ASPPB Psychopharmacology 5 — Questions and Answers
Question 1: Methylphenidate's primary pharmacological action in treating ADHD is:
- Releasing stored norepinephrine and dopamine from vesicles
- Blocking dopamine and norepinephrine reuptake transporters (DAT and NET) (Correct answer)
- Inhibiting monoamine oxidase type B selectively
- Acting as a D1 receptor full agonist in the prefrontal cortex
Correct answer: Blocking dopamine and norepinephrine reuptake transporters (DAT and NET)
Methylphenidate blocks DAT and NET, increasing synaptic dopamine and norepinephrine, particularly in prefrontal and striatal circuits.
Question 2: A patient on sertraline develops agitation, diaphoresis, myoclonus, and hyperthermia after adding tramadol for pain. The most likely diagnosis is:
- Neuroleptic malignant syndrome
- Serotonin syndrome (Correct answer)
- Anticholinergic toxidrome
- Malignant hyperthermia
Correct answer: Serotonin syndrome
Tramadol inhibits serotonin reuptake; combined with an SSRI this creates excess serotonergic activity causing serotonin syndrome.
Question 3: Lamotrigine's most serious dermatological risk is Stevens-Johnson syndrome; this risk is minimized by:
- Starting at the target dose and titrating down if rash occurs
- Slow titration, especially when co-administered with valproate (Correct answer)
- Avoiding all concomitant anticonvulsant use
- Pre-treatment screening for HLA-B*1502 allele
Correct answer: Slow titration, especially when co-administered with valproate
Slow titration is critical; valproate inhibits lamotrigine glucuronidation, nearly doubling its half-life and requiring even slower titration.
Question 4: Which pharmacodynamic principle explains why combining a full opioid agonist with buprenorphine can precipitate acute withdrawal?
- Buprenorphine's high receptor affinity and partial agonism displace full agonists (Correct answer)
- Buprenorphine induces CYP3A4, metabolizing the full agonist
- Full agonists downregulate mu receptors below baseline
- Buprenorphine activates kappa receptors causing dysphoria
Correct answer: Buprenorphine's high receptor affinity and partial agonism displace full agonists
Buprenorphine's exceptionally high mu-opioid receptor affinity displaces full agonists; its partial agonism then produces less intrinsic activity, precipitating withdrawal.
Question 5: Acamprosate reduces alcohol craving in abstinent individuals by:
- Inhibiting alcohol dehydrogenase in the liver
- Modulating glutamatergic NMDA receptors and GABA systems to restore balance (Correct answer)
- Blocking kappa-opioid receptors in the reward pathway
- Irreversibly inhibiting aldehyde dehydrogenase
Correct answer: Modulating glutamatergic NMDA receptors and GABA systems to restore balance
Acamprosate normalizes glutamate/GABA dysregulation caused by chronic alcohol exposure, reducing protracted withdrawal and craving.
Question 6: A patient prescribed valproate for bipolar disorder becomes pregnant. The most critical teratogenic concern is:
- Neonatal benzodiazepine withdrawal syndrome
- Neural tube defects and lower IQ scores in offspring (Correct answer)
- Cardiac septal defects similar to lithium exposure
- Ebstein's anomaly of the tricuspid valve
Correct answer: Neural tube defects and lower IQ scores in offspring
Valproate is the most teratogenic mood stabilizer, significantly increasing neural tube defect risk and associated with cognitive impairment in exposed children.
Question 7: When is a loading dose strategy most clinically appropriate?
- When the drug has a very short half-life and is renally cleared
- When rapid attainment of therapeutic plasma levels is needed for a drug with a long half-life (Correct answer)
- When the volume of distribution is extremely small
- When the drug undergoes extensive first-pass metabolism
Correct answer: When rapid attainment of therapeutic plasma levels is needed for a drug with a long half-life
Loading doses rapidly fill the volume of distribution to achieve therapeutic concentrations when waiting multiple half-lives for steady state would be clinically unacceptable.
ASPPB Psychopharmacology 5
Methylphenidate's primary pharmacological action in treating ADHD is: