Pharmacology Test 1 — Questions and Answers

Question 1: Ten months after starting procainamide therapy for cardiac arrhythmias, a 56-year-old man develops arthritis and other symptoms consistent with drug-induced systemic lupus erythematosus. Results of a blood test are positive for antinuclear antibodies. This finding is consistent with which of the following genetic polymorphisms in drug metabolism?

Debrisoquine 4-hydroxylase deficiency
Erythrocyte catechol-O-methyltransferase deficiency
Glucose 6-phosphate dehydrogenase deficiency
Phenytoin hydroxylase deficiency
Slow acetylator phenotype (Correct answer)

Correct answer: Slow acetylator phenotype

Procainamide-induced systemic lupus erythematosus is strongly associated with the slow acetylator phenotype. Individuals with this genetic polymorphism have reduced activity of N-acetyltransferase, an enzyme responsible for metabolizing procainamide. This leads to higher and prolonged plasma concentrations of the drug and its active metabolites, increasing the risk of developing the autoimmune reaction.

Question 2: An 83-year-old man has a 2-month history of akinesia, rigidity, and tremor. He has been taking a drug for the past 7 years to control severe behavioral and psychiatric symptoms associated with dementia, Alzheimer type. This adverse effect is most likely mediated through which of the following?

Anticholinergic effects
Antidopaminergic effects (Correct answer)
Downregulation of γ-aminobutyric acid (GABA)
Inhibition of norepinephrine reuptake
Inhibition of serotonin reuptak
Upregulation of GABA

Correct answer: Antidopaminergic effects

The patient's symptoms of akinesia, rigidity, and tremor are characteristic of drug-induced parkinsonism, also known as extrapyramidal symptoms. These adverse effects commonly occur with antipsychotic medications, which are often used for behavioral symptoms in dementia. Antipsychotics exert their effects by blocking dopamine D2 receptors in the brain, leading to an imbalance in the basal ganglia that mimics Parkinson's disease.

Question 3: A 23-year-old man with HIV infection has Pneumocystis jirovecii pneumonia. Therapy is started with trimethoprimsulfamethoxazole, and his pneumonia resolves. The pharmacotherapy was effective because of inhibition of which of the following?

Cell wall synthesis
Dihydrofolate reductase (Correct answer)
Incorporation of p-aminobenzoic acid
Incorporation of sterol into membranes
Topoisomerase II

Correct answer: Dihydrofolate reductase

Trimethoprim-sulfamethoxazole (TMP-SMX) is a synergistic antibiotic combination that targets the folate synthesis pathway in microorganisms. Sulfamethoxazole inhibits dihydropteroate synthase, while trimethoprim specifically inhibits dihydrofolate reductase. This dual blockade prevents the conversion of dihydrofolic acid to tetrahydrofolic acid, which is essential for DNA and RNA synthesis in Pneumocystis jirovecii, thereby resolving the pneumonia.

Question 4: A 62-year-old man comes to the physician because of burning pain and tenderness of his right great toe 1 day after heavy ethanol consumption. Physical examination shows erythema, swelling, warmth, and tenderness of the right great toe. After a 2-week course of nonsteroidal anti-inflammatory drug treatment, his symptoms decrease in severity but do not completely resolve. The serum concentration of which of the following is most likely increased in this patient?

Calcium
Carotene
Creatinine
Iron
Orotic acid
Phosphate
Uric acid (Correct answer)

Correct answer: Uric acid

The patient's symptoms of acute, severe pain, swelling, warmth, and erythema in the great toe, particularly after heavy ethanol consumption, are classic for an acute attack of gout. Gout is caused by the deposition of monosodium urate crystals in joints, which occurs when serum uric acid concentrations are elevated. Ethanol consumption can exacerbate gout by increasing uric acid production and decreasing its renal excretion.

Question 5: A 62-year-old man is being treated with cisplatin for small cell carcinoma of the lungs. The efficacy of cisplatin depends on interaction with which of the following?

DNA (Correct answer)
DNA polymerase
Growth factor receptors
Reverse transcriptase
Ribosomes

Correct answer: DNA

Cisplatin is a platinum-based antineoplastic agent used in chemotherapy. Its efficacy stems from its ability to form highly reactive platinum complexes that bind to and cross-link DNA strands within cancer cells. This DNA damage inhibits DNA replication and transcription, ultimately leading to apoptosis of rapidly dividing tumor cells, making it effective against small cell carcinoma of the lungs.

Question 6: An 18-year-old woman comes to the physician because of nausea, vomiting, and abdominal pain 1 hour after ingesting a glass of wine with dinner. Three days ago, she began antibiotic treatment for vaginitis after a wet mount preparation of vaginal discharge showed a motile protozoan. This patient most likely has been taking which of the following drugs?

Ceftriaxone
Chloroquine
Clindamycin
Metronidazole (Correct answer)

Correct answer: Metronidazole

The patient's symptoms of nausea, vomiting, and abdominal pain after consuming wine while on an antibiotic for a motile protozoan (likely metronidazole for Trichomonas vaginitis) are characteristic of a disulfiram-like reaction. Metronidazole inhibits aldehyde dehydrogenase, an enzyme crucial for alcohol metabolism. This inhibition leads to an accumulation of acetaldehyde, causing unpleasant symptoms like flushing, nausea, and vomiting.

Question 7: A 20-year-old woman comes to the emergency department after ingesting at least 30 tablets of an unknown drug. Initial physical examination shows no abnormalities. Thirty-six hours later, serum AST activity is 1500 U/L, and serum ALT activity is 2000 U/L. The drug this patient ingested is most likely which of the following?

Acetaminophen (Correct answer)
Aspirin
Chlorpheniramine
Ibuprofen
Prednisone

Correct answer: Acetaminophen

The delayed onset of significantly elevated serum AST and ALT levels (indicating severe liver damage) 36 hours after an unknown drug ingestion is highly characteristic of acetaminophen (paracetamol) overdose. Acetaminophen overdose leads to the depletion of glutathione, allowing the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) to accumulate and cause hepatocellular necrosis.

Question 8: A 42-year-old woman who is a chemist is brought to the emergency department because of a 1-hour history of severe abdominal cramps, nausea and vomiting, hypotension, bradycardia, sweating, and difficulty breathing due to bronchospasm and congestion. Exposure to which of the following is most likely?

Acrylamide
Cyanogen bromide
Isoflurophate (DFP) (Correct answer)
Phentolamine
Propranolol

Correct answer: Isoflurophate (DFP)

The patient's constellation of symptoms, including severe abdominal cramps, nausea, vomiting, hypotension, bradycardia, sweating, bronchospasm, and congestion, are classic signs of a cholinergic crisis. This clinical picture is consistent with exposure to an organophosphate compound like isoflurophate (DFP), which irreversibly inhibits acetylcholinesterase, leading to excessive acetylcholine accumulation and parasympathetic overstimulation.

Question 9: A 35-year-old woman is diagnosed with gastroesophageal reflux disease. Omeprazole is administered. Which of the following is the most likely mechanism of action of this drug?

Blockade of gastrin receptors
Blockade of H1 receptors
Blockade of M3 receptors
Inhibition of H + –K + ATPase activity (Correct answer)
Inhibition of synthesis of gastrin

Correct answer: Inhibition of H + –K + ATPase activity

Omeprazole is a proton pump inhibitor (PPI) used to treat gastroesophageal reflux disease (GERD). Its mechanism of action involves irreversibly binding to and inhibiting the H+/K+-ATPase enzyme, also known as the proton pump, located on the apical membrane of gastric parietal cells. This inhibition effectively blocks the final common pathway for acid secretion, significantly reducing gastric acid production.

Question 10: In a 40-year-old man with hypertension, which of the following agents has the greatest potential to activate presynaptic autoreceptors, inhibit norepinephrine release, and decrease sympathetic outflow?

α1-Adrenergic agonist
α2-Adrenergic agonist (Correct answer)
β1/β2-Adrenergic antagonist
Angiotensin-converting enzyme inhibitor
Calcium antagonist

Correct answer: α2-Adrenergic agonist

Alpha-2 adrenergic agonists, such as clonidine, act on presynaptic alpha-2 autoreceptors in the central nervous system. Activation of these receptors inhibits the release of norepinephrine from sympathetic nerve terminals. This leads to a reduction in sympathetic outflow from the brainstem, resulting in decreased peripheral vascular resistance, heart rate, and blood pressure, making them effective in treating hypertension.

Question 11: A 35-year-old woman is brought to the emergency department because of an 18-hour history of severe pain, nausea, vomiting, diarrhea, and anxiety. She was discharged with a pain medication from the hospital 2 weeks ago after treatment of multiple injuries sustained in a motor vehicle collision. She took her last dose 36 hours ago. Her temperature is 36.6°C (97.8°F), pulse is 105/min, respirations are 24/min, and blood pressure is 160/85 mm Hg. Physical examination shows rhinorrhea and piloerection. Bowel sounds are normal. She rates the pain as an 8 on a 10-point scale. Which of the following is the most likely diagnosis?

Acute appendicitis
Caffeine withdrawal
Ethanol withdrawal
Gastric ulcers
Gastroenteritis
Oxycodone withdrawal (Correct answer)

Correct answer: Oxycodone withdrawal

The patient's symptoms, including severe pain, nausea, vomiting, diarrhea, anxiety, rhinorrhea, piloerection, and autonomic hyperactivity (tachycardia, tachypnea, hypertension), occurring 36 hours after the last dose of a pain medication, are classic signs of opioid withdrawal. Oxycodone is a potent opioid, and abrupt cessation after prolonged use leads to a rebound overactivity of the sympathetic nervous system and other withdrawal symptoms.

Question 12: A 21-year-old woman comes to the physician for counseling prior to conception. She delivered a female newborn with anencephaly 1 year ago. The newborn died at the age of 4 days. She asks the physician if she can take any vitamins to decrease her risk for conceiving a fetus with anencephaly. It is most appropriate for the physician to recommend which of the following vitamins?

Biotin
Folic acid (Correct answer)
Vitamin B1 (thiamine)
Vitamin B2 (riboflavin)
Vitamin B6 (pyridoxine)
Vitamin B12 (cyanocobalamin)

Correct answer: Folic acid

Anencephaly is a severe neural tube defect (NTD) that occurs during early fetal development. Supplementation with folic acid (vitamin B9) before conception and during the first trimester of pregnancy has been extensively proven to significantly reduce the risk of NTDs. Folic acid is crucial for DNA synthesis and repair, and for cell division, which are vital processes during neural tube closure.

Question 13: A 38-year-old man comes to the physician because of a 6-month history of occasional episodes of chest tightness, wheezing, and cough. The symptoms are often mild and resolve spontaneously. He has been otherwise healthy. His respirations are 13/min. The lungs are clear to auscultation. Cardiac examination and chest x-ray show no abnormalities. Which of the following agents is most appropriate to treat acute episodes in this patient?

Albuterol (Correct answer)
Beclomethasone
Cromolyn
Ipratropium
Theophylline

Correct answer: Albuterol

The patient's symptoms of occasional, mild, and spontaneously resolving chest tightness, wheezing, and cough are consistent with mild intermittent asthma. For acute episodes of asthma, the most appropriate treatment is a short-acting beta-2 adrenergic agonist (SABA) like albuterol. Albuterol rapidly relaxes bronchial smooth muscle, leading to bronchodilation and quick relief of symptoms.

Question 14: A new drug, Drug X, relieves pain by interacting with a specific receptor in the body. Drug X binds irreversibly to this receptor, resulting in a long duration of action. Which of the following types of bonds is most likely formed between Drug X and its receptor?

Covalent (Correct answer)
Hydrogen
Hydrophobic
Ionic
van der Waals

Correct answer: Covalent

Irreversible binding of a drug to its receptor typically involves the formation of a strong, stable covalent bond. Unlike weaker non-covalent interactions, covalent bonds require the synthesis of new receptor molecules to restore function. This leads to a prolonged duration of action that is independent of the drug's plasma half-life, as the drug-receptor complex is not easily dissociated.

Question 15: A 49-year-old man with hypertension comes to the physician for a follow-up examination. At his last visit 2 months ago, his serum total cholesterol concentration was 320 mg/dL. He then began a low-cholesterol diet. His blood pressure is 145/95 mm Hg. Physical examination shows no other abnormalities. Serum studies show a total cholesterol concentration of 310 mg/dL. Kidney and liver function test results are within normal limits. The most appropriate pharmacotherapy for this patient is a drug that has which of the following mechanisms of action?

Activates peroxisome proliferator-activated receptors
Decreases hepatic production of VLDL cholesterol
Forms insoluble complexes with bile acids in the gut
Impairs absorption of cholesterol in the small intestine brush border
Inhibits 3-HMG-CoA reductase (Correct answer)

Correct answer: Inhibits 3-HMG-CoA reductase

The patient has significantly elevated total cholesterol that has not responded adequately to dietary changes, indicating a need for pharmacotherapy. The most appropriate first-line treatment for hypercholesterolemia is a statin, which works by inhibiting HMG-CoA reductase. This enzyme is the rate-limiting step in cholesterol synthesis in the liver, leading to decreased intracellular cholesterol and increased LDL clearance.

Question 16: A 17-year-old girl is brought to the physician by her parents 30 minutes after having a generalized tonic-clonic seizure while playing in a soccer game. She currently takes no medications. Physical examination shows no abnormalities. After further testing including 24-hour continuous EEG monitoring, carbamazepine is prescribed. This patient’s use of additional medications should be monitored because of which of the following changes in drug disposition after starting pharmacotherapy?

Decreased absorption in the intestine
Decreased distribution to the brain
Increased excretion by the kidneys
Increased metabolism by the liver (Correct answer)
Increased recirculation in the bile

Correct answer: Increased metabolism by the liver

Carbamazepine is a potent inducer of hepatic cytochrome P450 enzymes, particularly CYP3A4. This enzyme induction leads to increased metabolism of many co-administered drugs, as well as carbamazepine itself. Consequently, the plasma concentrations of other medications taken by the patient may decrease, potentially reducing their efficacy and requiring dose adjustments.

Question 17: A 14-year-old boy is brought to the physician for examination prior to participating on his school’s soccer team. Physical examination shows jaundice. Serum studies show a total bilirubin concentration of 2.5 mg/dL, ALT activity of 70 U/L, and ceruloplasmin concentration of 5 mg/dL (N=20–40). A slit-lamp examination shows the presence of brownish rings in the cornea, surrounding the iris. The most appropriate treatment at this time is a drug with which of the following mechanisms of action?

Decreases serum bilirubin concentration
Increases serum chloride concentration
Increases urine copper excretion
Increases urine lead excretion (Correct answer)

Correct answer: Increases urine lead excretion

The patient's clinical presentation, including jaundice, low ceruloplasmin, and Kayser-Fleischer rings, is highly suggestive of Wilson's disease, a disorder of copper accumulation. While the primary treatment for Wilson's disease involves chelating agents that increase urine copper excretion, some of these agents, such as D-penicillamine, are broad-spectrum chelators. D-penicillamine can also chelate lead, thus increasing its urinary excretion, making this a potential, albeit secondary, mechanism of action for such a drug.

Question 18: A 60-year-old woman comes to the physician because she recently was diagnosed with non-small cell lung carcinoma and she wants to discuss possible treatment options. She tells the physician that she is concerned about the possible adverse effects of chemotherapy. The physician says that serious toxicity caused by antineoplastic drugs is seen in the bone marrow. Which of the following best explains this finding?

Cells in the marrow divide rapidly (Correct answer)
Cells in the marrow have specific surface targets for most of these drugs
Cells in the marrow lack the enzymes to protect against the drugs
Chemotherapy drugs act preferentially against cells with no nucleus
Chemotherapy drugs penetrate well into the marrow because it is very vascular
Chemotherapy drugs tend to be lipid-soluble and concentrate in the marrow

Correct answer: Cells in the marrow divide rapidly

Antineoplastic drugs, especially conventional chemotherapy agents, primarily target rapidly dividing cells. Bone marrow cells, including hematopoietic stem cells and their precursors, are among the most rapidly proliferating cells in the body. This high rate of cell division makes them particularly susceptible to the cytotoxic effects of chemotherapy, leading to common adverse effects like myelosuppression.

Question 19: A 38-year-old woman with an 18-year history of type 1 diabetes mellitus and progressive renal failure is being considered for dialysis. Laboratory studies show normocytic, normochromic anemia. Which of the following medications is most appropriate to treat the anemia in this patient?

Erythropoietin (Correct answer)
Folic acid
Folinic acid
Vitamin B1 (thiamine)
Vitamin B12 (cyanocobalamin)

Correct answer: Erythropoietin

Patients with chronic renal failure, such as those with progressive renal failure due to type 1 diabetes, often develop normocytic, normochromic anemia. This is primarily due to decreased production of erythropoietin by the damaged kidneys. Erythropoietin is a hormone that stimulates red blood cell production in the bone marrow, making exogenous erythropoietin the most appropriate treatment for this type of anemia.

Question 20: A 47-year-old woman is admitted to the hospital for treatment of pneumococcal pneumonia. Treatment with gentamicin and penicillin is initiated. Within 10 minutes of the administration of antimicrobial therapy, her respirations increase to 30/min, and blood pressure decreases to 80/40 mm Hg. Epinephrine, antihistamine, and corticosteroid therapy is started. Her condition improves slowly during the next 2 hours. Her antimicrobial therapy is changed to gentamicin only, and her condition continues to improve. Administration of which of the following types of drugs is most likely to cause a similar adverse reaction in this patient?

Cephalosporins (Correct answer)
Macrolides
Quinolones
Tetracyclines

Correct answer: Cephalosporins

The patient experienced an acute anaphylactic reaction to penicillin, characterized by rapid onset of respiratory distress and hypotension. Penicillins and cephalosporins share a common beta-lactam ring structure, which is responsible for their antimicrobial activity but also for cross-reactivity in allergic reactions. Therefore, a patient with a severe penicillin allergy has an increased risk of experiencing a similar hypersensitivity reaction to cephalosporins.

Pharmacology Test 1

Ten months after starting procainamide therapy for cardiac arrhythmias, a 56-year-old man develops arthritis and other symptoms consistent with drug-induced systemic lupus erythematosus.
Results of a blood test are positive for antinuclear antibodies.
This finding is consistent with which of the following genetic polymorphisms in drug metabolism?