1: Vet Hum Toxicol. 2003 Dec;45(6):303-6.
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Death by quinine.
Section of Emergency Medicine, Louisiana State University, New Orleans, Louisiana, USA.
We report a case of a man with a 9.75 g ingestion of quinine. The patient presented with recurrent pulseless wide complex tachycardia for which he received sodium bicarbonate, defibrillation and overdrive mechanical pacing. Despite treatment, the patient died. Quinine is still available for the treatment of leg cramps and drug-resistant malaria. In overdose, quinine affects multiple organ systems, including vision, hearing, the cardiovascular, and renal systems. We review the current approach to quinine intoxication.
HUGE DOSE!!!!
1: Trop Med Int Health. 1998 Jun;3(6):482-9.
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Quinine pharmacokinetics: ototoxic and cardiotoxic effects in healthy Caucasian subjects and in patients with falciparum malaria.
Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, The Netherlands.
OBJECTIVE: To study the pharmacokinetic behaviour of quinine in Caucasians with and without malaria. METHOD: Quinine-dihydrochloride was administered intravenously as a single dose of 300 mg to 12 healthy subjects and as multiple doses of 600 mg in 4 h every 8 h in 10 patients with falciparum malaria. Plasma quinine concentrations were measured by high-performance liquid chromatography RESULTS: Quinine pharmacokinetics are time-dependent: the apparent elimination halftime is shorter in the accumulation phase than in the elimination phase; in malaria patients the maximal quinine concentration was reached in half the time calculated on the basis of the elimination phase after the last quinine infusion. Nevertheless a loading dose seemed advisable to reach adequate therapeutic levels quickly. In malaria patients the highest plasma concentrations during or at the end of the infusions were positively correlated with body weight. There was no correlation between body weight and the volume of distribution of quinine as calculated during the elimination phase. Hearing loss was audiometrically documented in 9 healthy subjects at a mean maximal plasma quinine concentration of only 2 mg/l. All malaria patients suffered serious cochlear hearing impairment. The ototoxic effects in both healthy subjects and patients appeared to be reversible. No electrographic changes were noted in the healthy subjects, whereas a clinically insignificant mean lengthening of the corrected QT interval was seen in the malaria patients. CONCLUSION: Intravenous quinine pharmacokinetics in healthy Caucasians were similar to those reported for Nigerian or Thai subjects. At effective doses quinine causes considerable but reversible cochlear hearing losses in both healthy persons and in patients. Our findings do support the need for a loading dose. The fact that in malaria patients there was no correlation between body weight and quinine VD as calculated during the elimination phase renders questionable the usefulness of dosing quinine according to body weight.
1: Trans R Soc Trop Med Hyg. 1997 Nov-Dec;91(6):694-6.
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Lack of a significant adverse cardiovascular effect of combined quinine and mefloquine therapy for uncomplicated malaria.
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Quinine dihydrochloride (10 mg salt/kg infused over one hour) and mefloquine (15 mg base/kg) were given simultaneously to 13 adults with uncomplicated falciparum malaria. Supine and standing blood pressures were recorded and the electrocardiogram monitored. Plasma concentrations of the 2 drugs were similar to those reported previously for the 2 compounds given individually to a similar group of patients. Although postural hypotension was common (6 cases before treatment and 7 after) and the electrocardiogram QTc interval was prolonged by a mean of 12% (SD = 8) following drug treatment, there was no evidence of a clinically significant cardiovascular pharmacodynamic interaction between these 2 structurally related antimalarial compounds.
Quinidine-induced potentiation of cardiovascular effects of nitrendipine: functional aspects and possible molecular mechanisms.
Department of Pharmacology, University of Kiel, Germany.
The functional interaction between the dihydropyridine calcium channel blocker nitrendipine and quinidine was studied in isolated preparations from guinea-pig cardiac ventricle and in mesenteric arterial segments under a variety of experimental conditions. The negative inotropic potency of nitrendipine is clearly enhanced by quinidine (3 x 10(-6)-10(-4) mol/l) by up to two orders of magnitude, i.e. cardiac nitrendipine effects are potentiated. Vasorelaxant effects, however, remain largely unaffected (nitrendipine potency is increased by half an order of magnitude maximally). To elucidate the mechanism of this interaction, the ability of quinidine to potentiate the negative inotropic effect of a series of 12 dihydropyridines was compared with their voltage-dependence of action in guinea-pig left atria. No significant correlation is found (r = 0.18). Furthermore, quinidine inhibits rather than stimulates binding of tritiated nitrendipine, nimodipine or (S)-isradipine to isolated cardiac membranes. Therefore, the mechanism of the quinidine-nitrendipine interaction differs from those previously proposed for modulation of dihydropyridine binding by other drugs. We hypothesize that quinidine-occupied calcium channels adopt an intermediate affinity for nitrendipine, higher than in resting channels, but lower than the high affinity present with inactivated channels. Model calculations which are based on this assumption are able to reproduce all experimental findings of this study.
PMID: 7675123 [PubMed - indexed for MEDLINE]
1: J Emerg Med. 1993 May-Jun;11(3):279-85.
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Delayed cardiotoxicity following quinine overdose: a case report.
Department of Emergency Medical Services, Denver General Hospital, Colorado 80204-4507.
Quinine poisoning typically results in a constellation of non-life threatening symptoms which include tinnitus, deafness, nausea, vomiting, vision changes, headache, and hypotension. Cardiac conduction defects, dysrhythmias, and cardiovascular collapse have all been reported after overdose and generally occur within 8 hours of ingestion. We report a unique case of delayed cardiotoxicity following quinine ingestion. Toxicity included marked ventricular conduction abnormalities for which serum alkalinization appeared to be therapeutically beneficial, and torsades de pointes requiring overdrive pacing for termination.
PMID: 8340583 [PubMed - indexed for MEDLINE]
Hope some of this helps.....
Victoria
