Fatal Bradycardia After Intentional Overdose of Cimetidine and Diazepam

Hiss, Jehuda; Hepler, BradfordR.; Falkowski, AndrewJ.; Sunshine, Irving

doi:10.1016/s0140-6736(82)90176-3

Cited by 13 publications

(3 citation statements)

References 12 publications

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“…Jfingere Uberblicke zur Cimetidin-Therapie an grogen Patientenkollektiven haben zur Schlugfolgerung geffihrt, dab der H2-Antagonist relativ frei von unerwfinschten Nebenwirkungen sei [28, 58,92]. Jfingere Uberblicke zur Cimetidin-Therapie an grogen Patientenkollektiven haben zur Schlugfolgerung geffihrt, dab der H2-Antagonist relativ frei von unerwfinschten Nebenwirkungen sei [28, 58,92].…”

Section: Kardiale Nebenwirkungen Von H2-rezeptor-antagonistenunclassified

“…Jfingere Uberblicke zur Cimetidin-Therapie an grogen Patientenkollektiven haben zur Schlugfolgerung geffihrt, dab der H2-Antagonist relativ frei von unerwfinschten Nebenwirkungen sei [28, 58,92]. Bei 2 Patienten war eine Cimetidiniiberdosierung [58,97], einmal simultan mit einer Diazepamiiberdosierung, im anderen Fall als Folge eines akuten Nierenversagens, vermutlich entscheidend an der Arrhythmieausl6sung beteiligt. Die H/iufigkeit unerwfinschter Reaktionen wird nach Analyse zahlreichef kontrollierter Studien auf 4-6 pro Million be- Mehrere Fallberichte lassen eine enge zeitliche Koinzidenz zwischen der H2-Blocker-Applikation und dem Beginn der jeweiligen Herzrhythmusst6rungen erkennen.…”

Section: Kardiale Nebenwirkungen Von H2-rezeptor-antagonistenunclassified

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Histaminwirkungen am Herzen unter besonderer Berücksichtigung kardialer Nebenwirkungen von H2-Rezeptor-Antagonisten

Baller

Huchzermeyer

1989

Klin Wochenschr

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The existence of cardiac h1- and h2-receptors is evidenced by pharmacologic studies. Despite of the relatively high content of cardiac histamine it is not clarified whether histamine actually plays a physiologic role - apart from pharmacologic effects - in the regulation of myocardial function and coronary blood flow. Under pathophysiologic conditions (during anaphylaxis, surgical procedures, accidents, stress etc.), however, when a local or systemic histamine release occurs both hemodynamic and arrhythmogenic effects are evident. Numerous studies in animal models conclusively demonstrated a role of cardiac histamine as a major mediator of serious arrhythmias. Consequently, a combination of h1- and h2-receptor antagonists (f.e. Dimetinden/Cimetidin) was recommended as a prophylactic treatment against severe anaphylaxis including life-threatening arrhythmias for cardiac patients at risk. There is pharmacologic evidence of both a positive inotropic and chronotropic effect in the human heart via h2-receptor and stimulation of adenylate cyclase. Histamine-induced coronary effects such as vasoconstriction via h1-receptor and coronary dilatation via h2-receptor are not yet sufficiently validated. Studies on the human heart in vitro using coronary strips from explanted hearts and in vivo investigations on the intact coronary system yielded conflicting results. H2-receptor blocking agents cimetidine, ranitidine and famotidine have qualitatively a different pharmocodynamic spectrum of side effects due to differences in chemical structure. Data on cardiac arrhythmias are mostly associated to cimetidine. Symptomatic bradycardia were reported for both ranitidine and cimetidine. A possible negative inotropic effect of famotidine, although presently not validated, requires further studies. Causative and adverse side effects of cimetidine on the cardiovascular system, however, are to be expected extremely seldom due to easily reversible competetive h2-receptor binding. For prophylaxis rapid intravenous injections of h2-blockers, particularly in elder patients with cardiac diseases, should be avoided. Compared to cimetidine, a tendency of explainable difference seems to become apparent for ranitidine and famotidine due to higher receptor affinity.

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“…Jfingere Uberblicke zur Cimetidin-Therapie an grogen Patientenkollektiven haben zur Schlugfolgerung geffihrt, dab der H2-Antagonist relativ frei von unerwfinschten Nebenwirkungen sei [28, 58,92]. Jfingere Uberblicke zur Cimetidin-Therapie an grogen Patientenkollektiven haben zur Schlugfolgerung geffihrt, dab der H2-Antagonist relativ frei von unerwfinschten Nebenwirkungen sei [28, 58,92].…”

Section: Kardiale Nebenwirkungen Von H2-rezeptor-antagonistenunclassified

“…Jfingere Uberblicke zur Cimetidin-Therapie an grogen Patientenkollektiven haben zur Schlugfolgerung geffihrt, dab der H2-Antagonist relativ frei von unerwfinschten Nebenwirkungen sei [28, 58,92]. Bei 2 Patienten war eine Cimetidiniiberdosierung [58,97], einmal simultan mit einer Diazepamiiberdosierung, im anderen Fall als Folge eines akuten Nierenversagens, vermutlich entscheidend an der Arrhythmieausl6sung beteiligt. Die H/iufigkeit unerwfinschter Reaktionen wird nach Analyse zahlreichef kontrollierter Studien auf 4-6 pro Million be- Mehrere Fallberichte lassen eine enge zeitliche Koinzidenz zwischen der H2-Blocker-Applikation und dem Beginn der jeweiligen Herzrhythmusst6rungen erkennen.…”

Section: Kardiale Nebenwirkungen Von H2-rezeptor-antagonistenunclassified

Histaminwirkungen am Herzen unter besonderer Berücksichtigung kardialer Nebenwirkungen von H2-Rezeptor-Antagonisten

Baller

Huchzermeyer

1989

Klin Wochenschr

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“…The final diagnosis was suicide by ingestion of cimetidine and diazepam (355). At autopsy, the blood concentration of cimetidine was 110 ,...g!ml (therapeutic 0.25 to 0.50 ,...g!ml), and 5.8 ,...g!ml diazepam (therapeutic 0.5 to 2.5 ,...g!ml) with desmethyldiazepam OJ ,...g!ml (therapeutic 0.1 to 2.2 ,...g!ml).…”

Section: Cimetidine (Tagumet)mentioning

confidence: 99%

Topics in Clinical Pharmacology and Therapeutics

Maronde¹

1986

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Cardiovascular Effects of H₂‐receptor Antagonists

Hughes

Dowling

DeMeersman

et al. 1989

The Journal of Clinical Pharma

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The type II histamine receptor antagonists, cimetidine and ranitidine, widely used in treatment of peptic ulcer disease have been reported to cause bradycardia. To evaluate the cardiovascular effects of H2 antagonists nineteen healthy volunteers were entered into a double-blind crossover comparison of cimetidine 300 mg qid, ranitidine 150 mg bid, and placebo. Subjects ingested study medicine for 7 days prior to being tested by the Bruce Exercise Test. Heart rate, blood pressure, oxygen consumption, expiratory volume, and fractional expiration of CO2 and O2 were measured at rest, exercise and recovery. A plasma sample for determination of cimetidine and ranitidine levels were obtained prior to the exercise period. Multivariate analysis and paired t test revealed no significant differences for the cardiovascular or pulmonary variables. However, in 5 subjects, the heart rate at 25% maximum VO2 was depressed 8% (P less than or equal to 0.03). This effect in a small percentage of the population suggests that further studies are needed to determine if subpopulations are affected.

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Fatal Bradycardia After Intentional Overdose of Cimetidine and Diazepam

Cited by 13 publications

References 12 publications

Histaminwirkungen am Herzen unter besonderer Berücksichtigung kardialer Nebenwirkungen von H2-Rezeptor-Antagonisten

Histaminwirkungen am Herzen unter besonderer Berücksichtigung kardialer Nebenwirkungen von H2-Rezeptor-Antagonisten

Topics in Clinical Pharmacology and Therapeutics

Cardiovascular Effects of H₂‐receptor Antagonists

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Fatal Bradycardia After Intentional Overdose of Cimetidine and Diazepam

Cited by 13 publications

References 12 publications

Histaminwirkungen am Herzen unter besonderer Berücksichtigung kardialer Nebenwirkungen von H2-Rezeptor-Antagonisten

Histaminwirkungen am Herzen unter besonderer Berücksichtigung kardialer Nebenwirkungen von H2-Rezeptor-Antagonisten

Topics in Clinical Pharmacology and Therapeutics

Cardiovascular Effects of H2‐receptor Antagonists

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Product

Resources

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Cardiovascular Effects of H₂‐receptor Antagonists