SPEX SPEX Pharmacology 5 — Questions and Answers
Question 1: A patient receiving aminoglycoside therapy develops nephrotoxicity. Which aminoglycoside dosing strategy best minimizes this risk while maintaining efficacy?
- Continuous infusion over 24 hours
- Divided doses every 6 hours
- Once-daily extended-interval dosing (Correct answer)
- Dose based on total body weight only
Correct answer: Once-daily extended-interval dosing
Once-daily extended-interval dosing exploits the aminoglycoside's concentration-dependent killing and post-antibiotic effect while allowing renal tubular cells to recover, reducing nephrotoxicity.
Question 2: Which opioid analgesic has the highest oral bioavailability and is least affected by first-pass metabolism?
- Morphine
- Codeine
- Methadone (Correct answer)
- Oxymorphone
Correct answer: Methadone
Methadone has high and variable oral bioavailability (~80%) partly because it undergoes less first-pass hepatic extraction compared to most other opioids.
Question 3: A patient with acute angle-closure glaucoma should NOT receive which drug class due to risk of worsening the condition?
- Beta-blockers
- Anticholinergics (Correct answer)
- Carbonic anhydrase inhibitors
- Alpha-2 agonists
Correct answer: Anticholinergics
Anticholinergics cause pupillary dilation (mydriasis), which can mechanically block aqueous humor outflow at the iridocorneal angle, acutely raising intraocular pressure.
Question 4: Selective COX-2 inhibitors (e.g., celecoxib) carry an increased cardiovascular risk primarily because they:
- Inhibit prostacyclin (PGI2) while sparing thromboxane A2 (TXA2) (Correct answer)
- Increase platelet aggregation directly
- Inhibit thromboxane A2 while sparing prostacyclin
- Elevate LDL cholesterol through PCSK9 upregulation
Correct answer: Inhibit prostacyclin (PGI2) while sparing thromboxane A2 (TXA2)
COX-2 is expressed in vascular endothelium and produces protective PGI2; its inhibition shifts the balance toward pro-thrombotic TXA2 activity from platelets, increasing MI and stroke risk.
Question 5: Which statement correctly describes the Vmax in Michaelis-Menten enzyme kinetics as applied to drug metabolism?
- It is the drug concentration at which reaction rate is half-maximal
- It is the maximum rate of metabolism achieved when all enzyme active sites are saturated (Correct answer)
- It represents the affinity of the drug for the metabolizing enzyme
- It decreases as drug concentration increases
Correct answer: It is the maximum rate of metabolism achieved when all enzyme active sites are saturated
Vmax is the theoretical maximum metabolic rate reached when all available enzyme molecules are fully occupied with substrate, making it independent of further drug concentration increases.
Question 6: A patient taking phenytoin for epilepsy is started on isoniazid (INH) for tuberculosis. What is the expected pharmacokinetic outcome?
- Phenytoin levels decrease due to CYP2C9 induction by INH
- Phenytoin levels increase due to CYP2C9 inhibition by INH (Correct answer)
- INH levels increase due to phenytoin inhibition of N-acetyltransferase
- No clinically significant interaction is expected
Correct answer: Phenytoin levels increase due to CYP2C9 inhibition by INH
Isoniazid inhibits CYP2C9 and CYP2C19, which are responsible for phenytoin hydroxylation, causing phenytoin accumulation and potential toxicity (nystagmus, ataxia).
Question 7: Which drug used in the treatment of Parkinson's disease works by inhibiting catechol-O-methyltransferase (COMT)?
- Selegiline
- Bromocriptine
- Entacapone (Correct answer)
- Amantadine
Correct answer: Entacapone
Entacapone and tolcapone inhibit COMT, the enzyme that degrades levodopa and dopamine peripherally, thereby prolonging levodopa's effect and reducing 'off' periods.
SPEX SPEX Pharmacology 5
A patient receiving aminoglycoside therapy develops nephrotoxicity.
Which aminoglycoside dosing strategy best minimizes this risk while maintaining efficacy?