Exposures to recreational drugs in domestic animals can be accidental, intentional, or malicious. Occasionally, drug-sniffing dogs ingest or are otherwise exposed to these substances. Because of the illegal nature of these drugs, some owners provide inaccurate, incomplete, or misleading exposure histories.
Recreational drugs are often adulterated with other pharmacologically active substances, making the diagnosis of related toxicoses even more difficult. In suspected cases of exposure, an attempt should be made to gather information about the patient's environment, the amount of drug ingested, the times at which exposure and the onset of clinical signs occurred, and the specific signs exhibited. These questions will help confirm possible exposure to a recreational drug.
Recreational drugs are often known by street names that vary from area to area. If the street name is known, a call to a local police station or to an animal or a human poison control center can help identify the substance.
Commonly available human point-of-care (POC) multidrug urine drug-screening kits can help exclude a suspected case of recreational-drug toxicosis. These kits are designed to detect drugs or metabolites in the human urine. Although they are not validated for use in animals, they can detect some recreational drugs, including amphetamines, cocaine, opioids, and barbiturates. The kits are inexpensive and easy to use; however, there are several options, and each one should be examined closely for a list of specific drugs that they test for. Their instructions for use should be followed carefully.
Some human hospitals and emergency clinics have developed screens for illicit drugs and can check for the presence of illicit drugs or their metabolites in different body fluids. The turnaround time, however, might be too long to help with treatment.
For legal cases, many veterinary diagnostic laboratories are able to process different sample types (blood, urine, gastric contents, kidney, liver) using gas chromatography–mass spectrometry (GC/MS) or liquid chromatography–mass spectrometry (LC/MS) to detect the presence of drugs.
In general, recreational drugs are either CNS stimulants or CNS depressants. The goals of treatment are to stabilize and decontaminate the patient and to provide supportive care. Patients showing clinical signs should be stabilized before decontamination is attempted.
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Induction of emesis is not typically recommended in clinically normal patients unless performed within 10–15 minutes after ingestion of a recreational drug. Often, a better choice is to administer a single dose of activated charcoal with a cathartic (AC+C). If the patient has neurological or cardiac signs, gastric lavage with a cuffed endotracheal tube to decrease the risk of aspiration should be performed and a dose of AC+C left in the stomach before the tube is removed.
Also see Toxicosis From Cannabidiol (CBD) and Toxicosis From Tetrahydrocannabinol (THC).
Toxicoses From Amphetamines and Their Derivatives
Amphetamines and their derivatives are CNS and cardiovascular system stimulants commonly used by humans for appetite suppression or as treatment for narcolepsy, attention-deficit/hyperactivity disorder (ADHD), parkinsonism, and some behavior disorders.
Currently, there are no therapeutic indications for the use of amphetamines in veterinary medicine.
Most amphetamines are Schedule II drugs. Commonly encountered human prescription amphetamines or related drugs include the following:
amphetamine
amphetamine and dextroamphetamine combination
dexmethylphenidate
dextroamphetamine
lisdexamfetamine
methamphetamine
methylphenidate
For specific information on the toxicity of prescription amphetamines and ADHD drugs, see Toxicoses From Amphetamines and ADHD Drugs.
Amphetamines sold on the street for recreational use have common names such as bennies, dexies, speed, or uppers.
Methamphetamine is currently the most popular recreational amphetamine and is casually referred to as blade, crystal, ice, or meth, among myriad other names. Despite being a prescription drug, methamphetamine is manufactured primarily for recreational use in clandestine laboratories either as a powder (“crank”) that can be injected, insufflated, or ingested, or as a crystal (“ice” or “glass”) that is smoked in a pipe.
Methamphetamine is rarely contaminated, but when it is, common adulterants include dimethyl sulfone, caffeine, and acetaminophen (1, 2).
Methylphenidate is rarely manufactured in clandestine laboratories; generally, it is purchased on the street as a stolen or “borrowed” prescription drug. It has its own names, including kiddy coke, kibbles and bits, smarties, and study buddies. The most common route of exposure is ingestion, but some methylphenidate products are smashed into a powder and snorted.
Street methylphenidate products are frequently adulterated with inert substances (such as talcum powder, to increase the volume) or with other drugs (such as caffeine, ephedrine, or cocaine, to alter or increase the effects).
Pharmacokinetics and Mechanisms of Amphetamine Toxicity
Amphetamines, in general, are lipid soluble and rapidly cross the blood-brain barrier, with CSF concentrations reaching 80% of the plasma concentration.
The minimum lethal dose for amphetamine sulfate in dogs is 20–27 mg/kg, PO (3). The minimum lethal dose for methamphetamine hydrochloride in dogs is 9–11 mg/kg, PO (4). Although the LD50 for methylphenidate has not yet been established, Beagles that received a daily dose of 20 mg/kg for 90 days survived (5).
Amphetamines stimulate the central and peripheral nervous systems. They increase the amounts of catecholamines at nerve endings by stimulating the release of norepinephrine and inhibiting its reuptake and metabolism.
Amphetamines also increase the activity of dopamine and induce the release of epinephrine, serotonin, and histamine. Increased CNS levels of dopamine result in euphoria.
Similarly, methylphenidate inhibits the reuptake of dopamine, resulting in increased dopaminergic activity in the brain.
Clinical Findings and Diagnosis of Amphetamine Toxicosis
Methamphetamine is rapidly absorbed, with clinical signs occurring within 20 minutes after oral absorption and within 4–5 minutes after nasal insufflation (snorting).
The most commonly reported clinical signs of amphetamine toxicoses in animals are hyperactivity, aggression, mydriasis, circling, head bobbing, vocalization, ataxia, seizures, and death. Hyperthermia can occur secondary to seizures or serotonin release. Tachycardia and arrhythmias, as well as hypertension and, more rarely, hypotension, have all been reported.
Death due to amphetamine toxicosis results from respiratory failure with, in some cases, DIC, cerebrovascular hemorrhages, lactic acidosis, and cardiac failure. Some human POC multidrug urine tests are useful to detect amphetamines in general, and one or two POC single-drug test kits might be specific for methamphetamine.
Using GC/MS or LC/MS, diagnostic laboratories can detect most amphetamines and their metabolites, as well as methylphenidate, in plasma and urine.
Treatment of Amphetamine Toxicosis
Treatment of amphetamine toxicosis depends on the specific substance and amount ingested. Because of the rapid onset of clinical signs, emesis is recommended only if it is done within 15 minutes after ingestion of the drug.
Activated charcoal should be administered within 30 minutes after ingestion, if possible. However, its use should be avoided in comatose animals and in animals with seizures because of aspiration risk.
Phenothiazine tranquilizers such as acepromazine (0.55–1.1 mg/kg, IV, IM, or SC, repeated as needed) or chlorpromazine (0.5 mg/kg, IV or IM, slowly to effect) generally work well to control the CNS effects of amphetamine toxicoses (6). Lower doses of acepromazine have been used to treat amphetamine toxicosis, but they are not always effective (4, 6, 7, 8).
The following drugs may be administered to treat seizures:
levetiracetam(30–60 mg/kg, IV) (9)
propofolto effect (3–4 mg/kg, IV, as needed, or administered as CRI [0.1–0.2 mg/kg/min] in cases of intractable seizure) (4, 6, 10)
phenobarbital (3–4 mg/kg, IV) (7)
Diazepam is not recommended as a first choice for treating amphetamine toxicoses, because it can cause a paradoxical reaction and exacerbate clinical signs. Other anticonvulsants, such as levetiracetam, propofol, and barbiturates may be administered, or masking with sevoflurane may be used as needed.
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Tremors generally respond well to methocarbamol (50–100 mg/kg, IV or PO, every 6–8 hours as needed, not to exceed 330 mg/kg per day) (4).
Typically, cardiac arrhythmias resolve in response to the treatment of CNS signs.
Cyproheptadine (in dogs, 1.1 mg/kg, PO or rectal, every 4–6 hours until resolution of clinical signs; in cats, 2–4 mg/cat, PO or rectal, every 4–6 hours until resolution of clinical signs) can be useful in animals with clinical signs of serotonin syndrome (4).
IV lipid emulsion has been used successfully and can be helpful for treating large amphetamine overdoses; however, it can decrease the efficacy of some medications (8).
Additional treatment is supportive, focusing on relief of clinical signs.
Toxicoses From Cocaine
Cocaine is a Schedule II stimulant drug approved in humans for topical administration as a local anesthetic and a vasoconstrictive agent on mucous membranes of the oral, laryngeal, and nasal cavities. There is no approved veterinary use.
For recreational use, raw cocaine is obtained from the leaves of the coca tree (Erythroxylum coca and Erythroxylum monogynum) and processed into cocaine hydrochloride, a white, powdery salt that can be snorted, swallowed, or injected. Street names for cocaine include baseball, C, coke, gold dust, stardust, snow, and white lady.
Cocaine alkaloid is formed when cocaine hydrochloride is reprocessed by being boiled with a base (often sodium bicarbonate) and cooled to form a solid product commonly referred to as "crack" or "rock cocaine." Crack cocaine is generally smoked.
Freebasing is the process by which cocaine hydrochloride is heated and processed with several chemicals to produce an almost pure form of cocaine, which is then inhaled. Cocaine is cut or diluted several times before it reaches the end user. Some cheap diluents (such as talcum powder, chalk, and meat tenderizer) are added to bulk up the product, and some adulterants (eg, levamisole, xylazine, xanthine alkaloids, local anesthetics, and amphetamine-type stimulants) are added to cocaine to enhance the high or produce a numbing sensation.
Pharmacokinetics and Mechanisms of Cocaine Toxicity
Cocaine is a lipophilic compound that is absorbed from most routes of administration and easily crosses the blood-brain barrier. Peak plasma concentrations occur between 15 minutes and 2 hours after exposure, and the half-life is 0.9–2.8 hours. Oral bioavailability is poor, with only approximately 20% of an oral dose absorbed in humans.
Cocaine is extensively metabolized by liver and plasma cholinesterases to several inactive metabolites that are excreted primarily in the urine.
The acute IV LD50 of cocaine hydrochloride in dogs is 13 mg/kg. The lowest published lethal dose in dogs is 3.5 mg/kg, SC; the lowest published lethal dose in cats is 7.5 mg/kg, IV, or 16 mg/kg, SC (11).
Cocaine has also been used for illegal performance enhancement in horses.
Cocaine use alters both the central and the autonomic nervous systems:
The reuptake of dopamine, serotonin, and norepinephrine in the CNS is blocked, leading to feelings of euphoria, restlessness, and increased motor activity.
Hyperthermia can develop as a result of norepinephrine effects or as a result of increased heat production due to increased muscular activity.
Cardiac effects are associated with myocardial sodium and potassium ion channel inhibition, as well as other changes.
Topical use of cocaine produces local anesthetic effects by inhibiting sodium ion channels.
Clinical Findings and Diagnosis of Cocaine Toxicosis
Early clinical signs of cocaine toxicosis are associated with CNS stimulation and include hyperexcitability, muscle tremors, and ataxia. Other clinical signs include mydriasis, altered mentation, vocalization, seizures, hypersalivation, vomiting, hyperthermia, tachycardia, and hypertension. In some animals, CNS depression and coma follow CNS excitation. Uncontrolled hyperthermia, cardiac arrest, or respiratory arrest are reported causes of death.
Nonspecific chemistry changes include hyperglycemia; increased lactate concentration, or lactic acidosis; increased CK concentration; or increased or decreased sodium concentration.
Diagnosis of cocaine toxicosis is based on a history of exposure and the presence of characteristic clinical signs. A human POC multidrug urine test can be useful in the diagnosis and, if needed, identification of cocaine or metabolites in plasma, gastric contents, or urine. GC/MS or LC/MS is used to confirm the diagnosis.
Treatment of Cocaine Toxicosis
Most animals are exposed to cocaine in the home via inhalation of smoke; however, ingestion occurs in some cases. Emesis for animals that have ingested cocaine is recommended only in the first 10–15 minutes after ingestion.
Cocaine is well adsorbed to activated charcoal, which may be administered at 1–4 g/kg every 6–8 hours as needed (12, 13, 14). Activated charcoal should not be administered to animals with seizures or to comatose animals, because of aspiration risk.
The onset of clinical signs of cocaine toxicosis is rapid, and the duration depends on the route of exposure. There is no antidote.
Clinical signs of CNS excitation due to cocaine toxicosis can be controlled with diazepam (0.5 mg/kg, IV, or 1 mg/kg per rectum) (15) or midazolam (0.1–0.3 mg/kg, IV or IM) (16).
Phenothiazine tranquilizers such as acepromazine(0.55–1.1 mg/kg, IV, IM, or SC, repeated as needed) or chlorpromazine (0.5 mg/kg, IV or IM, slowly to effect) generally work well to control the CNS effects (17).
Levetiracetam(30–60 mg/kg, IV) (9), propofol (2–8 mg/kg, IV slowly to effect [25% of total dose every 30 seconds until desired effect is achieved], and prepare to intubate) (18), or phenobarbital (3–4 mg/kg, IV) (7) may be administered to treat seizures.
If these measures do not control the CNS signs of cocaine toxicosis, administration of a gas anesthetic such as sevoflurane might be useful.
Methocarbamol(55–220 mg/kg, IV, given slowly to effect, with the rate of infusion not to exceed 2 mL/min (6); or 50–100 mg/kg, PO, every 6–8 hours as needed, not to exceed 330 mg/kg per day) (4) should be effective at controlling tremors. Blood pressure, heart rate and rhythm, ECG, and body temperature should be monitored frequently and treatment provided as needed.
Propranolol(0.02–0.1 mg/kg, slow IV) or other beta-blocking agents, such as esmolol(0.25–0.5 mg/kg, slow IV over 1 minute; or 10–200 mcg/kg/min as a CRI) can be administered to control tachycardia (19).
After CNS and cardiovascular effects have been stabilized, IV fluids should be administered, and electrolyte changes and acid-base status monitored and corrected as needed.
Cocaine is lipid soluble, and IV lipid emulsion(ILE) might be helpful in patients that do not respond to initial treatment of toxicosis (13).
Toxicoses From Gamma-Hydroxybutyrate (GHB)
Gamma-hydroxybutyrate (GHB) is a lipophilic, synthetic CNS depressant. Although some FDA-approved Schedule III drugs containing GHB are approved for treatment of narcolepsy when legally manufactured and distributed, illicit forms of GHB that are not FDA approved and are illegally distributed are categorized as Schedule I drugs in the US.
Commonly referred to as a “club drug” or “date rape drug," GHB is abused by teens and young adults at bars, dance parties, and raves. It is sold as a liquid product that is either ingested directly or (usually) added to an alcoholic beverage. Sildenafil has been reported as a common adulterant (20). Street names include easy lay, G, gib, liquid X, soap, and salty.
Pharmacokinetics and Mechanisms of GHB Toxicity
GHB is an endogenous compound with affinity for receptors in the CNS, especially those involved with sleep and memory. The drug is rapidly absorbed after oral ingestion and readily crosses the blood-brain barrier. It is metabolized and excreted as carbon dioxide, and only a small amount is eliminated unchanged in the urine.
Sleep was induced in rabbits and dogs with a GHB dose of 1 g/kg, IV. No specifics were provided regarding the lethal dose, but it might be close to 3 g/kg, IV (21).
In humans, drowsiness and sleep can be induced with GHB doses of 20–30 mg/kg, PO, and one death occurred after a total dose of 5.4 g, PO (22).
Respiratory depression is the cause of death from GHB toxicosis.
Clinical Findings and Diagnosis of GHB Toxicosis
Clinical signs of GHB toxicosis appear rapidly, often within 20–30 minutes after ingestion. Drowsiness, coma, hypotonia, hypothermia, bradycardia, and seizures have been reported in animals. Diagnosis is based on a history of exposure and a rapid onset of physical signs.
GHB is not currently included in any of the human POC multidrug urine screens. Blood and urine can be tested using GC/MS or LC/MS; interpretation of the results, however, could be difficult, because GHB is rapidly metabolized and normally present in the body as an endogenous substance.
A number of rapid detection urine/beverage test strips are available, but they have not been validated for use in veterinary species (23).
Treatment of GHB Toxicosis
Induction of emesis is not recommended in cases of GHB toxicosis, because of the very rapid absorption of GHB and rapid onset of clinical signs (24). Although the duration of signs in animals is unknown, recovery of respiratory and CNS function in humans typically occurs within 2–6 hours of intoxication (25). There is no antidote.
Treatment of GHB toxicosis is supportive. Hypothermic patients benefit from warming measures; however, care should be taken not to overheat them.
GHB-induced bradycardia may be treated with atropine (0.02–0.04 mg/kg, IV, IM, or SC, once) (17).
Seizures can be controlled with diazepam(0.5 mg/kg, IV, or 1 mg/kg per rectum) (15), midazolam(0.1–0.3 mg/kg, IV or IM) (16), propofol (2–8 mg/kg, IV slowly to effect [25% of total dose every 30 seconds until desired effect is achieved], and prepare to intubate) (18),levetiracetam (30–60 mg/kg, IV) (9), or phenobarbital (3–4 mg/kg, IV) (7).
Further monitoring is based on clinical signs and the clinician's judgment.
Toxicoses From Lysergic Acid Diethylamide (LSD)
Lysergic acid diethylamide (LSD), is a Schedule I hallucinogenic drug with no currently accepted use in human or veterinary medicine. It is manufactured in crystal form from lysergic acid in clandestine laboratories.
Before street sales, LSD crystals are converted to a soluble powder, applied to substances such as sugar cubes or absorbent paper, and sold either as small squares or tablets known as microdots or as gelatin squares known as windowpanes. Street names include acid, dots, cubes, L, pane, royal blue, sugar cubes, trip, and wedding bells.
According to Erowid, the amount of LSD currently present in street products is estimated to be approximately 0.04–0.06 mg/dot or pane.
Pharmacokinetics and Mechanisms of LSD Toxicity
The pharmacokinetics of LSD in domestic animals is poorly studied. In humans, absorption is rapid, and peak plasma concentrations are reached in 30 minutes to 5 hours after ingestion (26).
LSD is metabolized in the liver, and at least 80% is eliminated in feces. The elimination half-life is 2–5 hours.
Cats receiving 2.5 mcg/kg, IP, of LSD showed mild clinical signs; those receiving 50 mcg/kg, IP, showed serious signs (27).
Common adulterants of LSD include caffeine, synthetic cathinones, hallucinogens, ketamine and others.
The complete mechanism of action of LSD has not been delineated; most researchers agree, however, that it has some effect on the 5-hydroxytryptamine (5-HT) receptors in the CNS. Serotonin, dopamine, and glutamate receptors appear to be involved to some extent.
Clinical Findings and Diagnosis of LSD Toxicosis
Common clinical signs of LSD toxicosis include excitation or depression, disorientation, vocalization, mydriasis, and behavioral changes ranging from odd postural stances to pawing and licking at invisible objects. Diagnosis is based on a history of ingestion and on clinical signs.
Currently, no human POC urine test kits include LSD; the reader is encouraged to investigate this more fully, because the resurgence of human LSD use could mean that new POC tests become available.
Analysis of serum or urine submitted to a diagnostics laboratory that uses GC/MS and LC/MS will assist the diagnosis.
Treatment of LSD Toxicosis
The treatment of LSD toxicosis is primarily supportive. Induction of emesis and the use of activated charcoal is not recommended, because of the rapid onset of clinical signs. The duration of signs is unknown and might depend on the amount ingested. There is no antidote.
Diazepam(0.5–1 mg/kg, IV) or midazolam (0.1–0.3 mg/kg, IV or IM) might be useful to treat stimulant reactions or abnormal behaviors.
Cyproheptadine (in cats: 2–4 mg/cat, PO or rectal, every 4–6 hours until resolution of clinical signs; in dogs: 1.1 mg/kg, PO or rectal, every 4–6 hours until resolution of clinical signs) can be useful in animals with signs of serotonin syndrome (15).
Restraint of a patient with LSD toxicosis should be minimized to prevent rhabdomyolysis and hyperthermia, and intoxicated patients should be kept in a dark, calm environment and monitored until clinical signs have abated.
Toxicoses From Methylenedioxymethamphetamine (MDMA), or Ecstasy
Methylenedioxymethamphetamine (MDMA), or ecstasy, is a semisynthetic stimulant designer drug with psychoactive, hallucinogenic, and amphetamine-like properties. Street names include Adam, bibs, blue, love drug, E, X, XTC, and many others. Common adulterants include caffeine, synthetic cathinones, hallucinogens, amphetamine, ketamine, and others (28, 29).
Typically, ecstasy is sold on the street as a brightly colored tablet containing 50–150 mg MDMA; capsules and powdered forms are less common.
MDMA toxicosis is not common in household pets and most often is due to accidental ingestion of a product present in the home.
Pharmacokinetics and Mechanisms of MDMA (Ecstasy) Toxicity
Little is known about the pharmacokinetics of MDMA in domestic animals. In humans, clinical signs of MDMA toxicosis develop within 30 minutes to 2 hours after ingestion, and the half-life of MDMA is 7.6–8.7 hours.
Dogs receiving an MDMA dose of 3 mg/kg, PO, developed clinical signs within 45 minutes, and signs lasted 6–8 hours (30). A dog that received 15 mg/kg, PO, died (31).
MDMA affects the release of serotonin, dopamine, and norepinephrine, and it binds to the serotonin transporter responsible for removing serotonin from the synapse. Hallucinogenic effects might be associated with the increased levels of serotonin.
Clinical Findings and Diagnosis of MDMA (Ecstasy) Toxicosis
Clinical signs of MDMA toxicosis appear to be dose related and similar to those associated with amphetamine toxicosis.
Dogs receiving 3 mg/kg, PO, of MDMA showed hyperactivity and mydriasis; dogs receiving 9 mg/kg, PO, developed tachypnea, circling behavior, and hypersalivation; and dogs receiving 15 mg/kg, PO, became aggressive with vocalization, front-limb paralysis, seizures, and death (30).
In general, clinical signs of MDMA toxicosis consist of sympathomimetic effects (CNS excitation, agitation, hyperactivity, pacing, hyperthermia, tachycardia, hypertension, seizures [as with amphetamines]), sedation, or signs thought to be related to hallucinations (vocalization, disorientation, muscle rigidity).
Treatment of MDMA (Ecstasy) Toxicosis
Treatment for MDMA toxicosis is similar to that for amphetamine toxicosis.
Toxicoses From Opioids
The term opiate initially referred to all naturally occurring alkaloids obtained from the sap of Papaver somniferum, the opium poppy. The sap contains morphine, codeine, and several other alkaloids.
Currently, the term opioid refers to all drugs, natural or synthetic, that have morphinelike actions or actions mediated through opioid receptors. Some of the used opioids widely used in human and veterinary medicine that are often present in the home environment include codeine, buprenorphine, butorphanol, fentanyl, hydrocodone, hydromorphone, loperamide (antidiarrheal), morphine, and tramadol.
Opioids are used primarily for analgesia, for sedation before surgery, and, less often, for cough suppression or as an antidiarrheal agent.
Recreationally used opioids include oxymorphone, oxycodone, heroin, methadone, propoxyphene, and tincture of opium (paregoric). Many of these drugs are combined with other medications, such as acetaminophen, ibuprofen, and chlorpheniramine, complicating diagnosis and treatment of associated toxicoses.
Fentanyl patches, especially discarded ones, are a potential source of opioid intoxication, particularly in dogs that routinely ingest items found in the trash.
Heroin abuse continues to rise in the US, and exposure in dogs that are maliciously used as “body packers” and in dogs that detect drugs is well reported.
Pharmacokinetics and Mechanisms of Opioid Toxicity
Opioids are generally well absorbed after oral, rectal, or parenteral administration. Some lipophilic opioids are also absorbed through nasal, buccal, or respiratory routes (heroin, fentanyl, buprenorphine), or via transdermal routes (fentanyl). Distribution depends on the specific opioid and the physical characteristic.
Most opioids are rapidly cleared from the blood and stored in the kidney, liver, brain, lung, spleen, skeletal muscle, and placental tissue. Lipophilic opioids like heroin readily cross the blood-brain barrier.
In general, the bioavailability of opioids administered orally is lower than with parenteral administration because of a first-pass effect in the liver. Opioids generally undergo hepatic metabolism with some form of conjugation, hydrolysis, oxidation, dealkylation, or glucuronidation. Because cats are deficient in glucuronidase, the half-life of some opioids in cats might be prolonged. Most opioid metabolites are excreted through the kidneys.
The toxicity of opioids in animals is highly variable. In dogs, the lethal dose of morphine is 100–200 mg/kg, SC or IV. In cats, the lethal dose of morphine is 40 mg/kg, SC.
The reported minimum lethal dose of heroin in dogs is 25 mg/kg, SC; in cats, 20 mg/kg, PO (32, 33). However, clinical signs occur at far lower doses (sedation and respiratory depression at 0.2 mg/kg, IV; respiratory difficulty and aggression at 0.58 mg/kg, SC) (34).
The effects of opioids are due to their interaction with major opioid receptors in the central and autonomic nervous systems, as well as in the heart, kidney, adrenal glands, GI tract, pancreas, lymphocytes, vas deferens, and fat cells. Opioids can be agonists, partial agonists, or antagonists at these receptors.
Clinical Findings and Diagnosis of Opioid Toxicoses
The primary effects of opioid toxicoses depend on the specific opioid and the species of animal. Clinical signs are generally related to the CNS, respiratory, cardiovascular, and GI systems.
Dogs generally show early excitation and agitation followed by CNS depression, drowsiness, ataxia, vomiting, seizures, miosis, coma, respiratory depression, hypotension, constipation/defecation, and death. Some animals, especially cats, horses, cattle, and swine, show CNS excitation instead of CNS depression.
Diagnosis of opioid toxicosis is based on a history of exposure and clinical signs. Use of a human POC multidrug urine testing kit might help determine the exposure to some opioids.
Treatment of Opioid Toxicoses
The duration of an opioid's action is drug and species dependent, and clinical signs last longer with extended-release products. Emesis is generally not recommended for products that are rapid acting; however, it might be necessary in animals that have swallowed a fentanyl patch.
The treatment of opioid toxicoses is primarily supportive. If severe, clinical signs can be reversed by naloxone, an opioid antagonist, and the suggested antidote.
The recommended canine and feline naloxone dose (0.01–0.04 mg/kg, IV [1–2 mg/25 kg], as needed; or 0.04–0.16 mg/kg, IM or intranasal [2–4 mg/25 kg], as needed) (35, 36, 37, 38), might not be effective in some severely intoxicated patients, and a dose of 0.1–0.2 mg/kg, IM, might be needed to control clinical signs (39).
A human naloxone 4-mg inhaler can be used for animals; however, results have been inconsistent, and patients should be monitored closely for the recurrence of signs.
Administration of naloxone should be repeated as needed (often hourly), because its duration of action might be shorter than that of the opioid being treated. Patients should be closely monitored for respiratory depression, and mechanical ventilatory support should be provided if needed.
Agitation, aggression, and excitation can be treated with diazepam (0.5–1 mg/kg, IV), midazolam (0.1–0.3 mg/kg, IV or IM), or other benzodiazepines; however, benzodiazepines should not be used in animals with cardiovascular and respiratory compromise, because benzodiazepines can worsen respiratory depression or cause paradoxical CNS excitation.
The dysphoria or serotonin-like syndrome (vocalization, disorientation, muscle rigidity, agitation) that is induced by some opioids (tramadol, dextromethorphan, methadone, and meperidine) (40) is best treated with cyproheptadine (in dogs: 1.1 mg/kg, PO or per rectum, every 4–6 hours until resolution of clinical signs; in cats: 2–4 mg/cat, PO or per rectum, every 4–6 hours until resolution of clinical signs) (4).
Further treatment and monitoring is per the clinician's judgment.
Toxicoses From Phencyclidine (PCP)
Phencyclidine (PCP) is a Schedule II synthetic, lipophilic, dissociative drug with no current human or veterinary application.
PCP was developed in the 1950s as an IV anesthetic for humans. However, its use was discontinued in 1965 because of the postoperative delirium, confusion, and hallucinations it induced. It returned as a veterinary drug in 1967 but was discontinued after reports of human abuse.
PCP is currently manufactured in clandestine laboratories as a crystal, liquid, powder, or tablet. Street names include angel dust, lovely, rocket fuel, whack, and zombie dust. When combined with marijuana for smoking, it is referred to as a fry stick, killer joint, or supergrass.
Pharmacokinetics and Mechanisms of PCP Toxicity
When inhaled, PCP is absorbed through the respiratory system; when ingested, it is absorbed through the GI tract. PCP readily crosses the blood-brain barrier and, in addition to being found in the CNS, is well distributed to adipose tissue.
The metabolism of PCP is hepatic and species specific. Dogs excrete 32% of the parent compound in urine; cats excrete 89% of the parent compound.
The mechanism of action of PCP is poorly understood. PCP is a noncompetitive antagonist at the N-methyl-d-aspartate (NMDA) subtype of the glutamate receptor, which might be the source of schizophrenic signs. Sympathomimetic effects might be due to decreased reuptake of norepinephrine, dopamine, and serotonin. Other undefined mechanisms are likely at work as well.
Clinical Findings and Diagnosis of PCP Toxicosis
Clinical signs of PCP toxicosis in humans are reported to occur within 30–60 minutes and last 24–48 hours. Dogs show marked clinical signs with 2.5–10 mg/kg PO or 1 mg/kg IV. Cats show clinical signs with 1.1–12 mg/kg PO (11, 15, 41).
Clinical signs of PCP toxicosis in dogs depend on the dose; depression occurs at lower doses, stimulation at higher doses.
Psychomotor signs of PCP toxicosis in dogs include blank staring, odd facial expressions, jaw snapping, and head weaving. Other reported signs include nystagmus, opisthotonos, muscle rigidity, hyperthermia, incoordination, loss of motor function, seizures, and death from respiratory failure. Tachycardia, hypertension, and dysrhythmias have been reported in humans.
Diagnosis of PCP toxicosis is based on history and clinical signs. Some human POC urine kits do not include PCP in the testing milieu; the label should be examined closely before use to make sure it is included.
Treatment of PCP Toxicosis
Induction of emesis is not recommended as a treatment for PCP toxicosis, because of the drug's rapid onset of action. The duration of action is unknown; however, human cases suggest it could be 48 hours or longer. There is no antidote.
Because PCP is recirculated within the liver and intestine, a dose of activated charcoalwith a cathartic (AC+C), followed by two additional doses of activated charcoal without a cathartic, should be administered every 8 hours, to increase excretion of the drug through the GI tract. Care should be taken to monitor for hypernatremia. Further treatment is supportive.
Diazepam (0.5 mg/kg, IV, or 1 mg/kg per rectum) (15), midazolam (0.1–0.3 mg/kg, IV or IM) (15, 42), or other agents are recommended as needed to treat agitation. Methocarbamol (55–220 mg/kg, IV, given slowly to effect, with infusion rate not to exceed 2 mL/min) can be administered to treat tremors (6). Further care includes cooling measures as needed, and providing a dark, quiet environment without stimulation until clinical signs abate and the patient is neurologically sound.
For More Information
Also see pet owner content regarding poisonings from illicit and abused drugs.
References
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