ExCPT Test Pharmacology 3 — Questions and Answers

Question 1: Which drug class is primarily used to treat Type 2 diabetes by increasing insulin sensitivity in peripheral tissues?

Sulfonylureas
Thiazolidinediones (Correct answer)
DPP-4 inhibitors
Alpha-glucosidase inhibitors

Correct answer: Thiazolidinediones

Thiazolidinediones (e.g., pioglitazone, rosiglitazone) are insulin sensitizers that act on PPAR-gamma receptors to reduce insulin resistance in muscle and adipose tissue.

Thiazolidinediones (TZDs), also called glitazones, activate peroxisome proliferator-activated receptor gamma (PPAR-γ), a nuclear receptor that regulates gene expression related to glucose and lipid metabolism. This increases insulin sensitivity in peripheral tissues (muscle, fat, liver), lowering blood glucose. Examples include pioglitazone (Actos) and rosiglitazone (Avandia). TZDs can cause fluid retention, weight gain, and are contraindicated in heart failure.

Question 2: A patient is prescribed atorvastatin. What is the primary mechanism of action of this drug?

Inhibits bile acid reabsorption
Inhibits HMG-CoA reductase (Correct answer)
Activates LDL receptors directly
Inhibits cholesterol absorption in the gut

Correct answer: Inhibits HMG-CoA reductase

Atorvastatin (Lipitor) is an HMG-CoA reductase inhibitor (statin) that blocks the rate-limiting enzyme in cholesterol biosynthesis in the liver.

HMG-CoA reductase is the rate-limiting enzyme in hepatic cholesterol synthesis. Statins like atorvastatin competitively inhibit this enzyme, reducing intracellular cholesterol. This causes hepatocytes to upregulate LDL receptors on their surface, increasing clearance of LDL from the bloodstream. The net result is lower total cholesterol, LDL, and triglycerides, and modestly higher HDL. Key adverse effects include myopathy (muscle pain) and, rarely, rhabdomyolysis.

Question 3: Which of the following opioid analgesics has the HIGHEST risk of causing QT prolongation?

Morphine
Hydrocodone
Methadone (Correct answer)
Oxycodone

Correct answer: Methadone

Methadone has a unique pharmacological profile that includes potassium channel blockade, leading to QT interval prolongation and risk of torsades de pointes arrhythmia.

Methadone, while effective for chronic pain and opioid use disorder treatment, blocks cardiac hERG potassium channels, prolonging the QT interval on ECG. This can predispose patients to torsades de pointes (TdP), a potentially fatal ventricular arrhythmia. Risk is increased by high doses, drug interactions (CYP3A4/CYP2D6 inhibitors), hypokalemia, and concomitant QT-prolonging drugs. ECG monitoring and electrolyte management are essential in patients on methadone.

Question 4: Benzodiazepines exert their anxiolytic effects by acting on which receptor?

NMDA glutamate receptor
GABA-A receptor (Correct answer)
Serotonin 5-HT1A receptor
Dopamine D2 receptor

Correct answer: GABA-A receptor

Benzodiazepines bind to GABA-A receptors at the benzodiazepine binding site, enhancing the effect of GABA (gamma-aminobutyric acid) and increasing chloride ion influx.

GABA-A receptors are ligand-gated chloride ion channels and the primary inhibitory receptors in the CNS. Benzodiazepines act as positive allosteric modulators — they bind to a specific site between the alpha and gamma subunits of GABA-A receptors and increase the frequency of chloride channel opening in response to GABA binding. This enhances neuronal inhibition, producing anxiolytic, sedative, anticonvulsant, and muscle-relaxant effects. Tolerance and dependence develop with chronic use.

Question 5: Which drug is used as an antidote for acetaminophen (Tylenol) overdose?

Flumazenil
Naloxone
N-acetylcysteine (Correct answer)
Atropine

Correct answer: N-acetylcysteine

N-acetylcysteine (NAC) replenishes hepatic glutathione stores, allowing the liver to detoxify the toxic NAPQI metabolite that accumulates in acetaminophen overdose.

In acetaminophen overdose, the toxic metabolite NAPQI (N-acetyl-p-benzoquinone imine) overwhelms hepatic glutathione stores, causing oxidative liver cell damage. N-acetylcysteine (NAC) acts as a glutathione precursor and direct NAPQI scavenger. Given within 8–10 hours of ingestion, NAC prevents serious hepatotoxicity. It can be given orally or intravenously. The Rumack-Matthew nomogram helps determine treatment necessity based on serum acetaminophen levels and time post-ingestion.

Question 6: What is the primary pharmacological effect of selective serotonin reuptake inhibitors (SSRIs)?

Block dopamine reuptake in the prefrontal cortex
Inhibit the reuptake of serotonin at the presynaptic terminal (Correct answer)
Directly stimulate postsynaptic serotonin receptors
Prevent serotonin breakdown by MAO enzymes

Correct answer: Inhibit the reuptake of serotonin at the presynaptic terminal

SSRIs block the serotonin transporter (SERT), preventing serotonin reuptake into the presynaptic neuron, thereby increasing serotonin availability in the synaptic cleft.

SSRIs (e.g., fluoxetine, sertraline, escitalopram) selectively inhibit the serotonin transporter (SERT) on the presynaptic neuron, blocking serotonin reuptake from the synaptic cleft. This increases the concentration of serotonin available to bind postsynaptic receptors. With continued use, downstream neuroplastic changes (receptor desensitization, altered gene expression) produce the therapeutic antidepressant effect. SSRIs are first-line for depression, anxiety disorders, OCD, PTSD, and other conditions.

ExCPT Test Pharmacology 3

Which drug class is primarily used to treat Type 2 diabetes by increasing insulin sensitivity in peripheral tissues?