Antifungal therapeutic drug monitoring US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for Antifungal therapeutic drug monitoring. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Antifungal therapeutic drug monitoring US Medical PG Question 1: A 65-year-old female patient with a past medical history of diabetes mellitus and an allergy to penicillin develops an infected abscess positive for MRSA on the third day of her hospital stay. She is started on an IV infusion of vancomycin at a dose of 1000 mg every 12 hours. Vancomycin is eliminated by first-order kinetics and has a half life of 6 hours. The volume of distribution of vancomycin is 0.5 L/kg. Assuming no loading dose is given, how long will it take for the drug to reach 94% of its plasma steady state concentration?
- A. 30 hours
- B. 12 hours
- C. 6 hours
- D. 18 hours
- E. 24 hours (Correct Answer)
Antifungal therapeutic drug monitoring Explanation: ***24 hours***
- For a drug eliminated by **first-order kinetics**, it takes approximately **4 half-lives** to reach **93.75%** of steady state concentration, which is conventionally rounded to **94%**.
- Since the half-life of vancomycin is **6 hours**, reaching 94% of steady state requires: 4 × 6 hours = **24 hours**.
- This follows the pharmacokinetic principle that each half-life brings the drug closer to steady state: 1 t½ = 50%, 2 t½ = 75%, 3 t½ = 87.5%, 4 t½ = 93.75%.
*30 hours*
- This duration represents **five half-lives** (5 × 6 hours), at which point approximately **96.875%** (often rounded to 97%) of steady state would be reached.
- This exceeds the 94% target specified in the question.
*18 hours*
- This duration represents **three half-lives** (3 × 6 hours), at which point approximately **87.5%** of steady state concentration would be reached.
- This falls short of the 94% target.
*12 hours*
- This duration represents **two half-lives** (2 × 6 hours), at which point approximately **75%** of steady state concentration would be reached.
- This is insufficient time to reach 94% of plasma steady state concentration.
*6 hours*
- This duration represents **one half-life**, at which point approximately **50%** of steady state concentration would be reached.
- This is far too short to achieve near-steady state levels.
Antifungal therapeutic drug monitoring US Medical PG Question 2: A laboratory physician investigates the chromosomes of a fetus with a suspected chromosomal anomaly. She processes a cell culture obtained by amniocentesis. Prior to staining and microscopic examination of the fetal chromosomes, a drug that blocks cell division is added to the cell culture. In order to arrest chromosomes in metaphase, the physician most likely added a drug that is also used for the treatment of which of the following conditions?
- A. Trichomonas vaginitis
- B. Testicular cancer
- C. Herpes zoster
- D. Polycythemia vera
- E. Acute gouty arthritis (Correct Answer)
Antifungal therapeutic drug monitoring Explanation: ***Acute gouty arthritis***
- The drug used to arrest chromosomes in metaphase is likely **colchicine**, which inhibits **microtubule polymerization** and spindle formation, thus arresting cells in metaphase.
- **Colchicine** is a well-established treatment for **acute gouty arthritis** due to its anti-inflammatory properties, primarily through disrupting neutrophil functions.
*Trichomonas vaginitis*
- This condition is typically treated with **metronidazole** or **tinidazole**, which are antibiotics targeting protozoa and anaerobic bacteria.
- These drugs do not inhibit microtubule assembly or arrest cells in metaphase.
*Testicular cancer*
- Testicular cancer is primarily treated with **BEP regimen** (bleomycin, etoposide, cisplatin), which does not include microtubule-inhibiting agents.
- While vinca alkaloids (vincristine, vinblastine) do arrest cells in metaphase via microtubule inhibition similar to colchicine, they are not standard first-line agents for testicular cancer.
- The question specifically asks about the primary clinical use of colchicine, which is gout, not cancer chemotherapy.
*Herpes zoster*
- Herpes zoster (shingles) is a viral infection treated with **antiviral medications** like acyclovir, valacyclovir, or famciclovir.
- These antivirals work by interfering with viral DNA replication and do not target microtubule formation or cell division.
*Polycythemia vera*
- Polycythemia vera is a myeloproliferative neoplasm often managed with **phlebotomy**, **hydroxyurea**, or ruxolitinib.
- These treatments aim to reduce blood cell counts or inhibit specific signaling pathways, none of which primarily involve arresting cells in metaphase by disrupting microtubules.
Antifungal therapeutic drug monitoring US Medical PG Question 3: An 11-year-old boy with HIV and esophageal candidiasis is being treated with caspofungin. What is the mechanism of action of this drug?
- A. Pore formation in cell membranes
- B. Inhibition of ergosterol synthesis
- C. Inhibition of 1,3-Beta-glucan synthase (Correct Answer)
- D. Inhibition of squalene epoxidase
- E. Inhibition of pyrimidine synthesis
Antifungal therapeutic drug monitoring Explanation: ***Inhibition of 1,3-Beta-glucan synthase***
- **Caspofungin** is an **echinocandin** antifungal agent that works by inhibiting **1,3-beta-D-glucan synthase**.
- This enzyme is crucial for the synthesis of **glucan**, a vital component of the **fungal cell wall**, leading to cell wall disruption and fungal cell death.
*Pore formation in cell membranes*
- This mechanism of action is characteristic of **polyene antifungals** like **amphotericin B**.
- These drugs bind to **ergosterol** in the fungal cell membrane, forming pores that lead to leakage of cellular contents.
*Inhibition of ergosterol synthesis*
- This is the mechanism of action for **azole antifungals** (e.g., fluconazole, itraconazole) and **allylamines** (e.g., terbinafine).
- Azoles inhibit **14-alpha-demethylase**, an enzyme involved in converting lanosterol to ergosterol, while allylamines inhibit **squalene epoxidase**.
*Inhibition of squalene epoxidase*
- This is the specific mechanism for **allylamine antifungals** like **terbinafine**.
- Inhibition of **squalene epoxidase** prevents the synthesis of **ergosterol**, primarily used for superficial fungal infections.
*Inhibition of pyrimidine synthesis*
- This mechanism is characteristic of **flucytosine**, an antifungal pro-drug.
- Flucytosine is converted to **5-fluorouracil** within fungal cells, which then inhibits fungal DNA and RNA synthesis.
Antifungal therapeutic drug monitoring US Medical PG Question 4: An experimental drug, ES 62, is being studied. It prohibits the growth of vancomycin-resistant Staphylococcus aureus. It is highly lipid-soluble. The experimental design is dependent on a certain plasma concentration of the drug. The target plasma concentration is 100 mmol/dL. Which of the following factors is most important for calculating the appropriate loading dose?
- A. Volume of distribution (Correct Answer)
- B. Half-life of the drug
- C. Therapeutic index
- D. Clearance of the drug
- E. Rate of administration
Antifungal therapeutic drug monitoring Explanation: **Volume of distribution**
- The **loading dose** is primarily determined by the desired **plasma concentration** and the **volume of distribution (Vd)**, as it reflects how extensively a drug is distributed in the body.
- The formula for loading dose is: Loading Dose = (Target Plasma Concentration × Vd).
*Half-life of the drug*
- The **half-life** is crucial for determining the **dosing interval** and the time it takes to reach **steady-state concentrations**, not the initial loading dose.
- It reflects the rate at which the drug is eliminated from the body.
*Therapeutic index*
- The **therapeutic index** is a measure of a drug's relative safety, indicating the ratio between the **toxic dose** and the **effective dose**.
- While important for drug safety, it does not directly determine the magnitude of the loading dose itself.
*Clearance of the drug*
- **Clearance** is the rate at which the drug is removed from the body and is a primary determinant of the **maintenance dose** required to sustain a desired plasma concentration.
- It does not directly calculate the initial loading dose needed to achieve an immediate target concentration.
*Rate of administration*
- The **rate of administration** (e.g., infusion rate) primarily influences how quickly the drug reaches its target concentration, but not the total quantity of drug needed for the initial loading dose.
- It affects the kinetics of how the loading dose achieves the target concentration, rather than defining the dose amount.
Antifungal therapeutic drug monitoring US Medical PG Question 5: A 32-year-old woman presents with three-days of vaginal burning, itching, and pain with intercourse. She is in a monogamous relationship with her husband and has an intrauterine device for contraception. Her past medical history is unremarkable, except for recently being treated with antibiotics for sinusitis. Pelvic exam is remarkable for vulvar excoriations, vaginal wall edema, and thick, white discharge in the vault. Wet mount with KOH staining reveals budding filaments with pseudohyphae and hyphae. Which of the following is the most appropriate treatment?
- A. Voriconazole
- B. Posaconazole
- C. Metronidazole
- D. Itraconazole
- E. Fluconazole (Correct Answer)
Antifungal therapeutic drug monitoring Explanation: ***Fluconazole***
- The patient's symptoms (vaginal burning, itching, pain with intercourse, thick, white discharge) and **wet mount findings (budding filaments with pseudohyphae and hyphae)** are classic for **vulvovaginal candidiasis (VVC)**, often precipitated by recent antibiotic use.
- **Fluconazole** is a highly effective and commonly prescribed oral antifungal for uncomplicated VVC due to its convenience and excellent therapeutic profile.
*Voriconazole*
- **Voriconazole** is a broad-spectrum triazole antifungal primarily used for invasive fungal infections, such as **invasive aspergillosis** and candidemia, and is not a first-line treatment for uncomplicated VVC.
- Its use is typically reserved for more severe or refractory systemic fungal infections, and it has a more significant side effect profile than fluconazole.
*Posaconazole*
- **Posaconazole** is another extended-spectrum triazole antifungal primarily used for the prophylaxis and treatment of **invasive fungal infections** in immunocompromised patients, particularly those unresponsive to other antifungals.
- It is not indicated for the treatment of uncomplicated vulvovaginal candidiasis.
*Metronidazole*
- **Metronidazole** is an antibiotic and antiprotozoal agent used to treat bacterial vaginosis and trichomoniasis, both of which are common causes of vaginitis.
- It is **ineffective against fungal infections**, and the patient's symptoms and wet mount findings rule out bacterial vaginosis and trichomoniasis.
*Itraconazole*
- **Itraconazole** is an antifungal drug effective against superficial and systemic fungal infections, but it is typically used for more severe or recurrent VVC, or in cases of non-albicans Candida species.
- While effective, **fluconazole** is generally preferred as the first-line oral treatment for uncomplicated VVC due to its single-dose efficacy and established safety profile for this indication.
Antifungal therapeutic drug monitoring US Medical PG Question 6: A 72-year-old woman with type 2 diabetes mellitus comes to the physician because she is concerned about the appearance of her toenails. Examination shows yellowish discoloration of all toenails on both feet. The edges of the toenails are lifted, and there is subungual debris. Potassium hydroxide preparation of scrapings from the nails shows multiple branching septate hyphae. Treatment with oral terbinafine is begun. Which of the following is the primary mechanism of action of this drug?
- A. Inhibition of squalene epoxidase (Correct Answer)
- B. Formation of pores in cell membrane
- C. Inhibition of β-glucan synthesis
- D. Interference with mitosis during metaphase
- E. Prevention of lanosterol to ergosterol conversion
Antifungal therapeutic drug monitoring Explanation: ***Inhibition of squalene epoxidase***
- **Terbinafine** is an **allylamine** antifungal that inhibits the enzyme **squalene epoxidase**, an early step in fungal ergosterol synthesis
- This inhibition leads to the accumulation of **squalene**, which is toxic to the fungal cell, and a deficiency of **ergosterol**, disrupting cell membrane integrity and function
- Terbinafine is highly effective for **onychomycosis** (fungal nail infections) caused by dermatophytes
*Formation of pores in cell membrane*
- This mechanism is characteristic of **polyene antifungals** like **amphotericin B** and **nystatin**
- These drugs bind to **ergosterol** in the fungal cell membrane, creating pores that lead to leakage of intracellular contents and cell death
*Inhibition of β-glucan synthesis*
- This is the primary mechanism of action for **echinocandin** antifungals, such as **caspofungin**, **micafungin**, and **anidulafungin**
- These drugs inhibit **(1,3)-β-D-glucan synthase**, which is essential for the synthesis of glucan, a major component of the fungal cell wall
*Interference with mitosis during metaphase*
- This mechanism is characteristic of **griseofulvin**, another antifungal agent used for dermatophyte infections
- **Griseofulvin** interferes with **microtubule function**, disrupting mitotic spindle formation and preventing fungal cell division
*Prevention of lanosterol to ergosterol conversion*
- This mechanism is associated with **azole antifungals** (e.g., fluconazole, itraconazole), which inhibit fungal **cytochrome P450-dependent 14-α-demethylase**
- This enzyme is responsible for the conversion of **lanosterol** to **ergosterol**, leading to ergosterol depletion and accumulation of toxic sterol precursors
Antifungal therapeutic drug monitoring US Medical PG Question 7: A 41-year-old man comes to the physician because of a 3-week history of fatigue, cough, and a 4.5-kg (10-lb) weight loss. He does not smoke or drink alcohol. He appears emaciated. A chest x-ray shows a calcified nodule in the left lower lobe and left hilar lymphadenopathy. The physician initiates therapy for the condition and informs him that he will have to return for monthly ophthalmologic examination for the next 2 months. These examinations are most likely to evaluate the patient for an adverse effect of a drug with which of the following mechanisms of action?
- A. Impaired synthesis of mycolic acids
- B. Impaired protein synthesis due to binding to 50S ribosomes
- C. Impaired production of hemozoin from heme
- D. Impaired synthesis of cell wall polysaccharides (Correct Answer)
- E. Impaired protein synthesis due to binding to 30S ribosomes
Antifungal therapeutic drug monitoring Explanation: ***Impaired synthesis of cell wall polysaccharides***
- The patient's clinical presentation (fatigue, cough, weight loss, calcified nodule, hilar lymphadenopathy) is classic for **tuberculosis**.
- The requirement for **monthly ophthalmologic examinations** is pathognomonic for **ethambutol** therapy, as this drug causes **optic neuritis** (decreased visual acuity, red-green color blindness).
- **Ethambutol** inhibits **arabinosyl transferase**, which impairs the synthesis of **arabinogalactan**, a key polysaccharide component of the mycobacterial cell wall.
- Due to the risk of optic neuritis, patients on ethambutol require baseline and monthly ophthalmologic monitoring, especially during the first 2 months of therapy.
*Impaired synthesis of mycolic acids*
- This describes the mechanism of **isoniazid (INH)**, a first-line anti-TB drug that inhibits mycolic acid synthesis.
- The main adverse effects of isoniazid are **peripheral neuropathy** (prevented with pyridoxine/vitamin B6) and **hepatotoxicity**, not optic neuritis.
- Isoniazid does not require routine ophthalmologic monitoring.
*Impaired protein synthesis due to binding to 50S ribosomes*
- This mechanism describes **macrolides** (e.g., clarithromycin, azithromycin) and **chloramphenicol**.
- While macrolides may be used for atypical mycobacterial infections, they are not first-line TB therapy and do not cause optic neuritis requiring monthly eye exams.
*Impaired protein synthesis due to binding to 30S ribosomes*
- This mechanism describes **aminoglycosides** (e.g., streptomycin) and **tetracyclines**.
- While streptomycin is a second-line anti-TB drug, its main adverse effects are **ototoxicity** (hearing loss, vestibular dysfunction) and **nephrotoxicity**, not optic neuritis.
- These drugs do not require ophthalmologic monitoring.
*Impaired production of hemozoin from heme*
- This is the mechanism of **chloroquine** and **hydroxychloroquine**, which are antimalarial drugs.
- While chloroquine can cause retinopathy requiring ophthalmologic monitoring, this patient has **tuberculosis**, not malaria.
- The clinical scenario (calcified lung nodule, hilar lymphadenopathy) and TB treatment context make this mechanism incorrect for this case.
Antifungal therapeutic drug monitoring US Medical PG Question 8: 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)
Antifungal therapeutic drug monitoring 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.
Antifungal therapeutic drug monitoring US Medical PG Question 9: A 13-year-old Caucasian male presents with his father to the pediatrician’s office complaining of left lower thigh pain. He reports slowly progressive pain over the distal aspect of his left thigh over the past three months. He denies any recent trauma to the area. His temperature is 100.9°F (38.3°C). On exam, there is swelling and tenderness overlying the inferior aspect of the left femoral diaphysis. Laboratory evaluation is notable for an elevated white blood cell (WBC) count and erythrocyte sedimentation rate (ESR). Biopsy of the lesion demonstrates sheets of monotonous small round blue cells with minimal cytoplasm. He is diagnosed and started on a medication that inhibits transcription by intercalating into DNA at the transcription initiation complex. Which of the following adverse events will this patient be at highest risk for following initiation of this medication?
- A. Peripheral neuropathy
- B. Bone marrow suppression (Correct Answer)
- C. Gingival hyperplasia
- D. Pulmonary fibrosis
- E. Hemorrhagic cystitis
Antifungal therapeutic drug monitoring Explanation: ***Bone marrow suppression***
- The medication described, which inhibits transcription by intercalating into DNA at the transcription initiation complex, is likely **dactinomycin (actinomycin D)**.
- **Bone marrow suppression** is a common and severe adverse effect of dactinomycin, leading to issues like **neutropenia** and **thrombocytopenia**.
*Peripheral neuropathy*
- This is a common side effect of **vinca alkaloids** (e.g., vincristine, vinblastine) and **taxanes**, which are not described by the mechanism of action given.
- Dactinomycin does not typically cause significant peripheral neuropathy.
*Gingival hyperplasia*
- **Gingival hyperplasia** is a known side effect of medications such as **cyclosporine**, **phenytoin**, and **calcium channel blockers** like nifedipine.
- It is not associated with dactinomycin.
*Pulmonary fibrosis*
- This is a serious adverse effect of certain chemotherapeutic agents like **bleomycin** and **busulfan**, and other drugs like **amiodarone** and **methotrexate**.
- Dactinomycin is not primarily associated with pulmonary fibrosis.
*Hemorrhagic cystitis*
- **Hemorrhagic cystitis** is a classic adverse effect of **cyclophosphamide** and **ifosfamide**, caused by the metabolite **acrolein**.
- This adverse event is prevented by co-administration of **MESNA**, and is not a common side effect of dactinomycin.
Antifungal therapeutic drug monitoring US Medical PG Question 10: A 72-year-old woman comes to the physician because she is seeing things that she knows are not there. Sometimes she sees a dog in her kitchen and at other times she sees a stranger in her garden, both of which no one else can see. She also reports a lack of motivation to do daily tasks for the past week. Three years ago, she was diagnosed with Parkinson disease and was started on levodopa and carbidopa. Her younger brother has schizophrenia. The patient also takes levothyroxine for hypothyroidism. She used to drink a bottle of wine every day, but she stopped drinking alcohol 2 months ago. Neurologic examination shows a mild resting tremor of the hands and bradykinesia. Her thought process is organized and logical. Which of the following is the most likely underlying cause of this patient's symptoms?
- A. Alcohol withdrawal
- B. Adverse effect of medication (Correct Answer)
- C. Major depressive disorder
- D. Schizophrenia
- E. Poorly controlled hypothyroidism
Antifungal therapeutic drug monitoring Explanation: ***Adverse effect of medication***
- The patient's **visual hallucinations** and **apathy** are consistent with **dopaminergic medication-induced psychosis**, a common complication of **levodopa/carbidopa** in Parkinson's disease, especially in older patients.
- The hallucinations are typically **well-formed**, non-threatening, and the patient often retains insight into their unreality, as described ("she knows are not there").
*Alcohol withdrawal*
- **Alcohol withdrawal hallucinations** typically occur within 12-48 hours of cessation and are primarily visual, but often accompanied by autonomic instability (tremors, sweating, tachycardia) which is not mentioned here.
- Given she stopped drinking 2 months ago, acute withdrawal symptoms would have resolved much earlier.
*Major depressive disorder*
- While **apathy** and lack of motivation can be symptoms of depression, the prominent **visual hallucinations** are not typical of major depressive disorder without psychotic features (which would then be a specified subtype).
- Her thought process is described as **organized and logical**, making a primary thought disorder secondary to depression less likely.
*Schizophrenia*
- Schizophrenia typically presents in **early adulthood** (late teens to early 30s) and involves persistent psychosis, disorganized thought, and functional decline, which is not consistent with this patient's age of symptom onset or preserved thought process.
- The family history of schizophrenia is a risk factor, but the clinical presentation—especially the patient's insight into the hallucinations—is more indicative of a medication-induced effect or other organic cause in an older person.
*Poorly controlled hypothyroidism*
- **Hypothyroidism** can cause cognitive slowing, depression, and in severe cases, myxedema madness with psychotic symptoms, but her symptoms primarily manifest as formed visual hallucinations.
- There is no clinical or lab evidence provided to suggest her hypothyroidism is poorly controlled or severe enough to cause such distinct hallucinations.
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