When atropine and pralidoxime are used together, pralidoxime may potentiate the effect of atropine. When used in combination, signs of atropinization (flushing, mydriasis, tachycardia, dryness of the mouth and nose) may occur earlier than might be expected when atropine is used alone.
The following precautions should be kept in mind in the treatment of anticholinesterase poisoning, although they do not bear directly on the use of atropine and pralidoxime.
• Barbiturates are potentiated by the anticholinesterases; therefore, barbiturates should be used cautiously in the treatment of convulsions.
• Morphine, theophylline, aminophylline, succinylcholine, reserpine, and phenothiazine-type tranquilizers should be avoided in treating personnel with organophosphorus poisoning.
• Succinylcholine and mivacurium are metabolized by cholinesterases. Since pralidoxime reactivates cholinesterases, use of pralidoxime in organophosphorous poisoning may accelerate reversal of the neuromuscular blocking effects of succinylcholine and mivacurium.
Drug-drug interaction potential involving cytochrome P450 isozymes has not been studied.
Manifestations of atropine overdose are dose-related and include flushing, dry skin and mucous membranes, tachycardia, widely dilated pupils that are poorly responsive to light, blurred vision, and fever (which can sometimes be dangerously elevated). Locomotor difficulties, disorientation, hallucinations, delirium, confusion, agitation, coma, and central depression can occur and may last 48 hours or longer. In instances of severe atropine intoxication, respiratory depression, coma, circulatory collapse, and death may occur.
The fatal dose of atropine is unknown. In the treatment of organophosphorous poisoning, doses as high as 1000 mg have been given. The few deaths in adults reported in the literature were generally seen using typical clinical doses of atropine often in the setting of bradycardia associated with an acute myocardial infarction, or with larger doses, due to overheating in a setting of vigorous physical activity in a hot environment.
It may be difficult to differentiate some of the side effects due to pralidoxime from those due to organophosphorous poisoning. Symptoms of pralidoxime overdose may include: dizziness, blurred vision, diplopia, headache, impaired accommodation, nausea, and slight tachycardia. Transient hypertension due to pralidoxime may last several hours.
For atropine overdose, supportive treatment should be administered. If respiration is depressed, artificial respiration with oxygen is necessary. Ice bags, a hypothermia blanket, or other methods of cooling may be required to reduce atropine-induced fever, especially in children. Catheterization may be necessary if urinary retention occurs. Since atropine elimination takes place through the kidney, urinary output must be maintained and increased if possible; intravenous fluids may be indicated. Because of atropine-induced photophobia, the room should be darkened.
A short-acting barbiturate or diazepam may be needed to control marked excitement and convulsions. However, large doses for sedation should be avoided because central depressant action may coincide with the depression occurring late in severe atropine poisoning. Central stimulants are not recommended.
Physostigmine, given as an atropine antidote by slow intravenous injection of 1 to 4 mg (0.5 to 1.0 mg in children) rapidly abolishes delirium and coma caused by large doses of atropine. Since physostigmine has a short duration of action, the patient may again lapse into coma after one or two hours, and require repeated doses. Neostigmine, pilocarpine, and methacholine are of little benefit, since they do not penetrate the blood-brain barrier.
Pralidoxime-induced hypertension has been treated by administering phentolamine 5 mg intravenously, repeated if necessary due to phentolamine's short duration of action. In the absence of substantial clinical data regarding use of phentolamine to treat pralidoxime-induced hypertension, consider slow infusion to avoid precipitous corrections in blood pressure.