Successful first aid therapy for cyanide intoxication is dependent upon immediate administration of antidotes which directly or indirectly interact with the cyanide ion to remove it from circulation. Owing to the severe respiratory, cardiovascular and convulsive episodes following acute cyanide intoxication, the most practical approach is to administer antidotes by intramuscular injection. Exceptionally rapid methemoglobin formers-hydroxylamine hydrochloride (HH) and dimethylaminophenol (DMAP)-are usually able to prevent the lethal effect of cyanide following intramuscular injections in doses sufficient to induce 20% methemoglobin (HH = 20 mg kg-1 and DMAP = 2 mg kg-1). Sodium nitrite, the methemoglobin inducer approved for military use, must be administered by intravenous infusion because it is not an effective cyanide antidote by the intramuscular route. In the normal unintoxicated animal an intramuscular injection of 20 mg kg-1 sodium nitrite will form 20% methemoglobin; however, in acute cyanide intoxication the associated severe bradycardia appears to limit the rate of absorption and thus the rapid formation of methemoglobin. If the bradycardia is prevented or reversed by atropine, the rate of absorption of sodium nitrite and the formation of methemoglobin is able to reverse the otherwise lethal effects of cyanide. Thus, an intramuscularly administered combination of 20 mg kg-1 sodium nitrite and 1 mg kg-1 atropine sulfate, rapidly absorbed from the intramuscular site, appears to achieve the same degree of effectiveness against acute cyanide intoxication as intramuscularly administered HH or DMAP. It would appear from these studies that HH, DMAP and sodium nitrite with atropine are all potentially effective intramuscular antidotes for acute cyanide poisoning.

Aminophenols↗

PubMedDate not supplied

Enhancement of acute myocardial lesions by asthma drugs in rats.

Asthma morbidity and mortality have risen significantly in the last 10 years. The reasons for the increase are multifactorial. One proposed explanation is possible myocardial toxicity arising from the use of beta-agonists alone or in combination with methylxanthines. Previous studies have shown that beta-agonists given alone and beta-agonist/methylxanthine combinations given at higher than recommended clinical doses induced dose-related cardiotoxicity and sudden death in rats. The objective of the present study was to determine whether or not beta-agonists given alone and in combination with methylxanthines at recommended clinical doses also induce cardiotoxicity and sudden death in rats. The beta-agonists, isoproterenol hydrochloride (15 micrograms/kg), fenoterol hydrobromide (40 micrograms/kg), and terbutaline hemisulfate (0.4 mg/kg) were given in single sc doses separately and concurrently with the methylxanthines aminophylline hydrate (20 mg/kg) and caffeine (40 mg/kg), which were given up to a susceptible animal model, the heavy Sprague-Dawley rat. beta-agonist-induced myocardial toxicity (necrosis) was observed. The toxicity was enhanced by aminophylline resulting in the sudden death (most likely due to ventricular fibrillation) of some animals. A decrease in serum iron levels was observed in rats of all beta-agonist and/or methylxanthine-treated groups.

Acute Disease↗

PubMedDate not supplied

Cardiac effects of botulinal toxin.

Crystalline type A botulinal toxin rapidly caused temporary bradycardia and electrocardiographic (ECG) changes in mice, rats, rabbits and dogs. In addition, in the dog the force of contraction was measured and found to be depressed. The ECG changes were indicative of conduction defects. The hemagglutinin present in the toxin played no role in the effects on the heart, since a derivative toxin without hemagglutinin also caused these phenomena. The cardiac effects were spontaneously reversible in the intact animal without removal of the toxin. On the other hand, in the in vitro isolated heart of the rat, recovery from the cardiac effects occurred only after the toxin was washed out of the preparation. The findings are consistent with, but do not prove, a physical rather than a chemical mechanism for the effects of toxin on the heart.

Animals↗