All questions
Question 1
A 70-year-old man is hospitalized for a pulmonary embolism and started on a continuous intravenous infusion of an anticoagulant. Five days later, his platelet count drops from 250,000/mm³ to 40,000/mm³. A new thrombus is noted in his right leg despite being on anticoagulation. The development of this condition is caused by antibodies directed against a complex of the anticoagulant and which of the following endogenous molecules?
The development of this condition is caused by antibodies directed against a complex of the anticoagulant and which of the following endogenous molecules?
- Platelet factor 4 (correct answer)
- von Willebrand factor
- Factor V Leiden
- Antithrombin III
Explanation: This patient has developed heparin-induced thrombocytopenia (HIT), an immune-mediated adverse drug reaction. HIT is caused by the formation of IgG antibodies against the heparin-platelet factor 4 (PF4) complex. The binding of these antibodies to platelets leads to their activation, aggregation, and clearance, causing thrombocytopenia. Paradoxically, this platelet activation also creates a prothrombotic state, leading to new or worsening thrombosis.
Question 2
A 32-year-old pregnant woman at 10 weeks' gestation is being managed for chronic hypertension. Her physician reviews her medications and decides to switch her antihypertensive agent due to significant risks to the fetus, particularly in the second and third trimesters. Disruption of which of the following fetal systems is the primary concern with her current class of medication?
Disruption of which of the following fetal systems is the primary concern with her current class of medication?
- Central nervous system development
- Cardiac septation
- Limb bud formation
- Renal development and function (correct answer)
Explanation: ACE inhibitors (e.g., lisinopril) and angiotensin II receptor blockers (e.g., losartan) are contraindicated in pregnancy, especially during the second and third trimesters. Their teratogenic effect is primarily due to disruption of the fetal renin-angiotensin system, which is crucial for fetal renal development and function. This can lead to fetal hypotension, anuria, and oligohydramnios, resulting in pulmonary hypoplasia and limb contractures (Potter sequence).
Question 3
A 19-year-old woman is brought to the emergency department by her roommate who found her obtunded with an empty bottle of over-the-counter pain medication. On presentation, she is somnolent but arousable. Her vital signs are stable. Initial laboratory studies are significant for elevated aminotransferases. The patient is admitted and started on N-acetylcysteine. The toxicity of the ingested substance is primarily due to the depletion of which of the following?
The toxicity of the ingested substance is primarily due to the depletion of which of the following?
- Glutathione (correct answer)
- Folic acid
- Vitamin K
- Glucuronic acid
Explanation: The patient has acetaminophen toxicity, which causes hepatotoxicity. Acetaminophen is metabolized in the liver, with a small fraction converted by cytochrome P450 enzymes to a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Under normal conditions, NAPQI is detoxified by conjugation with glutathione. In an overdose, glutathione stores are depleted, allowing NAPQI to accumulate and cause hepatocellular injury. N-acetylcysteine acts as a glutathione precursor, replenishing hepatic stores.
Question 4
A 65-year-old man with a history of hypertension and type 2 diabetes mellitus presents to his primary care physician with a persistent, nonproductive cough that began two months ago. He denies fever, wheezing, or chest pain. He was started on a new medication for blood pressure control three months prior. Physical examination is unremarkable, and a chest X-ray shows no abnormalities. Which of the following medications is most likely responsible for this patient's symptom?
Which of the following medications is most likely responsible for this patient's symptom?
- Lisinopril (correct answer)
- Hydrochlorothiazide
- Losartan
- Amlodipine
Explanation: The patient is experiencing a dry, persistent cough, a well-known predictable (Type A) adverse effect of ACE inhibitors, such as lisinopril. This cough is thought to be caused by the accumulation of bradykinin, which is normally degraded by angiotensin-converting enzyme. Losartan, an angiotensin II receptor blocker, does not affect bradykinin levels and is a common alternative. Hydrochlorothiazide and amlodipine are not typically associated with a chronic cough.
Question 5
A 34-year-old woman with treatment-resistant schizophrenia is started on a new antipsychotic medication. She is monitored weekly with a complete blood count. Four weeks into treatment, she presents with fever, sore throat, and malaise. Her white blood cell count is 800/mm³ with an absolute neutrophil count of 150/mm³. The medication is immediately discontinued. Which of the following drugs is most likely responsible for these findings?
Which of the following drugs is most likely responsible for these findings?
- Risperidone
- Haloperidol
- Clozapine (correct answer)
- Olanzapine
Explanation: The patient has developed agranulocytosis, a severe form of neutropenia. This is a rare but life-threatening idiosyncratic adverse effect of clozapine. Due to this risk, patients on clozapine require regular monitoring of their white blood cell count. Other atypical antipsychotics like risperidone and olanzapine, and typical antipsychotics like haloperidol, have a much lower risk of causing agranulocytosis.
Question 6
A 28-year-old woman gives birth to a male infant with a lumbosacral myelomeningocele. The mother has a history of a seizure disorder that was managed with a single medication throughout her pregnancy. She reports that she did not take prenatal vitamins. Inhibition of which of the following enzymes by the mother's medication is most likely associated with this congenital anomaly?
Inhibition of which of the following enzymes by the mother's medication is most likely associated with this congenital anomaly?
- Dihydrofolate reductase
- HMG-CoA reductase
- Histone deacetylase (correct answer)
- Cyclooxygenase
Explanation: The infant has a neural tube defect (myelomeningocele), which is strongly associated with in utero exposure to valproic acid. Valproic acid is a teratogen that is thought to cause neural tube defects by inhibiting histone deacetylase, which alters gene expression crucial for neural tube closure. It also interferes with folate metabolism, but its primary teratogenic mechanism is distinct from dihydrofolate reductase inhibitors like methotrexate.
Question 7
A 72-year-old man is hospitalized for sepsis secondary to a urinary tract infection. He is treated with intravenous fluids and an antibiotic. On the fifth day of treatment, his serum creatinine rises from 1.0 mg/dL to 2.5 mg/dL. Urinalysis reveals muddy brown granular casts. The patient's hearing is also noted to be diminished. Which of the following antibiotics is the most likely cause of these findings?
Which of the following antibiotics is the most likely cause of these findings?
- Ceftriaxone
- Gentamicin (correct answer)
- Azithromycin
- Ciprofloxacin
Explanation: The patient has developed acute tubular necrosis (ATN), evidenced by the rising creatinine and muddy brown casts, along with ototoxicity (diminished hearing). These are classic, predictable (Type A) toxicities of aminoglycosides, such as gentamicin. These drugs accumulate in the renal proximal tubule cells and the endolymph of the inner ear, leading to nephrotoxicity and ototoxicity. The other listed antibiotics are not typically associated with this pattern of toxicity.
Question 8
A 68-year-old man with type 2 diabetes mellitus and chronic kidney disease (eGFR 25 mL/min/1.73 m²) is brought to the emergency department with nausea, vomiting, and abdominal pain. He appears lethargic. Laboratory studies show a pH of 7.20, PaCO2 of 28 mm Hg, and bicarbonate of 12 mEq/L. His serum lactate level is markedly elevated. Which of his diabetes medications is the most likely cause of this presentation?
Which of his diabetes medications is the most likely cause of this presentation?
- Glyburide
- Sitagliptin
- Metformin (correct answer)
- Empagliflozin
Explanation: The patient is presenting with high anion gap metabolic acidosis, specifically lactic acidosis. Metformin can cause lactic acidosis, a rare but serious predictable (Type A) adverse effect. The risk is significantly increased in patients with renal insufficiency, as metformin is cleared by the kidneys. Its accumulation inhibits hepatic gluconeogenesis from lactate, leading to elevated lactate levels. Glyburide causes hypoglycemia. Sitagliptin is generally well-tolerated. Empagliflozin can cause euglycemic diabetic ketoacidosis, not typically lactic acidosis.
Question 9
A 58-year-old woman with a history of atrial fibrillation has been on chronic medical therapy for rhythm control. She presents to her physician with complaints of joint pain, a malar rash on her face, and fatigue for the past month. Laboratory studies are positive for antinuclear antibodies (ANA) and anti-histone antibodies. Which of the following medications is the most likely cause of her symptoms?
Which of the following medications is the most likely cause of her symptoms?
- Amiodarone
- Diltiazem
- Metoprolol
- Procainamide (correct answer)
Explanation: The patient's presentation of arthralgias, a malar rash, and positive ANA and anti-histone antibodies is characteristic of drug-induced lupus erythematosus (DILE). Procainamide is a classic cause of DILE. Other drugs associated with DILE include hydralazine and isoniazid. The presence of anti-histone antibodies is highly specific for DILE. The other medications listed are less commonly or not associated with this immune-mediated reaction.
Question 10
A 55-year-old woman with metastatic breast cancer has completed her sixth cycle of a chemotherapy regimen. She presents with worsening shortness of breath on exertion and swelling in her legs. An echocardiogram reveals a decreased left ventricular ejection fraction of 30% and global hypokinesis. The patient's cardiomyopathy is most likely a cumulative, dose-dependent toxicity of which of the following agents?
The patient's cardiomyopathy is most likely a cumulative, dose-dependent toxicity of which of the following agents?
- Paclitaxel
- Cyclophosphamide
- Doxorubicin (correct answer)
- Trastuzumab
Explanation: Doxorubicin, an anthracycline antibiotic used in chemotherapy, is well-known for causing a cumulative, dose-dependent cardiotoxicity. This predictable (Type A) adverse effect is mediated by the generation of free radicals, which damage cardiomyocytes and lead to dilated cardiomyopathy and heart failure. The risk increases significantly with higher cumulative doses. While trastuzumab can also cause cardiotoxicity (typically reversible), doxorubicin is the classic cause of this type of irreversible, dose-dependent cardiomyopathy.
Question 11
A newborn is examined in the nursery. The infant is small for gestational age and has microcephaly, a smooth philtrum, and a thin upper lip. A cardiac murmur is auscultated, and an echocardiogram confirms a ventricular septal defect. The mother admits to heavy consumption of a substance throughout her pregnancy. Which of the following is the most likely substance?
Which of the following is the most likely substance?
- Cocaine
- Tobacco
- Alcohol (correct answer)
- Warfarin
Explanation: The infant's features—including microcephaly, facial dysmorphism (smooth philtrum, thin upper lip), and a congenital heart defect—are characteristic of fetal alcohol syndrome (FAS). This syndrome is a result of the teratogenic effects of alcohol consumption during pregnancy. Cocaine use is associated with placental abruption and low birth weight. Tobacco use is associated with low birth weight. Warfarin exposure can cause bone and cartilage defects (fetal warfarin syndrome).
Question 12
A 60-year-old man with rheumatoid arthritis has been treated with a high-dose oral medication for the past six months to control a severe flare. He now presents with weight gain, central obesity, facial rounding, and purple striae on his abdomen. His blood pressure is 160/95 mm Hg, and a random blood glucose is 180 mg/dL. These findings are a predictable consequence of therapy with which of the following drugs?
These findings are a predictable consequence of therapy with which of the following drugs?
- Methotrexate
- Prednisone (correct answer)
- Infliximab
- Hydroxychloroquine
Explanation: The patient's clinical presentation is classic for iatrogenic Cushing's syndrome, characterized by central obesity, moon facies, abdominal striae, hypertension, and hyperglycemia. This is a predictable (Type A) adverse effect of long-term, high-dose glucocorticoid therapy, such as with prednisone. These effects are due to the supraphysiologic levels of corticosteroids mimicking the effects of excess cortisol. Methotrexate, infliximab, and hydroxychloroquine have different side effect profiles.
Question 13
A 67-year-old man with a long history of schizophrenia has been managed on the same antipsychotic medication for over 20 years. During a follow-up visit, his physician notes repetitive, involuntary movements of the patient's mouth and tongue, including lip-smacking and chewing motions. The patient is unaware of these movements. This condition is a long-term consequence of the medication's effect on which of the following neuronal pathways?
This condition is a long-term consequence of the medication's effect on which of the following neuronal pathways?
- Mesolimbic
- Nigrostriatal (correct answer)
- Mesocortical
- Tuberoinfundibular
Explanation: The patient is exhibiting tardive dyskinesia, a delayed-onset movement disorder characterized by involuntary, repetitive movements. It is a serious, predictable (Type A) adverse effect of long-term treatment with dopamine D2 receptor antagonists, particularly first-generation antipsychotics. The underlying pathophysiology is thought to involve upregulation and supersensitivity of dopamine receptors in the nigrostriatal pathway, which is involved in motor control.
Question 14
A 28-year-old man with a seizure disorder controlled with lamotrigine develops a high fever and a diffuse morbilliform rash three weeks after his medication dose was increased. He also has prominent facial edema. Laboratory results show eosinophilia, atypical lymphocytes, and elevated liver enzymes. This constellation of findings is most characteristic of which of the following idiosyncratic drug reactions?
This constellation of findings is most characteristic of which of the following idiosyncratic drug reactions?
- Toxic epidermal necrolysis
- Serum sickness-like reaction
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) (correct answer)
- Acute generalized exanthematous pustulosis (AGEP)
Explanation: The patient's presentation of fever, rash, facial edema, eosinophilia, and systemic involvement (hepatitis) is classic for Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome. This is a severe, idiosyncratic reaction that typically occurs 2-8 weeks after starting a new medication. Anticonvulsants like lamotrigine, carbamazepine, and phenytoin are common culprits. DRESS is a type of delayed hypersensitivity reaction.
Question 15
A 10-year-old boy develops a fever, urticarial rash, and joint pain one week after completing a course of cefaclor for a streptococcal pharyngitis. Physical examination reveals lymphadenopathy and mild proteinuria. Laboratory findings are normal except for a slightly elevated erythrocyte sedimentation rate. This clinical picture is most consistent with which of the following types of adverse drug reactions?
This clinical picture is most consistent with which of the following types of adverse drug reactions?
- Type I hypersensitivity
- Type II hypersensitivity
- Type III hypersensitivity (correct answer)
- Type IV hypersensitivity
Explanation: The patient is presenting with classic signs and symptoms of serum sickness, which typically occur 1-2 weeks after exposure to a drug (e.g., beta-lactams like cefaclor). The constellation of fever, rash, arthralgias, and lymphadenopathy is characteristic. Serum sickness is a Type III hypersensitivity reaction, caused by the deposition of immune complexes (antigen-antibody complexes) in various tissues, leading to complement activation and inflammation.
Question 16
A 48-year-old woman with bipolar disorder presents to the emergency department with confusion, coarse tremor, and ataxia. She reports recent onset of nausea and diarrhea. Her medications include a mood stabilizer she has taken for years. She recently started taking a nonsteroidal anti-inflammatory drug for knee pain. A serum level of her mood stabilizer is found to be significantly elevated. Toxicity from which of the following medications best explains her presentation?
Toxicity from which of the following medications best explains her presentation?
- Valproic acid
- Carbamazepine
- Lamotrigine
- Lithium (correct answer)
Explanation: The patient's neurologic symptoms (confusion, tremor, ataxia) are classic signs of lithium toxicity. Lithium is a narrow therapeutic index drug that is excreted by the kidneys. Its clearance can be significantly reduced by factors that decrease renal blood flow or increase sodium and water reabsorption, such as NSAID use, dehydration (from diarrhea), and thiazide diuretics. The recent addition of an NSAID likely decreased renal clearance of lithium, leading to toxic accumulation.
Question 17
A 30-year-old woman in her first trimester of pregnancy is prescribed a medication for severe nausea and vomiting. She gives birth to an infant with bilateral limb defects characterized by a flipper-like appearance of the hands and feet. This classic teratogenic effect is associated with which of the following drugs?
This classic teratogenic effect is associated with which of the following drugs?
- Isotretinoin
- Phenytoin
- Lithium
- Thalidomide (correct answer)
Explanation: The infant's presentation of bilateral limb defects, specifically phocomelia (flipper-like limbs), is the classic teratogenic effect of thalidomide. Thalidomide was used in the late 1950s and early 1960s as a sedative and for morning sickness, leading to a major public health crisis. Isotretinoin causes craniofacial, cardiac, and CNS defects. Phenytoin is associated with fetal hydantoin syndrome. Lithium is associated with Ebstein anomaly.
Question 18
A 52-year-old man from Southeast Asia is started on prophylactic therapy for latent tuberculosis. Six weeks later, he presents with fatigue, nausea, and right upper quadrant abdominal pain. Laboratory studies show an AST of 450 U/L and an ALT of 510 U/L. His physician suspects drug-induced liver injury. This patient's reaction is most likely due to the formation of toxic metabolites from which of the following drugs?
This patient's reaction is most likely due to the formation of toxic metabolites from which of the following drugs?
- Ethambutol
- Pyrazinamide
- Isoniazid (correct answer)
- Rifampin
Explanation: Isoniazid (INH) is a cornerstone of tuberculosis treatment and prophylaxis and is well-known for causing idiosyncratic drug-induced liver injury. The hepatotoxicity is thought to be caused by toxic metabolites produced during its metabolism, which is influenced by N-acetyltransferase 2 (NAT2) acetylation status. Slow acetylators are at higher risk. While rifampin and pyrazinamide can also be hepatotoxic, INH is the classic cause of this type of delayed, idiosyncratic hepatitis. Ethambutol is associated with optic neuritis.
Question 19
A 25-year-old man presents to the emergency department with a widespread, blistering rash and mucosal erosions involving his mouth and eyes. The rash began 2 days ago and has progressed rapidly. He was treated for a bacterial skin infection with an oral antibiotic 10 days ago. Physical examination reveals bullae and epidermal detachment affecting 15% of his body surface area. A diagnosis of Stevens-Johnson syndrome is made. Which of the following medications is most commonly implicated in this type of immune-mediated reaction?
Which of the following medications is most commonly implicated in this type of immune-mediated reaction?
- Amoxicillin (correct answer)
- Doxycycline
- Metronidazole
- Clindamycin
Explanation: Stevens-Johnson syndrome (SJS) is a severe, immune-mediated mucocutaneous reaction often triggered by medications. Penicillins (like amoxicillin) and sulfonamides are among the most common drug classes implicated in SJS. The reaction is a Type IV hypersensitivity reaction. While other antibiotics can cause SJS, penicillins are a classic cause. Doxycycline, metronidazole, and clindamycin are less frequently associated with SJS.
Question 20
A 45-year-old woman with major depressive disorder is brought to the emergency department with altered mental status, agitation, and diaphoresis. Her temperature is 39.5°C (103.1°F), blood pressure is 170/100 mm Hg, and heart rate is 130/min. On examination, she has tremor, hyperreflexia, and myoclonus in her lower extremities. Her medication list includes sertraline. She recently started taking an over-the-counter supplement for mood enhancement. This patient's condition is caused by excessive agonism at which of the following receptors?
This patient's condition is caused by excessive agonism at which of the following receptors?
- Dopamine D2
- Serotonin 5-HT2A (correct answer)
- Muscarinic acetylcholine
- GABA-A
Explanation: This patient is presenting with serotonin syndrome, a predictable (Type A) adverse effect resulting from excessive serotonergic activity in the central nervous system. It is characterized by a triad of autonomic instability, altered mental status, and neuromuscular hyperactivity. It often occurs when two serotonergic agents are combined, such as an SSRI (sertraline) and an herbal supplement like St. John's wort (an MAOI). The pathophysiology involves overstimulation of central and peripheral serotonin receptors, particularly the 5-HT2A subtype.