A 34-year-old man comes to the office for evaluation of opioid use disorder. He was prescribed oxycodone for a sports-related injury in his mid-20s, developed dependency, and began using intravenous heroin in its place. In the past few years, the patient has had multiple overdoses requiring naloxone administration. He recently tried quitting heroin on his own but experienced recurrent relapses. He has now been abstinent for 2 days but reports significant cravings. After a discussion of various treatment options, the patient is prescribed buprenorphine. The dose-response curve of this medication is shown in the image below: Which of the following clinical pharmacologic effects of buprenorphine is most likely?

Question

A 34-year-old man comes to the office for evaluation of opioid use disorder.  He was prescribed oxycodone for a sports-related injury in his mid-20s, developed dependency, and began using intravenous heroin in its place.  In the past few years, the patient has had multiple overdoses requiring naloxone administration.  He recently tried quitting heroin on his own but experienced recurrent relapses.  He has now been abstinent for 2 days but reports significant cravings.  After a discussion of various treatment options, the patient is prescribed buprenorphine.  The dose-response curve of this medication is shown in the image below:  Which of the following clinical pharmacologic effects of buprenorphine is most likely?

Quizplus · Accepted Answer

11ec160b_3c56_42c2_9249_61990159a889_MD0001_00 This patient has developed opioid use disorder with dependency. Some patients benefit from opioid replacement therapy, either indefinitely or as a bridge to gradual cessation. Buprenorphine is a semisynthetic opioid used to replace and treat dependency on unregulated opioids (eg, heroin) due to its favorable pharmacokinetics. As a partial agonist at the mu opioid receptor (ie, mixed agonist and antagonist activity), buprenorphine has a ceiling effect. At higher doses, the agonist activity is equally opposed by the antagonist activity, leading to a plateau (ceiling) in the dose-response curve. This ceiling caps its analgesic potency but reduces unwanted adverse effects such as respiratory depression. Therefore, high doses of buprenorphine carry a lower risk of respiratory depression compared to full agonists such as heroin (Choice C). A key drawback of partial agonists (eg, buprenorphine) is the potential to displace full agonists from the receptor: partial agonists act as relative antagonists in the presence of full agonists. Therefore, buprenorphine can precipitate acute withdrawal if administered when receptors are still occupied by full agonists (eg, heroin). For this reason, patients must discontinue opioids and partially enter the withdrawal state (eg, wait 48 hours) prior to the initiation of buprenorphine. (Choice A) Complete reversal of a full agonist (eg, heroin) requires a full antagonist (eg, naloxone). Because buprenorphine is a partial agonist-antagonist, the degree of reversal is limited by the ceiling effect. (Choice D) The ability of antagonists to displace bound drugs is determined by the affinity of the drug-receptor interaction. Drugs that bind tightly have a steep binding curve; in other words, a lower concentration of drug is required to achieve the same effect. Buprenorphine has a higher affinity to the mu receptor than heroin, which is apparent from its steeper binding curve. Overdose with buprenorphine often requires repeated, high doses of naloxone due to this higher affinity. Educational objective: Buprenorphine is a semisynthetic opioid with mixed/partial agonist-antagonist activity, resulting in a therapeutic ceiling. Relative to full opioid agonists, this reduces the risk of dose-dependent adverse effects such as respiratory depression. __________ References: Treatment of opioid dependence with buprenorphine: current update. (http://www.ncbi.nlm.nih.gov/pubmed/29302227)

A 34-Year-Old Man Comes to the Office for Evaluation of Opioid