Pharmaceutical overdose in Malta : with special reference to paracetamol.

Abstract

Paracetamol has been in clinical use for some forty years, it is widely used prescription and over the counter analgesic. World wide the annual consumption exceeds 25,000 tons. In the last decade, international published data has shown a substantial increase in the number of self-poisoning patients being referred to district poison units. In Malta, data has never been compiled to date either about paracetamol overdose or about overdose with pharmaceutical preparations in general. Thus, the position of paracetamol overdose with respect to the general pharmaceutical overdose picture was uknown.

Knowledge about the formation and toxicity of paracetamol metabolite has been known for some years. In fact treatment of paracetamol overdose focuses on blocking the formation of this toxic metabolite, N-acetyl parabenzoquinoneimine. Peak plasma levels, which are usually reached within 30 – 60 minutes after ingestion of a normal dose, are delayed for up to four hours. Glutathione conjugation, which plays an important part in the detoxification of paracetamol, is a saturable process and when 70% of the available cellular glutathione is depleted, more of the toxic metabolite is formed. This then causes hepatocellular damage. The guidelines which have been issued about the treatment procedure are reviewed.

The aim of this research was to seek information regarding the general picture of pharmaceutical overdose cases in Malta and how paracetamol fits into this picture. The retrieval of information was extremely complex and arduous as it involved a retrospective compilation of information, collating of data from various division within the Health Department, such as the Health Information Unit. The Toxicology Laboratory, the Emergency Laboratory, the Admissions and Emergency (A & E) department at the general hospital, the Government Pharmaceutical Services section and the administrative section of the Health Department and correlating and analysing this fragmented noncomputerised data.

Data was obtained for overdose cases for seven years between 1995 and 2001. The main types of drugs responsible for drug overdose deaths in Malta were narcotics and psychodysleptics (39.2 %), anti-epileptic,sedative-hypnotic, anti-parkinsonian drugs and psychotropics (20.3 %), some gases and vapours (18.9 %), alcohol (8.1 %), anti-pyretics, anti-rheumatics and non-opoid analgesics (4.1 %) and other and unspecified drugs (9.3 %). The majority of the drug overdose victims (70.3 %) were between 20 and 49 years of age and 78.4 % were male. Most of the patients who were admitted to hospital because of drug overdose (66.7 %) were between 15 and 44 years while the male to female ratio of admissions is approximately 1: 1. From the data collected paracetamol overdose in Malta appears to be less common when compared to the data available from other countries such as UK where 42 % of all overdoses in Oxford in 1990 were due to paracetamol. In addition the consumption of some of the other drugs used commonly for overdose such as diazepam and bromazepam was calculated by means of the DDD methodology in an attempt to explain whether the different trends in overdose in Malta could be due to different consumption patterns for these drugs in Malta. The data collected was completely novel and in spite of the limitations which exist due to limited computerisation of the data in Malta, a general picture has emerged regarding pharmaceutical over dose in Malta including paracetamol overdose.