A 33-year-old man is being evaluated for malaise and fatigability. He says that he hasn’t been able to perform at work, can’t exercise like before, and is constantly tired. He also says that his clothes have ‘become larger’ in the past few months. Past medical history is significant for gastroesophageal reflux disease, which is under control with lifestyle changes. His blood pressure is 110/70 mm Hg, the temperature is 37.0°C (98.6°F), the respiratory rate is 17/min, and the pulse is 82/min. On physical examination, an enlarged, painless, mobile, cervical lymph node is palpable. A complete blood count is performed.
Hemoglobin 9.0 g/dL
Hematocrit 37.7%
Leukocyte count 5,500/mm3
Neutrophils 65%
Lymphocytes 30%
Monocytes 5%
Mean corpuscular volume 82.2 μm3
Platelet count 190,000 mm3
Erythrocyte sedimentation rate 35 mm/h
C-reactive protein 8 mg/dL
A biopsy of the lymph node is performed which reveals both multinucleated and bilobed cells. The patient is started on a regimen of drugs for his condition. Echocardiography is performed before treatment is started and shows normal ejection fraction, ventricle function, and wall motion. After 2 rounds of chemotherapy, another echocardiography is performed by protocol, but this time all heart chambers are enlarged, and the patient is suffering from severe exertion dyspnea. Which of the drugs below is most likely responsible for these side effects?
Q202
A 41-year-old man presents to the emergency department with several days of hand tremor, vomiting, and persistent diarrhea. His wife, who accompanies him, notes that he seems very “out of it.” He was in his usual state of health last week and is now having difficulties at work. He has tried several over-the-counter medications without success. His past medical history is significant for bipolar disorder and both type 1 and type 2 diabetes. He takes lithium, metformin, and a multivitamin every day. At the hospital, his heart rate is 90/min, respiratory rate is 17/min, blood pressure is 130/85 mm Hg, and temperature is 37.0°C (98.6°F). The man appears uncomfortable. His cardiac and respiratory exams are normal and his bowel sounds are hyperactive. His lithium level is 1.8 mEq/L (therapeutic range, 0.6–1.2 mEq/L). Which of the following may have contributed to this patient’s elevated lithium level?
Q203
A 47-year-old female with a history of poorly controlled type I diabetes mellitus and end-stage renal disease undergoes an allogeneic renal transplant. Her immediate post-operative period is unremarkable and she is discharged from the hospital on post-operative day 4. Her past medical history is also notable for major depressive disorder, obesity, and gout. She takes sertraline, allopurinol, and insulin. She does not smoke or drink alcohol. To decrease the risk of transplant rejection, her nephrologist adds a medication known to serve as a precursor to 6-mercaptopurine. Following initiation of this medication, which of the following toxicities should this patient be monitored for?
Q204
A 58-year-old woman comes to the physician for evaluation of worsening fatigue for 1 week. She also has a 1-year history of hand pain and stiffness. Four months ago, she started a new medication for these symptoms. Medications used prior to that included ibuprofen, prednisone, and hydroxychloroquine. Examination shows a subcutaneous nodule on her left elbow and old joint destruction with Boutonniere deformity. Her hemoglobin concentration is 10.1 g/dL, leukocyte count is 3400/mm3, and platelet count is 101,000/mm3. Methylmalonic acid levels are normal. Which of the following could have prevented this patient's laboratory abnormalities?
Q205
A 46-year-old woman comes to the physician because of a 3-day history of diarrhea and abdominal pain. She returned from a trip to Egypt 4 weeks ago. Her vital signs are within normal limits. There is mild tenderness in the right lower quadrant. Stool studies show occult blood and unicellular organisms with engulfed erythrocytes. Which of the following is the most appropriate initial pharmacotherapy for this patient?
Q206
A previously healthy 5-year-old boy is brought to the emergency department because of abdominal pain and vomiting for 6 hours. His mother immediately brought him after noticing that he had gotten into the medicine cabinet. He appears uncomfortable. His temperature is 37.2°C (99°F), pulse is 133/min and blood pressure is 80/50 mm Hg. Examination shows diffuse abdominal tenderness; there is no guarding or rigidity. Digital rectal examination shows dark-colored stools. Laboratory studies show:
Hemoglobin 13.2 g/dL
Leukocyte count 14,100/mm3
Serum
Na+ 136 mEq/L
K+ 3.3 mEq/L
Cl- 105 mEq/L
Urea nitrogen 26 mg/dL
Glucose 98 mg/dL
Creatinine 1.1 mg/dL
Arterial blood gas analysis on room air shows:
pH 7.31
pCO2 32 mm Hg
HCO3- 16 mEq/L
Intravenous fluids are administered. Which of the following is the most appropriate next step in management?
Q207
A 33-year-old man presents to the emergency room for diarrhea. He states it is profuse and watery and has not been improving over the past week. He is generally healthy; however, he was recently hospitalized during spring break and treated for alcohol intoxication and an aspiration pneumonia. While on spring break, the patient also went camping and admits eating undercooked chicken and drinking from mountain streams. His temperature is 100.5°F (38.1°C), blood pressure is 111/74 mmHg, pulse is 110/min, respirations are 16/min, and oxygen saturation is 98% on room air. Physical exam is notable for a fatigued appearing man. His abdomen is non-tender. Which of the following is the best management of this patient?
Q208
A 45-year-old man presents with worsening joint pain and stiffness. Past medical history is significant for rheumatoid arthritis, diagnosed 3 months ago and managed with celecoxib and methotrexate, and occasional gastric reflux, managed with omeprazole. His vitals are a pulse of 80/min, a respiratory rate of 16/min, and blood pressure of 122/80 mm Hg. On physical examination, the left wrist is swollen, stiff, and warm to touch, and the right wrist is red and warm. There is limited active and passive range of motion at the proximal interphalangeal and metacarpophalangeal joints of both hands. The remainder of the examination is unremarkable. A plain radiograph of the hands shows progressive degeneration of multiple joints. Another drug, etanercept, is added to help control progressive arthritis. Which of the following diagnostic tests should be ordered before starting this new medication in this patient?
Q209
A 54-year-old man with a past medical history significant for hypertension, type 2 diabetes, and chronic obstructive pulmonary disease presents with complaints of nausea and abdominal pain for the past month. The pain is located in the epigastric region and is described as “burning” in quality, often following food intake. The patient denies any changes in bowel movements, fever, or significant weight loss. Medications include metformin, lisinopril, hydrochlorothiazide, albuterol inhaler, and fluconazole for a recent fungal infection. Physical examination was unremarkable except for a mildly distended abdomen that is diffusely tender to palpation and decreased sensation at lower extremities bilaterally. A medication was started for the symptoms. Two days later, the patient reports heart palpitations. An EKG is shown below. Which of the following is the medication most likely prescribed?
Q210
Several weeks after starting a new medication for rheumatoid arthritis, a 44-year-old woman comes to the physician because of painful ulcers in her mouth. Oral examination shows inflammation and swelling of the tongue and oropharynx and ulcers on the buccal mucosa bilaterally. Skin examination shows soft tissue swelling over her proximal interphalangeal joints and subcutaneous nodules over her elbows. Serum studies show an alanine aminotransferase level of 220 U/L, aspartate aminotransferase level of 214 U/L, and creatinine level of 1.7 mg/dL. Which of the following is the most likely primary mechanism of action of the drug she is taking?
Antimicrobials US Medical PG Practice Questions and MCQs
Question 201: A 33-year-old man is being evaluated for malaise and fatigability. He says that he hasn’t been able to perform at work, can’t exercise like before, and is constantly tired. He also says that his clothes have ‘become larger’ in the past few months. Past medical history is significant for gastroesophageal reflux disease, which is under control with lifestyle changes. His blood pressure is 110/70 mm Hg, the temperature is 37.0°C (98.6°F), the respiratory rate is 17/min, and the pulse is 82/min. On physical examination, an enlarged, painless, mobile, cervical lymph node is palpable. A complete blood count is performed.
Hemoglobin 9.0 g/dL
Hematocrit 37.7%
Leukocyte count 5,500/mm3
Neutrophils 65%
Lymphocytes 30%
Monocytes 5%
Mean corpuscular volume 82.2 μm3
Platelet count 190,000 mm3
Erythrocyte sedimentation rate 35 mm/h
C-reactive protein 8 mg/dL
A biopsy of the lymph node is performed which reveals both multinucleated and bilobed cells. The patient is started on a regimen of drugs for his condition. Echocardiography is performed before treatment is started and shows normal ejection fraction, ventricle function, and wall motion. After 2 rounds of chemotherapy, another echocardiography is performed by protocol, but this time all heart chambers are enlarged, and the patient is suffering from severe exertion dyspnea. Which of the drugs below is most likely responsible for these side effects?
A. Dacarbazine
B. Vinblastine
C. Rituximab
D. Bleomycin
E. Adriamycin (Correct Answer)
Explanation: ***Adriamycin***
- **Adriamycin** (doxorubicin) is a known cardiotoxic agent, especially with cumulative doses, leading to **dilated cardiomyopathy** and heart failure, as described by the enlarged heart chambers and severe dyspnea.
- The delayed onset of cardiac symptoms after two rounds of chemotherapy is consistent with Adriamycin's mechanism of causing **oxidative stress** and damage to myocardial cells.
*Dacarbazine*
- **Dacarbazine** is an alkylating agent, primarily associated with side effects such as **myelosuppression**, nausea, vomiting, and flu-like symptoms.
- It does not typically cause the severe **cardiotoxicity** observed in this patient.
*Vinblastine*
- **Vinblastine** is a vinca alkaloid that primarily causes **neurotoxicity** (e.g., peripheral neuropathy, constipation), myelosuppression, and jaw pain.
- Significant **cardiac side effects** like dilated cardiomyopathy are not characteristic of vinblastine.
*Rituximab*
- **Rituximab** is a monoclonal antibody targeting CD20 and is generally well-tolerated, though it can cause **infusion-related reactions** and an increased risk of infections.
- It is not associated with direct **cardiotoxicity** leading to dilated cardiomyopathy.
*Bleomycin*
- **Bleomycin** is an antitumor antibiotic primarily known for its association with **pulmonary fibrosis** (bleomycin lung), hyperpigmentation, and skin toxicities.
- While it can cause some cardiac abnormalities, **dilated cardiomyopathy** is not its hallmark cardiac side effect; it's far less cardiotoxic than Adriamycin.
Question 202: A 41-year-old man presents to the emergency department with several days of hand tremor, vomiting, and persistent diarrhea. His wife, who accompanies him, notes that he seems very “out of it.” He was in his usual state of health last week and is now having difficulties at work. He has tried several over-the-counter medications without success. His past medical history is significant for bipolar disorder and both type 1 and type 2 diabetes. He takes lithium, metformin, and a multivitamin every day. At the hospital, his heart rate is 90/min, respiratory rate is 17/min, blood pressure is 130/85 mm Hg, and temperature is 37.0°C (98.6°F). The man appears uncomfortable. His cardiac and respiratory exams are normal and his bowel sounds are hyperactive. His lithium level is 1.8 mEq/L (therapeutic range, 0.6–1.2 mEq/L). Which of the following may have contributed to this patient’s elevated lithium level?
A. Large amounts of caffeine intake
B. Decreased salt intake (Correct Answer)
C. Weight loss
D. Addition of lurasidone to lithium therapy
E. Addition of fluoxetine to lithium therapy
Explanation: **Decreased salt intake**
- **Lithium** is reabsorbed in the renal tubules alongside **sodium**. When **sodium intake** is low, the kidneys reabsorb more sodium and, inadvertently, more lithium, leading to increased serum lithium levels and potential toxicity.
- The patient's **vomiting and diarrhea** can cause significant fluid and electrolyte loss, including sodium. This **depletion of sodium** would then lead to increased lithium reabsorption and toxicity.
*Large amounts of caffeine intake*
- **Caffeine** is a diuretic, which can increase **lithium excretion** and potentially *lower* lithium levels.
- Therefore, large amounts of caffeine intake are unlikely to contribute to an *elevated* lithium level.
*Weight loss*
- **Weight loss** itself does not directly influence **lithium metabolism** or excretion in a way that would cause an elevated lithium level.
- While dehydration associated with weight loss could theoretically impact lithium, mere weight loss is not a primary contributor to toxicity.
*Addition of lurasidone to lithium therapy*
- There is no significant pharmacological interaction between **lurasidone** and **lithium** that would directly lead to elevated lithium levels. Both medications are used in bipolar disorder, and lurasidone is not known to inhibit lithium excretion or metabolism.
- Adding lurasidone to lithium therapy is generally considered safe with respect to lithium levels.
*Addition of fluoxetine to lithium therapy*
- **Fluoxetine** (an SSRI) typically has *minimal or inconsistent effects* on **lithium levels**. Some reports suggest a possible *slight increase* in lithium levels in some individuals, but it is not a common or strong interaction that would explain a toxic level to the extent seen here.
- The more significant interactions leading to lithium toxicity are generally related to **sodium and fluid balance**, which are strongly affected by the patient's current symptoms.
Question 203: A 47-year-old female with a history of poorly controlled type I diabetes mellitus and end-stage renal disease undergoes an allogeneic renal transplant. Her immediate post-operative period is unremarkable and she is discharged from the hospital on post-operative day 4. Her past medical history is also notable for major depressive disorder, obesity, and gout. She takes sertraline, allopurinol, and insulin. She does not smoke or drink alcohol. To decrease the risk of transplant rejection, her nephrologist adds a medication known to serve as a precursor to 6-mercaptopurine. Following initiation of this medication, which of the following toxicities should this patient be monitored for?
A. Pancytopenia (Correct Answer)
B. Cytokine storm
C. Hyperlipidemia
D. Osteoporosis
E. Hirsutism
Explanation: ***Pancytopenia***
- The medication described, a precursor to **6-mercaptopurine (6-MP)**, is **azathioprine**. Azathioprine is an **antimetabolite** that suppresses the immune system by interfering with purine synthesis.
- Its main toxicity is **bone marrow suppression**, leading to **pancytopenia** (decreased red blood cells, white blood cells, and platelets), which necessitates close monitoring of **complete blood count (CBC)**.
*Cytokine storm*
- A **cytokine storm** is a severe systemic inflammatory response, often seen with certain immunotherapies (e.g., **CAR T-cell therapy**) or severe infections.
- It is not a typical side effect of **azathioprine** used for transplant rejection prophylaxis.
*Hyperlipidemia*
- **Hyperlipidemia** is a common side effect of some immunosuppressants like **corticosteroids** and **calcineurin inhibitors (e.g., cyclosporine, tacrolimus)**, which are also used in transplant patients.
- However, it is not a direct or primary toxicity associated with **azathioprine**.
*Osteoporosis*
- **Osteoporosis** is a significant long-term complication associated with **corticosteroid use** in transplant patients.
- While many transplant patients receive corticosteroids, **azathioprine** itself does not directly cause osteoporosis as a primary toxicity.
*Hirsutism*
- **Hirsutism** (excessive hair growth) is a characteristic side effect of **cyclosporine**, another immunosuppressant commonly used in transplant recipients.
- This symptom is not typically associated with **azathioprine** therapy.
Question 204: A 58-year-old woman comes to the physician for evaluation of worsening fatigue for 1 week. She also has a 1-year history of hand pain and stiffness. Four months ago, she started a new medication for these symptoms. Medications used prior to that included ibuprofen, prednisone, and hydroxychloroquine. Examination shows a subcutaneous nodule on her left elbow and old joint destruction with Boutonniere deformity. Her hemoglobin concentration is 10.1 g/dL, leukocyte count is 3400/mm3, and platelet count is 101,000/mm3. Methylmalonic acid levels are normal. Which of the following could have prevented this patient's laboratory abnormalities?
A. Vitamin B12
B. Vitamin B6
C. Amifostine
D. 2-Mercaptoethanesulfonate
E. Leucovorin (Correct Answer)
Explanation: **Leucovorin**
- The patient's pancytopenia (anemia, leukopenia, and thrombocytopenia) in the context of rheumatoid arthritis treatment points towards **methotrexate toxicity** as the cause.
- **Leucovorin (folinic acid)** is often co-administered with methotrexate or used as a rescue therapy to prevent or counteract its adverse effects by providing an alternative source of folate, bypassing the dihydrofolate reductase inhibition.
*Vitamin B12*
- While **vitamin B12 deficiency** can cause anemia and pancytopenia, the patient's normal **methylmalonic acid levels** rule out this possibility.
- B12 deficiency is typically associated with **macrocytic anemia** and neurological symptoms, which are not explicitly mentioned as the primary concern here.
*Vitamin B6*
- **Vitamin B6 (pyridoxine)** deficiency can lead to microcytic anemia, but it is not typically associated with the comprehensive pancytopenia observed here, nor is it related to methotrexate toxicity.
- It is crucial for **heme synthesis** and can be deficient in conditions like alcoholism.
*Amifostine*
- **Amifostine** is a cytoprotective agent used to prevent nephrotoxicity and ototoxicity associated with certain chemotherapy agents like **cisplatin**, and also to reduce xerostomia in head and neck radiation.
- It is not indicated for the prevention of methotrexate-induced myelosuppression.
*2-Mercaptoethanesulfonate*
- **2-Mercaptoethanesulfonate (Mesna)** is a uroprotectant used to prevent hemorrhagic cystitis caused by **oxazaphosphorine chemotherapeutic agents** like cyclophosphamide and ifosfamide.
- It has no role in preventing the hematologic toxicity of methotrexate.
Question 205: A 46-year-old woman comes to the physician because of a 3-day history of diarrhea and abdominal pain. She returned from a trip to Egypt 4 weeks ago. Her vital signs are within normal limits. There is mild tenderness in the right lower quadrant. Stool studies show occult blood and unicellular organisms with engulfed erythrocytes. Which of the following is the most appropriate initial pharmacotherapy for this patient?
A. Paromomycin
B. Doxycycline
C. Metronidazole (Correct Answer)
D. Ciprofloxacin
E. Albendazole
Explanation: **Metronidazole**
- **Unicellular organisms with engulfed erythrocytes** in stool are characteristic of **Entamoeba histolytica** infection, causing **amebic dysentery**.
- **Metronidazole** is the drug of choice for treating invasive amebiasis, including dysentery and amebic liver abscess.
*Paromomycin*
- **Paromomycin** is an **intraluminal amebicide** used to eradicate cysts and prevent recurrence, but it is not effective against invasive disease.
- It is often used as a follow-up therapy after metronidazole to clear any remaining luminal cysts.
*Doxycycline*
- **Doxycycline** is a **tetracycline antibiotic** used primarily for bacterial infections, such as those caused by Rickettsia, Chlamydia, and Mycoplasma.
- It has no significant activity against **Entamoeba histolytica**.
*Ciprofloxacin*
- **Ciprofloxacin** is a **fluoroquinolone antibiotic** used for various bacterial infections, including traveler's diarrhea caused by bacteria like E. coli.
- It is not effective against **protozoal infections** like amebiasis.
*Albendazole*
- **Albendazole** is an **anthelmintic drug** primarily used to treat infections caused by various parasitic worms, such as roundworms, hookworms, and tapeworms.
- It is not indicated for the treatment of **amebiasis**.
Question 206: A previously healthy 5-year-old boy is brought to the emergency department because of abdominal pain and vomiting for 6 hours. His mother immediately brought him after noticing that he had gotten into the medicine cabinet. He appears uncomfortable. His temperature is 37.2°C (99°F), pulse is 133/min and blood pressure is 80/50 mm Hg. Examination shows diffuse abdominal tenderness; there is no guarding or rigidity. Digital rectal examination shows dark-colored stools. Laboratory studies show:
Hemoglobin 13.2 g/dL
Leukocyte count 14,100/mm3
Serum
Na+ 136 mEq/L
K+ 3.3 mEq/L
Cl- 105 mEq/L
Urea nitrogen 26 mg/dL
Glucose 98 mg/dL
Creatinine 1.1 mg/dL
Arterial blood gas analysis on room air shows:
pH 7.31
pCO2 32 mm Hg
HCO3- 16 mEq/L
Intravenous fluids are administered. Which of the following is the most appropriate next step in management?
A. Syrup of ipecac
B. Deferoxamine (Correct Answer)
C. Sodium bicarbonate
D. Calcium EDTA
E. Activated charcoal
Explanation: ***Deferoxamine***
- The clinical presentation, including **abdominal pain**, **vomiting**, **hypotension**, and **dark-colored stools** (suggesting gastrointestinal bleeding), in a child who accessed a medicine cabinet, is highly suspicious for **iron poisoning**.
- **Deferoxamine** is a **chelating agent** specifically used to treat **acute iron toxicity** by binding to free iron and promoting its excretion.
*Syrup of ipecac*
- **Syrup of ipecac** is **contraindicated** in cases of suspected poisoning, especially with corrosive substances or in patients with altered mental status, due to the risk of aspiration and lack of proven benefit.
- It induces vomiting, which can be harmful given the patient's current symptoms and potential for further esophageal irritation if iron pills are still present.
*Sodium bicarbonate*
- While the patient has **metabolic acidosis** (pH 7.31, HCO3- 16), **sodium bicarbonate** is used for significant acidosis and hyperkalemia but does not treat the underlying **iron toxicity**.
- Addressing the underlying cause with a chelating agent is the priority before symptomatic treatment of acidosis unless it is severe and life-threatening.
*Calcium EDTA*
- **Calcium EDTA** is a chelating agent primarily used for **lead poisoning**, not iron poisoning.
- Using the wrong chelating agent will be ineffective and could potentially cause further harm due to adverse effects.
*Activated charcoal*
- **Activated charcoal** is **ineffective at binding iron** and is therefore not indicated in cases of iron poisoning.
- It is useful for adsorbing many other toxins in the gastrointestinal tract, but not heavy metals like iron.
Question 207: A 33-year-old man presents to the emergency room for diarrhea. He states it is profuse and watery and has not been improving over the past week. He is generally healthy; however, he was recently hospitalized during spring break and treated for alcohol intoxication and an aspiration pneumonia. While on spring break, the patient also went camping and admits eating undercooked chicken and drinking from mountain streams. His temperature is 100.5°F (38.1°C), blood pressure is 111/74 mmHg, pulse is 110/min, respirations are 16/min, and oxygen saturation is 98% on room air. Physical exam is notable for a fatigued appearing man. His abdomen is non-tender. Which of the following is the best management of this patient?
A. Ciprofloxacin
B. Ciprofloxacin and metronidazole
C. No treatment indicated
D. Vancomycin (Correct Answer)
E. Metronidazole
Explanation: ***Vancomycin***
- This patient's recent **hospitalization** and **pneumonia** treatment, followed by persistent watery diarrhea, strongly suggests **Clostridioides difficile infection (CDI)**.
- **Oral vancomycin** is a first-line treatment for non-severe C. difficile infection.
*Ciprofloxacin*
- **Fluoroquinolones** such as ciprofloxacin are often associated with an **increased risk of C. difficile infection**, as they can disrupt the normal gut flora.
- They are generally not indicated for watery diarrhea where C. difficile is suspected unless there is strong evidence of a different bacterial pathogen susceptible to ciprofloxacin.
*Ciprofloxacin and metronidazole*
- While metronidazole is used for C. difficile, **ciprofloxacin is contraindicated** due to its association with CDI development and potential for resistance.
- This combination is not appropriate for suspected C. difficile, and the patient's symptoms do not clearly indicate a need for broad-spectrum empirical coverage against other bacterial causes.
*No treatment indicated*
- The patient presents with **persistent, profuse watery diarrhea** for a week, a low-grade fever, and a history suggestive of C. difficile risk, indicating that medical intervention is needed.
- Delaying treatment could lead to worsening symptoms, **dehydration**, and more severe outcomes associated with CDI.
*Metronidazole*
- **Metronidazole** is an alternative treatment for **mild-to-moderate C. difficile infection**.
- However, **oral vancomycin** is generally preferred for its superior efficacy in initial episodes of non-severe CDI.
Question 208: A 45-year-old man presents with worsening joint pain and stiffness. Past medical history is significant for rheumatoid arthritis, diagnosed 3 months ago and managed with celecoxib and methotrexate, and occasional gastric reflux, managed with omeprazole. His vitals are a pulse of 80/min, a respiratory rate of 16/min, and blood pressure of 122/80 mm Hg. On physical examination, the left wrist is swollen, stiff, and warm to touch, and the right wrist is red and warm. There is limited active and passive range of motion at the proximal interphalangeal and metacarpophalangeal joints of both hands. The remainder of the examination is unremarkable. A plain radiograph of the hands shows progressive degeneration of multiple joints. Another drug, etanercept, is added to help control progressive arthritis. Which of the following diagnostic tests should be ordered before starting this new medication in this patient?
A. Malignancy screening
B. Bleeding time
C. Endoscopy
D. Tuberculosis screening (Correct Answer)
E. Antinuclear antibody (ANA) level
Explanation: ***Tuberculosis screening***
- **Etanercept** is a TNF-α inhibitor, which **suppresses the immune system** and increases the risk of **reactivation of latent infections**, particularly **tuberculosis**.
- Screening for latent tuberculosis with a **PPD test** or **interferon-gamma release assay (IGRA)** is crucial before initiating therapy with TNF-α inhibitors.
*Malignancy screening*
- While TNF-α inhibitors have been associated with a **slightly increased risk of certain malignancies**, routine general malignancy screening beyond age-appropriate guidelines is not typically required before starting these medications.
- The focus before initiating treatment is on **active infections** or reactivatable latent infections.
*Bleeding time*
- **Etanercept does not directly affect coagulation pathways** or platelet function in a way that necessitates a routine bleeding time test before administration.
- Bleeding time is generally not a standard pre-screening test for TNF-α inhibitors.
*Endoscopy*
- An endoscopy is not a standard pre-screening test for initiating etanercept therapy. The patient's history of **gastric reflux managed with omeprazole** does not, in itself, mandate an endoscopy before starting this medication.
- While GI issues can be present, there's no direct contraindication or increased risk associated with etanercept that would necessitate this procedure beforehand unless other specific symptoms arise.
*Antinuclear antibody (ANA) level*
- **ANA levels** are often elevated in autoimmune conditions like rheumatoid arthritis, but they are generally** not monitored or tested prior to initiating etanercept**.
- While **drug-induced lupus** is a rare side effect of TNF-α inhibitors, an elevated ANA beforehand does not contraindicate its use, nor does it typically trigger pre-treatment ANA testing.
Question 209: A 54-year-old man with a past medical history significant for hypertension, type 2 diabetes, and chronic obstructive pulmonary disease presents with complaints of nausea and abdominal pain for the past month. The pain is located in the epigastric region and is described as “burning” in quality, often following food intake. The patient denies any changes in bowel movements, fever, or significant weight loss. Medications include metformin, lisinopril, hydrochlorothiazide, albuterol inhaler, and fluconazole for a recent fungal infection. Physical examination was unremarkable except for a mildly distended abdomen that is diffusely tender to palpation and decreased sensation at lower extremities bilaterally. A medication was started for the symptoms. Two days later, the patient reports heart palpitations. An EKG is shown below. Which of the following is the medication most likely prescribed?
A. Aspirin
B. Metformin
C. Omeprazole
D. Ranitidine
E. Erythromycin (Correct Answer)
Explanation: ***Erythromycin***
- The EKG shows **QT prolongation** (long QT interval), which can lead to **torsades de pointes** and palpitations. Erythromycin is a macrolide antibiotic known to cause QT prolongation.
- **Critical drug interaction:** The patient is taking **fluconazole**, a strong **CYP3A4 inhibitor**, which increases erythromycin levels (a CYP3A4 substrate), significantly enhancing the risk of QT prolongation and cardiac arrhythmias.
- Given the patient's complaints of burning epigastric pain following food intake and diabetic neuropathy, a diagnosis of **diabetic gastroparesis** is suggested. Erythromycin can be used as a **prokinetic agent** for gastroparesis due to its agonistic effect on motilin receptors, thus explaining its prescription.
*Aspirin*
- Aspirin is a **non-steroidal anti-inflammatory drug (NSAID)** and an antiplatelet agent. While it can cause epigastric pain and is often used in cardiovascular disease patients, it does not typically cause QT prolongation or palpitations.
- It is unlikely to be prescribed for the patient's symptoms of nausea and burning epigastric pain, as it can **exacerbate gastric irritation**.
*Metformin*
- Metformin is an oral hypoglycemic agent already listed in the patient's current medication list and used for type 2 diabetes. Its primary side effects relate to **gastrointestinal upset** (e.g., nausea, diarrhea) but it doesn't cause QT prolongation.
- The question implies a *new* medication was started, and metformin is an existing medication *for diabetes*, not specifically for the new burning epigastric pain.
*Omeprazole*
- Omeprazole is a **proton pump inhibitor (PPI)** commonly prescribed for acid reflux and peptic ulcer disease, which might align with the burning epigastric pain.
- However, PPIs are generally not associated with **QT prolongation** or palpitations.
*Ranitidine*
- Ranitidine is an **H2 receptor antagonist** used to reduce stomach acid, similar to omeprazole, and could be prescribed for the epigastric pain.
- Like omeprazole, ranitidine is not known to cause **QT prolongation** or cardiac arrhythmias like palpitations.
Question 210: Several weeks after starting a new medication for rheumatoid arthritis, a 44-year-old woman comes to the physician because of painful ulcers in her mouth. Oral examination shows inflammation and swelling of the tongue and oropharynx and ulcers on the buccal mucosa bilaterally. Skin examination shows soft tissue swelling over her proximal interphalangeal joints and subcutaneous nodules over her elbows. Serum studies show an alanine aminotransferase level of 220 U/L, aspartate aminotransferase level of 214 U/L, and creatinine level of 1.7 mg/dL. Which of the following is the most likely primary mechanism of action of the drug she is taking?
A. Inhibition of thymidylate synthase
B. Inhibition of cyclooxygenase
C. Inhibition of inosine monophosphate dehydrogenase
D. Inhibition of dihydrofolate reductase (Correct Answer)
E. Inhibition of NF-κB
Explanation: ***Inhibition of dihydrofolate reductase***
- The patient's symptoms (oral ulcers, elevated liver enzymes, elevated creatinine) and history (rheumatoid arthritis, new medication) are highly suggestive of **methotrexate toxicity**.
- **Methotrexate** is a cornerstone in RA treatment, and its primary mechanism of action is the **inhibition of dihydrofolate reductase**, an enzyme essential for folate metabolism and DNA synthesis.
*Inhibition of thymidylate synthase*
- While inhibition of thymidylate synthase is a mechanism of some anticancer drugs like **5-fluorouracil**, it is not the primary mechanism of action of drugs commonly used for rheumatoid arthritis that would cause this constellation of side effects.
- This mechanism primarily affects **pyrimidine synthesis**, leading to DNA synthesis inhibition but is not characteristic of the likely drug here.
*Inhibition of cyclooxygenase*
- Inhibition of cyclooxygenase is the mechanism of action for **NSAIDs**, which are used for symptomatic relief in rheumatoid arthritis.
- While NSAIDs can cause gastrointestinal side effects and kidney injury, they do not typically cause severe oral ulceration and liver enzyme elevations to this extent, especially not as a primary treatment.
*Inhibition of inosine monophosphate dehydrogenase*
- Inhibition of inosine monophosphate dehydrogenase is the mechanism of action for drugs like **mycophenolate mofetil**, which is an immunosuppressant used in transplant patients and for some autoimmune conditions.
- While it has immunosuppressive effects and can cause gastrointestinal side effects, it's not a primary go-to for RA, and the described toxicity profile strongly points away from it.
*Inhibition of NF-κB*
- Inhibition of NF-κB is a mechanism associated with **glucocorticoids (corticosteroids)**, which are used to control inflammation in rheumatoid arthritis.
- While corticosteroids have significant side effects, they do not typically cause the specific pattern of severe oral ulcers, elevated liver enzymes, and acute kidney injury as seen here.