Nerve agents produce neuromuscular blockade and convulsions in exposed humans. Military personnel in areas of potential exposure take prophylactic pyridostigmine. They are instructed to self-administer atropine and pralidoxime at the first sign of nerve agent toxicity. The key to treatment of nerve agent poisoning is the administration of atropine in doses larger than is customary in most other disorders, repeated as often as needed. Mechanical ventilation may be required. Convulsions are treated with diazepam, but only after atropine has been administered.

Metoclopramide kinetics were examined in 24 adult patients with diminished renal function and in eight healthy subjects with normal renal function. Creatinine clearance correlated with metoclopramide plasma clearance, renal clearance, nonrenal clearance, and elimination t1/2. Regardless of renal function, renal clearance accounted for less than or equal to 21% of total plasma clearance. Nonrenal clearance was reduced in patients and accounted for most of the reduction in plasma clearance. The comparatively small plasma clearances in patients imply that maintenance doses should be reduced accordingly to avoid drug cumulation. Metoclopramide clearance by hemodialysis was also assessed in four patients. Metoclopramide losses from hemodialysis were relatively small compared to estimates of total body metoclopramide stores. Compensatory dosage increases are probably unnecessary for most patients. These data also suggest that hemodialysis is not likely to be effective in metoclopramide overdose.

A diazepam 10-mg autoinjector was evaluated in bioequivalence and dose proportionality studies; both involved 24 young, healthy subjects and used randomized, open-label, 2-treatment, 2-period crossover designs with a 3-week washout period between treatments. The bioequivalence study compared a single diazepam 10-mg autoinjector with a conventional needle and syringe containing 10 mg of diazepam injectable. The dose proportionality study compared the pharmacokinetics of a single diazepam 10-mg autoinjector with that of 2 diazepam 10-mg autoinjectors given simultaneously (20 mg). Injections were intramuscular in the midanterolateral thigh in both studies. The studies showed that the diazepam autoinjector produced consistent plasma diazepam levels, with a rapid onset of absorption. The diazepam 10-mg autoinjector given intramuscularly was bioequivalent to a conventional syringe containing diazepam 10 mg. A single (10-mg) autoinjector and 2 (20-mg) diazepam autoinjectors administered simultaneously produced plasma diazepam concentrations that were essentially dose proportional.

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