A 27-year-old man leaves the men's room of a bar after smoking an unknown substance. He soon becomes disoriented and belligerent. The man displays uncoordinated, jerky movements of his extremities and assaults a bouncer who tries to calm him. When police and emergency medical services personnel arrive, he fights off 4 officers before being restrained and appears immune to pain. In the emergency department, the patient has visual hallucinations, cannot cooperate with the interview, and alternates between agitation and sedation. He is hypertensive and tachycardic, and examination shows vertical nystagmus. The patient does not cooperate with urine toxicology testing. Several hours later, during questioning by the emergency physician, he does not remember most of the preceding events. Which of the following is the primary mechanism of action of the drug most likely used by this patient?

Question

A 27-year-old man leaves the men's room of a bar after smoking an unknown substance.  He soon becomes disoriented and belligerent.  The man displays uncoordinated, jerky movements of his extremities and assaults a bouncer who tries to calm him.  When police and emergency medical services personnel arrive, he fights off 4 officers before being restrained and appears immune to pain.  In the emergency department, the patient has visual hallucinations, cannot cooperate with the interview, and alternates between agitation and sedation.  He is hypertensive and tachycardic, and examination shows vertical nystagmus.  The patient does not cooperate with urine toxicology testing.  Several hours later, during questioning by the emergency physician, he does not remember most of the preceding events.  Which of the following is the primary mechanism of action of the drug most likely used by this patient?

Quizplus · Accepted Answer

This man likely experienced substance-induced psychosis from phencyclidine (PCP) intoxication. PCP is a hallucinogen that works primarily as an N-methyl-D-aspartate (NMDA) glutamate receptor antagonist. Although the exact mechanism is unknown, it is theorized that NMDA receptor hypofunction increases the risk of psychosis partially by causing dopamine dysregulation. Other NMDA receptor antagonists include ketamine and dextromethorphan. PCP can also inhibit the reuptake of norepinephrine, dopamine, and serotonin and affect neuronal sigma receptors. Moderate amounts of PCP cause dissociative symptoms. Agitation, hallucinations, and violent behavior can occur with higher doses. Fatalities are often associated not with direct PCP intoxication but with related trauma due to combative behavior. In addition to belligerence, PCP is known to cause loss of coordination, horizontal and vertical nystagmus, and a constellation of cognitive symptoms that includes disorientation, poor judgment, and memory loss. (Choice A) PCP is not a dopamine receptor antagonist. Dopamine receptor antagonism is the mechanism of action of most antipsychotics. (Choice B) GABA-A receptor modulation is the mechanism of action of benzodiazepines, a drug class with sedative, antianxiety, and anticonvulsant properties. PCP may have some effect on GABA receptors, but this is not its primary mechanism of action. (Choice C) Mu-opioid receptors are the primary site for the analgesic effects of opioids. (Choice E) Serotonin receptor agonism is the mechanism of action of triptans, buspirone (an anxiolytic), and many psychedelic drugs (eg, LSD, psilocybin). Educational objective: Phencyclidine (PCP) is primarily an N-methyl-D-aspartate receptor antagonist, with lesser effects on the reuptake inhibition of biogenic amines and other receptors. It can have dissociative and anesthetic effects but may also cause psychosis and severe agitation, leading to violent trauma. Ataxia, horizontal and vertical nystagmus, and memory loss can also be present. __________ References: Glutamatergic theories of schizophrenia. (http://www.ncbi.nlm.nih.gov/pubmed/20686195) Glutamate neurocircuitry: theoretical underpinnings in schizophrenia. (http://www.ncbi.nlm.nih.gov/pubmed/23189055)

A 27-Year-Old Man Leaves the Men's Room of a Bar