92.
    de Arriba G, Garcia-Martin F, Sanchez-Heras M, et al. Hepatotoxicity due to verapamil hydrochloride. Eur J Med 1993 Mar; 2(3): 179–81PubMedGoogle Scholar
  93. 93.
    Traverse JH, Swenson LJ, McBride JW. Acute hepatic injury after treatment with diltiazem. Am Heart J 1994 Jun; 127(6): 1636–9PubMedGoogle Scholar
  94. 94.
    Toft E, Vyberg M, Therkelsen K. Diltiazem-induced granulomatous hepatitis. Histopathology 1991 May; 18(5): 474–5PubMedGoogle Scholar
  95. 95.
    Sarachek H, London RL, Matulewicz TJ. Diltiazem and granulomatous hepatitis. Gastroenterology 1985; 88: 1260–2PubMedGoogle Scholar
  96. 96.
    Moriarty CM. Role of calcium in the regulation of adenohypophysial hormone release. Life Sci 1978; 23: 185–94PubMedGoogle Scholar
  97. 97.
    Geras EJ, Gershengorn MC. Evidence that TRH stimulates secretion of TSH by two calcium-mediated mechanisms. Am J Physiol 1982; 242: E109–14PubMedGoogle Scholar
  98. 98.
    Struthers AD, Millar JA, Beastall GH, et al. Calcium antagonists and hormone release: effect of nifedipine on luteinizing hormone-releasing hormone and thyrotropin-releasing hormone-induced pituitary hormone release. J Clin Endocrinol Metab 1983; 56: 410–3Google Scholar
  99. 99.
    Isles TE, Baty S, Dow RJ. The effect of nicardipine on pituitary hormone release in normal volunteers. Br J Clin Pharmacol 1985;20: 84S–7SPubMedGoogle Scholar
  100. 100.
    D’Armiento M, Pontecorvi A, Bigi F, et al. Lack of inhibition of anterior pituitary hormone release during chronic treatment with calcium antagonists. Clin Endocrinol 1984 Sep; 21(3): 233–7Google Scholar
  101. 101.
    Barbarino A, De Marinis L, Mancini A, et al. Calcium antagonists and hormone release. III. Role of calcium in the biphasic release of luteinizing hormone in response to gonadotrophin-releasing hormone in vivo. Acta Endocrinol 1982 Sep; 101(1): 5–9PubMedGoogle Scholar
  102. 102.
    Gluskin L, Strasberg B, Shah JH. Verapamil-induced hyper-prolactinemia and galactorrhea. Ann Int Med 1981; 95(1): 66–7PubMedGoogle Scholar
  103. 103.
    Velardo A, Ricci S, Zironi C, et al. Effects of prolonged treatment with diltiazem on pituitary secretion of luteinizing hormone, follicle-stimulating hormone, thyrotropin and prolactin. Horm Res 1992; 37: 137–40PubMedGoogle Scholar
  104. 104.
    Thompson DF, Carter JR. Drug-induced gynaecomastia. Pharmacotherapy 1993; 13(1): 37–45PubMedGoogle Scholar
  105. 105.
    Boyd IW. Adverse drug reactions advisory committee. Gynaecomastia in association with calcium antagonists. Med J Aust 1994 Sep 5; 161(5): 328PubMedGoogle Scholar
  106. 106.
    Tanner LA, Bosco LA. Gynaecomastia associated with calcium channel blocker therapy. Arch Intern Med 1988; 148: 379–80PubMedGoogle Scholar
  107. 107.
    Clyne CAC. Unilateral gynaecomastia and nifedipine [letter]. BMJ 1986; 292: 380Google Scholar
  108. 108.
    Grodsky GM, Bennett LL. Cation requirements for insulin secretion in the isolated perfused pancreas. Diabetes 1966; 15: 910–3PubMedGoogle Scholar
  109. 109.
    Malaisse WJ, Devis G, Pipeleers DG, et al. Calcium-antagonist function: effect of D600. Diabetologia 1976; 12: 77–81PubMedGoogle Scholar
  110. 110.
    Bhatnager SK, Amin MMA, Al-Yusuf AR. Diabetogenic effects of nifedipine [letter]. BMJ 1984; 289: 19Google Scholar
  111. 111.
    Roth A, Miller HI, Beihassen B. Slow-release verapamil and hyperglycemic metabolic acidosis. Ann Intern Med 1989 Jan 15; 110: 171–2PubMedGoogle Scholar
  112. 112.
    Pershadsingh HA, Grant N, MacDonald JM. Association of diltiazem therapy with increased insulin resistance in a patient with type I diabetes mellitus. JAMA 1987; 257: 930–1PubMedGoogle Scholar
  113. 113.
    Belleville I, Vaillant G, Farnier M, et al. La nicardipine peut avoir an effet deletere sur l’equilibre glycemique du diabetique non insulino-dependent [in French]. Presse Med 1987; 16: 1760–1PubMedGoogle Scholar
  114. 114.
    Trost BN. Glucose metabolism and calcium antagonists. Horm Metab Res Suppl 1990; 22: 48–56PubMedGoogle Scholar
  115. 115.
    Ramsay LE, Yeo WW, Jackson PR. Influence of diuretics, calcium antagonists, and alpha-blockers on insulin sensitivity and glucose tolerance in hypertensive patients. J Cardiovasc Pharmacol 1992; 20 Suppl. 11: S49–53PubMedGoogle Scholar
  116. 116.
    Sasaki H, Naka K, Kishi Y, et al. Nicardipine may impair glucose metabolism in hypertensive diabetic patients. Diabetes Res Clin Pract 1994; 26(1): 67–75PubMedGoogle Scholar
  117. 117.
    Singh G, Kaul R, Khan W, et al. Can nifedipine provoke menorrhagia [letter]? Lancet 1983; II: 1022Google Scholar
  118. 118.
    Rodger JC, Torrance TC. Can nifedipine provoke menorrhagia [letter]? Lancet 1983; II: 460Google Scholar
  119. 119.
    King BD, Pichon R, Stern EH, et al. Impotence during therapy with verapamil. Arch Intern Med 1983; 143: 1248–9PubMedGoogle Scholar
  120. 120.
    Lehav M, Arav R. Diltiazem and thrombocytopenia [letter]. Ann Intern Med 1989; 110: 327Google Scholar
  121. 121.
    Takayama Y, Ichikawa S, Samamaki T, et al. Increase in hematocrit by nifedipine in hypertensive patients. Tohoku J Exp Med 1990 Jul; 161(3): 251–2PubMedGoogle Scholar
  122. 122.
    Osmialowska Z, Nartowicz-Sloniewska M, Slominski JM, et al. Effect of nifedipine monotherapy on platelet aggregation in patients with untreated essential hypertension. Eur J Clin Pharmacol 1990; 39: 403–4PubMedGoogle Scholar
  123. 123.
    Winther K, Jesperson, CM, Rydberg B, et al. Dose-dependent effects of verapamil and nifedipine on in-vivo platelet function in normal volunteers. Eur J Clin Pharmacol 1990; 39: 291–3PubMedGoogle Scholar
  124. 124.
    Walley TJ, Woods KL, Barnett DB. The effects of intravenous and oral nifedipine on ex-vivo platelet function. Eur J Clin Pharmacol 1989; 37: 449–52PubMedGoogle Scholar
  125. 125.
    Fischer Hansen J, and the Danish Study Group on Verapamil in Myocardial Infarction. Treatment with verapamil during and after an acute myocardial infarction: a review based on the Danish Verapamil Infarction Trials I and II. J Cardiovasc Pharmacol 1991; 18 Suppl. 6: S20–5Google Scholar
  126. 126.
    Wagenknecht LE, Furberg CD, Hammon JW, et al. Surgical bleeding: unexpected effect of a calcium antagonist. BMJ 1995; 310: 776–7PubMedGoogle Scholar
  127. 127.
    Gore JM, Sloan M, Price TR, et al. Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the thrombolysis in myocardial infarction study. Thrombolysis in myocardial infarction, phase II, pilot and clinical trial. Circulation 1991; 83: 448–59PubMedGoogle Scholar
  128. 128.
    Becker RC, Caputo R, Ball S, et al. Hemorrhagic potential of combined diltiazem and recombinant tissue-type plasminogen activator administration. Am Heart J 1993; 126: 11–4PubMedGoogle Scholar
  129. 129.
    Boden WE, Scheldewaert R, Walters EG, et al. Design of a placebo-controlled clinical trial of long-acting diltiazem and aspirin versus aspirin alone in patients receiving thrombolysis with a first acute myocardial infarction. Am J Cardiol 1995; 75: 1120–3PubMedGoogle Scholar
  130. 130.
    Pitlik S, Manor RS, Lipshitz I, et al. Transient retinal ischaemia induced by nifedipine. BMJ 1983; 287: 1845–6PubMedGoogle Scholar
  131. 131.
    Van Heyningen R, Harding JJ. Do aspirin-like analgesics protect against cataract? Lancet 1986; I: 1111–3Google Scholar
  132. 132.
    Harding JJ, Van Heyningen R. Drugs, including alcohol, that act as risk factors for cataract, and possible protection against cataract by aspirin-like analgesics and cyclopenthiazide. Br J Ophthalmol 1988; 72: 809–14PubMedGoogle Scholar
  133. 133.
    Coulter DM. Eye pain with nifedipine and disturbances of taste with captopril: a mutually controlled study showing a method of postmarketing surveillance. BMJ 1988; 296: 1086–8PubMedGoogle Scholar
  134. 134.
    Stern R, Khalsa JK. Cutaneous adverse reactions associated with calcium channel blockers. Arch Intern Med 1989 Apr; 149: 829–32PubMedGoogle Scholar
  135. 135.
    Sadick NS, Katz AS, Schreiber TL. Angioedema from calcium channel blockers. J Am Acad Dermatol 1989; 21(1): 132–3PubMedGoogle Scholar
  136. 136.
    Brodmerkel GJ. Nifedipine and erythromelalgia [letter]. Ann Intern Med 1983; 99: 415PubMedGoogle Scholar
  137. 137.
    Thomas SE, Wood ML. Photosensitivity reactions associated with nifedipine [letter]. BMJ 1986; 292: 992Google Scholar
  138. 138.
    Collins P, Ferguson J. Photodistributed nifedipine-induced facial telangiectasia. Br J Dermatol 1993 Nov; 129(5): 630–3PubMedGoogle Scholar
  139. 139.
    Brenner S, Brau S. Vasculitis following nifedipine. Harefuah 1985: 108: 139–40PubMedGoogle Scholar
  140. 140.
    Alcalay J, David M. Generalised fixed drug eruptions associated with nifedipine [letter]. BMJ 1986; 292: 450Google Scholar
  141. 141.
    Leibovici V, Zlotogorski A, Heyman A, et al. Polymorphous drug eruption due to nifedipine. Cutis 1988; 41: 367PubMedGoogle Scholar
  142. 142.
    Kuo M, Winiarski N, Garella S. Nonthrombocytopenic purpura associated sequentially with nifedipine and diltiazem. Ann Pharmacother 1992 Sep; 26(9): 1089–90PubMedGoogle Scholar
  143. 143.
    Dacosta A, Mismetti P, Tardy B, et al. Non-thrombopenic purpura induced by amlodipine. Therapie 1994; 49(6): 515–7PubMedGoogle Scholar
  144. 144.
    Kim SC, Won JH, Ahn SK. Pemphigus foliaceus induced by nifedipine. Acta Derm Venereol 1993 Jun; 73(3): 210–1PubMedGoogle Scholar
  145. 145.
    Parish LC, Witkowski JA. Truncal morbilliform eruption due to nifedipine. Cutis 1992 Feb; 49(2): 113–4PubMedGoogle Scholar
  146. 146.
    Thulin T. Exfoliative dermatitis due to nifedipine. Scand J Prim Health Care Suppl 1990; 1: 81–4PubMedGoogle Scholar
  147. 147.
    Berbis P, Alfonso MJ, Levy JL, et al. Diltiazem associated erythema multiforme. Dermatologica 1990; 179: 90Google Scholar
  148. 148.
    Taylor JW, Cleary JD, Atkinson RC. Stevens-Johnson syndrome associated with diltiazem. Clin Pharm 1990 Dec; 9(12): 948–50PubMedGoogle Scholar
  149. 149.
    Hashimoto M, Tanaka S, Horio T. Photosensibility due to diltiazem hydrochloride. Acta Dermatol (Kyoto) 1979; 74: 181–4Google Scholar
  150. 150.
    Larvijsen APM, Van Dijke C, Vermeer BJ. Diltiazem-associated exfoliative dermatitis in a patient with psoriasis. Acta Dermatol Venereol (Stockh) 1986; 66: 536–8Google Scholar
  151. 151.
    Wakeel RA, Gavin MP, Keefe M. Severe toxic erythema caused by diltiazem. BMJ 1988; 296: 1071PubMedGoogle Scholar
  152. 152.
    Kitamura K, Kanasashi M, Suga C, et al. Cutaneous reactions induced by calcium channel blocker: high frequency of psoriasiform eruptions. J Dermatol 1993 May; 20(5): 279–86PubMedGoogle Scholar
  153. 153.
    Ilia R, Goldfarb B, Gueron M. Skin thickening and sensory loss of the feet during diltiazem therapy. Int J Cardiol 1992 Apr; 35(1): 115PubMedGoogle Scholar
  154. 154.
    Sheehan-Dare RA, Goodfield MJ. Severe cutaneous vasculitis induced by diltiazem. Br J Dermatol 1988; 119: 134PubMedGoogle Scholar
  155. 155.
    Scolnick B, Brinberg D. Diltiazem and generalised lymphadenopathy [letter]. Ann Intern Med 1985; 102: 558PubMedGoogle Scholar
  156. 156.
    Lin AY, Baker BA. Verapamil-associated Stevens-Johnson syndrome. DICP 1989 Dec; 23(12): 987–8PubMedGoogle Scholar
  157. 157.
    Drenth JP, Michiels JJ, Van-Joost T, et al. Verapamil-induced secondary erythermalgia. Br J Dermatol 1992 Sep; 127(3): 292–4PubMedGoogle Scholar
  158. 158.
    Sever PS. Hypertrichosis and verapamil. Lancet 1991; 338: 1215–6PubMedGoogle Scholar
  159. 159.
    Read GM. Verapamil and hair colour change [letter]. Lancet 1991; 338: 1520PubMedGoogle Scholar
  160. 160.
    Bewley AP, Feher MD, Staughton RC. Erythema multiforme following substitution of amlodipine for nifedipine [letter]. BMJ 1993 Jul; 307: 241PubMedGoogle Scholar
  161. 161.
    Silverstone PH. Periorbital oedema caused by nifedipine [letter]. BMJ 1984; 288: 1654Google Scholar
  162. 162.
    Gershanik OS. Drug-induced Parkinsonism in the aged. Drugs Aging 1994; 5(2): 127–32PubMedGoogle Scholar
  163. 163.
    Marti-Masso JF, Carreara N, Urtasun M. Drug-induced parkinsonism: a growing list [letter]. Mov Dis 1992; 7: 89–90Google Scholar
  164. 164.
    Garcia-Ruiz PJ, de Yebenes JG, Jimenez-Jimenez FJ, et al. Parkinsonism associated with calcium channel blockers: a prospective follow-up study. Clin Neuropharmacol 1992; 15(1): 19–26PubMedGoogle Scholar
  165. 165.
    Hullett FJ, Potkin SG, Levy AB, et al. Depression associated with nifedipine-induced calcium channel blockade. Am J Psychiatry 1988; 145: 1277–9PubMedGoogle Scholar
  166. 166.
    Lyndon RW, Johnson G, NcKeough G. Nifedipine-induced depression. Br J Psychiatry 1991; 159: 447–8PubMedGoogle Scholar
  167. 167.
    Eccleston D, Cole AJ. Calcium-channel blockade and depressive illness. Br J Psychiatry 1990; 156: 889–91PubMedGoogle Scholar
  168. 168.
    Dassylva B. Verapamil may cause depression. Can J Psychiatry 1993; 38: 299–300PubMedGoogle Scholar
  169. 169.
    Fogelman J. Verapamil caused depression, confusion and impotence. Am J Psychiatry 1988; 145: 380PubMedGoogle Scholar
  170. 170.
    Biriell C, McEwen J, Sanz E. Depression associated with diltiazem. BMJ 1989; 299: 796PubMedGoogle Scholar
  171. 171.
    Keidar S, Binenboim C, Palant A. Muscle cramps during treatment with nifedipine [letter]. BMJ 1982; 285: 1241–2PubMedGoogle Scholar
  172. 172.
    MacDonald JB. Muscle cramps during treatment with nifedipine [letter]. BMJ 1982; 285: 1744PubMedGoogle Scholar
  173. 173.
    de Medina A, Biasini O, Rivera A, et al. Nifedipine and myoclonic dystonia [letter]. Ann Intern Med 1985; 104: 125Google Scholar
  174. 174.
    Jeret JS, Somasundaram M, Asaiar S. Diltiazem-induced myoclonus. N Y State J Med 1992 Oct; 92(10): 447–8PubMedGoogle Scholar
  175. 175.
    Hicks CB, Abraham K. Verapamil and myoclonic dystonia [letter]. Ann Intern Med 1985; 103: 154PubMedGoogle Scholar

Copyright information

© Adis International Limited 1996

Authors and Affiliations

  • Hamish T. Dougall
    • 1
  • James McLay
    • 1
  1. 1.Department of Medicine and TherapeuticsUniversity of Aberdeen Medical SchoolForresterhill, AberdeenScotland

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