Page 538 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Organophosphates and Carbamates Chapter | 37 505

VetBooks.ir TREATMENT OF ACUTE POISONING (1992), the United States (1992), Venezuela (1998),
France (2000), and in many other countries. To date, OPs
Before instituting antidotal therapy, monogastric animals,
that are known to cause IMS include bromophos, chlor-
such as the dog, should be given gastric lavage. Animals
pyrifos, diazinon, dicrotophos, dimethoate, disulfoton,
of any species can be given activated charcoal to stop
fenthion, malathion, methamidophos, methyl parathion,
further absorption of OP/CM insecticides. Animals should
monocrotophos, omethoate, parathion, phosmet, and
be washed thoroughly with water if they are exposed to
trichlorfon. IMS is usually observed in individuals who
insecticides dermally. Intravenous fluid therapy is always
have ingested a massive dose of an OP insecticide either
beneficial.
accidentally or in a suicide attempt. A small number of
In the case of OP poisoning, antidotal treatment
human case studies have also suggested that some CMs
requires the combined use of atropine sulfate and pyridine-
(carbaryl and carbofuran) can cause IMS (Paul and
2-aldoxime methochloride (2-PAM). Atropine sulfate acts
Mannathukkaran, 2005; Indira et al., 2013).
by blocking the mAChRs from ACh. In ruminants, one-
IMS is clearly a separate clinical entity from acute
fourth of the total recommended dose (0.5 mg/kg) can be
toxicity and delayed polyneuropathy. Clinically, IMS is
given as a slow IV injection, and the remainder through
characterized by acute paralysis and weakness in the areas
IM or SC injection (Gupta, 1984). The total dose of atro-
of several cranial motor nerves, neck flexors and facial,
pine sulfate for an average size horse is about 65 mg, and
extraocular, palatal, nuchal, proximal limb and respiratory
for a dog is about 2 mg. Atropine sulfate treatment can be
muscles 24 96 h after poisoning. Generalized weakness,
repeated at an interval of every hour until all hypersecre-
depressed deep tendon reflexes, ptosis, and diplopia are
tory signs have subsided. 2-PAM reactivates the AChE
also evident. These symptoms may last for several days
inhibited by OPs. The recommended therapeutic dose of
or weeks depending on the OP involved. A similar syn-
2-PAM is 20 mg/kg, IV. The injection of 2-PAM can be
drome has also been observed in dogs and cats poisoned
repeated once after 1 h at half of its initial dose. Care
maliciously or accidentally with massive doses of certain
should be taken that only a freshly prepared solution of
OPs and CMs (Myberg and Gupta, 2007; Tinson et al.,
2-PAM be used. It needs to be emphasized that the com-
2017). It should be noted that despite severe AChE inhibi-
bined therapy of atropine sulfate and 2-PAM is superior to
tion, muscle fasciculations and muscarinic receptor-
any other treatment to date in the case of OP poisoning.
associated hypersecretory activities are absent.
Although many other oximes have been tested against
Although the exact mechanism involved in the patho-
many OPs, none has been proven to be better than 2-PAM.
genesis of IMS is unclear, studies suggest that decrease of
Furthermore, the depressant drugs, such as morphine and
AChE and nAChR mRNA expression occur after oral poi-
barbiturates, are contraindicated, since they aggravate the
soning with disulfoton in rats. Involvement of oxidative
condition. Diazepam without atropine sulfate also accentu-
stress is also suggested (Dandapani et al., 2003). Based
ates the toxicity of OPs.
on electromyographic (EMG) findings from OP-poisoned
Unlike OP poisoning, 2-PAM and other oximes are
patients and experimental studies on laboratory animals, it
ineffective in CM poisoning cases. In fact, in the case
has been found that the defect in IMS is at the neuromus-
of some carbamates, such as carbaryl and carbofuran,
cular endplate and postsynaptic level, but the effects of
2-PAM therapy accentuates toxicity. Some anticonvulsant
neural and central components in producing muscular
drugs, such as barbiturates and diazepam, also aggravate
weakness have not been ruled out. It seems clear that
the toxicity of CMs. Therefore, atropine sulfate, with
some OPs are greatly distributed to muscles and have a
doses as described for OPs, is the only preferred antidote.
higher affinity for nAChRs. Currently, very little is
However, when the animals are exposed to very high
known about the type of damage at the motor endplate or
doses of carbamates, atropine sulfate does not appear to
about risk factors contributing to its development. There
be a life-saving antidote.
is no specific treatment, and therapy relies upon atropine
sulfate and 2-PAM. The administration of atropine sulfate
and 2-PAM should be continued for a long period, even if
OP-INDUCED INTERMEDIATE SYNDROME
efficacy of these drugs on the development of IMS
OP insecticide-induced intermediate syndrome (IMS) was appears to be limited. For further details about IMS, read-
reported for the first time in human patients in Sri Lanka ers are referred to Gupta (2005), De Bleecker (2006) and
in 1987 (Senanayake and Karalliedde, 1987). The obser- Gupta and Milatovic (2012).
vations were made in 10 patients who presented 24 96 h
after acute cholinergic crisis from exposure to methami- CHRONIC TOXICITY
dophos, fenthion, dimethoate, and monocrotophos. This
syndrome has also been diagnosed in OP-poisoned Chronic toxicity is a major concern with OP pesticides.
patients in South Africa (1989), Turkey (1990), Belgium OP compounds that produce delayed neurotoxic effects