Petra A. Volmer,     Champaign, Illinois

Amphetamines

Amphetamines are a class of compounds that includes a number of prescription and illicit products, all derivatives of the parent compound amphetamine. Most animal exposures are a result of the accidental ingestion of human prescription products used for the treatment of obesity, narcolepsy, and attention-deficit hyperactivity disorder. Examples include dextroamphetamine (Dexedrine), methylphenidate (Ritalin, Concerta), pemoline (Cylert), phentermine (Fastin), and the combination of dextroamphetamine and amphetamine (Adderall). Exposure to unlawful amphetamine compounds can also occur. Street names for amphetamines can include speed, uppers, dex or dexies, and bennies. Methamphetamine production is on the rise in clandestine laboratories in many areas of the United States. Street names for methamphetamine can include ice and glass for the clear, translucent crystals and crystal, crank, and meth for the white or yellow powder form. Designer amphetamines include 4-methylaminorex (ice, U4EUh), methcathinone (cat), 3,4-methylenedioxy-N-methylamphetamine (MDMA [ecstasy, XTC, Adam, MDA]), and 3,4-methylenedioxy-N-ethylamphetamine (MDEA [Eve]) (Volmer, 2006; Llera and Volmer, 2006).

The amphetamines as a class are well absorbed orally, with peak plasma levels occurring by 1 to 3 hours; thus clinical signs can develop rapidly. Some pharmaceutical products are extended-release preparations, with the result of prolonging absorption and delaying the onset of signs. Amphetamine and its metabolites are excreted in the urine in a pH-dependent manner, so that a lower pH enhances excretion (Baggot and Davis, 1972). Amphetamines have a stimulant effect on the cerebral cortex through release of catecholamines, acting as a dopamine excitatory receptor agonist and enhancing release of serotonin. Toxic dosages of amphetamine products are low: the oral median lethal dosage for amphetamine sulfate in the dog is 20 to 27 mg/kg; for methamphetamine hydrochloride it is 9 to 11 mg/kg (Zalis et al, 1965). Signs in field cases can be seen at dosages much lower than experimental lethal dosages.

Exposed animals exhibit signs associated with stimulation. Behavioral effects can include initial restlessness, pacing, panting, and an inability to sit still. These signs can progress to pronounced hyperactivity, hypersalivation, vocalization, tachypnea, tachycardia, tremors, hyperthermia, seizures, and potentially death. In some cases animals may exhibit depression, weakness, and bradycardia.

Diagnosis is based on clinical signs and history of exposure. Amphetamines can be detected in urine. Over-the-counter drug-testing kits may be of use in diagnosing an exposure in the acute clinical setting.

Animals should be stabilized and then decontaminated. Animals with known ingestions of amphetamine products less than 30 minutes prior can undergo induction of emesis followed by administration of activated charcoal and a cathartic. Animals already exhibiting signs of stimulation such as restlessness or worse should not be induced to vomit because of the risk of aspiration. Similarly, if the product is rapidly absorbed with the possible rapid onset of signs, emesis is not recommended. For those cases gastric lavage followed by the instillation of activated charcoal and a cathartic is a safer approach. Sustained-release medications may require repeated doses of activated charcoal.

Excitability, tremors, seizures, and other stimulant signs associated with amphetamine intoxication can be treated with acepromazine (0.5 to 1 mg/kg slowly intravenously [IV]; allow 15 minutes for onset of action; repeat as needed and monitor arterial blood pressure) or chlorpromazine (10 to 18 mg/kg IV repeated as needed with blood pressure monitoring). Phenothiazine tranquilizers have been shown to have a protective effect when used to treat amphetamine toxicoses (Catravas et al, 1977). Diazepam is not recommended because it can exacerbate the stimulatory signs in some animals. Phenobarbital, pentobarbital, and propofol (dosed carefully “to effect”) may also be used to treat or mitigate severe central nervous system (CNS) signs. In addition, cyproheptadine, a serotonin antagonist, may help reduce the CNS signs. It has been used successfully to dampen the excessive stimulation from overexposure to antidepressant medications designed to increase serotonin in nerve synapses. Cyproheptadine is dosed at 1.1 mg/kg rectally in dogs.

Tachyarrhythmias should be treated with a β-blocker such as propranolol, esmolol, atenolol, or metoprolol. Hyperthermia should be corrected using a water mist and fans. Animals should be monitored to prevent subsequent hypothermia and housed in a dark, quiet environment to avoid external stimulation.

Intravenous fluids act to protect the kidneys and enhance elimination. Tremendous muscle stimulation can result in rhabdomyolysis and subsequent myoglobinuria, as well as a metabolic acidosis. Urinary acidification can promote elimination of amphetamines but must not be undertaken if the animal has compromised renal function or if acidosis is already present.