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Atnaa (Atropine / Pralidoxime Chloride) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Drug Interactions: When atropine and pralidoxime are used together, the signs of atropinization (flushing, mydriasis, tachycardia, dryness of the mouth and nose) may occur earlier than might be expected when atropine is used alone because pralidoxime may potentiate the effect of atropine.2,3,4

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. Since barbiturates are potentiated by the anticholinesterases, they 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 organophosphorous poisoning.

OVERDOSAGE

Symptoms:

Atropine

Serious overdosage with atropine is characterized by widespread paralysis of parasympathetically innervated organs. Dry mucous membranes, widely dilated and nonresponsive pupils, tachycardia, fever, and cutaneous flush are especially prominent, as are mental and neurological symptoms. Disorientation, mania, hallucinations, gait disturbances, and symptoms may last 48 hours or longer. In instances of severe intoxication, respiratory depression, coma, circulatory collapse, and death may occur.

The fatal dose of atropine is not known. In the treatment of organophosphorous poisoning, 200 mg doses have been used and doses as high as 1000 mg have been given.

In children, 10 mg or less may be fatal. With a dose as low as 0.5 mg, undesirable minimal symptoms or responses of overdosage may occur. These increase in severity and extent with larger doses of the drug (excitement, hallucinations, delerium, and coma with a dose of 10 mg or more). However, in the presence of organophosphate poisoning, higher doses of atropine may be tolerated.

Pralidoxime Chloride

Symptoms of pralidoxime chloride overdose have been observed in normal subjects only: dizziness, blurred vision, diplopia, headache, impaired accommodation, nausea, slight tachycardia. In therapy it has been difficult to differentiate side effects due to the drug from those due to effects of the poison.

Treatment:

Supportive treatment should be administered as indicated. If respiration is depressed, artificial respiration with oxygen is necessary. Ice bags, alcohol sponges or a hypothermia blanket may be required to reduce 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 the affected person's photophobia, the room should be darkened.

In the event of toxic overdosage, a short acting barbiturate or diazepam may be given as needed to control marked excitement and convulsions. Large doses for sedation should be avoided because central depressant action may coincide with the depression occurring late in 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 repeated doses are likely to be required. Neostigmine, pilocarpine, and methacholine are of little real benefit, since they do not penetrate the blood-brain barrier.

CONTRAINDICATIONS

In the face of life-threatening poisoning by organophosphorous nerve agents, there are no absolute contraindications for the use of the ATNAA (see WARNINGS).

DRUG ABUSE AND DEPENDENCE

Atropine and pralidoxime chloride are not subject to abuse and possess no known potential for dependence.

REFERENCES

  1. Landauer, W: Cholinomimetic teratogens. V. The effect of oximes and related cholinesterase reactivators. Teratology 15: 33 (Feb) 1977.
  2. Moller, K.O., Jensen-Holm, J. and Lausen, H.H.: Ugeskr Laeg. 123: 501,1961.
  3. Namba, T, Nolte, C.T., Jackrel, J. and Grob, D: Poisoning due to organophosphate insecticides. Acute and chronic manifestations. Amer. J. Med. 50: 475 (Apr), 1971.
  4. Arena, J.M.: Poisoning, Toxicology Symptoms, Treatments, ed. 4, Springfield, IL, Charles C.Thomas, 1979, p. 133.
  5. Brachfeld, J., and Zavon, M.R.: Organic phosphate (Phosdrin®) intoxication. Report of a case and the results of treatment with 2-PAM, Arch. Environ. Health 11: 859, 1965.
  6. Hayes, W.J., Jr.: Toxicology of Pesticides. Baltimore, The Williams &Wilkins Company, 1975, p. 416.

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