Cytomegalovirus antivirals US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for Cytomegalovirus antivirals. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Cytomegalovirus antivirals US Medical PG Question 1: A 45-year-old man comes to the emergency department with fever, nonproductive cough, and difficulty breathing. Three years ago, he underwent lung transplantation. A CT scan of the chest shows diffuse bilateral ground-glass opacities. Pathologic examination of a transbronchial lung biopsy specimen shows several large cells containing intranuclear inclusions with a clear halo. Treatment with ganciclovir fails to improve his symptoms. He is subsequently treated successfully with another medication. This drug does not require activation by viral kinases and also has known in-vitro activity against HIV and HBV. The patient was most likely treated with which of the following drugs?
- A. Lamivudine
- B. Foscarnet (Correct Answer)
- C. Elvitegravir
- D. Zanamivir
- E. Acyclovir
Cytomegalovirus antivirals Explanation: ***Foscarnet***
- The patient presents with **cytomegalovirus (CMV) pneumonitis** post-lung transplant, evidenced by **diffuse bilateral ground-glass opacities** and **intranuclear inclusions with a clear halo** on biopsy, and initial treatment with **ganciclovir failed**.
- **Foscarnet** is an alternative antiviral that does not require activation by viral kinases and is effective against viruses that develop **ganciclovir resistance** due to mutations in UL97 phosphotransferase, which activates ganciclovir. It also has known activity against **HIV** and **HBV**, fitting the description.
*Lamivudine*
- **Lamivudine** is a **nucleoside reverse transcriptase inhibitor (NRTI)** primarily used for **HIV** and **HBV** infections.
- It has **no activity against CMV** and would not be used to treat CMV pneumonitis, especially after ganciclovir failure.
*Elvitegravir*
- **Elvitegravir** is an **integrase inhibitor** used in combination therapy for **HIV infection**.
- It has **no activity against CMV** and would not be effective in treating CMV pneumonitis.
*Zanamivir*
- **Zanamivir** is a **neuraminidase inhibitor** used to treat and prevent **influenza A and B viruses**.
- It has **no activity against CMV** and is not indicated for the patient's condition.
*Acyclovir*
- **Acyclovir** is a guanosine analog primarily used to treat **herpes simplex virus (HSV)** and **varicella-zoster virus (VZV)** infections.
- It has **limited to no activity against CMV** at therapeutic doses and would not be effective in this case.
Cytomegalovirus antivirals US Medical PG Question 2: A 57-year-old man comes to the emergency department because he has been having problems seeing over the last week. He says that he has been seeing specks in his vision and his vision also becomes blurry when he tries to focus on objects. He says that he cannot recall anything that may have precipitated this; however, he has been homeless for several months. His CD4+ cell count is 27 cells/mL so he is started on a new medication. Notably, this drug has the following properties when mixed with various proteins:
Drug alone - drug remains unphosphorylated
Drug and HSV proteins - drug remains unphosphorylated
Drug and CMV proteins - drug remains unphosphorylated
Drug and human proteins - drug is phosphorylated
Which of the following drugs is most consistent with this set of findings?
- A. Cidofovir (Correct Answer)
- B. Oseltamivir
- C. Ganciclovir
- D. Acyclovir
- E. Foscarnet
Cytomegalovirus antivirals Explanation: ***Cidofovir***
- The patient's presentation with **seeing specks and blurry vision** (floaters) along with a **CD4+ count of 27 cells/mL** strongly suggests **CMV retinitis**, a common opportunistic infection in advanced HIV/AIDS.
- **Cidofovir** is a nucleotide analog that **does NOT require viral kinases for activation** - it remains unphosphorylated when mixed with HSV or CMV proteins, as stated in the question.
- However, cidofovir **DOES require phosphorylation by host cellular kinases** (specifically cellular kinases, not viral kinases) to become the active triphosphate form. This matches the drug property showing it **becomes phosphorylated with human proteins**.
- This unique activation mechanism (host-dependent, viral-independent) distinguishes it from other antivirals and matches the experimental findings described.
*Foscarnet*
- **Foscarnet** is also used for CMV retinitis and **does NOT require ANY phosphorylation** - neither viral nor host enzymes.
- It acts as a **pyrophosphate analog** that directly inhibits viral DNA polymerase without requiring activation.
- The drug properties show phosphorylation occurs with human proteins, which is **inconsistent with foscarnet** that remains unphosphorylated under all conditions.
*Ganciclovir*
- **Ganciclovir** requires phosphorylation by **viral kinase UL97 in CMV** (or thymidine kinase in HSV) for initial activation, followed by host kinases.
- The drug properties state it remains unphosphorylated with CMV proteins, which is **inconsistent with ganciclovir's mechanism**.
*Acyclovir*
- **Acyclovir** is primarily used for **HSV and VZV infections**, not CMV retinitis in AIDS patients.
- It requires initial phosphorylation by **viral thymidine kinase** (HSV-TK), which contradicts the finding that it remains unphosphorylated with HSV proteins.
*Oseltamivir*
- **Oseltamivir** is a **neuraminidase inhibitor** used for **influenza treatment**.
- It has no role in CMV retinitis and does not act via phosphorylation-dependent DNA polymerase inhibition.
Cytomegalovirus antivirals US Medical PG Question 3: An HIV-positive 48-year-old man comes to the emergency department because of a 3-month history of recurrent, painful mouth ulcers. This time, the pain is so severe that the patient cannot eat. He has a history of a seizure disorder but currently does not take any medications. He appears very ill. His temperature is 39.0°C (102.2°F). Physical examination shows numerous vesicular ulcerations on the lips and sloughing of the gums, buccal mucosa, and hard palate. Genetic analysis of the pathogen isolated from the lesions shows a mutation in a gene encoding viral phosphotransferases. Which of the following drugs is the most appropriate treatment?
- A. Acyclovir
- B. Famciclovir
- C. Cidofovir
- D. Ganciclovir
- E. Foscarnet (Correct Answer)
Cytomegalovirus antivirals Explanation: ***Foscarnet***
- The presence of **recurrent, painful vesicular ulcerations** in an HIV-positive patient, especially with **gingivostomatitis-like symptoms** (sloughing gums, buccal mucosa), points to a severe **herpes simplex virus (HSV) infection**, likely resistant to nucleoside analogues given the **phosphotransferase mutation**.
- **Foscarnet** is a pyrophosphate analog that directly inhibits viral DNA polymerase without requiring phosphorylation by viral thymidine kinase, making it effective against **acyclovir-resistant HSV** strains, which often develop resistance via mutations in viral phosphotransferases or thymidine kinase.
*Acyclovir*
- **Acyclovir** is a nucleoside analog that requires phosphorylation by viral thymidine kinase (a phosphotransferase) to become active.
- A **mutation in viral phosphotransferases** would render the virus resistant to acyclovir, making it an ineffective treatment.
*Famciclovir*
- **Famciclovir** is a prodrug of penciclovir, which is also a nucleoside analog that requires phosphorylation by viral thymidine kinase for activation.
- Similar to acyclovir, a **mutation in viral phosphotransferases** would lead to resistance and make famciclovir ineffective.
*Cidofovir*
- **Cidofovir** is a nucleotide analog that does not require phosphorylation by viral enzymes for its initial activation.
- While it can be effective against some resistant strains, **foscarnet is generally preferred** for severe, resistant HSV infections as cidofovir is primarily used for **CMV retinitis** and is associated with significant nephrotoxicity.
*Ganciclovir*
- **Ganciclovir** is a nucleoside analog primarily used for **CMV infections**, and it also requires phosphorylation by viral kinases for activation.
- It is not the first-line treatment for HSV, and the **phosphotransferase mutation** would likely confer resistance to ganciclovir as well.
Cytomegalovirus antivirals US Medical PG Question 4: A 56-year-old man comes to the emergency department because of progressively worsening shortness of breath and fever for 2 days. He also has a nonproductive cough. He does not have chest pain or headache. He has chronic myeloid leukemia and had a bone marrow transplant 3 months ago. His current medications include busulfan, mycophenolate mofetil, tacrolimus, and methylprednisolone. His temperature is 38.1°C (100.6°F), pulse is 103/min, respirations are 26/min, and blood pressure is 130/70 mm Hg. Pulse oximetry on room air shows an oxygen saturation of 93%. Pulmonary examination shows diffuse crackles. The spleen tip is palpated 4 cm below the left costal margin. Laboratory studies show:
Hemoglobin 10.3 g/dL
Leukocyte count 4,400/mm3
Platelet count 160,000/mm3
Serum
Glucose 78 mg/dL
Creatinine 2.1 mg/dL
D-dimer 96 ng/mL (N < 250)
pp65 antigen positive
Galactomannan antigen negative
Urinalysis is normal. An x-ray of the chest shows diffuse bilateral interstitial infiltrates. An ECG shows sinus tachycardia. Which of the following is the most appropriate pharmacotherapy?
- A. Levofloxacin
- B. Ganciclovir (Correct Answer)
- C. Valganciclovir
- D. Azithromycin
- E. Acyclovir
Cytomegalovirus antivirals Explanation: ***Ganciclovir***
- The patient's **positive pp65 antigen** confirms **cytomegalovirus (CMV) infection**, the most common viral infection in immunocompromised bone marrow transplant recipients.
- This patient has **severe, life-threatening CMV pneumonitis** evidenced by hypoxia (O2 sat 93%), tachypnea, and diffuse bilateral interstitial infiltrates.
- **Intravenous ganciclovir** is the **first-line treatment** for severe CMV disease due to its potent antiviral activity and reliable bioavailability in critically ill patients.
*Valganciclovir*
- **Valganciclovir** is an **oral prodrug of ganciclovir** with excellent bioavailability, but it is primarily reserved for **CMV prophylaxis** or **maintenance therapy** after initial IV treatment.
- In this patient with **acute, severe CMV pneumonitis** requiring urgent intervention (hypoxia, respiratory distress), **IV ganciclovir is strongly preferred** for faster, more reliable drug delivery and higher tissue concentrations.
*Levofloxacin*
- This **fluoroquinolone antibiotic** treats **bacterial infections**, not viral pathogens like CMV.
- The **positive pp65 antigen** specifically identifies CMV as the etiology, and negative galactomannan rules out invasive aspergillosis.
- While empiric antibacterial coverage might be considered in febrile neutropenic patients, the clear viral diagnosis directs therapy toward antivirals.
*Azithromycin*
- **Azithromycin** is a macrolide antibiotic effective against atypical bacteria (Mycoplasma, Chlamydophila) and some other bacterial pathogens.
- It has **no activity against CMV** and would not address the confirmed viral etiology.
*Acyclovir*
- **Acyclovir** is effective against **herpes simplex virus (HSV)** and **varicella-zoster virus (VZV)**, but has **poor activity against CMV** due to inadequate phosphorylation by CMV enzymes.
- The positive pp65 antigen specifically indicates CMV, for which ganciclovir (not acyclovir) is required.
Cytomegalovirus antivirals US Medical PG Question 5: A thymidine kinase-deficient varicella-zoster virus strain has been isolated at a retirement home. Many of the elderly had been infected with this strain and are experiencing shingles. Which of the following would be the best antiviral agent to treat this population?
- A. Famciclovir
- B. Ganciclovir
- C. Cidofovir (Correct Answer)
- D. Amantadine
- E. Acyclovir
Cytomegalovirus antivirals Explanation: ***Cidofovir***
- This is the best choice because **cidofovir** does not require **thymidine kinase** for its activation; it is phosphorylated by cellular kinases.
- Since the varicella-zoster virus (VZV) strain is **thymidine kinase-deficient**, drugs dependent on this enzyme (like acyclovir, famciclovir, ganciclovir) would be ineffective.
*Famciclovir*
- This is a prodrug that is converted to **penciclovir**, which requires **viral thymidine kinase** for its initial phosphorylation.
- Due to the VZV strain's **thymidine kinase deficiency**, famciclovir would not be effectively activated and thus not offer therapeutic benefit.
*Ganciclovir*
- Similar to acyclovir, ganciclovir requires **phosphorylation by viral thymidine kinase** (or phosphotransferase in CMV) for its antiviral activity.
- The **thymidine kinase-deficient VZV** would render ganciclovir ineffective against this specific resistant strain.
*Amantadine*
- **Amantadine** is an antiviral agent specifically used for **influenza A virus** and has no activity against VZV.
- Its mechanism of action involves inhibiting the M2 proton channel of influenza A, which is not relevant for herpesviruses.
*Acyclovir*
- **Acyclovir** is a nucleoside analog that requires **viral thymidine kinase** for its initial phosphorylation and subsequent activation.
- A **thymidine kinase-deficient VZV** strain would be resistant to acyclovir, making it an ineffective treatment.
Cytomegalovirus antivirals US Medical PG Question 6: A scientist is studying the mechanisms by which bacteria become resistant to antibiotics. She begins by obtaining a culture of vancomycin-resistant Enterococcus faecalis and conducts replicate plating experiments. In these experiments, colonies are inoculated onto a membrane and smeared on 2 separate plates, 1 containing vancomycin and the other with no antibiotics. She finds that all of the bacterial colonies are vancomycin resistant because they grow on both plates. She then maintains the bacteria in liquid culture without vancomycin while she performs her other studies. Fifteen generations of bacteria later, she conducts replicate plating experiments again and finds that 20% of the colonies are now sensitive to vancomycin. Which of the following mechanisms is the most likely explanation for why these colonies have become vancomycin sensitive?
- A. Point mutation
- B. Gain of function mutation
- C. Viral infection
- D. Plasmid loss (Correct Answer)
- E. Loss of function mutation
Cytomegalovirus antivirals Explanation: ***Plasmid loss***
- The initial **vancomycin resistance** in *Enterococcus faecalis* is often mediated by genes located on **plasmids**, which are extrachromosomal DNA.
- In the absence of selective pressure (vancomycin), bacteria that lose the plasmid (and thus the resistance genes) have a **growth advantage** over those that retain the energetically costly plasmid, leading to an increase in sensitive colonies over generations.
*Point mutation*
- A **point mutation** typically involves a change in a single nucleotide and could lead to loss of resistance if it occurred in a gene conferring resistance.
- However, since there was no selective pressure for loss of resistance, it is less likely that 20% of the population would acquire such a specific point mutation to revert resistance.
*Gain of function mutation*
- A **gain of function mutation** would imply that the bacteria acquired a *new* advantageous trait, not the *loss* of resistance.
- This type of mutation would not explain why some colonies became sensitive to vancomycin after the drug was removed.
*Viral infection*
- **Viral infection** (bacteriophages) can transfer genes through transduction or cause bacterial lysis, but it's not the primary mechanism for a widespread reversion of resistance in the absence of antibiotic pressure.
- It would not explain the observed increase in vancomycin-sensitive colonies due to evolutionary pressure.
*Loss of function mutation*
- While a **loss of function mutation** in a gene conferring resistance could lead to sensitivity, it's generally less likely to explain a 20% shift without selective pressure than **plasmid loss**.
- Plasmids are often unstable and are easily lost in the absence of selection, whereas a specific gene mutation causing loss of function would need to arise and become prevalent in the population.
Cytomegalovirus antivirals US Medical PG Question 7: An 8-year-old boy is brought to the emergency department by his parents because of vomiting, abdominal pain, and blurry vision for the past hour. The parents report that the boy developed these symptoms after he accidentally ingested 2 tablets of his grandfather’s heart failure medication. On physical examination, the child is drowsy, and his pulse is 120/min and irregular. Digoxin toxicity is suspected. A blood sample is immediately sent for analysis and shows a serum digoxin level of 4 ng/mL (therapeutic range: 0.8–2 ng/mL). Which of the following electrolyte abnormalities is most likely to be present in the boy?
- A. Hypermagnesemia
- B. Hypokalemia
- C. Hypercalcemia
- D. Hyperkalemia (Correct Answer)
- E. Hypocalcemia
Cytomegalovirus antivirals Explanation: ***Hyperkalemia***
- **Digoxin** inhibits the **Na+/K+-ATPase pump**, leading to an increase in intracellular sodium and a decrease in intracellular potassium.
- The decreased function of the Na+/K+-ATPase pump results in reduced cellular uptake of potassium, causing **elevated extracellular potassium** levels.
*Hypermagnesemia*
- **Magnesium** is not directly affected by digoxin toxicity in a way that would lead to hypermagnesemia; in fact, hypomagnesemia can exacerbate digoxin toxicity.
- High magnesium levels are typically associated with renal failure or excessive intake of magnesium-containing antacids or laxatives.
*Hypokalemia*
- While hypokalemia can **predispose to digoxin toxicity** (by increasing digoxin binding to the Na+/K+-ATPase pump), acute digoxin overdose, as described here, often leads to **hyperkalemia** due to the direct inhibition of the pump's ability to drive potassium into cells.
- The classic association of hypokalemia with digoxin refers more to its role as a risk factor for toxicity, especially with diuretic use, rather than a direct consequence of acute overdose.
*Hypercalcemia*
- **Calcium** levels are not directly altered to hypercalcemia by digoxin toxicity.
- Digoxin's mechanism involves increasing intracellular calcium by promoting calcium influx and inhibiting its efflux via the Na+/Ca2+ exchanger, but this typically does not manifest as measurable serum hypercalcemia.
*Hypocalcemia*
- Digoxin toxicity does not directly cause hypocalcemia.
- Digoxin actually leads to **increased intracellular calcium**, which is responsible for its positive inotropic effect, but this change is primarily intracellular and does not result in systemic hypocalcemia.
Cytomegalovirus antivirals US Medical PG Question 8: A 61-year-old woman presents to her primary care physician complaining of left-sided facial pain that started yesterday. She describes the pain as stinging, burning, and constant. It does not worsen with jaw movement or chewing. Her past medical history includes hyperlipidemia and multiple sclerosis (MS), and she had chickenpox as a child but received a shingles vaccination last year. Medications include simvastatin and glatiramer acetate. The patient’s last MS flare was 5 weeks ago, at which time she received a prednisone burst with taper. At this visit, her temperature is 99.9 °F (37.7°C), blood pressure is 139/87 mmHg, pulse is 82/min, and respirations are 14/min. On exam, there is no rash or skin change on either side of the patient’s face. Gentle palpation of the left cheek and mandible produce significant pain, but there is full range of motion in the jaw. Which of the following medications is the most likely to prevent long-term persistence of this patient’s pain?
- A. Carbamazepine
- B. Topical corticosteroids
- C. Oral acyclovir (Correct Answer)
- D. Amitriptyline
- E. Gabapentin
Cytomegalovirus antivirals Explanation: ***Oral acyclovir***
- The patient's symptoms (stinging, burning, constant facial pain, history of chickenpox, recent MS flare, and prednisone use) are highly suggestive of a **herpes zoster (shingles) reactivation**, despite prior vaccination. Early antiviral therapy, such as oral acyclovir, is crucial to reduce the duration and severity of the acute pain and, more importantly, to prevent **postherpetic neuralgia (PHN)**.
- Starting acyclovir within 72 hours of symptom onset significantly decreases the risk of developing long-term pain complications like PHN by inhibiting viral replication and reducing nerve damage.
*Carbamazepine*
- This medication is a first-line treatment for **trigeminal neuralgia**, characterized by brief, excruciating, shock-like pain triggered by specific stimuli, which differs from the patient's constant burning pain.
- While it can manage neuropathic pain, it does not address the underlying viral cause of herpes zoster and will not prevent PHN.
*Topical corticosteroids*
- Topical corticosteroids are primarily used to reduce **inflammation and itching** associated with skin rashes, such as those that may occur with herpes zoster.
- They do not possess antiviral properties and therefore will not *prevent* the long-term neurological complication of PHN.
*Amitriptyline*
- Amitriptyline, a tricyclic antidepressant, is a common treatment for **postherpetic neuralgia** once it has already developed, as well as other neuropathic pain conditions.
- However, it is not used to prevent the development of PHN in the acute phase of a herpes zoster infection; early antiviral treatment is the preventative strategy.
*Gabapentin*
- Gabapentin is an effective medication for established **neuropathic pain**, including postherpetic neuralgia.
- Similar to amitriptyline, gabapentin treats the *symptoms* of PHN once it is present but does not prevent its occurrence when used during the acute viral stage.
Cytomegalovirus antivirals US Medical PG Question 9: A 29-year-old female presents to her gynecologist complaining of a painful rash around her genitals. She has multiple sexual partners and uses condoms intermittently. Her last STD screen one year ago was negative. On examination, she has bilateral erosive vesicles on her labia majora and painful inguinal lymphadenopathy. She is started on an oral medication that requires a specific thymidine kinase for activation. Which of the following adverse effects is associated with this drug?
- A. Photosensitivity
- B. Deafness
- C. Renal failure (Correct Answer)
- D. Gingival hyperplasia
- E. Pulmonary fibrosis
Cytomegalovirus antivirals Explanation: ***Renal failure***
- The patient's symptoms (painful genital rash, erosive vesicles, inguinal lymphadenopathy) are highly suggestive of **herpes simplex virus (HSV) infection**, likely genital herpes.
- The drug described is an antiviral agent like **acyclovir, valacyclovir, or famciclovir**, which require **viral thymidine kinase** for activation and are known to cause **renal impairment** (nephrotoxicity) as an adverse effect, especially with high doses or in dehydrated patients due to crystal nephropathy.
*Photosensitivity*
- **Photosensitivity** is a common side effect of some antibiotics (e.g., tetracyclines, sulfonamides), diuretics (e.g., thiazides), and antifungals, but it is **not a prominent adverse effect of acyclovir or its derivatives**.
- While theoretical, it is not a clinically significant or frequently observed adverse effect associated with the class of antiviral drugs used for HSV.
*Deafness*
- **Ototoxicity**, leading to deafness or hearing loss, is a well-known adverse effect of certain classes of drugs, such as **aminoglycoside antibiotics** (e.g., gentamicin) and **loop diuretics** (e.g., furosemide).
- It is **not an adverse effect** associated with antiviral medications like acyclovir.
*Gingival hyperplasia*
- **Gingival hyperplasia** (overgrowth of gum tissue) is a recognized side effect of specific medications including **phenytoin** (an anticonvulsant), **cyclosporine** (an immunosuppressant), and **calcium channel blockers** (e.g., nifedipine, amlodipine).
- This adverse effect is **not associated with antiviral drugs** used to treat herpes simplex.
*Pulmonary fibrosis*
- **Pulmonary fibrosis** is a serious adverse effect linked to various drugs like **amiodarone** (an antiarrhythmic), **bleomycin** (a chemotherapeutic agent), **methotrexate** (an immunosuppressant/chemotherapeutic), and **nitrofurantoin** (an antibiotic).
- **Antiviral medications for HSV** do not typically cause pulmonary fibrosis.
Cytomegalovirus antivirals US Medical PG Question 10: A 65-year-old patient presents with symptoms of bone pain, anemia, hypercalcemia, and renal impairment. A bone marrow biopsy confirms the diagnosis of multiple myeloma. The patient is started on a treatment regimen. Which of the following treatments is most likely associated with the reactivation of herpes zoster?
- A. Bortezomib (Correct Answer)
- B. Lenalidomide
- C. Daratumumab
- D. Melphalan
- E. Dexamethasone
Cytomegalovirus antivirals Explanation: ***Bortezomib***
- **Bortezomib**, a **proteasome inhibitor**, is known to increase the risk of herpes zoster reactivation in patients with multiple myeloma due to its immunosuppressive effects.
- Prophylaxis with antiviral agents (e.g., acyclovir) is often recommended during bortezomib treatment to prevent this complication.
- Studies show herpes zoster incidence of 10-15% in bortezomib-treated patients without prophylaxis.
*Lenalidomide*
- While lenalidomide is an **immunomodulatory drug** used in multiple myeloma, it is generally associated with a lower risk of herpes zoster reactivation compared to proteasome inhibitors.
- It primarily acts by inhibiting angiogenesis and stimulating T-cell and natural killer cell activity.
*Daratumumab*
- **Daratumumab** is a **monoclonal antibody** targeting CD38 on myeloma cells, leading to their destruction.
- Although it has immunosuppressive effects, it is less commonly associated with herpes zoster reactivation than bortezomib.
*Melphalan*
- **Melphalan** is an **alkylating agent** used in chemotherapy for multiple myeloma, particularly in conditioning regimens for stem cell transplantation.
- While it causes myelosuppression and general immunosuppression, the direct association with herpes zoster reactivation is not as prominent or specific as with bortezomib.
*Dexamethasone*
- **Dexamethasone** is a **corticosteroid** commonly used in combination regimens for multiple myeloma (e.g., RVD, VCD).
- While corticosteroids cause immunosuppression and can increase infection risk, the specific association with herpes zoster reactivation is less pronounced than with bortezomib.
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