To the Editor:
We report a 31-year-old woman who was admitted with polydipsia a few weeks after she had received the diagnosis of diabetes based on the presence of hyperglycemia. She had a known asymptomatic long QT syndrome, for which she was taking low-dose atenolol. At age 19 years, she had undergone implantation of a pacemaker because of asymptomatic second-degree atrioventricular block. Her older brother and sister had died of sudden death when they were about 30 years old.
Shortly after admission, she developed frequent convulsive syncopes due to torsade de pointes. Electrolyte level, thyroid function, and glycemia were normal. The QTc interval was 0.58 seconds. Treatment with intravenous magnesium sulfate and metoprolol had no effect on the duration and incidence of torsade de pointes. Overdrive ventricular pacing was not tolerated. Further investigation revealed that she had been drinking excessive amounts of grapefruit juice and quinine-containing tonic water because of her polydipsia. Forty-eight hours after the discontinuation of these drinks, the torsade de pointes disappeared. The QTc interval was 0.45 seconds after 2 days. No arrhythmias were induced with programmed electrical stimulation. However, a cardiac defibrillator was implanted because of her family history of the long QT syndrome. The patient was discharged. She was instructed to take metoprolol (100 mg) once a day, as well as about maintaining an appropriate diabetic diet. She also received a list of products that may prolong the QT interval or induce torsade de pointes.
Torsade de pointes in this patient may have been brought about by the concomitant excessive intake of grapefruit juice containing naringin and tonic water containing quinidine. Quinidine, the optical isomer to quinine, prolongs the QT interval (
1). It may also trigger torsade de pointes during, for example, astemizole therapy (
- Bigger Jr, J.T.
- Hoffman B.F.
in: Gilman A.G. Goodman L.S. Rial T.W. The Pharmacological Basis of Therapeutics. MacMillan Press, New York1985: 748-783
2). The inhibitory effect of the flavonoid naringin on the liver cytochrome P450 3A4, which is involved in the metabolism of quinine, is less well known. Concomitant use of naringin and quinine is associated with increased oral bioavailability (
- Martin E.S.
- Rogalski K.
- Black J.N.
Quinine may trigger torsades de pointes during astemizole therapy.
Pacing Clin Electrophysiol. 1997; 20: 2024-2025
3). However, reports of the effect of naringin on the pharmacokinetics of quinine have been conflicting (
- Zhang H.
- Wong C.W.
- Coville P.F.
- Wanwimolruk S.
Effects of the grapefruit flavonoid naringin on pharmacokinetics of quinine in rats.
Drug Metab Drug Interact. 2000; 17: 351-363
- Min D.I.
- Ku Y.M.
- Geraets D.R.
- Lee L.H.
Effect on the grapefruit juice on the pharmacodynamics of quinidine in healthy volunteers.
J Clin Pharmacol. 1996; 36: 469-476
5). Further information about the concomitant use of both substances in patients with the long QT syndrome is needed since these patients are especially vulnerable to rhythm disorders. Autonomic neuropathy can cause the long QT syndrome in patients with diabetes (
- Ho P.C.
- Chalcroft S.C.
- Coville P.F.
- Wanwimolruk S.
Grapefruit has no effect on quinine pharmacokinetics.
Eur J Clin Pharmacol. 1999; 55: 393-398
6). Beta-blockers have been shown to be efficacious in about 90% of patients, with a significant reduction in rate of sudden death (
- Ewing D.J.
Diabetic autonomic neuropathy and the heart.
Diabetes Res Clin Pract. 1996; 30: 31-36
7). Implantation of a cardiac defibrillator should be considered in high-risk patients. Left stellectomy and overdrive pacing may be useful in patients with bradycardia. Recent therapies that affect the ion channels are being tested. A list of potentially harmful products should be given to patients with the long QT syndrome. Clinical, electrocardiographic, and genetic screening of family members may also be helpful in identifying young adults who are at risk of sudden death.
- Moss A.J.
- Schwartz P.J.
- Crampton R.S.
- et al.
The long QT syndrome a prospective international study.
Circulation. 1985; 71: 17-21
- Antiarrhythmic drugs.in: Gilman A.G. Goodman L.S. Rial T.W. The Pharmacological Basis of Therapeutics. MacMillan Press, New York1985: 748-783
- Quinine may trigger torsades de pointes during astemizole therapy.Pacing Clin Electrophysiol. 1997; 20: 2024-2025
- Effects of the grapefruit flavonoid naringin on pharmacokinetics of quinine in rats.Drug Metab Drug Interact. 2000; 17: 351-363
- Effect on the grapefruit juice on the pharmacodynamics of quinidine in healthy volunteers.J Clin Pharmacol. 1996; 36: 469-476
- Grapefruit has no effect on quinine pharmacokinetics.Eur J Clin Pharmacol. 1999; 55: 393-398
- Diabetic autonomic neuropathy and the heart.Diabetes Res Clin Pract. 1996; 30: 31-36
- The long QT syndrome.Circulation. 1985; 71: 17-21
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