Canine and Feline Epilepsy. Luisa De Risio
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Levamisole is an anthelmintic, microfilaricide and immunostimulant (Bradley, 1976; Vandevelde et al., 1978). Levamisole toxicity has been reported with accidental overdosing (about four times the therapeutic dose) in companion animals.
Mechanism of action
Levamisole is a nicotine-like stimulant producing both muscarinic and nicotinic effects at cholinergic receptors.
Clinical presentation
Clinical signs of levamisole toxicosis include nausea, vomiting, hypersalivation, frequent urination and defecation, muscle tremors, ataxia, anxiety, hyperesthesia with irritability, clonic seizures, obtunded mental status, dyspnoea and cardiac arrhythmias.
Management
Treatment includes gastrointestinal decontamination, AEMs (see Table 4.1 and Chapters 12 and 24) and supportive care (including fluid therapy and oxygenation).
Methylxanthines
Overview
Methylxanthine compounds such as caffeine, theophylline, aminophylline and theobromine are CNS stimulants that are sometimes involved in accidental or malicious poisoning of companion animals (O’Brien, 1998). Intoxication most commonly occurs following ingestion of chocolate, caffeine-based tablets or elixirs. Dark chocolate and cocoa beans have much higher theobromine content than milk or white chocolate. Animals ingesting 20 mg/kg of caffeine or theobromine have mild clinical signs. Ingestion of 60 mg/kg causes seizures.
Mechanism of action
Methylxanthines enhance catecholamine effects both directly and indirectly through phosphodiesterase inhibition, elevation in intracellular cyclic AMP (AMPc) and increased calcium influx into neurons (O’Brien, 1998). This results in increased neuromuscular excitability and a positive inotropic effect. Competitive inhibition of cellular adenosine receptors further increases intracellular AMPc and results in CNS stimulation.
Clinical presentation
Clinical signs generally occur within 1–2 h post-ingestion and include restlessness, hyper-activity, vomiting, diarrhoea, tachycardia, cardiac arrhythmias, tachypnoea, polydipsia/ polyuria, ataxia, muscle tremors, tonic seizures, hyperthermia, cyanosis, coma and death (Glauberg and Blumenthal, 1983; Tawde et al., 2012).
Diagnosis
Diagnosis is based on the history of methylxanthine (generally theobromine, which is present in chocolate) ingestion, clinical signs and presence of chocolate (or other source of methylxanthine) in gastric content from vomitus or lavage fluids. Methylxanthine concentrations in gastric content, serum, plasma or urine can be analysed.
Management
Treatment is symptomatic and supportive, including induction of emesis (in asymptomatic animals within 2–4 h post-ingestion), activated charcoal with a cathartic (Table 4.1), intravenous fluids to promote methylxanthine excretion, antiarrythmic agents, skeletal muscle relaxants, AEMs (see Table 4.1 and Chapters 12 and 24) and supportive care. Removal of urine though an indwelling catheter prevents reabsorption of the toxin across the bladder mucosa (Hooser and Beasley, 1986).
Prognosis
The prognosis is generally favourable for animals with mild to moderate clinical signs that are treated promptly and aggressively.
Amphetamine and amphetamine-like compounds
Overview
Amphetamine and amphetamine-like compounds such as such as methylphenidate (Ritalin, Concerta), pemoline (Cylert) and dextroamphetamine/amphetamine combinations (Adderall, Dexedrine) are used to treat behaviour disorders in people, including attention deficit disorders in children and adults (Albretsen, 2002). Pets may be exposed by accidental ingestion of their owner’s medications. Toxic doses of amphetamines in dogs and cats can be as low as 1 mg/kg. Pemoline is known to cause clinical signs in dogs at oral doses greater than 2.8 mg/kg (Albretsen, 2002).
Mechanism of action
Amphetamine and amphetamine-like compounds stimulate the release of catecholamine and/or serotonin and prevent their reuptake and metabolism with consequent CNS stimulation (O’Brien, 1998; Stern and Schell, 2012).
Clinical presentation
Clinical signs include hyperactivity, restlessness, irritability or other behavioural changes, mydriasis, muscle tremors, tachycardia or other cardiac arrhythmias, hypertension, tachypnea, hyperthermia, vomiting, diarrhoea and, rarely, seizures (O’Brien, 1998; Albretsen, 2002; Stern and Schell, 2012). Coma and death (attributed to DIC secondary to hyperthermia and respiratory failure) can occur in severe intoxication.
Diagnosis
Diagnosis is based on the history of ingestion, clinical signs, and recovery of pills or capsules in the gastric content from vomitus or lavage fluids. Amphetamines can be detected in urine or plasma by laboratory analysis.
Management
There is no specific antidote for amphetamines or amphetamine-like drug intoxication. Treatment involves decontamination (induction of emesis in asymptomatic animals or gastric lavage followed by the administration of activated charcoal and a cathartic) (Table 4.1), supportive care (including fluid therapy and convective whole body cooling), methocarbamol in animals with tremors and AEMs in seizuring animals (see Table 4.1 and Chapters 12 and 24). Diazepam administration has been reported to increase excitability in some dogs with amphetamine toxicosis and it is therefore avoided to control hyperactivity, restlessness, irritability or other excitatory behavioural changes; however, it can be used in the acute management of seizures (Albretsen, 2002; Stern and Schell, 2012). Phenothiazine tranquilizers have been recommended to control hyperactivity, restlessness, irritability or other behavioural changes (Stern and Schell, 2012). Acepromazine can initially be administered at 0.05 mg/kg IV and titrated to effect. The dose can be gradually increased to 0.1 to 1.0 mg/kg if clinical signs do not resolve with lower doses. Alternatively, chlorpromazine can initially be administered at 0.5 mg/kg IV and subsequently titrated up to effect. Blood pressure should be monitored at higher doses of phenothiazine to ensure that hypotension does not occur. Animals should be kept in a dark and quiet area and stimulation should be minimized (Stern and Schell, 2012). Treatment of tachycardia or other cardiac arrhythmias may sometimes be required. Urinary acidification has been recommended (to a pH of between 4.5 and 5.5) to enhance the elimination of amphetamines. This can be achieved with ammonium chloride administration at 100 to 200 mg/kg/day PO divided four