Abstract
A 20-year-old male patient on oral treatment with ranitidine 300 mg/day in a single bedtime dose was admitted to hospital for a brief episode of syncope which had occurred 20 min earlier. All clinical, laboratory and instrumental examinations yielded negative findings, except for electrocardiographic evidence of first-degree atrioventricular block. Administration of atropine produced transient disappearance of the block, which disappeared altogether after discontinuing ranitidine treatment. Two separate rechallenges with ranitidine each produced recurrence of (asymptomatic) first-degree atrioventricular block at electrocardiographic examination, but oral treatment with cimetidine (400–800 mg/day) and famotidine (40–80 mg/day) induced no electrocardiographic abnormalities. The hypothesis that this patient may be abnormally susceptible to the cholinergic or cholinergic-like effect of ranitidine, a side effect unrelated to the drug's primary H2-blocking action, would appear to be consistent with evidence of an increased vagal tone of the atrioventricular node as revealed by atrial pacing. However, the ability of ranitidine to release histamine in man and the potential dysrhythmia-inducing effect of histamine should also be taken into consideration.
Similar content being viewed by others
References
A. J. Riley and P. R. Salmon,Ranitidine. Excerpta Medica, Amsterdam 1982.
J. J. Misiewicz and K. G. Wormsley,The Clinical Use of Ranitidine. Medicine Publishing Foundation, Oxford 1982.
J. J. Misiewicz and J. R. Wood,Ranitidine: Therapeutic Advances. Excerpta Medica, Amsterdam 1984.
G. Bertaccini and G. Coruzzi,H 2-receptor antagonists: side effects and adverse effects. It. J. Gastroenterol.16, 119–125 (1984).
J. Penston and K. G. Wormsley,Adverse reactions and interactions with H 2-receptor antagonists. Medical Toxicology1, 192–216 (1986).
W. Kirch, H. Hoensch and H. D. Janish,Interactions and non-interactions with ranitidine. Clin. Pharmacokinet.9, 485–510 (1984).
E. Camarri, E. Chirone, G. Fanteria and M. Zocchi,Ranitidine-induced bradycardia (letter). Lancetii, 160 (1982).
R. R. Shah,Symptomatic bradycardia in association with H 2-antagonist (letter). Lancetii, 1108 (1982).
D. Jack, R. N. Smith and D. A. Richards,Histamine H 2-antagonists and the heart (letter). Lancetii, 1281 (1982).
G. Jackson and J. W. Upward,Cimetidine, ranitidine and heart rate (letter). Lancetii, 265 (1982).
G. Liedberg, E. Flechter and J. Davies,Cimetidine, ranitidine and heart rate (letter). Lancetii, 265 (1982).
A. Azzolini, R. Gianrossi, S. Livi et al.,Cardiac function during ranitidine long-lasting administration. Curr. Ther. Res.33, 1023–1028 (1983).
S. F. Habba, E. Fletcher and J. S. Dayle,The response of heart rate and blood pressure and electrocardiographic changes induced by exercise in patients with oral ranitidine. Ir. J. Med. Sci.152, 238–241 (1983).
A. Mangiameli, G. Condorelli, A. Dato and S. Monaco,Resposte cardiovascolari alla somministrazione acuta di ranitidina. InProblemi di gastroenterologia e ranitidina (eds. L. Barbara and G. Dobrilla) pp. 301–304, Edizioni Libreria Cortina 1984.
A. Azzolini, R. Gianrossi, S. Livi, M. C. Nizzo, M. Olivieri and P. Mangini,Valutazione comparativa di alcuni parametri cardiovascolari in corso di somministrazione e.v. di ranitidina. Boll. Soc. It. Biol. Sper.58, 891–894 (1982).
J. S. F. Chow, R. Y. C. Wang, P. H. C. Wong, W. W. C. Chen and C. L. Lai,Intravenous ranitidine has no hemodynamic effects in subjects with chronic obstructive airway disease and patients with normal lung function.Austr. N.Z. J. Med. 13, 261–263 (1983).
E. Braito, R. Oberlechner, R. Comberlato, S. Amplatz and G. Dobrilla,Heart rate and blood pressure in noncardiopathic volunteers receiving acute intravenous loads of H 2-antagonists. Trial based on Holter-Edwards dynamic electrocardiography (abstract). It. J. Gastroenterol.17, 176 (1985).
G. Condorelli, A. Mangiameli, A. Dato, F. Marotta and A. Grazioso,H 2-receptor antagonists and human heart: effects of ranitidine and cimetidine on atrio-ventricular conduction (abstract). It. J. Gastroenterol.17, 174 (1985).
J. J. Gallagher, W. M. Smith and C. R. Kerr et al.,Esophageal pacing: a diagnostic and therapeutic tool. Circulation65, 336–341 (1982).
G. Bertaccini and G. Coruzzi, Cholinergic-like effects of new histamine H2-receptor antagonist ranitidine. Agents and Actions12, 168–171 (1982).
L. Re, M. L. Cingolani, C. Concettoni et al.,Cholinergic effects of cimetidine and ranitidine. Pharm. Res. Comm.15, 485–517 (1983).
M. Ishizaki, Y. Yamada, T. Kido et al.,First-degree atrioventricular block induced by oral cimetidine (letter). Lanceti, 225–226 (1987).
F. G. Van den Brink and E. J. Lien,Competitive and non-competitive antagonism. In Handbook of Experimental Pharmacology, Vol. 18/2, Histamineand Antihistaminics. (Eds. M. Rocha e Silva) pp. 333–367, Springer, New York 1978.
R. Levi, A. A. Chenouda, J. P. Trzeciakowski, Z. G. Guo, L. M. Aaronson, R. D. Luskind, C. H. Lee, W. A. Gay, V. A. Subramanian, J. C. MaCabe and J. C. Alexander,Dysrhythmias induced by histamine in guinea-pig and human hearts. Klin. Wschr.60, 965–971 (1982).
W. Lorenz, A. Doenicke, B. Schöning, Ch. Ohmann, B. Grote and E. Neugebauer,Definition and classification of the histamine-release response to drugs in anaesthesia and surgery: studies in the conscious human subject. Klin. Wschr.60, 896–913 (1982).
J. V. Parkin, E. B. Ackroyd, S. Glickman, M. Hobsley and W. Lorenz,Release of histamine by H 2-receptor antagonists, Lancetii, 938–939 (1982).
W. Lorenz, A. Doenicke and W. Dietz,Release of histamine by H 2-receptor antagonists. Lancetii, 1098 (1987).
W. K. Man, C. J. H. Ingolaby and J. Spencer,Is pentagastrin-stimulated secretion mediated by histamine? Gut25, 965–970 (1984).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Allegri, G., Pellegrini, K. & Dobrilla, G. First-degree atrioventricular block in a young duodenal ulcer patient treated with a standard oral dose of ranitidine. Agents and Actions 24, 237–242 (1988). https://doi.org/10.1007/BF02028277
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02028277