Introduction
Background
Phencyclidine, 1-(1-phenylcyclohexyl) piperidine (PCP), is a dissociative anesthetic that was originally synthesized for intravenous use in 1957 and was marketed under the trade name Sernylan. Because of its postoperative emergence reactions (ie, hallucinations, prolonged abnormal level of consciousness, agitation), it fell out of favor; its use as an anesthetic in humans was discontinued in 1963. Subsequently, it was used primarily as an animal tranquilizer and was distributed for veterinary use until 1978, when the US government added the drug to its list of controlled substances. Today, several of its congeners (eg, ketamine) are used in anesthesia or are under investigation for use as anesthetics.
PCP emerged as an oral drug of abuse, known as the PeaCe Pill on the streets of San Francisco in 1967. However, its reputation for bad trips (ie, unexpected and unpleasant reactions), coupled with its unpredictable effects, quickly filtered through the drug community and caused the drug to wane in popularity. In the early 1970s, smoking PCP was recognized as an effective method of use because its mind-altering effects could be titrated.
Pathophysiology
PCP is a commonly abused street drug sold under many different names and in many different forms. It may be sold on the street in tablet or capsule form, as a powder, or as a solution. The PCP content in each form differs widely, commonly containing only 10-30% PCP. Angel dust, the powdered form of PCP, generally has a higher PCP content, occasionally reaching 100%. Angel dust may be sniffed, smoked, ingested, or injected intravenously. Percutaneous absorption has also been reported to occur in individuals handling PCP (eg, law enforcement officers). Smoking PCP remains the desired method of use; the substance is commonly sprinkled onto dried leaf material (eg, marijuana, tobacco, oregano, mint) and then smoked.
PCP is easy to synthesize, and a number of its analogs or byproducts of synthesis may be found on the streets. These include phenylcyclohexylethylamine (PCE), thienylcyclohexylpiperidine (TCP), and phenylcyclohexylpyrrolidine (PHP), which have similar pharmacologic activity to PCP but may be more toxic. One byproduct, piperidinocyclohexane carbonitrile (PCC), can cause cyanide poisoning.
Pharmacokinetics
PCP is a dissociative anesthetic because it renders the patient motionless (ie, rigid muscles, flat facies, staring gaze) while maintaining a wakeful, although amnestic, state. The anesthetic effect of PCP results from PCP's ability to block selected sensory stimuli, such as pain. PCP produces profound analgesia and anesthesia while preserving spontaneous respiration and without major effects on the cardiovascular system.
PCP is an arylcyclohexylamine compound, and, like other arylcyclohexylamines, it interacts with most neurotransmitter systems, resulting in a combination of CNS stimulant and depressant effects. For example, PCP blocks the N-methyl-D-aspartic acid (NMDA)–type glutamate receptors located in both the cortex and limbic regions of the brain, it inhibits GABA, and it increases dopamine synthesis and release while inhibiting its presynaptic reuptake. PCP also blocks acetylcholine receptors, thus resulting in anticholinergic activity; however, PCP may also inhibit acetylcholinesterase, resulting in cholinergic activity. Additionally, PCP has some interaction with the sigma opiate receptors in the hippocampus and competitively inhibits norepinephrine and serotonin. Although PCP’s predominant effect is sympathomimetic, a number of other effects may be observed to varying degrees in individuals who are intoxicated with PCP.
PCP is a weak base (pKa 8.6-9.4) that is absorbed well orally, nasally, and percutaneously, especially when in liquid form. When ingested, PCP has an oral bioavailability of approximately 50-90%, and it is absorbed best from the alkaline environment of the intestines. When smoked, almost all the PCP that reaches the alveoli is absorbed. Once in the blood, PCP undergoes extensive first-pass metabolism in the liver and extensive enterohepatic recirculation. PCP is also secreted into the stomach, where it is ionized and trapped by gastric acid, only to be released to the alkaline environment of the duodenum, where it is reabsorbed. This gastroenteric recirculation may help explain the waxing and waning effects of PCP as plasma levels decrease when PCP is secreted into the stomach and rise again when it is reabsorbed from the duodenum.
PCP is highly lipid-soluble and may be found in high concentrations in the brain and adipose tissue. PCP is ion-trapped and tightly bound in many tissues, particularly the liver and the brain. PCP has a volume of distribution of approximately 6.2 L/kg and is approximately 65-78% protein-bound.
The onset of action of PCP depends on the route of administration and may be as quick as a few minutes to 30 minutes, depending on the route. The onset of action is 2-5 minutes when inhaled or smoked and 15-30 minutes when ingested. Peak plasma levels occur in 5-30 minutes when inhaled or smoked and 2.5 hours when ingested orally. The half-life and the duration of PCP’s clinical effects also vary and depend on the long-term nature of use and individual variations. Effects usually last from 4-6 hours but may last as long as a week in those who have used it long-term. Severe symptoms lasting longer than 24 hours should raise the possibility of continued absorption, as in the case of a ruptured body pack (eg, worn by smugglers).
PCP is metabolized by the liver via hydroxylation, which produces metabolites that are excreted by the kidneys. Approximately 9% of absorbed PCP is excreted unchanged in the urine. This may increase to approximately 50% with urinary acidification (pH 6.1-7.4). PCP and its metabolites remain in the urine for an average of 2 weeks after use but may persist for up to a month.
PCP is capable of crossing the placental membrane and has been found in amniotic fluid, umbilical cord blood, and neonatal urine. PCP also may be excreted in breast milk. Although long-term intrauterine exposure has occasionally been linked to an increased incidence of cerebral palsy and facial dysmorphogenesis, these reports did not control for other substances of abuse and, therefore, are difficult to interpret. Long-term intrauterine exposure to PCP has been reported to lead to dependence, as evidenced by a withdrawal syndrome, similar to narcotic withdrawal.
Frequency
United States
According to the latest National Household Survey on Drug Abuse, 3.2% of persons aged 12 years and older have used PCP at least once in their lifetime.
According to data from the Drug Abuse Warning Network (DAWN), which examines the number of emergency department records that mention drug use in the diagnosis, for the third and fourth quarters of 2003, PCP was involved in 4,581 of all drug-related ED visits nationwide (n= 627,923), nearly 0.75% of all drug-related ED visits.1
Mortality/Morbidity
In 2003, 785 exposures were reported to US Poison Control Centers, including 8 deaths and 83 cases with severe morbidity due to phencyclidine (PCP).2
Morbidity and mortality from PCP are related directly to trauma sustained during intoxication. PCP may also cause status epilepticus, hyperthermia, rhabdomyolysis, intracranial hemorrhage, and respiratory arrest. A fatal dose is 1 mg/kg. Lethal PCP blood concentration is 100-500 mcg/dL.
Race
No racial or ethnic predilection is recognized among those who abuse PCP.
Sex
No sexual predilection is recognized among those who abuse PCP.
Age
PCP use is observed most commonly in older teenagers and in young adults.
Clinical
History
The clinical presentation of PCP intoxication is highly variable and depends on the amount consumed, the route of administration, the presence of co-ingestants, and individual variations. PCP symptoms generally fluctuate and depend on the degree of sympathomimetic, serotoninergic, cholinergic, anticholinergic, and narcotic effects. These generally result in abnormal behavior and thought processes, along with an altered level of consciousness.
Most intoxications are without complications. Patients present for medical care when they are having a particularly bad trip or when they develop complications of PCP use. Life-threatening PCP complications include those relating to major traumatic injuries, convulsions, and hyperthermia.
Physical
The clinical manifestations of PCP intoxication are also extremely variable. Although no pathognomonic signs of PCP intoxication exist, nystagmus and hypertension are present in more than half of the patients. These physical findings, along with a history of an acute episode of bizarre behavior and urine toxicology screen results that are positive for PCP, are usually enough to make the diagnosis. Other symptoms present in those with PCP poisoning include the following:
- Central nervous system: Patients with PCP intoxication may be alert and oriented, comatose or catatonic, markedly agitated, and violent. They may exhibit amnesia, opisthotonos, torticollis, choreoathetoid movements, and seizures. Coma has been reported in as many as 10.6% of patients; seizures have been reported in 3.1% of patients and are more common in children. Cerebellar symptoms such as dysarthria and ataxia may also be present.
- Psychiatric: In a study of 1000 patients with PCP intoxication, 35% were violent, 34% were agitated, 29% exhibited bizarre behavior, 19% had delusions or hallucinations, and many were dysphoric. Paranoid delusions were especially common, and the hallucinations were both auditory and visual.
- Head, ears, eyes, nose, and throat: Nystagmus (horizontal, vertical, or rotary) is a hallmark of PCP intoxication and is present in more than half the patients studied. Patients also commonly exhibit a blank stare and occasionally have dysconjugate gaze, miosis, or mydriasis. Miosis is more common in children with PCP intoxication. Hypersalivation may also be observed.
- Respiratory: Tachypnea and irregular respiratory patterns have been reported in patients with PCP intoxication. Apnea is rare and may be due to co-ingestants or to one of the complications of PCP intoxication. Bronchorrhea and bronchospasm have also been reported.
- Cardiovascular: Mild tachycardia is common (present in 30% of patients with PCP intoxication), but hypertension (systolic and diastolic) is a hallmark of PCP intoxication and is present in 57% of patients. It commonly resolves within 4 hours but may persist longer than 24 hours. The occurrence of hypertension beyond the first 24 hours should raise the possibility of an intracerebral complication. In the absence of trauma or preexisting heart disease, cardiac arrest is very rare.
- Musculoskeletal: Symptoms of PCP intoxication include muscle rigidity, dystonia, opisthotonos, torticollis, akinesis, and hyperkinesis.
- Skin: Diaphoresis is common in patients intoxicated with PCP.
Causes
PCP poisoning occurs when PCP is substituted for marijuana. Children may be poisoned by ingesting PCP solutions, PCP-laden leaves, PCP tablets, and sometimes by inhaling PCP smoke in a smoke-filled room. PCP poisoning has also been reported in body packers (ie, smugglers) who transport PCP across different territories.
More on Toxicity, Phencyclidine |
 Overview: Toxicity, Phencyclidine |
| Differential Diagnoses & Workup: Toxicity, Phencyclidine |
| Treatment & Medication: Toxicity, Phencyclidine |
| Follow-up: Toxicity, Phencyclidine |
| References |
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Further Reading
Keywords
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