A 34-year-old woman with sleep problems comes to the office. Over the last year, she has had increasing difficulty falling asleep at night and is exhausted during the day. The patient does not use alcohol, tobacco, or illicit drugs. She has a family history of heart disease and depression. The patient has failed a number of nonpharmacological approaches, including cognitive-behavioral therapy for insomnia. She requests pharmacologic treatment and is prescribed a short course of zolpidem. Which of the following is the most likely mechanism of action of this medication?

Question

A 34-year-old woman with sleep problems comes to the office.  Over the last year, she has had increasing difficulty falling asleep at night and is exhausted during the day.  The patient does not use alcohol, tobacco, or illicit drugs.  She has a family history of heart disease and depression.  The patient has failed a number of nonpharmacological approaches, including cognitive-behavioral therapy for insomnia.  She requests pharmacologic treatment and is prescribed a short course of zolpidem.  Which of the following is the most likely mechanism of action of this medication?

Quizplus · Accepted Answer

Zolpidem is a short-acting nonbenzodiazepine hypnotic agent. Other medications in this class include zaleplon and eszopiclone. Like benzodiazepines, these medications bind to the GABA_A receptor at the benzodiazepine receptor site, where they act as GABA_A agonists. However, they are chemically distinct from benzodiazepines, and their binding is more specific for certain receptor subtypes. As a result, nonbenzodiazepines are primarily hypnotics and do not produce the anxiolytic, muscle relaxant, or anticonvulsant effects associated with benzodiazepines. Nonbenzodiazepines cause similar side effects to benzodiazepines (eg, next-day somnolence, cognitive dysfunction, increased risk of falls in older adults). They should be used for the shortest time possible and at the lowest effective dose. (Choice A) Dopamine receptor antagonism is the mechanism of action of antipsychotic medication (eg, haloperidol, risperidone). (Choice C) Histamine receptor antagonism is the mechanism of action of antihistamines (eg, diphenhydramine). Although antihistamines are often used as over-the-counter sleep aids, there is little evidence for benefit in insomnia. (Choice D) Melatonin receptor agonism is the mechanism of action of the insomnia medication ramelteon. (Choice E) Orexin receptor antagonism is the mechanism of action of the insomnia medication suvorexant. (Choice F) Serotonin receptor agonism is the mechanism of action of triptans used to treat migraine headaches and of psychedelics (eg, psilocybin, LSD). Educational objective: Nonbenzodiazepine medications (eg, zolpidem, zaleplon, eszopiclone) stimulate specific subtypes of GABA_A receptors. As a result, nonbenzodiazepines are primarily hypnotics and do not produce the anxiolytic, muscle relaxant, or anticonvulsant effects associated with benzodiazepines. __________ References: Randomised clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people. (http://www.ncbi.nlm.nih.gov/pubmed/25922426) Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. (http://www.ncbi.nlm.nih.gov/pubmed/27998379) Pharmacotherapy of insomnia. (http://www.ncbi.nlm.nih.gov/pubmed/29881321)

A 34-Year-Old Woman with Sleep Problems Comes to the Office