Page 1219 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

1150 SECTION | XVIII Prevention and Treatment

VetBooks.ir which includes salivation, lacrimation, urinary inconti- produce those effects would be at least 10 times higher
(0.2 mg/kg).
nence, increased peristalsis and diarrhea, increased bron-
Pralidoxime chloride (2-PAM) is used with atropine in
chial secretions and dyspnea, miosis, nausea, emesis, and
abdominal discomfort. Excessive stimulation of the nico- the treatment of OP poisoning to relieve nicotinic signs,
tinic receptors, which are found in the skeletal muscles such as tremors and muscle fasciculations (Fikes, 1990).
and autonomic ganglia, leads to tremors, and possibly sei- 2-PAM reactivates the AChE enzyme that has been inacti-
zures, potentially followed by muscle fatigue, weakness vated by the OP. Normally, acetylcholine (ACh) binds to
and paralysis (Meerdink, 1989; Gupta and Milatovic, the enzyme at the anionic binding site. OPs and carba-
2012; Gupta et al., 2015). mates bind nearby on the esteric site, thus physically
Atropine competes with the accumulated ACh in the blocking the anionic site from ACh and inactivating the
synapse to block only the muscarinic effects. Atropine enzyme. 2-PAM is able to squeeze in via nucleophilic
does not block the nicotinic effects. The dosage used to attack and bind to the anionic binding site. It then attaches
counter anticholinesterase agents is: dogs and cats to the OP forming a pralidoxime OP complex. This com-
0.2 2 mg/kg; cattle 0.5 mg/kg; and horses 0.2 mg/kg. In plex detaches from the enzyme reactivating it and is then
all of those species, one-quarter of the dose is given IV excreted in the urine (Fikes, 1990; Mowry et al., 1994;
and the remainder intramuscularly (IM) or subcutaneously Plumb, 2015).
(SC) (Plumb, 2015). In some cases, administration of Administration of 2-PAM is most effective if given
atropine may need to be repeated, but great care should within 24 h of exposure (Plumb, 2015). If the OP remains
be exercised to prevent over-atropinization. Auscultation attached to the AChE much longer, aging of the bond
should be performed to monitor the patient for bradycar- may occur so that it can no longer be broken by 2-PAM
dia and continued bronchial secretions, since these are the (Meerdink, 1989; Mowry et al., 1994; Marrs and Vale,
most life threatening of the muscarinic signs. Additional 2006; Gupta and Milatovic, 2012). There are instances
atropine should only be given if these signs are present. when later administration is warranted. For example, in
The patient will not die from miosis or hypersalivation. large OP exposures, pralidoxime may still be of some
Horses are quite susceptible to ileus caused by atropine benefit if given within 36 48 h (Plumb, 2015). And
administration, and a total dose of no more than 65 mg is 2-PAM may still be indicated even later if clinical signs
recommended for a horse of average weight (Meerdink, have been present for an extended period of time (Fikes,
2004). 1992). Please see Table 82.2 for dosing information.
Atropine is not an effective antidote for other types of Treatment with 2-PAM should continue until the ani-
insecticides including pyrethroids. When presented with a mal is asymptomatic. If no improvement is seen after
suspected case of anticholinesterase exposure, the clini- 24 36 h following initiation of treatment, 2-PAM should
cian can use a test dose of atropine to assist in making a be discontinued (Fikes, 1990). In acute feline chlorpyrifos
preliminary diagnosis. The patient should be given the toxicosis, cats with persistent tremors can be maintained
preanesthetic dose of atropine (0.02 mg/kg) IV. If this on 1 2 times daily treatment for up to 4 weeks. The typi-
dose is able to produce typical anticholinergic signs such cal presentation in these cats differs from the classical
as mydriasis and tachycardia, then the patient has likely signs expected from other OPs. The onset may be delayed
not been poisoned by an anticholinesterase agent (Fikes, 1 5 days and the cats have neurological signs, including
1990). If the patient truly had been poisoned by an anti- tremors, especially of the muscles of the back, neck and
cholinesterase agent, the dose of atropine required to top of head, ataxia and seizures in addition to nonspecific

TABLE 82.2 Pralidoxime Dosing in OP Treatment

Species Dosing Instructions
Dogs and cats Pralidoxime works best when combined with atropine
Pralidoxime at 20 mg/kg, 2 3 times a day
Initial dose may be given either IM or slow IV
Subsequent doses may be given IM or SQ
Cattle 30 mg/kg IM q 8 h
Horses 20 mg/kg (may require up to 35 mg/kg) slow IV and repeat every 4 6h