CARN Pharmacology of Addictive Substances 2 — Questions and Answers
Question 1: Which receptor subtype is primarily responsible for the euphoric effects of opioids?
- Kappa (κ)
- Delta (δ)
- Mu (μ) (Correct answer)
- Sigma (σ)
Correct answer: Mu (μ)
Mu (μ) opioid receptors mediate euphoria, analgesia, and respiratory depression, making them the primary target for opioid misuse.
Question 2: A patient on buprenorphine/naloxone reports that injecting the medication produces little to no euphoria. Which pharmacological property of naloxone best explains this?
- Naloxone has a longer half-life than buprenorphine
- Naloxone blocks opioid receptors when administered parenterally (Correct answer)
- Naloxone induces CYP3A4 metabolism of buprenorphine
- Naloxone causes histamine release that blunts reward
Correct answer: Naloxone blocks opioid receptors when administered parenterally
Naloxone has poor sublingual bioavailability but becomes active when injected, blocking opioid receptors and precipitating withdrawal, deterring misuse.
Question 3: Cocaine's primary mechanism of action involves blocking the reuptake of which neurotransmitter most responsible for its reinforcing effects?
- Serotonin
- GABA
- Dopamine (Correct answer)
- Norepinephrine
Correct answer: Dopamine
Cocaine blocks dopamine transporter (DAT), causing dopamine accumulation in the nucleus accumbens, which drives its reinforcing and euphoric effects.
Question 4: Which benzodiazepine property makes diazepam particularly prone to misuse compared to oxazepam?
- Diazepam has active metabolites; oxazepam does not
- Diazepam has a faster onset of action due to higher lipophilicity (Correct answer)
- Diazepam requires hepatic glucuronidation; oxazepam does not
- Diazepam has higher protein binding than oxazepam
Correct answer: Diazepam has a faster onset of action due to higher lipophilicity
Diazepam's high lipophilicity allows rapid CNS penetration and faster onset, producing a more intense euphoric effect that increases its misuse potential.
Question 5: Which mechanism explains why alcohol withdrawal can be life-threatening, unlike opioid withdrawal?
- Alcohol causes upregulation of GABA-A receptors leading to CNS hyperexcitability upon cessation (Correct answer)
- Alcohol downregulates dopamine receptors causing severe dysphoria
- Alcohol depletes glycogen stores leading to fatal hypoglycemia
- Alcohol causes permanent destruction of serotonin neurons
Correct answer: Alcohol causes upregulation of GABA-A receptors leading to CNS hyperexcitability upon cessation
Chronic alcohol use downregulates GABA-A receptors and upregulates NMDA receptors; abrupt cessation causes CNS hyperexcitability, risking seizures and death.
Question 6: Naltrexone reduces alcohol cravings primarily by which pharmacological mechanism?
- Blocking NMDA glutamate receptors
- Blocking opioid receptors that mediate alcohol-induced dopamine release (Correct answer)
- Inhibiting aldehyde dehydrogenase to cause aversive reactions
- Enhancing GABA-A receptor activity to reduce anxiety
Correct answer: Blocking opioid receptors that mediate alcohol-induced dopamine release
Naltrexone blocks mu-opioid receptors, preventing the endorphin-mediated dopamine release that reinforces alcohol consumption.
Question 7: A patient who smokes methamphetamine develops severe hyperthermia and rhabdomyolysis. Which pharmacological mechanism most directly contributes to hyperthermia?
- Direct toxicity to the hypothalamic temperature set-point
- Massive norepinephrine release causing peripheral vasoconstriction and excess heat retention (Correct answer)
- Dopamine receptor overstimulation in the motor cortex
- Inhibition of monoamine oxidase preventing heat dissipation
Correct answer: Massive norepinephrine release causing peripheral vasoconstriction and excess heat retention
Methamphetamine causes massive norepinephrine release, producing intense vasoconstriction that impairs heat dissipation and raises core body temperature.
CARN Pharmacology of Addictive Substances 2
Which receptor subtype is primarily responsible for the euphoric effects of opioids?