Phencyclidine, or PCP [1-(1-phenylcyclohexyl)-piperidine], is an arylcyclohexylamine dissociative anesthetic agent with stimulant properties. It was previously marketed for veterinary use and became popular as an inexpensive street drug in the late 1960s. PCP is most commonly smoked but may also be snorted, ingested, or injected. It is frequently substituted for or added to psychoactive drugs such as marijuana and, rarely, mescaline or LSD. PCP is known by a variety of street names, including “peace pill,” “angel dust,” and “animal tranquilizer.” “Sherms” is slang for cigarettes laced with PCP, and a “KJ” is a marijuana cigarette laced with PCP. Various structural analogs of PCP have been synthesized, including PCC (1-piperidonocyclohexanecarbinol), PCE (eticyclidine; 1-phenyl-cyclohexylethylamine), PHP (rolicyclidine; phenylcyclohexylpyrrolidine), and TCP [tenocyclidine; 1-(1-cyclohexyl) piperidine]. Newer analogs such as 3- and 4-methoxy-PCP, 3- and 4-methoxy-PCE, and 3- and 4-hydroxymethyl-PCP have entered drug markets disguised as “research chemicals.”

Ketamine [2-(2-chlorophenyl)-2-(methylamino)cyclohexanone] shares many structural, pharmacologic, and clinical characteristics with PCP. Although currently used as an anesthetic agent and for procedural sedation, ketamine is a popular drug of abuse owing to its dissociative, analgesic, and hallucinogenic properties. It was first used as a street drug in the 1970s and gained popularity in the club scene of the 1990s. Street names for ketamine include “K,” “special K,” “vitamin K,” and “jet.” A severe ketamine intoxication is referred to as “falling into the K-hole.” Methoxetamine [MXE; 2-(3-methoxyphenyl)-2-(amino)cyclohexanone] is a structural analog of ketamine that may be associated with worse side effects of cerebellar ataxia and mood disturbances. Additional ketamine analogs include 2-methoxy-ketamine, deschloroketamine, and fluoroketamine.

1. PCP, ketamine, and their analogs are dissociative anesthetics that produce generalized loss of pain perception with little or no depression of airway reflexes or ventilation. Psychotropic effects are primarily mediated through N-methyl-D-aspartate (NMDA) receptor antagonism. They also inhibit reuptake of dopamine, norepinephrine, and serotonin and block potassium conductance in the brain. PCP stimulates the sigma-opioid receptor, and ketamine stimulates the mu-, delta-, sigma-, and kappa-opioid receptors. PCP also binds to a site within the L-type calcium channel, thus attenuating the influx of calcium when excitatory neurotransmitters bind to this receptor.
2. Pharmacokinetics
   1. PCP is absorbed rapidly by inhalation or ingestion. It is highly lipophilic and has a large volume of distribution of about 6 L/kg. The duration of clinical effects after an overdose is highly variable and ranges from 11 to 14 hours in one report to 1-4 days in another. PCP is eliminated mainly by hepatic metabolism, although renal and gastric excretion accounts for a small fraction and is pH-dependent.
   2. Ketamine is well absorbed after snorting and injection and poorly with oral and rectal ingestion. Effect onset occurs 30 seconds to 30 minutes after use and lasts up to 3 hours, depending on the route of administration. It is metabolized by the liver. The kidney is an important route of elimination for norketamine, the active metabolite of ketamine. The volume of distribution of ketamine is approximately 2-4 L/kg.
   3. Methoxetamine effects occur 30-90 minutes after use and last 5-7 hours.

1. PCP. In tablet form, the usual street dose is 1-6 mg, which results in hallucinations, euphoria, and disinhibition. Ingestion of 6-10 mg causes toxic psychosis and signs of sympathomimetic stimulation. Acute ingestion of 150-200 mg has resulted in death. Smoking PCP has a rapid onset of effects and may be an easier route for users to titrate to the desired level of intoxication.
2. Ketamine. Usual therapeutic anesthetic doses are 1-2 mg/kg IV or 4-10 mg/kg IM (see ketamine). Recreational doses range from 10 to 250 mg nasally, 40 to 450 mg orally or rectally, and 10 to 100 mg IM.

Clinical effects may be seen within minutes of smoking PCP and can last 24 hours or longer, depending on the dose. Because users of PCP and ketamine may have been using many other drugs simultaneously (eg, cocaine, marijuana, alcohol, methamphetamine), the initial presentation may be difficult to discern from other toxidromes. Although the clinical effects of PCP and ketamine are similar, reports of ketamine causing similar degrees of agitation and violent behavior are lacking.

1. Mild intoxication causes lethargy, euphoria, hallucinations, and occasionally bizarre or violent behavior. Hypersalivation and lacrimation may occur. Patients may abruptly swing between quiet catatonia and loud or agitated behavior. Vertical and horizontal nystagmus may be prominent with PCP intoxication.
2. Severe intoxication produces signs of adrenergic hyperactivity, including hypertension, tachycardia, diaphoresis, hyperthermia, rigidity, localized dystonic reactions, pulmonary edema, convulsions, and coma. The pupils are sometimes paradoxically small. Death from PCP may occur as a result of self-destructive behavior or as a complication of hyperthermia and subsequent multiple-organ system dysfunction (eg, rhabdomyolysis, renal failure, coagulopathy, or brain damage). Sudden death, probably from ventricular arrhythmia, has occurred during restraint for agitated delirium (such as in police custody). Acute methoxetamine intoxication has resulted in cerebellar ataxia.
3. Chronic ketamine abuse may cause dependence and tolerance, memory impairment, impaired concentration, and depression. It has been linked to urinary problems from bladder wall fibrosis. Animal studies have shown similar chronic bladder effects from methoxetamine.

Is suggested by the presence of rapidly fluctuating behavior, vertical nystagmus, and sympathomimetic signs.

1. Specific levels
   1. Specific serum PCP and ketamine levels are not readily available and do not correlate reliably with the degree of intoxication. PCP levels of 30-100 ng/mL have been associated with toxic psychosis.
   2. Qualitative urine screening for PCP is widely available; however, most PCP immunoassays produce false-positive results to venlafaxine, dextromethorphan, diphenhydramine, and many other drugs. PCP analogs may not be detected on routine screening, although they can cross-react in some immunologic assays (see Table I-32,). Ketamine and its analogs are not detected on routine urine drug screening.
2. Other useful laboratory studies include electrolytes, glucose, BUN, creatinine, creatine kinase (CK), and urinalysis dipstick for occult blood (positive with myoglobinuria).

1. Emergency and supportive measures
   1. Maintain an open airway and assist ventilation if necessary.
   2. Treat coma, seizures, hypertension, hyperthermia, and rhabdomyolysis if they occur.
   3. Agitated behavior may respond to limiting sensory stimulation but may require sedation with high doses of benzodiazepines (midazolam, lorazepam, or diazepam) and haloperidol or other antipsychotic drugs. In the initial management of an extremely agitated patient, midazolam or haloperidol may be given IM if IV access is absent.
   4. Monitor temperature and other vital signs for a minimum of 6 hours and admit all patients with hyperthermia or other evidence of significant intoxication.
2. Specific drugs and antidotes. There is no specific antidote. Clonidine at a dose of 2.5-5 mcg/kg orally has been used to attenuate the sympathomimetic effects of ketamine seen during anesthesia.
3. Decontamination. No decontamination measures are necessary after snorting, smoking, or injecting PCP or ketamine. For ingestion, administer activated charcoal if conditions are appropriate (see Table I-37,). Gastric lavage is not necessary after small-to-moderate ingestions if activated charcoal can be given promptly.
4. Enhanced elimination. Because of their large volume of distribution, PCP and ketamine are not effectively removed by dialysis, hemoperfusion, or other enhanced removal procedures.
   1. Repeat-dose activated charcoal has not been studied but may marginally increase elimination by adsorbing PCP partitioned into the acidic stomach fluid. Continuous nasogastric suction has also been proposed for removal of gastrically partitioned PCP.
   2. Although urinary acidification increases the urinary concentration of PCP, there is no evidence that this significantly enhances systemic elimination, and it may be dangerous because urinary acidification can aggravate myoglobinuric renal failure.