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Chapter: Modern Medical Toxicology: Neurotoxic Poisons: Hallucinogens (Psychedelic Drugs)

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Phencyclidine - Hallucinogen(Psychedelic Drug)

Chemically, phencyclidine is 1 -(1 -phenylcyclohexyl)piperi-dine, and is commonly referred to by addicts as “angel dust” or “PCP”.

PHENCYCLIDINE

·              Chemically, phencyclidine is 1 -(1 -phenylcyclohexyl)piperi-dine, and is commonly referred to by addicts as “angel dust” or “PCP”. It was developed in the 1950s as a potential general anaesthetic by Parke-Davis under the brand name Sernyl. It was termed a “dissociative anaesthetic” because unlike conventional anaesthetics which induced a state of relaxed sleep, PCP induced a state of catatonia with flat facies, open mouth, fixed staring, rigid posturing, and waxy flexibility. Patients seemed dissociated from the environment without classical coma. However, a significant proportion of patients showed severe adverse reactions during emergence, including agitation and hallucinations. Some suffered from psychosis for up to 10 days. PCP was therefore quickly withdrawn. Today, ketamine a less potent PCP derivative is quite popular as ananaesthetic.

Source

·              PCP, a phenylcyclohexylamine, is easily synthesised from piperazine, cyclohexanone, and potassium cyanide.

Mode of Intake

·              PCP is abused by smoking, insufflation, ingestion, or rarely IV injection.

·              It is commonly sold on the street as tablets (about 5 mg), capsules, powder, aqueous or alcoholic solution, or as “rock salt” crystal. It is often mixed with parsley, mint, oregano, or marijuana.

·     Sometimes “crack” is dipped in PCP and smoked (“tragic magic”), or cannabis is dipped in PCP (“love boat”).

Mode of Action

■■   Phencyclidine antagonizes the action of glutamate at the NMDA (N-methyl-d-aspartate) receptor. It binds within the ion channel (PCP binding site) to block Ca++ influx which results from glutamate binding. Unlike the other types of glutamate receptor channels, NMDA channels are perme-able to both Ca++ and Na+.

■■  Following NMDA receptor activation, NMDA-mediated Ca++ flux may lead to stimulation of calmodulin-dependant kinases with activation of postsynaptic second-messenger pathways. Opening the NMDA channel facilitates access of PCP to its receptor, accelerating the rate at which PCP-induced blockade of NMDA receptor-mediated neuro-transmission takes place.

■■  At doses much higher than at which it exerts its unique behavioural effects by blocking NMDA receptor-mediated neurotransmission, PCP also blocks presynaptic mono-amine reuptake, thus directly increasing synaptic levels of dopamine and noradrenaline.

■■  At even higher doses, PCP blocks neuronal Na+ and K+ channels, as well as muscarinic cholinergic receptors. This may explain the occurrence of convulsions in PCP overdose.

Toxicokinetics

·              The volume of distribution of phencyclidine is 6.2 L/kg.

·              The volume of distribution of phencyclidine is 6.2 L/kg.

·              Since it is highly lipid soluble, it accumulates in brain and adipose tissue. Metabolism of the latter causes release of PCP which contributes to the recurrence of symptoms.

·              PCP can be detected in urine up to 20 to 30 days (usually 2 weeks).

Clinical (Toxic) Features

CNS:

·              Level of consciouness ranges from fully alert to coma-tose. The coma is usually preceded as well as followed (upon recovery) by agitation and psychosis.

·              Confusion, disorientation, amnesia.

·              Catatonia with unusual posturing, mutism and staring.

·              Myoclonic and dystonic movements, opisthotonus, torticollis.

·              Acute toxic psychosis with bizarre behaviour, agitation, and violence.

·              Cholinergic (sweating, miosis, salivation, bronchos-pasm), or anticholingeric (mydriasis, tachycardia, urinary retention) signs may be present.

·              Hallucinations (auditory and visual).

·              Convulsions.

·              Hyperthermia.

Eye:

·              Blank stare.

·              Dysconjugate gaze.

·              Nystagmus (horizontal, vertical, or rotatory).

·            Blurred vision.

·              Miosis (occasionally mydriasis).

CVS:

·              Sinus tachycardia.

·              Hypertension.

GIT:

·              Vomiting.

RS:

·              Tachypnoea.

Renal:

·              Myoglobinuria.

·              Acute renal failure.

Usual Fatal Dose

■■  Approximately 100 mg or more.

■■  Lethal blood level: 0.1 mg/100 ml.

Diagnosis

·              Serum PCP levels usually do not correlate well with clinical picture. Therefore, a qualitative test is adequate in most cases.

·      Laboratory findings:

o     Leucocytosis

o     Hypoglycaemia

o     Hyperkalaemia

o     Elevated muscle enzymes.

·      EEG: Diffuse slowing with theta and delta waves.

Treatment

·      The need for gastric lavage should be assessed carefully. Often such measures may exacerbate agitation and violence.

·      Activated charcoal is highly beneficial and can be admin-istered at a dose of 1 gm/kg every 4 hours for several doses.

·      A single dose of a suitable cathartic such as sorbitol can be given (unless there are specific contraindications).

·      Some authors recommend urinary acidification to enhance excretion of PCP (which is a weak base). But only 10% of the drug is excreted in the urine, while the remaining 90% is metabolised in the liver. Hence the practical utility of urinary acidification is negligible.

·      Haemodialysis and haemoperfusion are not beneficial.

·      As of now there is no antidote for PCP, though efforts are on to develop PCP-specific antigen binding fragmens (Fab) which can prove to be very useful.

·      Agitated patients should be restrained, at first physically and later pharmaceutically. Hypoglycaemia, if present, must be treated with 50% dextrose in water. Subsequently if agitation persists, administer titrated doses of diazepam 5 to 10 mg IV, every 10 minutes, until the patient is calmed. Phenothiazines should be avoided since they can worsen dystonic reactions, hypotension, hyperthermia, and lower the seizure threshold.

·      Specific antihypertensive therapy should be instituted in patients with very high blood pressure.

·              Myoglobinuria should be treated with IV infusion of 1 litre of 5% dextrose in water (containing 25 grams of mannitol and 100 mEq of sodium bicarbonate), at a rate of 250 ml/hour. Monitor the patient for hypokalaemia. If renal failure has occurred, haemodialysis should be undertaken.

 

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