A 45-year-old female with a history of gastroesophageal reflux disease presents to her family physician with symptoms of epigastric pain right after a meal. The physician performs a urea breath test which is positive and the patient is started on appropriate medical therapy. Three days later at a restaurant, she experienced severe flushing, tachycardia, hypotension, and vomiting after her first glass of wine. Which of the following is the mechanism of action of the medication causing this side effect?
Q252
A 14-year-old girl is brought to the physician after she accidentally cut her right forearm earlier that morning while working with her mother's embroidery scissors. She has no history of serious illness. The mother says she went to elementary and middle school abroad and is not sure if she received all of her childhood vaccinations. She appears healthy. Her temperature is 37°C (98.6 °F), pulse 90/min, and blood pressure is 102/68 mm Hg. Examination shows a clean 2-cm laceration on her right forearm with surrounding edema. There is no erythema or discharge. The wound is irrigated with water and washed with soap. Which of the following is the most appropriate next step in management?
Q253
A 24-year-old woman of Ashkenazi Jewish descent presents with recurrent bloody diarrhea and abdominal pain. She says she feels well otherwise. Review of systems is significant for a 4 kg weight loss over the past month. Physical examination is significant for multiple aphthous oral ulcers. Colonoscopy reveals a cobblestone pattern of lesions of the mucosa of the intestinal wall with skip lesions involving the terminal ileum and colon. The patient is informed of the diagnosis and medication to treat her condition is prescribed. On a follow-up visit 6 weeks later, the patient presents with non-productive cough, chest pain, dyspnea on exertion, and worsening oral lesions. A chest radiograph reveals a diffuse interstitial pattern. Which of the following enzymes is inhibited by the medication most likely prescribed for her initial diagnosis?
Q254
A 17-year-old male is diagnosed with acne vulgaris during a visit to a dermatologist. He is prescribed a therapy that is a derivative of vitamin A. He has no other significant past medical history. Which of the following is a major side-effect of this therapy that requires regular monitoring during treatment?
Q255
A 7-year-old boy is brought to the emergency department because of sudden-onset abdominal pain that began 1 hour ago. Three days ago, he was diagnosed with a urinary tract infection and was treated with nitrofurantoin. There is no personal history of serious illness. His parents emigrated from Kenya before he was born. Examination shows diffuse abdominal tenderness, mild splenomegaly, and scleral icterus. Laboratory studies show:
Hemoglobin 9.8 g/dL
Mean corpuscular volume 88 μm3
Reticulocyte count 3.1%
Serum
Bilirubin
Total 3.8 mg/dL
Direct 0.6 mg/dL
Haptoglobin 16 mg/dL (N=41–165 mg/dL)
Lactate dehydrogenase 179 U/L
Which of the following is the most likely underlying cause of this patient's symptoms?
Q256
A 25-year-old man presents to the emergency department with bilateral eye pain. The patient states it has slowly been worsening over the past 48 hours. He admits to going out this past weekend and drinking large amounts of alcohol and having unprotected sex but cannot recall a predisposing event. The patient's vitals are within normal limits. Physical exam is notable for bilateral painful and red eyes with opacification and ulceration of each cornea. The patient's contact lenses are removed and a slit lamp exam is performed and shows bilateral corneal ulceration. Which of the following is the best treatment for this patient?
Q257
A 35-year-old woman that has recently immigrated from Southeast Asia is brought to the emergency department due to a 3-week history of fatigue, night sweats, and enlarged lymph nodes and persistent fever. These symptoms have been getting worse during the past week. She has no history of any cardiac or pulmonary disease. A chest X-ray reveals ipsilateral hilar enlargement and a rounded calcified focus near the right hilum. A Mantoux test is positive. Sputum samples are analyzed and acid-fast bacilli are identified on Ziehl-Neelsen staining. The patient is started on a 4 drug regimen. She returns after 6 months to the emergency department with complaints of joint pain, a skin rash that gets worse with sunlight and malaise. The antinuclear antibody (ANA) and anti-histone antibodies are positive. Which of the following drugs prescribed to this patient is the cause of her symptoms?
Q258
A 62-year-old man comes to the physician because of a 5-day history of fatigue, fever, and chills. For the past 9 months, he has had hand pain and stiffness that has progressively worsened. He started a new medication for these symptoms 3 months ago. Medications used prior to that included ibuprofen, prednisone, and hydroxychloroquine. He does not smoke or drink alcohol. Examination shows a subcutaneous nodule at his left elbow, old joint destruction with boutonniere deformity, and no active joint warmth or tenderness. The remainder of the physical examination shows no abnormalities. His hemoglobin concentration is 10.5 g/dL, leukocyte count is 3500/mm3, and platelet count is 100,000/mm3. Which of the following is most likely to have prevented this patient's laboratory abnormalities?
Q259
A patient with HCC and a long history of alcohol dependence and chronic hepatitis C has been using the mTOR inhibitor sirolimus 100 mg for cancer treatment. Her cancer has shown a partial response. She also has a history of hypertension and poorly controlled type 2 diabetes mellitus complicated by diabetic retinopathy. Current medications include enalapril and insulin. She asks her oncologist and hepatologist if she could try everolimus for its purported survival benefit in treating HCC. Based on clinical considerations, which of the following statements is most accurate?
Q260
A general surgery intern is paged to the bedside of a 59-year-old male who underwent a successful sigmoidectomy for treatment of recurrent diverticulitis. The patient's nurse just recorded a temperature of 38.7 C, and relates that the patient is complaining of chills. The surgery was completed 8 hours ago and was complicated by extensive bleeding, with an estimated blood loss of 1,700 mL. Post-operative anemia was diagnosed after a hemoglobin of 5.9 g/dL was found; 2 units of packed red blood cells were ordered, and the transfusion was initiated 90 minutes ago. The patient's vital signs are as follows: T 38.7 C, HR 88, BP 138/77, RR 18, SpO2 98%. Physical examination does not show any abnormalities. After immediately stopping the transfusion, which of the following is the best management of this patient's condition?
Antimicrobials US Medical PG Practice Questions and MCQs
Question 251: A 45-year-old female with a history of gastroesophageal reflux disease presents to her family physician with symptoms of epigastric pain right after a meal. The physician performs a urea breath test which is positive and the patient is started on appropriate medical therapy. Three days later at a restaurant, she experienced severe flushing, tachycardia, hypotension, and vomiting after her first glass of wine. Which of the following is the mechanism of action of the medication causing this side effect?
A. Binds to the 30S ribosomal subunit preventing attachment of the aminoacyl-tRNA
B. Blocks protein synthesis by binding to the 50S ribosomal subunit inhibiting protein translocation
C. Blocks the synthesis of the peptidoglycan layer
D. Inhibits the H+/K+ ATPase
E. Forms toxic metabolites that damage bacterial DNA (Correct Answer)
Explanation: ***Forms toxic metabolites that damage bacterial DNA***
- The patient likely has a **_H. pylori_ infection** causing epigastric pain, diagnosed by a **positive urea breath test**.
- **Metronidazole**, a common treatment for _H. pylori_, causes a **disulfiram-like reaction** with alcohol, leading to flushing, tachycardia, hypotension, and vomiting. Metronidazole's mechanism involves forming **toxic free radicals** that damage bacterial DNA.
*Binds to the 30S ribosomal subunit preventing attachment of the aminoacyl-tRNA*
- This is the mechanism of action for **tetracyclines** (e.g., doxycycline) and **aminoglycosides** (e.g., gentamicin), which are sometimes used in _H. pylori_ regimens but do not typically cause this severe alcohol interaction.
- While tetracyclines are part of some _H. pylori_ treatment regimens, they are not primarily associated with a disulfiram-like reaction.
*Blocks protein synthesis by binding to the 50S ribosomal subunit inhibiting protein translocation*
- This describes the mechanism of action of **macrolide antibiotics** (e.g., clarithromycin), which are commonly used in _H. pylori_ treatment protocols.
- Although clarithromycin can cause gastrointestinal upset, it does not typically induce the severe disulfiram-like reaction described with alcohol.
*Blocks the synthesis of the peptidoglycan layer*
- This is the mechanism of action of **beta-lactam antibiotics** (e.g., amoxicillin), frequently included in _H. pylori_ eradication regimens.
- Amoxicillin does not cause a disulfiram-like reaction when combined with alcohol.
*Inhibits the H+/K+ ATPase*
- This describes **proton pump inhibitors (PPIs)** like omeprazole or pantoprazole, which are part of nearly all _H. pylori_ treatment regimens to reduce acid production.
- PPIs do not have a direct interaction with alcohol that causes this specific constellation of symptoms; their primary role is acid suppression, not antibacterial action leading to disulfiram effects.
Question 252: A 14-year-old girl is brought to the physician after she accidentally cut her right forearm earlier that morning while working with her mother's embroidery scissors. She has no history of serious illness. The mother says she went to elementary and middle school abroad and is not sure if she received all of her childhood vaccinations. She appears healthy. Her temperature is 37°C (98.6 °F), pulse 90/min, and blood pressure is 102/68 mm Hg. Examination shows a clean 2-cm laceration on her right forearm with surrounding edema. There is no erythema or discharge. The wound is irrigated with water and washed with soap. Which of the following is the most appropriate next step in management?
A. Administer Tdap only (Correct Answer)
B. Administer DTaP only
C. No further steps are necessary
D. Administer TIG only
E. Intravenous metronidazole
Explanation: ***Administer Tdap only***
- A 14-year-old with an unknown or incomplete vaccination history requires a **Tdap (tetanus, diphtheria, acellular pertussis) booster** for **tetanus prophylaxis** after a wound.
- The wound is clean, and there are no signs of active infection or high-risk features that would necessitate tetanus immune globulin (TIG).
*Administer DTaP only*
- **DTaP (diphtheria, tetanus, acellular pertussis)** is typically administered to children younger than 7 years of age.
- This patient is 14 years old, making Tdap the more appropriate vaccine formulation for her age group.
*No further steps are necessary*
- Given the patient's **unknown vaccination history** and a laceration, tetanus prophylaxis is crucial to prevent **tetanus**, a potentially life-threatening condition.
- Simply cleaning the wound is insufficient protection without adequate vaccination status.
*Administer TIG only*
- **Tetanus immune globulin (TIG)** is typically reserved for patients with **dirty or severe wounds** and an unknown or incomplete vaccination history, or for those who are immunocompromised.
- This patient has a **clean laceration** with no indication of high-risk features that would warrant TIG.
*Intravenous metronidazole*
- **Metronidazole** is an antibiotic used to treat **anaerobic bacterial infections** and certain parasitic infections.
- The patient has no signs of infection (no erythema, discharge, or fever) that would necessitate antibiotic treatment at this time.
Question 253: A 24-year-old woman of Ashkenazi Jewish descent presents with recurrent bloody diarrhea and abdominal pain. She says she feels well otherwise. Review of systems is significant for a 4 kg weight loss over the past month. Physical examination is significant for multiple aphthous oral ulcers. Colonoscopy reveals a cobblestone pattern of lesions of the mucosa of the intestinal wall with skip lesions involving the terminal ileum and colon. The patient is informed of the diagnosis and medication to treat her condition is prescribed. On a follow-up visit 6 weeks later, the patient presents with non-productive cough, chest pain, dyspnea on exertion, and worsening oral lesions. A chest radiograph reveals a diffuse interstitial pattern. Which of the following enzymes is inhibited by the medication most likely prescribed for her initial diagnosis?
A. Thymidine kinase
B. DNA polymerase
C. Dihydrofolate reductase (Correct Answer)
D. Hypoxanthine guanine-phosphoribosyltransferase (HGPRT)
E. Thymidylate synthase
Explanation: ***Dihydrofolate reductase***
- The patient's initial symptoms (recurrent **bloody diarrhea**, **abdominal pain**, **weight loss**, **oral ulcers**, **cobblestone pattern** of lesions in the sigmoid colon) are highly suggestive of **Crohn's disease**. The patient's **Ashkenazi Jewish descent** is also a risk factor for Crohn's disease.
- The worsening oral lesions, cough, chest pain, and **diffuse interstitial pattern** on chest radiograph 6 weeks later are classic signs of **methotrexate toxicity**. Methotrexate, a common treatment for Crohn's disease, inhibits **dihydrofolate reductase**, an enzyme essential for **folate metabolism** and **DNA synthesis**.
*Thymidine kinase*
- **Thymidine kinase** is an enzyme involved in the salvage pathway of pyrimidine synthesis. It is typically inhibited by antiviral drugs like **acyclovir** and **ganciclovir**, which are not used for Crohn's disease.
- Inhibition of thymidine kinase is not associated with the lung and oral toxicities seen in this patient.
*DNA polymerase*
- **DNA polymerase** is crucial for DNA replication and repair. Drugs inhibiting DNA polymerase, such as some **antivirals** (e.g., foscarnet) and **chemotherapeutics** (e.g., cytarabine), are not primary treatments for Crohn's disease.
- Inhibition of DNA polymerase does not directly lead to the specific constellation of symptoms observed from methotrexate toxicity.
*Hypoxanthine guanine-phosphoribosyltransferase (HGPRT)*
- **HGPRT** is an enzyme central to the purine salvage pathway. Its deficiency leads to **Lesch-Nyhan syndrome**.
- While some immunosuppressants like **azathioprine** and **mercaptopurine** act as purine analogs and affect purine metabolism, they do not directly inhibit HGPRT and do not typically cause the acute pulmonary toxicity seen with methotrexate.
*Thymidylate synthase*
- **Thymidylate synthase** is an enzyme involved in the synthesis of pyrimidine deoxyribonucleotides, particularly dTMP, which is essential for DNA synthesis. It is a target for some **chemotherapeutic agents** like **5-fluorouracil**.
- While methotrexate indirectly affects thymidylate synthesis by depleting folate precursors, its direct mechanism of action is the inhibition of **dihydrofolate reductase**, not thymidylate synthase itself, and 5-fluorouracil toxicity differs from the presented symptoms.
Question 254: A 17-year-old male is diagnosed with acne vulgaris during a visit to a dermatologist. He is prescribed a therapy that is a derivative of vitamin A. He has no other significant past medical history. Which of the following is a major side-effect of this therapy that requires regular monitoring during treatment?
A. Alopecia
B. Hyperglycemia
C. Fatigue
D. Hyperlipidemia (Correct Answer)
E. Xerophthalmia
Explanation: ***Hyperlipidemia***
- **Isotretinoin**, a vitamin A derivative, is known to cause significant alterations in lipid metabolism, necessitating regular monitoring of **triglycerides** and **cholesterol** levels.
- Elevated lipid levels, particularly triglycerides, can lead to serious complications such as **pancreatitis** if not controlled.
*Alopecia*
- While hair thinning can occur with isotretinoin, it is not considered a **major side effect** that routinely requires the same level of close periodic monitoring as hyperlipidemia.
- Hair changes are generally less common and often reversible upon discontinuation of the drug.
*Hyperglycemia*
- Although there have been rare reports of altered glucose metabolism, **hyperglycemia** is not a common or major side effect of isotretinoin that mandates routine and frequent monitoring in most patients.
- The direct link and clinical significance are not as robust as for lipid abnormalities.
*Fatigue*
- Fatigue can be a general, non-specific side effect of many medications, including isotretinoin, but it is not typically a serious concern requiring regular laboratory monitoring.
- It is often managed symptomatically and does not carry the same risk of organ damage as unmonitored hyperlipidemia.
*Xerophthalmia*
- **Dry eyes (xerophthalmia)** are a common and expected side effect of isotretinoin due to its systemic drying effects.
- While it can be uncomfortable, it is typically managed with artificial tears and does not require regular laboratory monitoring or pose the same severe systemic risks as hyperlipidemia.
Question 255: A 7-year-old boy is brought to the emergency department because of sudden-onset abdominal pain that began 1 hour ago. Three days ago, he was diagnosed with a urinary tract infection and was treated with nitrofurantoin. There is no personal history of serious illness. His parents emigrated from Kenya before he was born. Examination shows diffuse abdominal tenderness, mild splenomegaly, and scleral icterus. Laboratory studies show:
Hemoglobin 9.8 g/dL
Mean corpuscular volume 88 μm3
Reticulocyte count 3.1%
Serum
Bilirubin
Total 3.8 mg/dL
Direct 0.6 mg/dL
Haptoglobin 16 mg/dL (N=41–165 mg/dL)
Lactate dehydrogenase 179 U/L
Which of the following is the most likely underlying cause of this patient's symptoms?
A. Defective red blood cell membrane proteins
B. Lead poisoning
C. Defect in orotic acid metabolism
D. Absent hemoglobin beta chain
E. Enzyme deficiency in red blood cells (Correct Answer)
Explanation: ***Enzyme deficiency in red blood cells***
- The patient's symptoms (abdominal pain, scleral icterus, mild splenomegaly, anemia, elevated reticulocyte count, increased unconjugated bilirubin, low haptoglobin, and elevated LDH) are consistent with **hemolytic anemia**. The recent use of **nitrofurantoin**, an oxidative stressor, in a patient of African descent, strongly suggests a diagnosis of **Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency**.
- G6PD deficiency is an **X-linked recessive** inherited enzyme defect causing red blood cells to be susceptible to oxidative damage, leading to hemolysis when exposed to certain drugs (like nitrofurantoin) or infections.
*Defective red blood cell membrane proteins*
- This describes conditions like **hereditary spherocytosis** or **hereditary elliptocytosis**. While these cause hemolytic anemia, the acute onset triggered by a drug (nitrofurantoin) is less typical.
- Hereditary spherocytosis is characterized by **microspherocytes** on a peripheral smear and is usually diagnosed earlier in life or has a chronic course, often without an acute precipitating drug.
*Lead poisoning*
- Lead poisoning typically causes **microcytic anemia** with **basophilic stippling** and neurological symptoms, not the type of hemolytic anemia and jaundice described.
- It does not present as an acute hemolytic crisis triggered by an oxidative drug.
*Defect in orotic acid metabolism*
- This can lead to conditions like **hereditary orotic aciduria**, which presents with **megaloblastic anemia** (without B12 or folate deficiency) and developmental delay.
- It is not associated with acute hemolytic episodes triggered by oxidative drugs or the specific lab findings seen here.
*Absent hemoglobin beta chain*
- This refers to **beta-thalassemia major**, which causes **microcytic hypochromic anemia** that is typically chronic and presents early in childhood with severe anemia requiring regular transfusions.
- Beta-thalassemia does not present as an acute hemolytic crisis triggered by nitrofurantoin, and the MCV in this patient is normal (88 μm³), not microcytic.
Question 256: A 25-year-old man presents to the emergency department with bilateral eye pain. The patient states it has slowly been worsening over the past 48 hours. He admits to going out this past weekend and drinking large amounts of alcohol and having unprotected sex but cannot recall a predisposing event. The patient's vitals are within normal limits. Physical exam is notable for bilateral painful and red eyes with opacification and ulceration of each cornea. The patient's contact lenses are removed and a slit lamp exam is performed and shows bilateral corneal ulceration. Which of the following is the best treatment for this patient?
A. Topical dexamethasone and refrain from wearing contacts
B. Intravitreal vancomycin and ceftazidime
C. Gatifloxacin eye drops (Correct Answer)
D. Erythromycin ointment
E. Acyclovir
Explanation: ***Gatifloxacin eye drops***
- The patient's presentation with **bilateral painful red eyes**, **corneal opacification and ulceration**, and a history of **contact lens use** strongly suggests **bacterial keratitis**.
- **Gatifloxacin** is a **fourth-generation fluoroquinolone** that provides broad-spectrum coverage against common bacterial pathogens causing keratitis, including gram-positive and gram-negative organisms, and is administered as a topical eye drop.
*Topical dexamethasone and refrain from wearing contacts*
- While refraining from contact lens use is crucial, **topical corticosteroids** like dexamethasone are generally **contraindicated in active bacterial keratitis** as they can worsen the infection by suppressing the immune response.
- Corticosteroids are primarily used in inflammatory conditions, and their use in suspected infections can delay healing and promote microbial growth.
*Intravitreal vancomycin and ceftazidime*
- This treatment regimen is typically reserved for severe **endophthalmitis**, an intraocular infection, not for keratitis which is an infection of the cornea.
- **Intravitreal injections** are significantly more invasive and carry higher risks than topical treatments for corneal infections.
*Erythromycin ointment*
- **Erythromycin ointment** is a macrolide antibiotic with a **narrower spectrum of activity** compared to fluoroquinolones, particularly against some gram-negative bacteria common in contact lens-related keratitis.
- While it can be used for some superficial ocular infections, it is likely **insufficient for severe keratitis** presenting with significant ulceration.
*Acyclovir*
- **Acyclovir** is an **antiviral medication** used to treat **herpes simplex keratitis** or **herpes zoster ophthalmicus**.
- While corneal ulcers can be caused by viruses, the clinical picture, especially the **contact lens use** and rapid progression, points more strongly towards **bacterial keratitis**.
Question 257: A 35-year-old woman that has recently immigrated from Southeast Asia is brought to the emergency department due to a 3-week history of fatigue, night sweats, and enlarged lymph nodes and persistent fever. These symptoms have been getting worse during the past week. She has no history of any cardiac or pulmonary disease. A chest X-ray reveals ipsilateral hilar enlargement and a rounded calcified focus near the right hilum. A Mantoux test is positive. Sputum samples are analyzed and acid-fast bacilli are identified on Ziehl-Neelsen staining. The patient is started on a 4 drug regimen. She returns after 6 months to the emergency department with complaints of joint pain, a skin rash that gets worse with sunlight and malaise. The antinuclear antibody (ANA) and anti-histone antibodies are positive. Which of the following drugs prescribed to this patient is the cause of her symptoms?
A. Isoniazid (Correct Answer)
B. Pyrazinamide
C. Ethambutol
D. Streptomycin
E. Rifampicin
Explanation: ***Isoniazid***
- The patient developed symptoms of **drug-induced lupus erythematosus (DILE)**, characterized by joint pain, photosensitive rash, and positive ANA and anti-histone antibodies, which is a known side effect of isoniazid.
- Isoniazid is a common cause of DILE because it is metabolized to a compound that can induce autoantibody production, particularly **anti-histone antibodies**.
*Pyrazinamide*
- Pyrazinamide is primarily associated with **hepatotoxicity** and **hyperuricemia**, which can lead to Gout.
- It does not commonly cause drug-induced lupus erythematosus.
*Ethambutol*
- **Optic neuritis** (blurred vision, red-green color blindness) is the most significant side effect of ethambutol.
- It is not associated with drug-induced lupus erythematosus.
*Streptomycin*
- Streptomycin, an aminoglycoside, primarily causes **ototoxicity** (hearing loss, vertigo) and **nephrotoxicity**.
- It is not implicated in drug-induced lupus erythematosus.
*Rifampicin*
- Rifampicin's notable side effects include **hepatotoxicity**, **red-orange discoloration of body fluids**, and **gastrointestinal upset**.
- While rifampicin can rarely cause drug-induced lupus, **isoniazid is a far more common cause** and is the more likely culprit given the classic DILE presentation with anti-histone antibodies.
Question 258: A 62-year-old man comes to the physician because of a 5-day history of fatigue, fever, and chills. For the past 9 months, he has had hand pain and stiffness that has progressively worsened. He started a new medication for these symptoms 3 months ago. Medications used prior to that included ibuprofen, prednisone, and hydroxychloroquine. He does not smoke or drink alcohol. Examination shows a subcutaneous nodule at his left elbow, old joint destruction with boutonniere deformity, and no active joint warmth or tenderness. The remainder of the physical examination shows no abnormalities. His hemoglobin concentration is 10.5 g/dL, leukocyte count is 3500/mm3, and platelet count is 100,000/mm3. Which of the following is most likely to have prevented this patient's laboratory abnormalities?
A. Amifostine
B. Pyridoxine
C. Mesna
D. Leucovorin (Correct Answer)
E. Cobalamin
Explanation: ***Leucovorin***
- The patient's presentation with **fatigue, fever, chills, subcutaneous nodules, boutonniere deformity, and pancytopenia** strongly suggests **methotrexate toxicity**, likely from the new medication started 3 months ago for his worsening hand pain and stiffness.
- **Leucovorin** (folinic acid) is used as a "rescue" treatment to replenish folate stores and **prevent myelosuppression, mucositis, and gastrointestinal toxicity** associated with methotrexate, which inhibits **dihydrofolate reductase**.
*Amifostine*
- **Amifostine** is a cytoprotective agent primarily used to reduce **renal toxicity** associated with platinum-based chemotherapy and salivary gland dysfunction from radiation therapy.
- It does not specifically reverse or prevent the myelosuppressive effects of methotrexate.
*Pyridoxine*
- **Pyridoxine (Vitamin B6)** is important for various metabolic functions and is used to prevent **neuropathy** associated with certain drugs like isoniazid.
- It has no role in preventing the hematologic or gastrointestinal toxicities of methotrexate.
*Mesna*
- **Mesna** is a uroprotectant agent used to prevent **hemorrhagic cystitis** caused by oxazaphosphorine chemotherapy agents like cyclophosphamide and ifosfamide.
- It does not mitigate the side effects of methotrexate.
*Cobalamin*
- **Cobalamin (Vitamin B12)** is crucial for DNA synthesis and neurologic function; its deficiency can lead to **macrocytic anemia and neurological symptoms**.
- While important for hematopoiesis, it does not directly counteract the mechanism of methotrexate toxicity or prevent its myelosuppressive effects.
Question 259: A patient with HCC and a long history of alcohol dependence and chronic hepatitis C has been using the mTOR inhibitor sirolimus 100 mg for cancer treatment. Her cancer has shown a partial response. She also has a history of hypertension and poorly controlled type 2 diabetes mellitus complicated by diabetic retinopathy. Current medications include enalapril and insulin. She asks her oncologist and hepatologist if she could try everolimus for its purported survival benefit in treating HCC. Based on clinical considerations, which of the following statements is most accurate?
A. The patient should start everolimus 50 mg because of the survival benefit relative to sirolimus 100 mg
B. The patient is not a good candidate for everolimus due to her history of hypertension
C. The patient should start everolimus 100 mg because of the survival benefit relative to sirolimus 100 mg
D. The patient should start everolimus 50 mg because of her history of alcohol use disorder and hepatitis C
E. The patient is not a good candidate for everolimus due to her history of diabetes (Correct Answer)
Explanation: ***The patient is not a good candidate for Noxbinle due to her history of diabetes***
- The current medication is sirolimus, an **mTOR inhibitor** and its successor everolimus, also an mTOR inhibitor, is not beneficial for this patient due to her **poorly controlled type 2 diabetes mellitus**.
- mTOR inhibitors, including everolimus, are known to **worsen hyperglycemia** and **accelerate the progression of diabetes**, making it contraindicated in patients with already complicated diabetes.
*The patient should start everolimus 50 mg because of the survival benefit relative to sirolimus 100 mg*
- There is **no established evidence** that everolimus at any dose offers a superior survival benefit compared to sirolimus in HCC, particularly after a partial response to sirolimus.
- **Switching mTOR inhibitors** without a compelling clinical reason, especially with existing comorbidities, is not standard practice.
*The patient is not a good candidate for everolimus due to her history of hypertension*
- While mTOR inhibitors can contribute to **hypertension**, this patient is already on **enalapril** for her existing hypertension.
- Her **poorly controlled diabetes** presents a more direct and severe contraindication due to the metabolic side effects of everolimus.
*The patient should start everolimus 100 mg because of the survival benefit relative to sirolimus 100 mg*
- No clinical data supports a **superior survival benefit** of everolimus 100 mg over sirolimus 100 mg in HCC.
- Given the patient's existing **poorly controlled diabetes**, increasing the dose of an mTOR inhibitor or switching to an equivalent dose of another would heighten the risk of severe metabolic complications.
*The patient should start everolimus 50 mg because of her history of alcohol use disorder and hepatitis C*
- The patient's history of alcohol dependence and chronic hepatitis C are **risk factors for HCC** but do not directly contraindicate a specific dose of everolimus more than her diabetes.
- While liver impairment due to these conditions might influence dosing of various medications, the **primary concern for everolimus** in this case remains the uncontrolled diabetes.
Question 260: A general surgery intern is paged to the bedside of a 59-year-old male who underwent a successful sigmoidectomy for treatment of recurrent diverticulitis. The patient's nurse just recorded a temperature of 38.7 C, and relates that the patient is complaining of chills. The surgery was completed 8 hours ago and was complicated by extensive bleeding, with an estimated blood loss of 1,700 mL. Post-operative anemia was diagnosed after a hemoglobin of 5.9 g/dL was found; 2 units of packed red blood cells were ordered, and the transfusion was initiated 90 minutes ago. The patient's vital signs are as follows: T 38.7 C, HR 88, BP 138/77, RR 18, SpO2 98%. Physical examination does not show any abnormalities. After immediately stopping the transfusion, which of the following is the best management of this patient's condition?
A. Hydrate with 1 L bolus of normal saline followed by maintenance fluids at 125 cc/hr
B. Prescribe diphenhydramine
C. Monitor patient and administer acetaminophen (Correct Answer)
D. Start supplemental oxygen by nasal cannula
E. Initiate broad spectrum antibiotics
Explanation: ***Monitor patient and administer acetaminophen***
- This patient is experiencing a **febrile non-hemolytic transfusion reaction (FNHTR)**, characterized by a temperature increase of ≥1°C during or within hours of transfusion, and chills, in the absence of other causes. **Acetaminophen** is the primary treatment for fever and discomfort, and careful monitoring is crucial to rule out more severe reactions.
- The patient's vital signs are otherwise stable, and there are no signs of anaphylaxis, hemolysis, or bacterial contamination, making supportive care with antipyretics the most appropriate initial management after stopping the transfusion.
*Hydrate with 1 L bolus of normal saline followed by maintenance fluids at 125 cc/hr*
- While hydration is generally important post-surgery, there is **no indication of hypovolemia or dehydration** (BP 138/77, HR 88, SpO2 98%) that would necessitate an immediate fluid bolus for this specific reaction.
- Excessive fluid administration could potentially worsen underlying cardiac conditions or lead to fluid overload, especially in an elderly patient.
*Prescribe diphenhydramine*
- **Diphenhydramine** (an antihistamine) is primarily used for **allergic transfusion reactions**, which typically present with urticaria, pruritus, or respiratory symptoms like wheezing, none of which are observed in this patient.
- This patient's symptoms are fever and chills, not allergic manifestations.
*Start supplemental oxygen by nasal cannula*
- The patient's **oxygen saturation is 98%**, indicating he is not hypoxic.
- There is no clinical sign of respiratory distress or hypoxemia that would warrant supplemental oxygen.
*Initiate broad spectrum antibiotics*
- While fever is present, there is **no evidence of bacterial infection** (e.g., hypotension, rapid deterioration, signs of sepsis) that would require immediate broad-spectrum antibiotics for a transfusion reaction at this early stage.
- Unnecessary antibiotic use contributes to antibiotic resistance and can have side effects.
