A 24-year-old man is found unconscious in the basement of his house. His mother calls emergency responders and informs them that the patient has a history of substance abuse and was recently hospitalized for major depressive disorder. In the emergency department, the patient is found to be cyanotic and unresponsive to painful stimuli. Temperature is 36.7 C (98.1 F), blood pressure is 101/62 mm Hg, pulse is 61/min, and respirations are 4/min. His pupils are constricted and minimally responsive to light. Resuscitation efforts are initiated. The patient receives intravenous medication and regains consciousness 2 minutes later. The drug most likely used to treat this patient has the greatest affinity for which of the following receptors?

Question

A 24-year-old man is found unconscious in the basement of his house.  His mother calls emergency responders and informs them that the patient has a history of substance abuse and was recently hospitalized for major depressive disorder.  In the emergency department, the patient is found to be cyanotic and unresponsive to painful stimuli.  Temperature is 36.7 C (98.1 F), blood pressure is 101/62 mm Hg, pulse is 61/min, and respirations are 4/min.  His pupils are constricted and minimally responsive to light.  Resuscitation efforts are initiated.  The patient receives intravenous medication and regains consciousness 2 minutes later.  The drug most likely used to treat this patient has the greatest affinity for which of the following receptors?

Quizplus · Accepted Answer

This patient's history of substance abuse, miosis, profound sedation, and respiratory depression with rapid reversal of signs/symptoms with antidotal therapy is consistent with an opioid overdose. Several opioid receptor subtypes, including mu, delta, and kappa, have been identified. Available opioid medications (eg, morphine, hydromorphone) produce therapeutic analgesic effects by binding to these receptors and modulating pain perception. Naloxone is a pure opioid receptor antagonist devoid of any agonist properties. Although it antagonizes opioid effects at all receptor types, it has the greatest affinity for mu receptors (responsible for opioid-induced cardiorespiratory depression). Naloxone competes with opioid medications, displacing them from opioid receptors; it is therefore an ideal agent for reversing opioid intoxication/overdose. Reversal effects can occur within minutes, and the duration is dose dependent (usually 1-4 hours). Naloxone must be given parenterally because it is metabolically inactivated by the liver when administered orally. (Choice A) Medications with an affinity for 5-HT (serotonin) receptors do not have a role in the treatment of opioid overdose. Cyproheptadine, a 5-HT1A and 5-HT2A antagonist, is an oral medication that can be used to treat serotonin syndrome. Ondansetron is a 5-HT3 antagonist that may be administered intravenously for nausea and vomiting. (Choices B and E) Delta and kappa are also opioid receptors that modulate pain. Although naloxone does bind to these receptors, it binds to mu opioid receptors with greatest affinity. (Choices C and D) GABA is the primary inhibitory neurotransmitter in the brain and is the target of many drugs. Benzodiazepines and barbiturates work by binding to specific sites on GABA A receptors to facilitate inhibitory effects of GABA. Flumazenil is a GABA A benzodiazepine receptor antagonist used to reverse benzodiazepine intoxication. Baclofen is an agonist at the GABA B receptor that acts as a skeletal muscle relaxant. This patient's miosis and profound respiratory depression are more indicative of opioid overdose than benzodiazepine or baclofen intoxication. (Choice G) Glutamate is an excitatory neurotransmitter that binds to NMDA receptors. Ketamine, a general anesthetic, is an example of an NMDA receptor antagonist. Naloxone does not have effects on NMDA receptors. Educational objective: Naloxone is a pure opioid receptor antagonist used to treat opioid intoxication or overdose. Although it binds to mu, kappa, and delta opioid receptors, it has the greatest affinity for mu receptors (which mediate opioid-induced bradycardia and respiratory depression), making it an ideal agent for treating opioid intoxication. __________ References: Reducing the harm of opioid overdose with the safe use of naloxone: a pharmacological review. (http://www.ncbi.nlm.nih.gov/pubmed/25865597)

A 24-Year-Old Man Is Found Unconscious in the Basement of His