The pharmacodynamics of cocaine involve the complex relationships of multiple neurotransmitters.

       It directly prevents the re‐uptake of dopamine, serotonin, and norepinephrine into presynaptic neurons.

       Like other local anesthetics, it produces direct effects on cell membranes – cocaine blocks sodium channel activity and thus prevents the generation and conduction of nerve impulses in electrically active cells, such as myocardial and nerve cells.

       Cocaine has not been well studied in the horse. Based on the scientific literature examining the effects of cocaine in other species, however, in the horse one would expect it to be well absorbed when administered via mucous membranes (e.g. intranasally) or the GI tract.

       In humans, peak concentrations occur within 5–10 minutes of smoking and within 60 minutes of intranasal administration.

       Some cocaine is excreted unchanged in the urine, but the vast majority is metabolized to benzoylecgonine, ecgonine methyl ester, norcocaine and other metabolites.

       Although cocaine has a short elimination half‐life, the half‐lives of cocaine metabolites are substantially longer.

       The lethal dose for cocaine in horses has not been determined and there are no reports of acute toxicity in the scientific literature.

       In mice the LD50 is reported to be 96 mg/kg following oral administration.

       In humans, recreational cocaine abusers typically have peak serum concentrations between 0.5 and 5 μM, but lethal toxicity has been observed with serum concentrations of cocaine of 10 μM.

       Neurological – ataxia, disorientation, euphoria, agitation, anxiety, seizures.

       Cardiovascular – tachydysrhythmia, severe hypertension, acute coronary syndrome in humans, stroke.

       Musculoskeletal – hyperthermia, cocaine‐induced rhabdomyolysis.

       Accidental ingestion is unlikely.

       Illicit administration for performance‐enhancing effects in racehorses could occur.

       Inadvertent exposure from by a human abuser or from a contaminated environment is theoretically possible.

       Owners and trainers may be reluctant to admit possession and use.

       In many cases, the source may not be identified.

       Worldwide problem, not just limited to the United States.

       Intentional exposure by direct administration to horse.

       Unintentional exposure by careless placement of product or inadvertent transfer from personnel could theoretically cause detectable concentrations of cocaine or its metabolites to be present in blood and urine samples, but toxic concentrations are unlikely.

       With pharmacologically significant doses:CNS stimulation.Tachycardia.Arrhythmias.Bilateral mydriasis.Increased locomotor activity.

       Many exposures are not pharmacologically significant, although they produce detectable concentrations of cocaine metabolites in urine and blood samples.

       CNS stimulants (amphetamines, methamphetamine).

       High doses of beta2‐adrenergic agonists.

       High doses of caffeine or other methylxanthines.

       BUN, creatinine, and creatine kinase for evidence of rhabdomyolysis

       Immunoassay screening.

       LC‐MS.

       ECG as needed for tachydysrhythmia and cardiac effects.

       None reported in the horses, but from other species, if dose was high enough one would predict:Myocardial necrosis and hemorrhage.Pulmonary hemorrhage.

       Monitor ECG and treat arrhythmias.

       Maintain blood volume, pH, and electrolyte balance.

       Monitor for hyperthermia.

       Avoid CNS stimulation; dark quiet stall if possible.

       IV fluids as needed.

       For excitation:Detomdine 20–40 μg/kg IV.Romifidine 40–120 μg/kg IV.

       Control life‐threatening cardiac arrhythmias:Propranolol 0.02 mg/kg IV slowly, maximum of 1 mg/kg.Esmolol CRI 25–75 μg/kg/min.

       Ethanol potentiates the effects and may increase the risk of toxicity.

       Protection