A 42-year-old man is brought to the hospital after a motor vehicle collision. The patient was driving while intoxicated with alcohol and collided with another car. Evaluation reveals a left tibia and fibula fracture but no other major injuries. He reports no prior medical conditions. The patient is hospitalized and operative repair of the fracture is performed. On the third day in the hospital, he becomes agitated and demands to leave. Temperature is 37.2 C (99 F), blood pressure is 162/94 mm Hg, and pulse is 125/min. On physical examination, the patient is diaphoretic, tremulous, and disoriented. There are mild hand tremors but no other neurologic abnormalities. Increased activity of which of the following central nervous system receptors is the most likely cause of this patient's condition?

Question

A 42-year-old man is brought to the hospital after a motor vehicle collision.  The patient was driving while intoxicated with alcohol and collided with another car.  Evaluation reveals a left tibia and fibula fracture but no other major injuries.  He reports no prior medical conditions.  The patient is hospitalized and operative repair of the fracture is performed.  On the third day in the hospital, he becomes agitated and demands to leave.  Temperature is 37.2 C (99 F), blood pressure is 162/94 mm Hg, and pulse is 125/min.  On physical examination, the patient is diaphoretic, tremulous, and disoriented.  There are mild hand tremors but no other neurologic abnormalities.  Increased activity of which of the following central nervous system receptors is the most likely cause of this patient's condition?

Quizplus · Accepted Answer

This patient is agitated, disoriented, and tremulous with autonomic hyperactivity (eg, hypertension, tachycardia). Development of these symptoms after a period of forced abstinence (ie, admission to the hospital) is consistent with alcohol withdrawal, particularly in patients with known problematic alcohol use. Alcohol is a strong CNS depressant that binds to the GABA A receptor complex, enhancing the inhibitory action of GABA (the major inhibitory neurotransmitter in the brain), leading to sedation. Chronic ethanol use causes compensatory downregulation of GABA A receptors in an attempt to maintain CNS homeostasis. In addition to its effects on GABA neurotransmission, alcohol also inhibits excitatory NMDA glutamate receptors in the brain; similar to GABA receptors, chronic exposure leads to compensatory upregulation of NMDA receptors. Abrupt cessation of alcohol use leads to significantly decreased GABA activity due to the decreased number of GABA A receptors (Choice A) and increased glutamate activity due to the increased number of NMDA receptors, resulting in CNS overexcitation and the symptoms of alcohol withdrawal. (Choice C) Increased activity of alpha-2 adrenergic receptors in the CNS decreases sympathetic output and results in peripheral vasodilation, decreased heart rate, and reduced blood pressure. (Choice D) Increased activation of the opioid mu receptor occurs with opioid intoxication. It would lead to somnolence with shallow breathing and a decreased respiratory rate. Bradycardia, rather than tachycardia, would be expected. (Choice E) Serotonin syndrome is caused by overactivation of 5-HT receptors. Although it also results in increased sympathetic activity, it is caused by use of serotonergic agents (eg, SSRIs) rather than alcohol use. Educational objective: Chronic alcohol use downregulates inhibitory GABA receptors and upregulates excitatory NMDA glutamate receptors. Therefore, sudden cessation of alcohol leads to decreased GABA activity and increased glutamate activity, resulting in CNS overexcitation (eg, agitation, disorientation, tremulousness, autonomic hyperactivity).

A 42-Year-Old Man Is Brought to the Hospital After a Motor