2 AC poisoning – mechanism of action, symptoms, toxicity, and metabolism

The exact mechanisms of action of AC are not well defined, but the compound has been shown to have both a dose-dependent depressant and stimulant effect on the central nervous system (CNS) in various animal species and in humans (1). Intoxication may lead to sudden onset of lethargy, ataxia, hypersensitivity, muscle tremors, seizures and comatose state. Increased drooling, and symptoms of cranial nerve disorders such as contracted or dilated pupils is frequently described in reports on intoxication in humans and other animal species. In individuals where lethargy is present or consciousness is lost, bradycardia, hypotension, bradypnea and hypothermia may be present, and if not treated or reversed in time hypothermia could contribute to a lethal outcome (6, 1). As there is no antidote or specific treatment for AC intoxication, treatment is supportive and symptomatic, including maintaining a normal body temperature, minimising external stimuli and, when indicated, anticonvulsants (2).
The toxicity of AC, including lethal dose (LD50), is reported to vary between different species (table 1). The therapeutic index in cats has never been fully determined, although reports on use of AC as a feline anaesthetic are available. For example, Kullman et al. used continuous intravenous infusion of AC at a dose of 5mg/kg/h after an initial bolus of 65–75mg/kg as anaesthesia in cats used for experimental research not related to AC toxicosis (7).
 Species
Rats
Mice
Cats
Dogs
Starlings
Crows
Lethal dose (mg/kg)
400
300
100
600–1000
76
42
Table 1: Lethal dose (LD50) of alphachloralose for different animal species (8)
The cats were over-represented compared to e.g., dogs in the emerging AC-poisoning cases. The high susceptibility to AC in cats may among other reasons be related to their limited capacity to form glucuronide metabolites for drugs compared with other species (6). Glucuronic acid conjugation is a metabolic process that increases the polarity of xenobiotics and hence facilitates the excretion of several compounds including drugs and toxins via urine or bile. While the human UDP-glucuronosyltransferase gene (UGT1A) codes for nine different UGT enzymes, and the canine gene ten, the feline gene only encodes two different UGT enzymes that catalyses the conjugation with glucuronic acid, thereby leading to reduced excretion of substances secreted by this mechanism. Cats are also deficient in other enzymes responsible for conjugation reaction, e.g., N-acetyltransferase and thiopurine methyltransferase (1).
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