CARN Pharmacology of Addictive Substances 5 — Questions and Answers
Question 1: A patient with cocaine use disorder asks about FDA-approved pharmacotherapy. Which statement is most accurate?
- Modafinil is FDA-approved and highly effective for cocaine use disorder
- There are currently no FDA-approved medications specifically for cocaine use disorder (Correct answer)
- Naltrexone is FDA-approved for cocaine use disorder
- Disulfiram is FDA-approved as first-line treatment for cocaine use disorder
Correct answer: There are currently no FDA-approved medications specifically for cocaine use disorder
As of 2025, no medications are FDA-approved specifically for cocaine use disorder, though several (topiramate, disulfiram) show limited evidence in research settings.
Question 2: Nicotine replacement therapy (NRT) works by delivering nicotine via a non-tobacco route. What is the primary therapeutic goal of NRT?
- Producing the same CNS euphoria as cigarettes to prevent relapse
- Reducing withdrawal symptoms and craving without the harmful tobacco combustion products (Correct answer)
- Blocking nicotinic receptors to prevent nicotine from producing any effect
- Sensitizing nicotinic receptors to make future smoking aversive
Correct answer: Reducing withdrawal symptoms and craving without the harmful tobacco combustion products
NRT reduces nicotine withdrawal and craving by providing controlled nicotine exposure, allowing the patient to quit smoking without the harmful chemicals in tobacco smoke.
Question 3: Inhalant abuse (e.g., toluene) produces CNS effects primarily through which mechanism?
- Strong agonism at dopamine D1 receptors
- Potentiation of GABA-A and inhibition of NMDA receptors, similar to alcohol (Correct answer)
- Blockade of serotonin reuptake transporters
- Selective activation of kappa-opioid receptors
Correct answer: Potentiation of GABA-A and inhibition of NMDA receptors, similar to alcohol
Toluene and other inhalants potentiate GABA-A receptors and block NMDA receptors, producing CNS depression, disinhibition, and euphoria similar to alcohol intoxication.
Question 4: Which pharmacological property of kratom makes it relevant to opioid use disorder treatment discussions?
- Kratom's active alkaloids act as partial agonists at mu-opioid receptors (Correct answer)
- Kratom blocks dopamine reuptake transporters, producing stimulant effects only
- Kratom selectively antagonizes kappa-opioid receptors, reducing dysphoria
- Kratom enhances endogenous endorphin release without receptor binding
Correct answer: Kratom's active alkaloids act as partial agonists at mu-opioid receptors
Kratom's active alkaloids (mitragynine, 7-hydroxymitragynine) are partial mu-opioid receptor agonists, producing opioid-like effects and carrying dependence and withdrawal risk.
Question 5: Clonidine is sometimes used in opioid withdrawal management. What is its primary mechanism in this context?
- It blocks mu-opioid receptors to prevent relapse
- It stimulates alpha-2 adrenergic receptors, suppressing noradrenergic hyperactivity that drives withdrawal symptoms (Correct answer)
- It enhances GABA release to reduce anxiety during withdrawal
- It inhibits dopamine reuptake to compensate for reward deficits
Correct answer: It stimulates alpha-2 adrenergic receptors, suppressing noradrenergic hyperactivity that drives withdrawal symptoms
Opioid withdrawal activates the locus coeruleus; clonidine's alpha-2 agonism suppresses this noradrenergic hyperactivity, reducing sweating, anxiety, and GI distress.
Question 6: A patient on methadone maintenance develops a prolonged QTc interval on ECG. Which factor most directly explains methadone's cardiac risk?
- Methadone blocks cardiac hERG potassium channels, prolonging cardiac repolarization (Correct answer)
- Methadone stimulates sympathetic outflow, increasing heart rate and QTc
- Methadone induces electrolyte wasting through renal mechanisms
- Methadone activates mu-opioid receptors in the sinoatrial node
Correct answer: Methadone blocks cardiac hERG potassium channels, prolonging cardiac repolarization
Methadone blocks hERG (IKr) potassium channels responsible for cardiac repolarization, prolonging the QTc interval and increasing torsades de pointes risk.
Question 7: Which of the following best explains the phenomenon of opioid-induced hyperalgesia (OIH)?
- Tolerance to opioid analgesia requires dose escalation, which the patient perceives as increased pain
- Chronic opioid exposure sensitizes NMDA receptors and reduces endogenous opioid production, paradoxically increasing pain sensitivity (Correct answer)
- Opioids deplete serotonin stores, removing descending pain inhibition
- Physical dependence causes patients to report pain to obtain more opioids
Correct answer: Chronic opioid exposure sensitizes NMDA receptors and reduces endogenous opioid production, paradoxically increasing pain sensitivity
OIH involves NMDA receptor sensitization and dynorphin-mediated mechanisms that increase pain sensitivity in patients on chronic opioids, distinct from tolerance.
CARN Pharmacology of Addictive Substances 5
A patient with cocaine use disorder asks about FDA-approved pharmacotherapy.
Which statement is most accurate?