ORGANOPHOSPHATE INTOXICATION:
Acute, subacute and chronic forms of organophosphate intoxication occur. The chronic
form is due to a dying-back neuropathy which occurs relatively infrequently and was caused by
older forms of organophosphates no longer in use. Treatment of the acute and subacute forms of
organophosphate intoxication will be discussed here.
In the acute syndrome, the main signs are associated with muscarinic receptor over
stimulation, including salivation, vomition, diarrhea and tachycardia. Central cholinergic
receptor over stimulation results in hyperexcitability, body tremors and seizure activity. The
muscarinic signs are best treated with atropine (0.04 mg/kg IV or SQ), which blocks the
muscarinic receptor overstimulation. The central cholinergic signs may be treated with diazepam
(0.5-1.0 mg/kg IV), if necessary to stop seizure discharges. The seizures can be controlled
further with pentobarbital (1 mg/kg IV) and/or phenobarbital (1-2 mg/kg IV). Additional therapy
for acute organophosphate intoxication (in the dog, only), within the first 24 hours, should
include the use of pralidoxime chloride (2-PAM, 20 mg/kg IV, IM or SQ) in order to bind any
free organophosphate in the blood stream and aid in the elimination of the intoxicant. Following
the initial 24 hours, the organophosphate compound will already be irreversibly bound to
acetylcholinesterase and 2-PAM may not be beneficial. To maintain the control over the
muscarinic receptor overstimulation and to prevent the development of signs of subacute
organophosphate intoxication, continued treatment of acute organophosphate intoxication should
include diphenhydramine (Benadryl) orally (1-4 mg/kg) every 8 hours for, at least, 21 days of total therapy. Continued use of atropine in combination with diphenhydramine is not
recommended, since overt sedation can result. One initial dose of atropine followed by
diphenhydramine for maintenance is sufficient to minimize the signs of acute organophosphate
intoxication.
The clinical signs of subacute organophosphate intoxication include muscle weakness,
exercise intolerance, bradycardia, central depression, acute dystonia and central vestibular signs
and are secondary to diminished nicotinic and central cholinergic receptor function. Since the
muscarinic receptor rapidly develops tolerance, the muscarinic signs of acute organophosphate
intoxication decrease, and the signs of nicotinic receptor paralysis dominate. Nicotinic receptor
paralysis may be delayed in development for 7-10 days after exposure and are much more likely
to occur following high or repeated exposure to organophosphate. Anti-muscarinic drugs and
2-PAM are ineffective in treating these signs. Diphenhydramine will stabilize the nicotinic
receptor and improve the clinical signs. In subacute organophosphate intoxication, nicotinic
paralysis often results in a decremental response seen following repetitive nerve stimulation,
producing a myasthenic-like syndrome. This decremental response is worsened by edrophonium
HCl, but resolves following diphenhydramine therapy. The mental depression caused by central
cholinergic receptor dysfunction and acute dystonia improve with diphenhydramine treatment, as
well. Treatment with diphenhydramine should be started IV or IM medication (IM only in the
cat) at 4 mg/kg every 4-6 hours. Parenteral therapy should continue until there is improvement in
clinical signs, usually by 24-72 hours. Then, oral diphenhydramine is continued at 4 mg/kg every
8 hours. In small and large dogs, sedation may occur at this dosage. Reducing the dose of
diphenhydramine to 1-2 mg/kg may be necessary in these patients. Oral diphenhydramine should
be continued for, at least, 3 weeks, or until the acetylcholinesterase enzyme has been replaced.
While it may require a number of weeks for the plasma cholinesterase to return to normal levels,
the functional pool (approximately 20% of the total) usually returns within 3 weeks. This method
of therapy for the subacute organophosphate disorders has been highly successful except where
the intoxication is extreme. While the exact mechanism of action of diphenhydramine is not
known, it is an antihistamine with anticholinergic properties. It is useful as a central
anticholinergic, reducing cholinergic activation. While it does not block nicotinic receptor
activity, diphenhydramine appears to prevent nicotinic receptor overstimulation. Over the past
10 years, diphenhydramine has been used successfully to reduce the morbidity and mortality of
subacute organophosphate intoxication in the dog and cat.
fuente: Universidad de Florida (USA) |
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