Cisapride - not without extrapyramidal reactions
Cisapride is a gastrointestinal prokinetic drug used to improve gut motility. It is a benzamide derivative chemically related to the antiemetic drug metoclopramide. The ability of this drug to induce extrapyramidal reactions such as tremors and dystonia is known. However, over the past few years, such reactions are being reported with increased frequency. Not surprisingly, elderly patients with parkinsonism appear to be particularly prone to developing aggravation of tremor while on cisapride therapy. Patients previously free from central nervous system (CNS) symptoms have also developed typical parkinsonian features - tremor, rigidity, slowness of movement and a shuffling gait - shortly after starting cisapride intake. When used to treat gastroesophageal reflux in infants, cisapride has induced paroxysmal dystonia. It is difficult to explain these extrapyramidal reactions from the known modes of action of the drug. Cisapride is known to act as a stimulant at gut serotonin receptors (probably the 5-HT4 subtype) and may also enhance acetylcholine release form the myenteric plexus of the gut. But these do not explain the central reactions. Metoclopramide, which can induce alarming dystonic reactions, blocks central dopamine receptors. This has not been confirmed with cisapride. Nevertheless cisapride shares the extrapyramidal reaction inducing ability of its chemical congener, metoclopramide. Physicians now need to be aware of this tendency. Fortunately, these reactions have not been serious and in most cases have subsided with drug withdrawal and reassurance.

References:

1. Naito Y, Kuzuhara S. Parkinsonism induced or worsened by cisapride. Nippon Ronen Igakkai Zasshi 1994; 31 (11): 899-902.
2. Sempere AP, Duarte J, Cabezas C, Claveria LE, Coria F. Aggravation of parkinsonian tremor by cisapride. Clin Neuropharmacol 1995; 18 (1): 76-8.
3. Bucci KK, Haverstick DE, Abercrombie SA. Dystonia-like reaction following cisapride therapy. J Fam Pract 1995; 40 (1): 86-8.
4. Angelini L, Zorzi G, Rumi V, Nardocci N, Mennini T. Transient paroxysmal dystonia in an infant possibly induced by cisapride. Ital J Neurol Sci 1996; 17 (2): 157-9.

International study on oral contraception and heart attack risk provides interesting results
The results of a World Health Organization collaborative case-control study on steroidal oral contraception and risk of acute myocardial infarction (AMI) were published in the 26th April, 1997 issue of The Lancet. The study looked at 368 women in the 20 - 44 year age group from 21 centres in 17 developed and developing countries. Women who are free from cardiovascular disease or associated risk factors accrue very little risk from use of combined oral contraceptive pills (OCP). However pill users who smoke or have high blood pressure face substantial risk above the age of 35. This is applicable to both developed and developing countries. AMI in women is rare below age 35 (0.83 cases per million women) but the incidence becomes significant above this age (9.5 cases per million). The overall relative risk in pill users compared to non-users went up in women of all ages who smoked 10 or more cigarettes daily or were hypertensive. Over age 35, pill use and smoking combined increase the risk to a surprisingly high 485 per million women. Below age 35, most extra cases in OCP-users could probably be avoided if subjects were screened appropriately for smoking, high blood pressure and other predisposing factors.
Reference: Acute myocardial infarction and combined oral contraceptives: results of an international multicentre case-control study. Lancet 1997; 349: 1202-9.

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