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PHENCYCLIDINE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Phencyclidine is a potent analgesic and anesthetic. It is no longer prescribed for humans due to its severe adverse effects, but still has veterinary uses. It is a hallucinogenic and drug of abuse. Prevalence of abuse is highly regionalized.

Specific Substances

    1) PCP
    2) 1-(1-phenylcyclohexyl)piperidine
    3) Phenylcyclohexylpiperidine
    4) CI-395
    5) Angel dust
    6) Mist
    7) Hog
    8) Peace pill
    9) Kay Jay
    10) KJ
    11) Crystal Joint
    12) Elephant Tranquilizer
    13) Super Grass
    14) Super Weed
    15) Rocket fuel
    16) Scuffle
    17) Sheets
    18) Space Basing: PCP + Cocaine (Crack)
    19) Surfer
    20) T
    21) D.O.A.
    22) Cyclones
    23) Snorts
    24) Soma
    25) Goon
    26) Horse franks
    27) Green (PCP-impregnated parsley)
    28) Dust
    29) CAS 77-10-1
    30) CAS 956-90-1 (hydrochloride)
    31) SHERMS (TOBACCO LACED WITH PCP)
    32) SPACE BASING (PCP + CRACK COCAINE)
    33) 2-methoxydiphenidine
    1.2.1) MOLECULAR FORMULA
    1) C17-H25-N

Available Forms Sources

    A) FORMS
    1) Phencyclidine (PCP, Sernylan(R)), a general anesthetic in veterinary medicine, was voluntarily withdrawn from the market in 1978. Although structurally similar to the anesthetic ketamine hydrochloride (Ketalar(R)) phencyclidine is not indicated for human use because of its potent psychomimetic properties. It has also been found in a variety of illicitly manufactured hallucinogens alleged to be tetrahydrocannabinol (THC), lysergic acid (LSD), psilocybin and mescaline (HSDB , 2002).
    2) PHP (phenylcyclohexylpyrrolidine) is an analogue of PCP with the same effects. Other PCP analogues include cyclohexamine (PCE), phenylcyclopentylpiperidine (PCPP) and thienylcyclo hexylpiperidine (TCP) (Budd, 1980).
    3) The percentage of phencyclidine found on the illicit market varies greatly. Most have been reported to contain phencyclidine hydrochloride although the free base has also been seen. The percentage of phencyclidine found in street formulations on the west coast was reported in 1976 : Crystal (50% to 100%); Angel dust (88% to 100%); Other names (10% to 30%); Tablet forms (most 5 mg; range from 1 to 6 mg); Joints of leaf mixtures (0.24% to 7.9%; 1 mg PCP/150 mg leaves; Joints range from 100 to 400 mg total weight) (Burns & Lerner, 1976).
    4) "Clickers" or "Primos" are marijuana cigarettes in which PCP has been soaked into the leaves as an aqueous solution or in dilute formaldehyde (Garey et al, 1987).
    5) SPACE BASING: Combined smoking of cocaine (crack) and phencyclidine (Giannini et al, 1987).
    6) 2-METHOXYDIPHENIDINE
    a) 2-Metoxydiphenidine, also known as MXP (or 2-MXP), has been available since 2013 as a research chemical and a purported alternative to the dissociative anesthetics methoxetamine and ketamine. The use of dissociative anesthetics has occurred since the development of PCP. In two fatalities, the cause of death was due 2-methoxydiphenidine based on laboratory confirmation (Elliott et al, 2015).
    7) 3-METHOXY-PHENCYCLIDINE AND 4-METHOXY-PHENCYCLIDINE
    a) In a Swedish (STRIDA project) observational study of patients (n=1243) with exposure to new psychoactive substances (NPS), positive tests for 3-methoxy-phencyclidine (3-MeO-PCP), for 4-methoxy-phencyclidine (4-MeO-PCP), and for both agents were observed in 56, 11, and 8 patients, respectively. Poly-drug use was reported in 52 patients and only 7 patients had exposure to a single agent, 3-MeO-PCP. In the single-substance exposure group, the following clinical effects were reported: hypertension (systolic BP 140 mmHg or higher; n=7), tachycardia (heart rate 100 beats/min or higher; n=5), altered mental status (eg, confusion, disorientation, dissociation, hallucinations; n=4), agitation (n=2), nystagmus (n=2), renal deficiency (n=2), mitotic pupils (n=2), pupils with slow or no response to light (n=1), rhabdomyolysis (n=1), and diaphoresis (n=1). Patients with poly-susbtance exposure developed similar adverse effects, but also had more sympathomimetic effects (eg, agitation [38%], dilated pupils [33%])(Backberg et al, 2015).
    8) ADULTERANTS
    a) Illicit phencyclidine is rarely available as the pure crystalline substance. Liquid products contain solvents used in the manufacturing process, such as benzene, toluene, cyclohexanol, isopropanol, phenol, and ether (Tschirgi, 1990; Shesser et al, 1991).
    b) A common contaminant is PCC, an intermediate in synthesis that releases hydrogen cyanide when smoked or heated; amounts range from 10 to 70%. At the usual recreational doses of 2.5 to 6 mg, acute cyanide toxicity is unlikely (Tschirgi, 1990), however nausea, vomiting, abdominal cramps, cyanosis, and coma have been attributed to PCC (Soine et al, 1979).
    c) Other pharmacologically active adulterants include phenylpropanolamine, benzocaine, procaine, ephedrine, caffeine, ketamine, and piperidine (precursor) (Shesser et al, 1991).
    B) USES
    1) INTENTIONAL MISUSE: Powdered PCP has been mixed with an organic solvent or embalming fluid. Tobacco or marijuana cigarettes are dipped in the fluid and then smoked. Alternatively, marijuana, soaked in the liquid PCP preparation, is made into a cigarette or the PCP laced marijuana is put into a hollowed out cigar for smoking. The cigarette/cigar is smoked dry or still wet for slower burning and perceived enhanced effect. Street names for this form of drug abuse have included: "getting wet", "fry house", and "dipping" (Morocco & Osterhoudt, 2003).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Phencyclidine (PCP, 1-(1-phenylcyclohexyl)-piperidine) is a dissociative anesthetic, and is abused for its hallucinogenic properties. It is related to ketamine, which is widely used as a sedation medication, but ketamine is much less potent than phencyclidine.
    B) TOXICOLOGY: Phencyclidine is thought to stimulate alpha-adrenergic receptors, potentiating the effects and/or inhibition of reuptake of norepinephrine, epinephrine, and serotonin. It is also thought to stimulate opioid receptors and inhibit NMDA receptors. In overdose, acute psychosis and sympathomimetic toxidrome can produce agitated delirium. In large overdoses, patients may progress to coma.
    C) EPIDEMIOLOGY: Exposure to phencyclidine is uncommon. Severe toxicity is rare. Deaths have been reported but are most often due to trauma rather than to direct drug effects.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Mild toxicity results in tachycardia, hypertension, hallucinations, euphoria, and disinhibition. Phencyclidine can also cause mild agitation and acute changes in mood. Nystagmus is often prominent on physical exam.
    2) SEVERE TOXICITY: Severe toxicity can cause psychosis, severe psychomotor agitation and hyperthermia. Rhabdomyolysis, multisystem organ failure, and metabolic acidosis can result from the hyperstimulation. Seizures, followed by coma and death are ultimate CNS outcomes in severe toxicity.
    0.2.20) REPRODUCTIVE
    A) PCP crosses the placenta and may result in neonatal irritability, jitteriness, coarse tremors, nystagmus, and poor feeding.

Laboratory Monitoring

    A) Monitor vital signs and mental status.
    B) Evaluate patient carefully for evidence of trauma.
    C) In symptomatic patients, monitor serum electrolytes, renal function, liver enzymes, CK, and coagulation studies to investigate for complications from prolonged agitation and hyperthermia.
    D) Specific PCP concentrations are not readily available and not useful in managing acute intoxication. They also do not correlate well with level of intoxication/symptoms. Some urine drug screens include PCP as part of their screening, but many do not and false positive results are not uncommon.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment for mild to moderate toxicity includes minimizing external stimulus, and the use of benzodiazepines for agitation. Antipsychotics may be considered in cases of acute psychosis.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) For severe toxicity, including hyperthermia and psychomotor agitation, high-dose benzodiazepines may be required. If symptoms do not improve, sedation, paralysis and intubation may be indicated. For hyperthermia, control agitation and enhance evaporative heat loss by keeping the skin moist and using fans. Ice water immersion can be used in severe cases. Benzodiazepines can be used for seizures; add barbiturates or propofol if seizures persist. Aggressive fluid resuscitation and supportive care should be used in cases of metabolic acidosis, rhabdomyolysis, and multisystem organ failure.
    C) DECONTAMINATION
    1) PREHOSPITAL: Prehospital charcoal is typically not recommended in PCP ingestion because of the risk of abrupt changes in mental status.
    2) HOSPITAL: Gastric lavage is not indicated for PCP ingestion. Activated charcoal can be offered, but should be given to cooperative, awake alert patients. It should be used with caution as mental status can deteriorate. Overall it is not likely to affect the course of PCP intoxication
    D) AIRWAY MANAGEMENT
    1) Definite airway management may be needed if CNS depression develops. It may also be needed if large doses of sedatives are needed to decrease the sympathomimetic stimulation.
    E) ANTIDOTE
    1) None
    F) ENHANCED ELIMINATION PROCEDURE
    1) Dialysis or other methods of enhance elimination are not recommended. Urinary acidification will increase the excretion of PCP but the risk of systemic acidosis exceeds the potential benefit and it is not recommended. Continuous nasogastric suction has also been advocated but may increase the risk of aspiration or injury in a patient with altered mental status, so it should not be used.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: Adults who are asymptomatic after a low dose ingestion can be watched at home provided a sober adult can monitor them.
    2) OBSERVATION CRITERIA: Any symptomatic patient, and a patient with a self-harm ingestion, and any exposed child should be sent to an emergency department for evaluation, treatment and monitoring.
    3) ADMISSION CRITERIA: Patients with severe or prolonged symptoms, or requiring medication treatment should be admitted for further care.
    4) CONSULT CRITERIA: Consult a medical toxicologist or poison center for any large and/or severely symptomatic exposures. Child protective services should be involved for exposed children. Consider referral for substance abuse counselling as appropriate.
    H) PITFALLS
    1) Not aggressively treating psychomotor agitation and hyperthermia. Placing patient in physical restraints for psychomotor agitation without proper sedation. Not investigating other etiologies of altered mental status (such as traumatic head injury or meningitis).
    I) TOXICOKINETICS
    1) Absorption is fast via the typical routes of administration: insufflation or ingestion. It is primarily metabolized by the liver via oxidative hydroxylation, after hepatic metabolism, it is excreted by the kidneys. Half-life is about an hours after small doses but can be very prolonged after large doses (7 hours to more than 50 hours).
    J) DIFFERENTIAL DIAGNOSIS
    1) Other arylcyclohexylamines (eg, ketamine), analogs of PCP, other stimulants (eg, amphetamines/methamphetamines), cocaine, MDMA, hallucinogenics such as LSD, peyote, and anticholinergic agents (eg, Jimson weed)

Range Of Toxicity

    A) TOXICITY: Symptoms are expected at doses of approximately 0.05 to 0.1 mg/kg. A dose of 1 to 5 mg will normally result in euphoria and numbness, resembling ethanol intoxication. Doses of 5 to 10 mg often result in excitation, confusion, ataxia, and dysarthria. Prolonged coma, seizures, and death may result from 20 mg or more. Fatalities are more often related to trauma than to direct drug effects.
    B) Blood levels of 20 to 30 ng/mL may cause excitation and catatonia; 30 to 100 ng/mL may cause coma and myoclonus; above 100 ng/mL may cause seizures and hypotension.

Clinical Effects

Summary Of Exposure

    A) USES: Phencyclidine (PCP, 1-(1-phenylcyclohexyl)-piperidine) is a dissociative anesthetic, and is abused for its hallucinogenic properties. It is related to ketamine, which is widely used as a sedation medication, but ketamine is much less potent than phencyclidine.
    B) TOXICOLOGY: Phencyclidine is thought to stimulate alpha-adrenergic receptors, potentiating the effects and/or inhibition of reuptake of norepinephrine, epinephrine, and serotonin. It is also thought to stimulate opioid receptors and inhibit NMDA receptors. In overdose, acute psychosis and sympathomimetic toxidrome can produce agitated delirium. In large overdoses, patients may progress to coma.
    C) EPIDEMIOLOGY: Exposure to phencyclidine is uncommon. Severe toxicity is rare. Deaths have been reported but are most often due to trauma rather than to direct drug effects.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Mild toxicity results in tachycardia, hypertension, hallucinations, euphoria, and disinhibition. Phencyclidine can also cause mild agitation and acute changes in mood. Nystagmus is often prominent on physical exam.
    2) SEVERE TOXICITY: Severe toxicity can cause psychosis, severe psychomotor agitation and hyperthermia. Rhabdomyolysis, multisystem organ failure, and metabolic acidosis can result from the hyperstimulation. Seizures, followed by coma and death are ultimate CNS outcomes in severe toxicity.

Vital Signs

    3.3.3) TEMPERATURE
    A) HYPERTHERMIA and hypothermia are uncommon (McCarron et al, 1981b).
    1) Fever (39.5 degrees C) was reported in a 42-year-old woman following PCP intoxication (Stein et al, 2005).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) SUMMARY: Horizontal nystagmus is often an initial finding (incidence 57.4%). With increasing severity of intoxication vertical nystagmus, loss of lid and corneal reflexes (often observed as an open-eyed blank stare), then roving "Groucho" eyes with dilated pupils, and finally fixed, dilated pupils occur. Miosis is common in children.
    2) NYSTAGMUS: Present on admission in 57.4%; in mild intoxication appears in response to stimulation and is horizontal. With increasing severity, spontaneous vertical and/or rotary nystagmus occurs. Patients may have 2 or 3 types simultaneously (McCarron et al, 1981b; Stein et al, 2005; Rappolt & Gay, 1979; Grant & Schuman, 1993).
    3) MYDRIASIS occurs with more severe intoxication (incidence 6.2%); initially accompanied by loss of lid and corneal reflexes (often observed as an open-eyed blank stare; incidence 11.7%) and roving "Groucho" eyes, progressing to fixed, dilated pupils in deep intoxication (Stein et al, 2005; Rappolt & Gay, 1979; McCarron et al, 1981b).
    4) MIOSIS is uncommon in adults (incidence 2.1%), but reported in 7 of 33 pediatric exposures (accidental ingestion or passive inhalation) (McCarron et al, 1981b; Karp et al, 1980), and in an adult case involving ingestion of a plastic bag which was believed to contain phencyclidine (Young & Crapo, 1992).
    5) UNCOMMON EFFECTS: Lacrimation, conjunctival hyperemia, and ptosis have been reported (McCarron et al, 1984; (Reynolds, 1982; Fisher & McDonald, 1984).
    6) 3-Me-PCP and 4-Me-PCP: In a Swedish (STRIDA project) observational study of patients (n=1243) with exposure to new psychoactive substances (NPS), positive tests for 3-methoxy-phencyclidine (3-MeO-PCP), for 4-methoxy-phencyclidine (4-MeO-PCP), and for both agents were observed in 56, 11, and 8 patients, respectively. Poly-drug use was reported in 52 patients and only 7 patients had exposure to a single agent, 3-MeO-PCP. In the single-substance exposure group, the following clinical effects were reported: hypertension (systolic BP 140 mmHg or higher; n=7), tachycardia (heart rate 100 beats/min or higher; n=5), altered mental status (eg, confusion, disorientation, dissociation, hallucinations; n=4), agitation (n=2), nystagmus (n=2), renal deficiency (n=2), mitotic pupils (n=2), pupils with slow or no response to light (n=1), rhabdomyolysis (n=1), and diaphoresis (n=1). Patients with poly-susbtance exposure developed similar adverse effects, but also had more sympathomimetic effects (eg, agitation [38%], dilated pupils [33%])(Backberg et al, 2015).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) SALIVA INCREASED
    a) Hypersalivation was reported in 1.7% of cases (McCarron et al, 1981b).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPERTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) INCIDENCE: Hypertension is common (Young & Crapo, 1992), occurring in 57% in one large series (McCarron et al, 1981b).
    b) ONSET: Generally present on admission, but can be delayed. May follow periods of agitation. Delayed hypertensive crisis several days after exposure is usually related to complications, such as seizures, intracerebral hemorrhage, or hemodynamic changes during dialysis (Eastman & Cohen, 1975; McCarron et al, 1981b).
    c) DURATION: Resolves within 4 hours in 62%; remains elevated for 5 to 12 hours in 19%, for 13 to 24 hours in 8%, and more than 24 hours in 11% (McCarron et al, 1981b).
    d) FINDINGS: Isolated systolic hypertension occurs in 25%. Diastolic pressures over 110 mmHg were only found in 3.3% of hypertensive cases; patients with underlying essential hypertension are at higher risk for significant elevations. Usually resolves spontaneously without treatment (McCarron et al, 1981b).
    e) 3-Me-PCP and 4-Me-PCP: In a Swedish (STRIDA project) observational study of patients (n=1243) with exposure to new psychoactive substances (NPS), positive tests for 3-methoxy-phencyclidine (3-MeO-PCP), for 4-methoxy-phencyclidine (4-MeO-PCP), and for both agents were observed in 56, 11, and 8 patients, respectively. Poly-drug use was reported in 52 patients and only 7 patients had exposure to a single agent, 3-MeO-PCP. In the single-substance exposure group, the following clinical effects were reported: hypertension (systolic BP 140 mmHg or higher; n=7), tachycardia (heart rate 100 beats/min or higher; n=5), altered mental status (eg, confusion, disorientation, dissociation, hallucinations; n=4), agitation (n=2), nystagmus (n=2), renal deficiency (n=2), mitotic pupils (n=2), pupils with slow or no response to light (n=1), rhabdomyolysis (n=1), and diaphoresis (n=1). Patients with poly-susbtance exposure developed similar adverse effects, but also had more sympathomimetic effects (eg, agitation [38%], dilated pupils [33%])(Backberg et al, 2015).
    B) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: Mild tachycardia, up to 140 beats/minute, was found in 30% of cases in one large series (McCarron et al, 1981b).
    b) 3-Me-PCP and 4-Me-PCP: In a Swedish (STRIDA project) observational study of patients (n=1243) with exposure to new psychoactive substances (NPS), positive tests for 3-methoxy-phencyclidine (3-MeO-PCP), for 4-methoxy-phencyclidine (4-MeO-PCP), and for both agents were observed in 56, 11, and 8 patients, respectively. Poly-drug use was reported in 52 patients and only 7 patients had exposure to a single agent, 3-MeO-PCP. In the single-substance exposure group, the following clinical effects were reported: hypertension (systolic BP 140 mmHg or higher; n=7), tachycardia (heart rate 100 beats/min or higher; n=5), altered mental status (eg, confusion, disorientation, dissociation, hallucinations; n=4), agitation (n=2), nystagmus (n=2), renal deficiency (n=2), mitotic pupils (n=2), pupils with slow or no response to light (n=1), rhabdomyolysis (n=1), and diaphoresis (n=1). Patients with poly-susbtance exposure developed similar adverse effects, but also had more sympathomimetic effects (eg, agitation [38%], dilated pupils [33%])(Backberg et al, 2015).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) APNEA
    1) WITH POISONING/EXPOSURE
    a) Apnea occurs in about 2.8% of cases, often preceding or following a grand mal seizure. Respiratory arrest occurs in about 10% of apneic patients (McCarron et al, 1981b). Mechanical ventilation is rarely required for several hours or days (Aronow & Done, 1978).
    B) STRIDOR
    1) WITH POISONING/EXPOSURE
    a) Stridor may be noted during severe muscle contractions and seizures (Aronow & Done, 1978).
    C) BRONCHOSPASM
    1) WITH POISONING/EXPOSURE
    a) RARE EFFECTS: Tachypnea (4%), bronchospasm after smoking or sniffing (2.1%), and bronchorrhea (0.6%) have been reported (McCarron et al, 1981b).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH POISONING/EXPOSURE
    a) COMMON FINDINGS: Acute brain syndrome (disorientation, confusion, lack of judgment, inappropriate affect, recent memory loss) is the most common pattern (incidence 37%). Behavior is often violent, agitated, bizarre, or delusional; may display catalepsy or posturing.
    b) UNCOMMON FINDINGS: Coma (11%), lethargy (7%), generalized rigidity (5%), generalized seizures (3% in adults, up to 21% in children), localized dystonias (2%), dyskinesias (2%), athetosis (1%), and nudism (3%) may occur.
    c) ONSET: Typically, acute brain syndrome develops suddenly, followed sometimes by coma; coma can also occur abruptly. Symptoms tend to wax and wane, alternating between lethargic and excited states.
    d) DURATION: Coma has lasted for less than 30 minutes to 7 days. Acute brain syndrome, catatonia, and toxic psychosis may appear on emergence from coma and last several hours to several days or months (for psychosis).
    e) 3-Me-PCP and 4-Me-PCP: In a Swedish (STRIDA project) observational study of patients (n=1243) with exposure to new psychoactive substances (NPS), positive tests for 3-methoxy-phencyclidine (3-MeO-PCP), for 4-methoxy-phencyclidine (4-MeO-PCP), and for both agents were observed in 56, 11, and 8 patients, respectively. Poly-drug use was reported in 52 patients and only 7 patients had exposure to a single agent, 3-MeO-PCP. In the single-substance exposure group, the following clinical effects were reported: hypertension (systolic BP 140 mmHg or higher; n=7), tachycardia (heart rate 100 beats/min or higher; n=5), altered mental status (eg, confusion, disorientation, dissociation, hallucinations; n=4), agitation (n=2), nystagmus (n=2), renal deficiency (n=2), mitotic pupils (n=2), pupils with slow or no response to light (n=1), rhabdomyolysis (n=1), and diaphoresis (n=1). Patients with poly-susbtance exposure developed similar adverse effects, but also had more sympathomimetic effects (eg, agitation [38%], dilated pupils [33%])(Backberg et al, 2015).
    B) TOXIC ENCEPHALOPATHY
    1) WITH POISONING/EXPOSURE
    a) INCIDENCE: 36.9% (McCarron et al, 1981b).
    b) FINDINGS: The most common pattern of toxicity. Characterized by disorientation, confusion, lack of judgment, inappropriate or labile affect, recent memory loss, and anxiety; often with slurred speech and ataxia. Frequently leads to traumatic injury (McCarron et al, 1981a).
    c) ONSET: May occur initially or on emergence from coma (McCarron et al, 1981a).
    d) DURATION: Often lasts only a few hours, but can remain symptomatic for up to 21 days (McCarron et al, 1981a).
    e) In a series of 59 patients presenting to the ED after using illy (active component PCP) 25% were oriented and conversed normally, 39% were oriented and conversed but were slow to respond, 24% were disoriented and used inappropriate words, 10% were unresponsive and one presented in cardiac arrest (D'Onofrio et al, 2006). Of these same patients 47% were cooperative, 28% were combative, and 17% were irritable. Physical restraints were used in 90% and chemical restraints in 21% due to risk of harm because of altered mental status.
    C) COMA
    1) WITH POISONING/EXPOSURE
    a) INCIDENCE: 10.6% (McCarron et al, 1981b).
    b) FINDINGS: Coma has been classified as mild, moderate, or severe, based on duration (McCarron et al, 1981a):
    1) MILD: Usually lasts for 30 minutes or less, up to 2 hours; not associated with apnea unless multiple ingestion. Accounts for 43% of comas.
    2) MODERATE: Lasts 2 to 24 hours; associated with more vital sign and autonomic disturbances. Accounts for 38% of comas.
    3) SEVERE: Lasts more than 24 hours (up to 146 hours); associated with higher incidence of aspiration pneumonia and rhabdomyolysis.
    c) Prolonged coma (24 days) was reported in a 29-year-old man with prolonged intestinal absorption secondary to swallowing a plastic bag containing phencyclidine (Young & Crapo, 1992).
    D) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Seizures occur in 3.1% overall; 15% in comatose patients. Physical findings suggesting grand mal seizures without epileptiform activity by EEG has been reported (Young & Crapo, 1992). Status epilepticus is uncommon (McCarron et al, 1981b; Jackson, 1989)
    E) DYSTONIA
    1) WITH POISONING/EXPOSURE
    a) INCIDENCE: Generalized dystonia occurs in about 5%; localized dystonia in 2.4% (McCarron et al, 1981b).
    b) FINDINGS: Generalized dystonia is associated with rigidity of all extremities or body stiffness, jerky/thrashing movements, coarse tremor, or twitching. Localized dystonia may manifest as trismus, oculogyric crisis, torticollis, tongue spasm, opisthotonos, or rigidity of one or more extremities (McCarron et al, 1981b).
    F) DYSKINESIA
    1) WITH POISONING/EXPOSURE
    a) Dyskinesia may occur alone or in combination with dystonia. Signs include facial grimacing, circumoral muscle twitching, lip smacking, or chewing movements. Occurs in about 1.7% and is usually very transient (McCarron et al, 1981b).
    G) INTRACRANIAL HEMORRHAGE
    1) WITH POISONING/EXPOSURE
    a) Although extremely rare, massive fatal intracranial hemorrhage (possibly due to the acute hypertensive effect of PCP) in the absence of trauma has been reported in one patient (Bessen, 1982). Noncardiogenic pulmonary edema occurred at the time of the bleed.
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) ENCEPHALOPATHY
    a) In a rat model, 10 mg to 50 mg PCP was toxic to Purkinje cells in the rodent cerebellum (Nakki et al, 1995).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) WITH POISONING/EXPOSURE
    a) Vomiting may occur (Reynolds, 1982).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ACUTE RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) Rhabdomyolysis (incidence 2.2%), myoglobinuria, acute uric acid nephropathy and associated acute renal failure have been reported following PCP intoxication (Barton et al, 1980; Patel et al, 1979; Cogen et al, 1978; Patel et al, 1980; Patel, 1982).
    b) CASE REPORT: Acute renal failure (serum creatinine 4.06 mg/dL}, severe hyperkalemia (9.35 mEq/L), and rhabdomyolysis (creatine phosphokinase level greater than 5,000 units/L) was reported in a 42-year-old woman who had prolonged coma following PCP and ethanol intoxication. Despite aggressive supportive care, the patient continued to deteriorate clinically and subsequently died, due to multi-organ failure, approximately 3 days post-admission (Stein et al, 2005).
    B) RETENTION OF URINE
    1) WITH POISONING/EXPOSURE
    a) Urinary retention has been reported rarely (McCarron et al, 1981b).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) WITH POISONING/EXPOSURE
    a) Mild metabolic acidosis may occur (Young & Crapo, 1992).
    b) CASE REPORT: Severe metabolic and respiratory acidosis (pH 6.94; HCO3 10.6 mEq/L; pCO2 76.2 mmHg; pO2 76.8 mmHg; base excess 18.9 mEq/L) were reported in a 42-year-old woman who developed rhabdomyolysis, and multi system organ failure after prolonged coma from PCP and ethanol (Stein et al, 2005).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) COAG./BLEEDING TESTS ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: The INR was elevated (2.9 {normal 0.9 to 1.3}) and the clotting factor V levels were 4% (normal 50% to 150%) in a 42-year-old woman who developed multi system organ failure following prolonged coma from PCP and ethanol intoxication (Stein et al, 2005).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) EXCESSIVE SWEATING
    1) WITH POISONING/EXPOSURE
    a) Diaphoresis is uncommon (McCarron et al, 1981b).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) INCREASED MUSCLE TONE
    1) WITH POISONING/EXPOSURE
    a) Hyperreflexia, increased muscle tone, and excessive strength have been reported (Aronow et al, 1980; Morgan & Solomon, 1978).
    B) RHABDOMYOLYSIS
    1) WITH POISONING/EXPOSURE
    a) Rhabdomyolysis may develop in patients with prolonged agitation, coma, or seizures (Young & Crapo, 1992).
    b) CASE REPORT: Rhabdomyolysis (CPK greater than 5,000 units/L) with associated compartment syndrome of the right arm, necessitating fasciotomy, was reported in a 42-year-old woman who had prolonged coma following PCP and ethanol intoxication (Stein et al, 2005).
    c) 3-Me-PCP and 4-Me-PCP: In a Swedish (STRIDA project) observational study of patients (n=1243) with exposure to new psychoactive substances (NPS), positive tests for 3-methoxy-phencyclidine (3-MeO-PCP), for 4-methoxy-phencyclidine (4-MeO-PCP), and for both agents were observed in 56, 11, and 8 patients, respectively. Poly-drug use was reported in 52 patients and only 7 patients had exposure to a single agent, 3-MeO-PCP. In the single-substance exposure group, the following clinical effects were reported: hypertension (systolic BP 140 mmHg or higher; n=7), tachycardia (heart rate 100 beats/min or higher; n=5), altered mental status (eg, confusion, disorientation, dissociation, hallucinations; n=4), agitation (n=2), nystagmus (n=2), renal deficiency (n=2), mitotic pupils (n=2), pupils with slow or no response to light (n=1), rhabdomyolysis (n=1), and diaphoresis (n=1). Patients with poly-susbtance exposure developed similar adverse effects, but also had more sympathomimetic effects (eg, agitation [38%], dilated pupils [33%])(Backberg et al, 2015).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) HYPOGLYCEMIA
    1) WITH POISONING/EXPOSURE
    a) Hypoglycemia frequently reported (incidence 22%) (McCarron et al, 1981b).
    b) Persistent hypoglycemia (17 mg/dL) was reported in a 42-year-old woman who developed multi organ system failure after prolonged coma following PCP and ethanol intoxication (Stein et al, 2005).

Reproductive

    3.20.1) SUMMARY
    A) PCP crosses the placenta and may result in neonatal irritability, jitteriness, coarse tremors, nystagmus, and poor feeding.
    3.20.3) EFFECTS IN PREGNANCY
    A) PLACENTAL BARRIER
    1) PCP crosses the placenta. Neonatal irritability, jitteriness, coarse tremors (incidence 95%), nystagmus, poor feeding, poor attention, hypertonia (incidence 62%), depressed neonatal reflexes, abnormal attachment behavior (incidence 17%), continuous crying, and possibly anatomic abnormalities may occur (Golden et al, 1982; Ahmad, 1987; Wachsman et al, 1989; Tabor et al, 1990; Briggs et al, 1998).
    a) Newborns with PCP-positive cord levels did not differ from newborns with PCP-negative cord levels in neonatal weight, Apgar scores, and neonatal complications (Lipton, 1983; Strauss et al, 1981).
    b) A majority of newborns with PCP positive cord levels were of mothers with PCP negative maternal blood samples and this could indicate maternal exposure weeks before delivery (Lipton, 1983) Kaufman, 1983).
    B) PREGNANCY CATEGORY
    PHENCYCLIDINEX
    Reference: Briggs et al, 1998
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Phencyclidine appears in human milk, and animal studies suggest that it may be concentrated in milk (Nicholas, 1982).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS77-10-1 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and mental status.
    B) Evaluate patient carefully for evidence of trauma.
    C) In symptomatic patients, monitor serum electrolytes, renal function, liver enzymes, CK, and coagulation studies to investigate for complications from prolonged agitation and hyperthermia.
    D) Specific PCP concentrations are not readily available and not useful in managing acute intoxication. They also do not correlate well with level of intoxication/symptoms. Some urine drug screens include PCP as part of their screening, but many do not and false positive results are not uncommon.
    4.1.2) SERUM/BLOOD
    A) ACID/BASE
    1) Monitor blood gases.
    B) BLOOD/SERUM CHEMISTRY
    1) In symptomatic patients, monitor serum electrolytes, renal function, liver enzymes, CK, and coagulation studies to investigate for complications from prolonged agitation and hyperthermia.
    4.1.3) URINE
    A) SPECIFIC AGENT
    1) Urinary excretion of PCP is pH dependent. Urine PCP level may be undetectable in patients with alkaline urine. A urine pH should always be obtained along with the urine PCP level.
    2) NIDA guidelines stipulate a cutoff for PCP in urine of 25 ng/mL.
    B) ASSAY INTERFERENCE
    1) False positives on urine screening tests may occur, with potentially adverse medico-legal consequences. One case report attributes a false positive urine PCP screen to dextromethorphan (Rogowski & Krenzelok, 1997).
    2) In a retrospective study, the frequency of false-positive urine screens for PCP was evaluated. During a 4-year period, 491 (1.4%) of 33,972 urine drug screens were positive for PCP; 391 cases were confirmed positive for PCP by gas chromatography-mass spectrometry (GC-MS) and 88 failed to confirm. False-positive urine screens for PCP were significantly associated with the use of tramadol, dextromethorphan, alprazolam, clonazepam, and carvedilol. Although diphenhydramine was frequently associated with false-positive screens for PCP, it did not reach statistical significance (Rengarajan & Mullins, 2013).
    3) In one study, 24 (45%) of 53 positive PCP urine drug immunoassays were confirmed to be true positives. Interfering substances were found in only 6 (21%; dextromethorphan [n=3], tramadol [n=2], diphenhydramine and dextromethorphan combination [n=1]) of the false positive samples (Castelli et al, 2015).
    4) DEXTROMETHORPHAN: One study reported false positive phencyclidine test results with HPLC-based urine drug screens following dextromethorphan intoxication (Budai & Iskandar, 2002). False positive phencyclidine results have also been reported with immune-based assays. GC/MS does not yield false positive results for PCP.
    5) KETAMINE: A urine tox screen was falsely positive for phencyclidine (PCP) several days after intramuscular administration of ketamine. Confirmatory analysis via gas chromatography-mass spectrometry (GC-MS) came back negative for PCP, but this laboratory method did identify ketamine metabolites (Shannon, 1998). Ketamine and phencyclidine, structurally-related chemicals, and their metabolites can be excreted in the urine for several days which may have been the reason that the patient's urine tox screen came back positive. The authors recommend that a positive drug screen should be confirmed with a GC-MS analysis.
    6) LAMOTRIGINE: In 2 case reports, lamotrigine produced false positive results for phencyclidine (PCP) on Bio-Rad Tox rapid urine tests (Geraci et al, 2010).
    7) TRAMADOL: Tramadol and its metabolites can produce a false-positive Emit II Plus phencyclidine (PCP) test result. In 2 cases (an adult and child) of tramadol overdose, both developed a false-positive result for phencyclidine using the Emit II Plus Drugs-of-Abuse Assay. Follow-up with a comprehensive gas chromatography/mass spectrometry qualitative urine drug screen demonstrated a large peak of tramadol in both cases (King et al, 2013).
    8) VENLAFAXINE: Venlafaxine in high concentrations may give false positive results for phencyclidine on the Abbot AxSYM fluorescent polarized immunoassay (Bond et al, 2001). False positive results for phencyclidine have also been reported for the Alpha Laboratories INSTANT-VIEW Multi-Drug Screen Urine Test. These findings occurred with therapeutic dosing of venlafaxine (Santos et al, 2007).
    C) OTHER
    1) The urine should be frequently monitored for the presence of myoglobin which will indicate a patient that is at risk of developing myoglobinuric renal failure.

Methods

    A) CHROMATOGRAPHY
    1) In one study, gas chromatography and mass spectrometry (GC/MS) were used to detect phencyclidine in urine samples using the CEDIA immunoassay (sensitivity 25 ng/mL) (D'Onofrio et al, 2006).
    2) Gas chromatography with flame ionization detection (GC-FID) is not sufficiently sensitive to detect clinically relevant PCP levels, even in acidified specimens (Fallis et al, 1982).
    3) Gas chromatography with a nitrogen detector (GC-N2) is able to detect levels of PCP nondetectable by GC-FID. It has been reported that the rate of false negative test for PCP using GC-FID (with GC-N2 as a reference) is more than 80% (Fallis et al, 1982).
    B) IMMUNOASSAY
    1) Three Emit(R) homogeneous enzyme immunoassays are available for the measurement of phencyclidine: semiquantitative and qualitative urine assays with detection limits (sensitivities) of 150 ng/mL for PCP, and a qualitative assay for serum or plasma that detects as little as 50 ng/mL of PCP.
    a) According to CDC proficiency testing and clinical studies, this method shows excellent correlation with GC, HPLC, RIA, and TLC.
    b) Elsohly & Stanford (1990) have developed a protocol for running Syva Emit(R) d.a.u.(TM) phencyclidine assay with a 25 ng/mL cutoff on the Syva ETS(R) analyzer.
    2) RADIOIMMUNOASSAY - There are radioimmunoassay reagents commercially available that can detect PCP in human hair at a sensitivity of 0.1 ng/10 mg hair (Baumgartner et al, 1981; Sramek et al, 1985).
    a) Adulteration with bleach produced false negative results in urine testing with a commercial RIA kit (Bronner et al, 1990).
    C) OTHER
    1) HAIR: Methods for detecting phencyclidine in hair have been described (DuPont & Baumgarter, 1995).
    2) Major laboratories can perform specific PCP levels and identify active metabolites as well. Gastric levels are usually 50 times plasma levels. Phencyclidine analogs, such as PCE, cross react variably with screening assays and may not be routinely detected (Baldridge & Bessen, 1990).
    D) ASSAY INTERFERENCE
    1) TRAMADOL INTERFERENCE: Tramadol and its metabolites can produce a false-positive Emit II Plus phencyclidine (PCP) test result. In 2 cases (an adult and child) of tramadol overdose, both developed a false-positive result for phencyclidine using the Emit II Plus Drugs-of-Abuse Assay. Follow-up with a comprehensive gas chromatography/mass spectrometry qualitative urine drug screen demonstrated a large peak of tramadol in both cases (King et al, 2013).
    2) KETAMINE: In a blinded study of patients receiving parenteral ketamine, five point of care urine immunoassays were assessed for the ability of ketamine and metabolites to produce false positive results for PCP. The immunoassays included devices produced by Forefront Diagnostics, Princeton BioMeditech, Roche Diagnostic Systems, American BioMedica, and Technical Chemicals and Products. No urine tested positive for PCP using these assays, although several post-ketamine urine samples appeared to give a weak partial reaction and careful inspection was required to determine a negative result (Hoffman et al, 2001).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with severe or prolonged symptoms, or requiring medication treatment should be admitted for further care.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Adults who are asymptomatic after a low dose ingestion can be watched at home provided a sober adult can monitor them.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a medical toxicologist or poison center for any large and/or severely symptomatic exposures. Child protective services should be involved for exposed children. Consider referral for substance abuse counselling as appropriate.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Any symptomatic patient, and a patient with a self-harm ingestion, and any exposed child should be sent to an emergency department for evaluation, treatment and monitoring.

Monitoring

    A) Monitor vital signs and mental status.
    B) Evaluate patient carefully for evidence of trauma.
    C) In symptomatic patients, monitor serum electrolytes, renal function, liver enzymes, CK, and coagulation studies to investigate for complications from prolonged agitation and hyperthermia.
    D) Specific PCP concentrations are not readily available and not useful in managing acute intoxication. They also do not correlate well with level of intoxication/symptoms. Some urine drug screens include PCP as part of their screening, but many do not and false positive results are not uncommon.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Prehospital charcoal is typically not recommended in PCP ingestion because of the risk of abrupt changes in mental status.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Gastric lavage is not indicated for PCP ingestion. Activated charcoal can be offered, but should be given to cooperative, awake alert patients. It should be used with caution as mental status can deteriorate. Overall, it is not likely to affect the course of PCP intoxication.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    3) Although no data exist regarding the efficacy of multiple dose charcoal in humans, PCP undergoes enterohepatic and gastroenteric recycling and would theoretically be a candidate for enhanced elimination (Aronow et al, 1980; Picchioni & Consroe, 1979). PCP was adsorbed to single doses of activated charcoal in animals (Picchioni & Consroe, 1979). Routine administration is not recommended because of the risk of aspiration in patients with significant toxicity..
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) Monitor vital signs and mental status.
    2) Evaluate patient carefully for evidence of trauma.
    3) In symptomatic patients, monitor serum electrolytes, renal function, liver enzymes, CK, and coagulation studies to investigate for complications from prolonged agitation and hyperthermia.
    4) Specific PCP concentrations are not readily available and not useful in the acute intoxication. They also do not correlate well with level of intoxication/symptoms. Some urine drug screens include PCP as part of their screening, but many do not and false positive results are not uncommon.
    B) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    7) PHENYTOIN/FOSPHENYTOIN
    a) Benzodiazepines and/or barbiturates are preferred to phenytoin or fosphenytoin in the treatment of drug or withdrawal induced seizures (Wallace, 2005).
    b) PHENYTOIN
    1) PHENYTOIN INTRAVENOUS PUSH VERSUS INTRAVENOUS INFUSION
    a) Administer phenytoin undiluted, by very slow intravenous push or dilute 50 mg/mL solution in 50 to 100 mL of 0.9% saline.
    b) ADULT DOSE: A loading dose of 20 mg/kg IV; may administer an additional 5 to 10 mg/kg dose 10 minutes after loading dose. Rate of administration should not exceed 50 mg/minute (Brophy et al, 2012).
    c) PEDIATRIC DOSE: A loading dose of 20 mg/kg, at a rate not exceeding 1 to 3 mg/kg/min or 50 mg/min, whichever is slower (Loddenkemper & Goodkin, 2011; Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    d) CAUTIONS: Administer phenytoin while monitoring ECG. Stop or slow infusion if dysrhythmias or hypotension occur. Be careful not to extravasate. Follow each injection with injection of sterile saline through the same needle (Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    e) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over next 12 to 24 hours for maintenance of therapeutic concentrations. Therapeutic concentrations of 10 to 20 mcg/mL have been reported (Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    c) FOSPHENYTOIN
    1) ADULT DOSE: A loading dose of 20 mg phenytoin equivalent/kg IV, at a rate not exceeding 150 mg phenytoin equivalent/minute; may give additional dose of 5 mg/kg 10 minutes after the loading infusion (Brophy et al, 2012).
    2) CHILD DOSE: 20 mg phenytoin equivalent/kg IV, at a rate of 3 mg phenytoin equivalent/kg/minute, up to a maximum of 150 mg phenytoin equivalent/minute (Loddenkemper & Goodkin, 2011).
    3) CAUTIONS: Perform continuous monitoring of ECG, respiratory function, and blood pressure throughout the period where maximal serum phenytoin concentrations occur (about 10 to 20 minutes after the end of fosphenytoin infusion) (Prod Info CEREBYX(R) intravenous injection, 2014).
    4) SERUM CONCENTRATION MONITORING: Monitor serum phenytoin concentrations over the next 12 to 24 hours; therapeutic levels 10 to 20 mcg/mL. Do not obtain serum phenytoin concentrations until at least 2 hours after infusion is complete to allow for conversion of fosphenytoin to phenytoin (Prod Info CEREBYX(R) intravenous injection, 2014).
    8) In a dog model of severe phencyclidine toxicity, the combination of phenytoin (25 milligrams/kilogram iv) and ventilatory support increased the lethal dose of phencyclidine, reduced seizures, acidosis, hyperthermia, arrhythmias, and cardiac output (Davis et al, 1991).
    9) RECURRING SEIZURES
    a) If seizures are not controlled by the above measures, patients will require endotracheal intubation, mechanical ventilation, continuous EEG monitoring, a continuous infusion of an anticonvulsant, and may require neuromuscular paralysis and vasopressor support. Consider continuous infusions of the following agents:
    1) MIDAZOLAM: ADULT DOSE: An initial dose of 0.2 mg/kg slow bolus, at an infusion rate of 2 mg/minute; maintenance doses of 0.05 to 2 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: 0.1 to 0.3 mg/kg followed by a continuous infusion starting at 1 mcg/kg/minute, titrated upwards every 5 minutes as needed (Loddenkemper & Goodkin, 2011).
    2) PROPOFOL: ADULT DOSE: Start at 20 mcg/kg/min with 1 to 2 mg/kg loading dose; maintenance doses of 30 to 200 mcg/kg/minute continuous infusion dosing, titrated to EEG; caution with high doses greater than 80 mcg/kg/minute in adults for extended periods of time (ie, longer than 48 hours) (Brophy et al, 2012); PEDIATRIC DOSE: IV loading dose of up to 2 mg/kg; maintenance doses of 2 to 5 mg/kg/hour may be used in older adolescents; avoid doses of 5 mg/kg/hour over prolonged periods because of propofol infusion syndrome (Loddenkemper & Goodkin, 2011); caution with high doses greater than 65 mcg/kg/min in children for extended periods of time; contraindicated in small children (Brophy et al, 2012).
    3) PENTOBARBITAL: ADULT DOSE: A loading dose of 5 to 15 mg/kg at an infusion rate of 50 mg/minute or lower; may administer additional 5 to 10 mg/kg. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusion dosing, titrated to EEG (Brophy et al, 2012). PEDIATRIC DOSE: A loading dose of 3 to 15 mg/kg followed by a maintenance dose of 1 to 5 mg/kg/hour (Loddenkemper & Goodkin, 2011).
    4) THIOPENTAL: ADULT DOSE: 2 to 7 mg/kg, at an infusion rate of 50 mg/minute or lower. Maintenance dose of 0.5 to 5 mg/kg/hour continuous infusing dosing, titrated to EEG (Brophy et al, 2012)
    b) Endotracheal intubation, mechanical ventilation, and vasopressors will be required (Brophy et al, 2012) and consultation with a neurologist is strongly advised.
    c) Neuromuscular paralysis (eg, rocuronium bromide, a short-acting nondepolarizing agent) may be required to avoid hyperthermia, severe acidosis, and rhabdomyolysis. If rhabdomyolysis is possible, avoid succinylcholine chloride, because of the risk of hyperkalemic-induced cardiac dysrhythmias. Continuous EEG monitoring is mandatory if neuromuscular paralysis is used (Manno, 2003).
    C) AIRWAY MANAGEMENT
    1) Definite airway management may be needed if CNS depression develops. It may also be needed if large doses of sedatives are needed to decrease the sympathomimetic stimulation.
    2) ANIMAL STUDY: In a dog model of severe phencyclidine toxicity, ventilatory support increased the lethal dose of phencyclidine, reduced acidosis and improved oxygenation without affecting dysrhythmias (Davis et al, 1991). Pancuronium plus ventilatory support increased the lethal dose of phencyclidine, prevented seizures and acidosis but did not affect dysrhythmias.
    D) RHABDOMYOLYSIS
    1) Patients presenting soon after exposure with agitation should be kept well hydrated with intravenous fluids.
    2) SUMMARY: Early aggressive fluid replacement is the mainstay of therapy and may help prevent renal insufficiency. Diuretics such as mannitol or furosemide may be added if necessary to maintain urine output but only after volume status has been restored as hypovolemia will increase renal tubular damage. Urinary alkalinization is NOT routinely recommended.
    3) Initial treatment should be directed towards controlling acute metabolic disturbances such as hyperkalemia, hyperthermia, and hypovolemia. Control seizures, agitation, and muscle contractions (Erdman & Dart, 2004).
    4) FLUID REPLACEMENT: Early and aggressive fluid replacement is the mainstay of therapy to prevent renal failure. Vigorous fluid replacement with 0.9% saline (10 to 15 mL/kg/hour) is necessary even if there is no evidence of dehydration. Several liters of fluid may be needed within the first 24 hours (Walter & Catenacci, 2008; Camp, 2009; Huerta-Alardin et al, 2005; Criddle, 2003; Polderman, 2004). Hypovolemia, increased insensible losses, and third spacing of fluid commonly increase fluid requirements. Strive to maintain a urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hour) (Walter & Catenacci, 2008; Camp, 2009; Erdman & Dart, 2004; Criddle, 2003). To maintain a urine output this high, 500 to 1000 mL of fluid per hour may be required (Criddle, 2003). Monitor fluid input and urine output, plus insensible losses. Monitor for evidence of fluid overload and compartment syndrome; monitor serum electrolytes, CK, and renal function tests.
    5) DIURETICS: Diuretics (eg, mannitol or furosemide) may be needed to ensure adequate urine output and to prevent acute renal failure when used in combination with aggressive fluid therapy. Loop diuretics increase tubular flow and decrease deposition of myoglobin. These agents should be used only after volume status has been restored, as hypovolemia will increase renal tubular damage. If the patient is maintaining adequate urine output, loop diuretics are not necessary (Vanholder et al, 2000).
    6) URINARY ALKALINIZATION: Alkalinization of the urine is not routinely recommended, as it has never been documented to reduce nephrotoxicity, and may cause complications such as hypocalcemia and hypokalemia (Walter & Catenacci, 2008; Huerta-Alardin et al, 2005; Brown et al, 2004; Polderman, 2004). Retrospective studies have failed to demonstrate any clinical benefit from the use of urinary alkalinization (Brown et al, 2004; Polderman, 2004; Homsi et al, 1997).
    E) PSYCHOMOTOR AGITATION
    1) Minimize noise, light and touch. Significant reduction of psychotomimetic effects from bad trips can be achieved by providing a quiet and non-threatening environment. Protect the agitated and excited patient from self-inflicted injuries.
    2) NOTE: It may be difficult to tell PCP psychosis from non-PCP psychosis. It is best to do as little intervention as possible until the patient's diagnosis is clarified.
    3) INDICATION
    a) If patient is severely agitated, sedate with IV benzodiazepines.
    4) DIAZEPAM DOSE
    a) ADULT: 5 to 10 mg IV initially, repeat every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    5) LORAZEPAM DOSE
    a) ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed (Manno, 2003).
    b) CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    6) Extremely large doses of benzodiazepines may be required in patients with severe intoxication in order to obtain adequate sedation. Titrate dose to clinical response and monitor for hypotension, CNS and respiratory depression, and the need for endotracheal intubation.
    7) Butyrophenones should generally be avoided because they reduce seizure threshold and may increase the risk of hyperthermia and dysrhythmias.
    a) HALOPERIDOL: In a non-blinded retrospective case series, haloperidol (average dose: 5.6 mg; range: 1 to 15 mg) was given to 59 phencyclidine-intoxicated patients (age range: 19 to 54 years) via IV (n=25; 16.6%), IM (n=33; 21.9%), and oral (n=93; 61.6%) routes. Most patients received only 1 dose (range: 1 to 10 doses) with 30 patients receiving more than 1 dose. Overall, haloperidol was well tolerated in most cases with only 2 minor adverse events reported. One patient had a prolonged QTc of 0.475 after a 5 mg IV dose and another developed a hypoxic event with a pulse oximetry reading of 80% after receiving haloperidol 5 mg IM. Another patient had transient hypotension (BP 69/47 mmHg) after receiving haloperidol (2 mg orally) and lorazepam. A direct causal relationship to haloperidol was not established in any of these cases (MacNeal et al, 2012).
    8) Restraints should be avoided if possible, as their use may contribute to rhabdomyolysis (Lahmeyer & Stock, 1983). The use of phenothiazines has resulted in severe hypotension (Morgan & Solomon, 1978).
    F) BODY TEMPERATURE ABOVE REFERENCE RANGE
    1) Control agitation with benzodiazepines. External cooling methods should be employed aggressively. Enhance evaporative cooling by undressing the patient, spraying the skin with water and directing fans to enhance air flow across the skin. Ice packs may also be employed.
    G) MALIGNANT HYPERTENSION
    1) Mild to moderate hypertension is usually self-limited and does not require treatment unless the patient has persistent severe blood pressure elevations or end-organ damage (Baldridge & Bessen, 1990). Control agitation with benzodiazepines. If severe hypertension persists treat intravenous nitroprusside.
    2) DOSE: ADULT & CHILD: Initially 1 microgram/kilogram/minute by intravenous infusion; titrate up to 10 micrograms/kilogram/minute as needed to achieve desired effect.
    3) ALTERNATE: Intravenous PHENTOLAMINE (ADULT: 2.5 to 5 milligrams every 5 minutes until hypertension is controlled then every 2 to 4 hours as needed; CHILD: 0.05 to 0.1 milligram/kilogram/dose every 5 minutes until hypertension is controlled then every 1 to 4 hours as needed).
    H) ACIDIFICATION REGIME
    1) Urinary acidification is NOT recommended. The presence of rhabdomyolysis or closed head injury are absolute contraindications to acidification.
    I) EXPERIMENTAL THERAPY
    1) VERAPAMIL: There is insufficient clinical experience available to recommend that verapamil should be used.
    a) Verapamil as an intravenous bolus dose given over 2 minutes (0.075 milligram/kilogram) is being evaluated in the treatment of PCP-induced psychosis. Verapamil appeared to be of benefit in a 29-year-old man who was reported to have ingested a large amount of phencyclidine (Price et al, 1986).
    b) Verapamil was given to a 42-year-old man as an intravenous drip containing 5 milligrams verapamil in 100 milliliters normal saline given over 20 minutes. Ten minutes after the start of the drip, he appeared to improve clinically (Montgomery & Mueller, 1985).
    c) A controlled study in rats revealed a significant potentiation of PCP-induced radial maze performance reduction by verapamil (McCann et al, 1986). These authors caution against the use of verapamil.
    2) In a dog model, monoclonal anti-phencyclidine Fab fragments decrease the volume of distribution of phencyclidine, decrease systemic and renal clearance and increase the percentage of dose recovered in urine (Valentine et al, 1994).

Enhanced Elimination

    A) SUMMARY
    1) Dialysis or other methods of enhance elimination are not recommended. Urinary acidification will increase the excretion of PCP but the risk of systemic acidosis exceeds the potential benefit and it is not recommended.

Abstracts

Case Reports

    A) ADVERSE EFFECTS
    1) A 28-year-old exhibited bizarre behavior while on an airline flight and was admitted for evaluation. He passed two plastic bags through his rectum 13 days after ingestion and 11 days after hospitalization. One bag was ruptured. Analysis of the contents identified phencyclidine that was approximately 90% pure. No other toxins were detected by gas-liquid and thin-layer chromatography, or enzyme-mediated immunoassays. His clinical course had improved on day 1. He had received activated charcoal on admission. Over the next several days he developed rigidity, diaphoresis, fever (39.2 degrees C), mental status deterioration, respiratory failure requiring intubation, subcutaneous emphysema, mediastinal emphysema without pneumothorax, protracted seizures, and rhabdomyolysis. Once the bags had passed through his rectum, he made a rapid neurologic recovery. He was discharged on day 24 with clear consciousness, orientation, and cognition. He did have persistent dystonic jerking of his extremities. The maximum recorded serum PCP concentration was 1,879 ng/mL on day 4 of hospitalization (Jackson, 1989).
    B) ADULT
    1) A 21-year-old man with a history of poly drug abuse presented with violent and aggressive behavior. The onset of the psychiatric symptoms correlated well with a reported behavior following a 3-day PCP "trip." Initially, he responded well and was reported to be apparently under control with intramuscular fluphenazine treatment prior to this admission. Haloperidol was started at 20 mg/day and increased to 200 mg/day because of worsening behavior. Ten days after initiation of therapy haloperidol was decreased to 80 mg/day and fluphenazine enanthate 40 mg/day orally was begun. The fluphenazine was increased to 120 mg/day and intramuscular fluphenazine decanoate 37.5 mg every 4 to 7 days was started. Haloperidol was discontinued. Diazepam was ordered as needed up to 40 mg/day without improvement. One month after admission emergency bilateral ECT was given because of an increase in violence toward staff and patients. A total of 10 ECTs were given over 20 days. Oral fluphenazine was gradually decreased and then discontinued; IM fluphenazine was continued at 25 mg every 10 to 14 days. The patient's symptoms were under control and three weeks after conclusion of ECT treatment the patient was discharged (Grover et al, 1986).
    2) A 32-year-old male was found unresponsive with marked muscle rigidity and fasciculations. Horizontal and, later, vertical nystagmus was seen. A drug screen was positive for PCP and ethanol. An initial CPK was 124,500 mu/ml; creatinine and BUN peaked at 12.3 mg/100ml and 139 mg/100ml, respectively. The patient required hemodialysis for several days. The patients course was complicated by elevated liver enzymes secondary to hyperalimentation and hemoptysis secondary to a coagulopathy treated with fresh frozen plasma and bronchoscopy to remove clots. CNS and renal function gradually improved and he was discharged with normal mental status, renal and liver function on day 31 (Milhorn, 1990).

Range Of Toxicity

Summary

    A) TOXICITY: Symptoms are expected at doses of approximately 0.05 to 0.1 mg/kg. A dose of 1 to 5 mg will normally result in euphoria and numbness, resembling ethanol intoxication. Doses of 5 to 10 mg often result in excitation, confusion, ataxia, and dysarthria. Prolonged coma, seizures, and death may result from 20 mg or more. Fatalities are more often related to trauma than to direct drug effects.
    B) Blood levels of 20 to 30 ng/mL may cause excitation and catatonia; 30 to 100 ng/mL may cause coma and myoclonus; above 100 ng/mL may cause seizures and hypotension.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) Although structurally similar to the anesthetic ketamine hydrochloride (Ketalar(R)), phencyclidine is not indicated for human use because of its potent psychomimetic properties. Phencyclidine is used either by smoking (amounts of 1 to 3 milligrams applied to plant material), by oral ingestion (2 to 6 milligrams), by intravenous injection (1 to 3 milligrams) or by nasal insufflation. Lethargy, disorientation, hallucinations and loss of coordination have been observed with these doses (Baselt, 2000).
    2) Phencyclidine (PCP, Sernylan(R)), a general anesthetic in veterinary medicine, was voluntarily withdrawn from the market in 1978 (HSDB , 2002).

Minimum Lethal Exposure

    A) CASE REPORTS
    1) Ingestion of 150 to 200 mg in an acute overdose has resulted in death (Fisher & McDonald, 1984).
    2) Many deaths have occurred from the psychological effects of phencyclidine secondary to delusions of invulnerability. Acts of self-mutilation and violence have been reported (Fisher & McDonald, 1984).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) A dose of 1 to 5 mg will normally result in euphoria and numbness, resembling ethanol intoxication. Doses of 5 to 10 mg often result in excitation, confusion, ataxia, and dysarthria. Prolonged coma, seizures, and death may result from 20 mg or more (Young et al, 1987).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CONCENTRATION LEVEL
    a) Blood levels of 20 to 30 nanograms/milliliter may cause excitation and catatonia. 30 to 100 nanograms/milliliter may cause coma and some myoclonus. Above 100 nanograms/milliliter may cause seizures and hypotension (Aronow & Done, 1978).
    b) Caution needs to be exercised in interpreting PCP levels as "street" PCP may contain an active precursor (PCC) or other psycho-active congeners. Urine PCP levels do not correlate with clinical toxicity (Walker et al, 1981).
    c) Plasma concentrations of PCP vary widely after overdose and have been reported to range from 49 to 3755 nanograms/milliliter (Domino & Wilson, 1977). Urine concentrations have been reported to be 10 to 20 times greater than plasma concentrations (Morgan & Solomon, 1978).

Workplace Standards

    A) ACGIH TLV Values for CAS77-10-1 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS77-10-1 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS77-10-1 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS77-10-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAPERITONEAL)MOUSE:
    1) 2800 mcg/kg
    B) LD50- (ORAL)MOUSE:
    1) 75 mg/kg

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Phencyclidine was developed as a synthetic anesthetic agent and is closely related to ketamine. Phencyclidine and about 30 or so analogues are arylcyclohexylamines.
    B) Phencyclidine is a dissociative anesthetic with sympathomimetic and hallucinogenic properties. Pharmacologic effects are generally dose related. PCP is thought to stimulate alpha-adrenergic receptors, potentiating the effects of norepinephrine, epinephrine and serotonin.

Toxicologic Mechanism

    A) In a rat model, phencyclidine's (PCP) pharmacological actions were explained by three mechanisms. PCP increased pre-frontal cortex monoamine (dopamine and serotonin) release. PCP decreased GABA release and exhibited no net effect on glutamate release. The monoamine release was the result of a reduction in NMDA receptor glutamate release, reduced GABAergic inhibition via inhibition of the NMDA receptor and a direct enhancement of endoplasmic reticulum monoamine exocytosis (Zhu et al, 2004).

Physicochemical

Physical Characteristics

    A) odorless white crystalline powder

Ph

    A) 2-5 (10% aqueous solution)

Molecular Weight

    A) 243.38

Animal Toxicology

Kinetics

    11.5.1) ABSORPTION
    A) LACK OF INFORMATION
    1) There was no specific information on absorption at the time of this review.
    11.5.2) DISTRIBUTION
    A) DOG
    1) VOLUME OF DISTRIBUTION - 20 L/kg in dogs (Jackson, 1989)

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