EFFECTS OF CATECHOLAMINES AND DIAZEPAM IN CHLOROQUINE POISONING IN BARBITURATE ANESTHETIZED RATS

The recommended treatment of human chloroquine poisoning is diazepam a nd adrenaline but neither has been evaluated in controlled clinical tr ials. We, investigated whether diazepam provided any added benefit ove r barbiturate anaesthesia and whether the protective effect of catecho lamines in chloroquine poisoning was mediated through alpha or beta re ceptor stimulation. Rats, anaesthetised with thiobutobarbitone had a c ontinuous intravenous infusion of 3 mg/kg/min of chloroquine. This cau sed a steady decline in pulse rate and blood pressure. When diazepam ( 3 mg/kg iv) was administered 5-10 min later, heart rates decreased at a faster rate (P=0.005), blood pressure was consistently lower (P=0.01 ) and there was a shorter time to arrhythmias and death (P <0.05). Adr energic agents were given by titration to attempt to maintain mean blo od pressure >75 mmHg. Compared with the phenylephrine (selective alpha agonist) group, the group treated with isoprenaline (selective beta a gonist) had faster heart rates which decreased more slowly (P <0.0001) , higher blood pressure (P=0.005) and longer time to arrhythmias and d eath (P=0.005). Adrenaline and noradrenaline had intermediate effects. Thus beta agonist effect appears to explain the beneficial effects of adrenaline but alpha agonist activity may be harmful. This animal wor k suggests that a combination of barbiturate anaesthesia and isoprenal ine may be better than the diazepam and adrenaline in combatting the e ffects of chloroquine.