Pathologic physiology, pharmacology, and therapeutics of tetanus

Abstract

Experimental evidence for the routes of tramport of tetanus toxin from the site of its formation to the central nervous system is reviewed. The possible sites and mechanisms of action of toxin are discussed, and an attempt is made to correlate the mode of action with that of drugs used to suppress convulsions. Despite the total absence until recently of any valid therapeutic comparisom, an attempt is made to evaluate the principal controversial therapeutic techniques, including antitoxin, care of the wound, chemotherapy, central anticonvulsants, neuromuscular blocking agents, tracheostomy, and adrenocortical steroids.

Antitetanus Activity of Central Muscle Relaxants

“…The activity ratio of mephenesin and meprobamate on experimental local tetanus was found to be 1: 0.43 (Webster, 1961), which does not significantly differ from the activity ratio of 1: 0.31 obtained in the present study. The value of meprobamate in clinical tetanus is doubtful (Laurence & Webster, 1963). Of the two new compounds chemically related to mephenesin (SQ 10220 and SQ 4909), the p-chloro-derivative (SQ 10220) was more potent.…”

“…More recent work has demonstrated that both tetanus toxin and strychnine have a specific blocking action in the central nervous system upon inhibitory synaptic transmission (Bradley, Easton & Eccles, 1953;Brooks, Curtis & Eccles, 1957;Purpura & Grundfest, 1957). Tetanus toxin presumably acts by preventing the release, rather than the action, of an inhibitor transmitter (Laurence & Webster, 1963). Experimentally, mephenesin produces a selective depression of the interneurones and exhibits powerful antagonism to strychnine.…”

The place of tracheostomy in tetanus neonatorum.

“…The dose of antitetanus serum was 50,000 units intramuscularly (i.m.) (Laurence and Webster, 1963). Procaine penicillin 150,000 units i.m., the antibiotic routinely used, was given for 10 days.…”

Assisted respiration in the treatment of neonatal tetanus.

“…Initial sedation for all infants consisted of either 10 or 12 -5 mg. chlorpromazine and 60 mg. phenobarbitone. A single dose of 50,000 units of tetanus antitoxin was given (Laurence and Webster, 1963). Procaine penicillin 150,000 units was given daily for 10 days but other antibiotics were prescribed when indicated.…”