A physician scientist is looking for a more efficient way to treat HIV. Patients infected with HIV mount a humoral immune response by producing antibodies against the HIV envelope proteins. These antibodies are the same antibodies detected by the ELISA and western blot assays used to diagnose the disease. The physician scientist is trying to generate a new, more potent antibody against the same HIV envelope proteins targeted by the natural humoral immune response. Of the following proteins, which is the most likely target of the antibody he is designing?
Q42
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?
Q43
A 35-year-old man comes to the physician because of a 6-month history of fatigue and increased sweating at night. He says that he feels “constantly tired” and needs more rest than usual although he sleeps well. In the morning, his sheets are often wet and his skin is clammy. He has not had any sore throat, runny nose, or cough recently. He has not traveled anywhere. Over the past 4 months, he has had a 6.8-kg (15-lb) weight loss, despite having a normal appetite. He does not drink or urinate more than usual. He is 181 cm (5 ft 11 in) tall and weighs 72 kg (159 lb); BMI is 22 kg/m2. His temperature is 37.9°C (100.2°F), pulse is 65/min, and blood pressure is 120/70 mm Hg. Physical examination shows no abnormalities. An HIV screening test and confirmatory test are both positive. The CD4 count is 600 cells/μl and the viral load is 104 copies/mL. Treatment with lamivudine, zidovudine, and indinavir is begun. The patient is at greatest risk for which of the following adverse effects?
Q44
A 29-year-old man comes to the physician for a routine health maintenance examination. He feels well. He works as a nurse at a local hospital in the city. Three days ago, he had a needlestick injury from a patient whose serology is positive for hepatitis B. He completed the 3-dose regimen of the hepatitis B vaccine 2 years ago. His other immunizations are up-to-date. He appears healthy. Physical examination shows no abnormalities. He is concerned about his risk of being infected with hepatitis B following his needlestick injury. Serum studies show negative results for hepatitis B surface antigen, hepatitis B surface antibody, and hepatitis C antibody. Which of the following is the most appropriate next step in management?
Q45
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?
Q46
A 42-year-old male with a history significant for IV drug use comes to the emergency department complaining of persistent fatigue and malaise for the past three weeks. On physical exam, you observe a lethargic male with icteric sclera and hepatomegaly. AST and ALT are elevated at 600 and 750, respectively. HCV RNA is positive. Albumin is 3.8 g/dL and PT is 12. A liver biopsy shows significant inflammation with bridging fibrosis. What is the current first-line treatment?
Q47
A 5-day-old male newborn is brought to the emergency department 1 hour after having a seizure. It lasted approximately 1 minute, and involved blinking and lip-smacking movements as well as left-sided jerking of the hand and foot. His mother says she measured a temperature of 38.2°C (100.7°F) at that time. He has had increasing difficulty feeding since yesterday. He was born at 39 weeks' gestation and weighed 3189 g (7 lb, 1 oz); he currently weighs 2980 g (6 lb, 9 oz). The mother's prenatal course was significant for gonorrhea infection diagnosed early in pregnancy and treated with ceftriaxone and azithromycin combination therapy. The boy appears irritable and lethargic. His temperature is 36.0°C (96.8°F). Examination shows clusters of vesicular lesions with an erythematous base on the patient's face and trunk. There is profuse lacrimation. Laboratory studies show:
Leukocyte count 16,200/mm3
Segmented neutrophils 25%
Bands 5%
Lymphocytes 65%
Monocytes 3%
Eosinophils 2%
Serum
Glucose 80 mg/dL
A lumbar puncture is performed. Cerebrospinal fluid analysis shows a leukocyte count of 117/μL, a protein concentration of 52 mg/dL, and a glucose concentration of 58 mg/dL. Results of blood cultures are pending. Which of the following is the most appropriate pharmacotherapy?
Q48
A 64-year-old man presents with unilateral severe chest pain which started a day ago. He describes the chest pain as sharp in nature and localized mainly to his right side. He also complains of mild shortness of breath but says that it is tolerable. He denies any recent history of fever, sweating, dizziness, or similar episodes in the past. Past medical history is significant for chronic lymphocytic leukemia a few months ago for which he was started on chemotherapy. He has currently completed 3 cycles with the last one being few days ago. His temperature is 36.5°C (97.7°F), blood pressure is 118/75 mm Hg, pulse is 95/min, and respirations are 20/min. Lung are clear to auscultation bilaterally. There is severe tenderness to palpation over the right chest and a painful stripe of vesicular lesions, but no evidence of lesions, bruising or trauma. An electrocardiogram is normal and a chest radiograph is unremarkable. Cardiac enzymes are pending. Laboratory studies show:
Laboratory test
BUN 40 mg/dL
Serum creatinine 3.0 mg/dL
Urinalysis
Protein +
Glucose absent
RBC absent
WBC 3/HPF
Nitrite absent
Leukocyte esterase negative
Sediments negative
Which of the following is the best course of treatment for this patient?
Q49
A 25-year-old sexually active male presents to an internal medicine physician for a routine health check up after having several unprotected sexual encounters. After appropriate testing the physician discusses with the patient that he is HIV+ and must be started on anti-retroviral treatment. Which of the following medications prescribed acts on the gp41 subunit of the HIV envelope glycoprotein?
Q50
A 41-year-old woman presents with acute onset severe epigastric pain radiating to the back that began a few hours ago. She also complains of nausea and has vomited twice in the past hour. She denies any history of similar symptoms or trauma in the past. Past medical history is significant for diabetes type 2 and HIV infection diagnosed 6 months ago, long-standing mild intermittent asthma, and generalized anxiety disorder. She takes metformin for her diabetes but does not remember the names of her HIV medications. She reports moderate social alcohol use. Her vital signs include temperature 37.6°C (99.6 °F), pulse 95/min, blood pressure 110/74 mm Hg, respiratory rate 12/min. Her body mass index (BMI) is 21 kg/m2. Laboratory findings are significant for the following:
Serum amylase: 415 U/L
Serum lipase: 520 U/L
A contrast CT of the abdomen reveals an edematous pancreas with peripancreatic fluid collection with a normal gallbladder. Which of the following is the most likely etiology of this patient's condition?
Antivirals US Medical PG Practice Questions and MCQs
Question 41: A physician scientist is looking for a more efficient way to treat HIV. Patients infected with HIV mount a humoral immune response by producing antibodies against the HIV envelope proteins. These antibodies are the same antibodies detected by the ELISA and western blot assays used to diagnose the disease. The physician scientist is trying to generate a new, more potent antibody against the same HIV envelope proteins targeted by the natural humoral immune response. Of the following proteins, which is the most likely target of the antibody he is designing?
A. p24
B. CXCR4
C. CCR5
D. p17
E. gp120 (Correct Answer)
Explanation: ***gp120***
- **gp120** is an **envelope glycoprotein** on the surface of HIV, responsible for binding to CD4 receptors on host cells.
- Antibodies against **gp120** are generated during natural infection and are detected by diagnostic assays, making it a primary target for therapeutic antibody development.
*p24*
- **p24** is a **capsid protein** of HIV, forming the conical core of the virus, but it is not an envelope protein.
- While antibodies against **p24** are produced during infection and are detectable, it's an internal protein, not exposed on the viral surface for direct neutralization.
*CXCR4*
- **CXCR4** is a **chemokine co-receptor** found on the surface of host cells (e.g., T-lymphocytes), used by some HIV strains (T-tropic) for entry.
- It is a host cell protein, not an HIV viral protein, so it would not be a target for antibodies aiming to directly neutralize the virus.
*CCR5*
- **CCR5** is another **chemokine co-receptor** on host cells (e.g., macrophages, T-lymphocytes) used by other HIV strains (M-tropic) for viral entry.
- Similar to CXCR4, it is a host cell protein, not an HIV envelope protein, and therefore not a direct target for neutralizing antibodies against the virus itself.
*p17*
- **p17** is an HIV **matrix protein** located just beneath the viral envelope, playing a role in viral assembly and budding.
- Similar to p24, it is an internal structural protein, not an external envelope protein, making it less accessible for neutralizing antibodies.
Question 42: 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
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.
Question 43: A 35-year-old man comes to the physician because of a 6-month history of fatigue and increased sweating at night. He says that he feels “constantly tired” and needs more rest than usual although he sleeps well. In the morning, his sheets are often wet and his skin is clammy. He has not had any sore throat, runny nose, or cough recently. He has not traveled anywhere. Over the past 4 months, he has had a 6.8-kg (15-lb) weight loss, despite having a normal appetite. He does not drink or urinate more than usual. He is 181 cm (5 ft 11 in) tall and weighs 72 kg (159 lb); BMI is 22 kg/m2. His temperature is 37.9°C (100.2°F), pulse is 65/min, and blood pressure is 120/70 mm Hg. Physical examination shows no abnormalities. An HIV screening test and confirmatory test are both positive. The CD4 count is 600 cells/μl and the viral load is 104 copies/mL. Treatment with lamivudine, zidovudine, and indinavir is begun. The patient is at greatest risk for which of the following adverse effects?
A. Urolithiasis (Correct Answer)
B. Stevens-Johnson syndrome
C. Hypersensitivity reaction
D. Chronic kidney disease
E. Pancreatitis
Explanation: ***Urolithiasis***
- The patient is receiving **indinavir**, a protease inhibitor known to cause **nephrolithiasis** (kidney stones) due to the drug's poor solubility.
- Patients on indinavir should be well-hydrated to reduce the risk of stone formation.
*Stevens-Johnson syndrome*
- This severe skin reaction is more commonly associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) like **nevirapine** and **efavirenz**, or with sulfonamide antibiotics, rather than indinavir.
- While possible with many drugs, it is not the *greatest risk* among the options for this specific regimen.
*Hypersensitivity reaction*
- While hypersensitivity can occur with many drugs, particularly abacavir (an NRTI not included in this regimen), it is not the most prominent or specific adverse effect for the given combination, especially indinavir.
- Symptoms usually include fever, rash, and multi-organ involvement, which can be acute.
*Chronic kidney disease*
- While some antiretrovirals, particularly **tenofovir disoproxil fumarate (TDF)**, can cause renal tubular dysfunction and lead to chronic kidney disease, TDF is not part of this patient's regimen.
- Indinavir's primary renal complication is acute stone formation, not typically chronic kidney disease in the absence of pre-existing conditions or other nephrotoxic drugs.
*Pancreatitis*
- Pancreatitis is a known adverse effect of some NRTIs, particularly **didanosine** and **stavudine**, neither of which are in this patient's treatment plan.
- Lamivudine and zidovudine have a lower risk of pancreatitis compared to other NRTIs.
Question 44: A 29-year-old man comes to the physician for a routine health maintenance examination. He feels well. He works as a nurse at a local hospital in the city. Three days ago, he had a needlestick injury from a patient whose serology is positive for hepatitis B. He completed the 3-dose regimen of the hepatitis B vaccine 2 years ago. His other immunizations are up-to-date. He appears healthy. Physical examination shows no abnormalities. He is concerned about his risk of being infected with hepatitis B following his needlestick injury. Serum studies show negative results for hepatitis B surface antigen, hepatitis B surface antibody, and hepatitis C antibody. Which of the following is the most appropriate next step in management?
A. Revaccinate with 3-dose regimen of hepatitis B vaccine
B. Revaccinate with two doses of hepatitis B vaccine
C. Administer hepatitis B immunoglobulin
D. Administer hepatitis B immunoglobulin and 3-dose regimen of hepatitis B vaccine (Correct Answer)
E. Administer hepatitis B immunoglobulin and single dose hepatitis B vaccine
Explanation: ***Administer hepatitis B immunoglobulin and 3-dose regimen of hepatitis B vaccine***
- This patient had prior vaccination but current serology shows **negative HBsAb**, indicating **non-response** to the vaccine (failure to develop protective antibodies).
- Given exposure to a hepatitis B positive patient, immediate post-exposure prophylaxis with **HBIG** is crucial for passive immunity and immediate protection.
- A **complete 3-dose revaccination series** should be initiated simultaneously, as per **CDC/ACIP guidelines** for vaccine non-responders with occupational exposure [1].
- This provides both immediate passive protection (HBIG) and attempts to establish active immunity through revaccination [1].
*Revaccinate with 3-dose regimen of hepatitis B vaccine*
- While revaccination is necessary due to the non-response, starting a 3-dose regimen alone without **HBIG** would leave the patient vulnerable during the initial period before vaccine response develops.
- After high-risk exposure in a non-responder, both passive (HBIG) and active (vaccine) immunity are required.
*Revaccinate with two doses of hepatitis B vaccine*
- A 2-dose regimen is insufficient; the standard revaccination schedule for non-responders is **3 doses** at 0, 1, and 6 months [1].
- Additionally, this option lacks **HBIG** for immediate protection after the high-risk exposure.
*Administer hepatitis B immunoglobulin*
- **HBIG** alone provides immediate passive immunity, which is crucial given the recent exposure and the patient's non-immune status.
- However, offering only HBIG without initiating active immunization (vaccine series) would leave the patient unprotected once the passive immunity wanes (approximately 3-6 months).
- This approach fails to address the need for long-term protection through revaccination.
*Administer hepatitis B immunoglobulin and single dose hepatitis B vaccine*
- While HBIG is appropriate for immediate protection, giving only a **single dose** of vaccine is inadequate.
- Standard post-exposure management for vaccine non-responders requires initiating a **complete 3-dose revaccination series**, not just one dose [1].
- A single dose would not provide adequate long-term protection for this non-responder.
Question 45: 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
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.
Question 46: A 42-year-old male with a history significant for IV drug use comes to the emergency department complaining of persistent fatigue and malaise for the past three weeks. On physical exam, you observe a lethargic male with icteric sclera and hepatomegaly. AST and ALT are elevated at 600 and 750, respectively. HCV RNA is positive. Albumin is 3.8 g/dL and PT is 12. A liver biopsy shows significant inflammation with bridging fibrosis. What is the current first-line treatment?
A. Sofosbuvir/Velpatasvir (Correct Answer)
B. Glecaprevir/Pibrentasvir
C. Sofosbuvir/Ledipasvir
D. Ribavirin monotherapy
E. Interferon monotherapy
Explanation: ***Sofosbuvir/Velpatasvir***
- This is a **pan-genotypic direct-acting antiviral (DAA)** combination that is highly effective for all HCV genotypes and is recommended as a **first-line regimen** by AASLD/IDSA guidelines.
- It is particularly appropriate for patients with **significant fibrosis or compensated cirrhosis**, as seen in this patient with bridging fibrosis on biopsy.
- The standard treatment duration is **12 weeks** for treatment-naive patients, with high sustained virologic response (SVR) rates exceeding 95%.
- It has a favorable safety profile and is effective regardless of baseline viral load or HCV genotype.
*Glecaprevir/Pibrentasvir*
- While this is also an excellent **pan-genotypic DAA** combination with high efficacy, it requires longer treatment duration (12-16 weeks) in patients with **significant fibrosis (F3)** or cirrhosis.
- It is **contraindicated in decompensated cirrhosis (Child-Pugh B/C)**, making sofosbuvir-based regimens more universally applicable for patients with advanced liver disease.
- The often-cited 8-week treatment advantage applies primarily to patients **without cirrhosis**, not to this patient with bridging fibrosis.
*Sofosbuvir/Ledipasvir*
- This combination is primarily effective for **HCV genotypes 1, 4, 5, and 6** but is not truly pan-genotypic like sofosbuvir/velpatasvir.
- It is an acceptable alternative for genotype 1 infection but has been largely superseded by newer pan-genotypic regimens that don't require genotype testing.
- Treatment duration is typically **12 weeks** for treatment-naive patients without cirrhosis.
*Ribavirin monotherapy*
- **Ribavirin** is a nucleoside analog with **minimal antiviral activity** against HCV when used as monotherapy.
- It is only used as an **adjunctive agent** in combination with DAAs in specific circumstances (e.g., treatment-experienced patients with cirrhosis).
- Major side effect is **hemolytic anemia**, requiring close monitoring.
*Interferon monotherapy*
- **Interferon-alpha** monotherapy has very **poor efficacy** for chronic HCV, with sustained virologic response (SVR) rates of only 10-20%.
- It is associated with significant side effects including flu-like symptoms, depression, and cytopenias, making it **poorly tolerated**.
- This regimen is now **obsolete** and has been replaced by highly effective and well-tolerated DAA combinations.
Question 47: A 5-day-old male newborn is brought to the emergency department 1 hour after having a seizure. It lasted approximately 1 minute, and involved blinking and lip-smacking movements as well as left-sided jerking of the hand and foot. His mother says she measured a temperature of 38.2°C (100.7°F) at that time. He has had increasing difficulty feeding since yesterday. He was born at 39 weeks' gestation and weighed 3189 g (7 lb, 1 oz); he currently weighs 2980 g (6 lb, 9 oz). The mother's prenatal course was significant for gonorrhea infection diagnosed early in pregnancy and treated with ceftriaxone and azithromycin combination therapy. The boy appears irritable and lethargic. His temperature is 36.0°C (96.8°F). Examination shows clusters of vesicular lesions with an erythematous base on the patient's face and trunk. There is profuse lacrimation. Laboratory studies show:
Leukocyte count 16,200/mm3
Segmented neutrophils 25%
Bands 5%
Lymphocytes 65%
Monocytes 3%
Eosinophils 2%
Serum
Glucose 80 mg/dL
A lumbar puncture is performed. Cerebrospinal fluid analysis shows a leukocyte count of 117/μL, a protein concentration of 52 mg/dL, and a glucose concentration of 58 mg/dL. Results of blood cultures are pending. Which of the following is the most appropriate pharmacotherapy?
A. IV acyclovir (Correct Answer)
B. IV ceftriaxone
C. Pyrimethamine
D. IV ganciclovir
E. IV vancomycin
Explanation: ***IV acyclovir***
- The combination of **seizures**, **vesicular lesions** on the face and trunk, **profuse lacrimation**, and **lymphocytic pleocytosis** in the CSF in a newborn is highly suggestive of **Neonatal Herpes Simplex Virus (HSV) infection**.
- **Acyclovir** is the antiviral drug of choice for treating HSV infections, especially severe systemic or CNS forms in neonates, to reduce morbidity and mortality.
*IV ceftriaxone*
- **Ceftriaxone** is a broad-spectrum antibiotic primarily used to treat bacterial infections like neonatal sepsis or meningitis, but it has no activity against viruses.
- The patient's clinical presentation, including vesicular lesions and specific CSF findings, points away from a primary bacterial infection.
*Pyrimethamine*
- **Pyrimethamine** is an antiparasitic drug used in combination with sulfadiazine for treating **toxoplasmosis**.
- The patient's symptoms are not consistent with congenital toxoplasmosis, which typically involves chorioretinitis, hydrocephalus, and intracranial calcifications.
*IV ganciclovir*
- **Ganciclovir** is an antiviral primarily used for treating **cytomegalovirus (CMV) infections**, particularly in immunocompromised patients.
- While CMV can cause CNS disease in neonates, the characteristic **vesicular lesions** and **profuse lacrimation** are far more indicative of HSV.
*IV vancomycin*
- **Vancomycin** is an antibiotic used to treat severe bacterial infections, especially those caused by **methicillin-resistant Staphylococcus aureus (MRSA)** or other gram-positive bacteria.
- It is not effective against viral infections, and the clinical picture does not suggest a bacterial etiology requiring vancomycin.
Question 48: A 64-year-old man presents with unilateral severe chest pain which started a day ago. He describes the chest pain as sharp in nature and localized mainly to his right side. He also complains of mild shortness of breath but says that it is tolerable. He denies any recent history of fever, sweating, dizziness, or similar episodes in the past. Past medical history is significant for chronic lymphocytic leukemia a few months ago for which he was started on chemotherapy. He has currently completed 3 cycles with the last one being few days ago. His temperature is 36.5°C (97.7°F), blood pressure is 118/75 mm Hg, pulse is 95/min, and respirations are 20/min. Lung are clear to auscultation bilaterally. There is severe tenderness to palpation over the right chest and a painful stripe of vesicular lesions, but no evidence of lesions, bruising or trauma. An electrocardiogram is normal and a chest radiograph is unremarkable. Cardiac enzymes are pending. Laboratory studies show:
Laboratory test
BUN 40 mg/dL
Serum creatinine 3.0 mg/dL
Urinalysis
Protein +
Glucose absent
RBC absent
WBC 3/HPF
Nitrite absent
Leukocyte esterase negative
Sediments negative
Which of the following is the best course of treatment for this patient?
A. Acyclovir
B. Rest and NSAIDs
C. Cardiac catheterization
D. Famciclovir (Correct Answer)
E. Ganciclovir
Explanation: ***Famciclovir***
- This patient presents with hallmark symptoms and signs of **herpes zoster** (shingles), including **unilateral severe, sharp chest pain**, **dermatomal distribution**, and a **painful stripe of vesicular lesions**. Given his recent **chemotherapy** for CLL, he is **immunocompromised**, increasing his risk for severe or complicated zoster.
- **Famciclovir** is an antiviral agent effective against **varicella-zoster virus (VZV)** and is a first-line treatment for shingles. It offers **better oral bioavailability** (~77%) compared to acyclovir (~15-30%) and **less frequent dosing** (3 times daily vs 5 times daily), which improves compliance.
- While the patient has **renal impairment** (Cr 3.0 mg/dL), famciclovir can still be used with **appropriate dose adjustment** based on creatinine clearance. Treatment should be initiated promptly (ideally within 72 hours of rash onset) to reduce severity, duration, and risk of **postherpetic neuralgia**.
*Acyclovir*
- **Acyclovir** is also an effective first-line antiviral for herpes zoster and would be an acceptable alternative, particularly when given **intravenously** in severely immunocompromised patients.
- However, oral acyclovir has **poor bioavailability** (15-30%) and requires **5 times daily dosing**, which may reduce compliance. Like famciclovir, it requires **dose adjustment** in renal impairment.
- Both acyclovir and famciclovir are appropriate choices; the question favors famciclovir based on **pharmacokinetic advantages** (better bioavailability and dosing convenience), though either would require renal dose adjustment in this patient.
*Rest and NSAIDs*
- **Rest and NSAIDs** provide only symptomatic pain relief and do not address the underlying **VZV infection**.
- Without antiviral therapy, especially in an **immunocompromised patient**, the disease severity and duration are prolonged, and the risk of complications including **postherpetic neuralgia**, **dissemination**, and **visceral involvement** is significantly increased.
*Cardiac catheterization*
- The **normal ECG** and **unremarkable chest radiograph**, combined with the presence of a **dermatomal vesicular rash**, make acute coronary syndrome highly unlikely.
- The **unilateral, sharp, localized chest pain** with **tenderness to palpation** and **characteristic rash** clearly indicates herpes zoster, not a cardiac etiology, making catheterization unnecessary and inappropriate.
*Ganciclovir*
- **Ganciclovir** is primarily indicated for **cytomegalovirus (CMV) infections**, particularly in immunocompromised patients (e.g., transplant recipients, HIV/AIDS).
- While ganciclovir has some activity against VZV, it is **not first-line** for herpes zoster. Additionally, it carries significant risk of **myelosuppression** (bone marrow toxicity), which is particularly problematic in this patient already receiving **chemotherapy** for CLL.
Question 49: A 25-year-old sexually active male presents to an internal medicine physician for a routine health check up after having several unprotected sexual encounters. After appropriate testing the physician discusses with the patient that he is HIV+ and must be started on anti-retroviral treatment. Which of the following medications prescribed acts on the gp41 subunit of the HIV envelope glycoprotein?
A. Zidovudine
B. Saquinavir
C. Enfuvirtide (Correct Answer)
D. Amantadine
E. Rimantadine
Explanation: ***Enfuvirtide***
- **Enfuvirtide** is a **fusion inhibitor** that binds specifically to the **gp41 subunit** of the HIV envelope glycoprotein.
- By binding to gp41, Enfuvirtide prevents the **fusion of the viral and host cell membranes**, thereby blocking viral entry and replication.
*Zidovudine*
- **Zidovudine** is a **nucleoside reverse transcriptase inhibitor (NRTI)**.
- It works by inhibiting the enzyme **reverse transcriptase**, which is responsible for converting viral RNA into DNA.
*Saquinavir*
- **Saquinavir** is a **protease inhibitor (PI)**.
- This drug works by inhibiting the **HIV protease enzyme**, which is crucial for cleaving viral polyproteins into functional proteins required for viral assembly and maturation.
*Amantadine*
- **Amantadine** is an **antiviral agent** primarily used to treat **influenza A**.
- It works by interfering with the **M2 proton channel** of the influenza A virus, thus inhibiting viral uncoating.
*Rimantadine*
- **Rimantadine** is another **antiviral agent** used for **influenza A treatment and prophylaxis**.
- Similar to amantadine, it targets the **M2 proton channel** of the influenza A virus, preventing the uncoating step necessary for viral replication.
Question 50: A 41-year-old woman presents with acute onset severe epigastric pain radiating to the back that began a few hours ago. She also complains of nausea and has vomited twice in the past hour. She denies any history of similar symptoms or trauma in the past. Past medical history is significant for diabetes type 2 and HIV infection diagnosed 6 months ago, long-standing mild intermittent asthma, and generalized anxiety disorder. She takes metformin for her diabetes but does not remember the names of her HIV medications. She reports moderate social alcohol use. Her vital signs include temperature 37.6°C (99.6 °F), pulse 95/min, blood pressure 110/74 mm Hg, respiratory rate 12/min. Her body mass index (BMI) is 21 kg/m2. Laboratory findings are significant for the following:
Serum amylase: 415 U/L
Serum lipase: 520 U/L
A contrast CT of the abdomen reveals an edematous pancreas with peripancreatic fluid collection with a normal gallbladder. Which of the following is the most likely etiology of this patient's condition?
A. Abdominal trauma
B. HIV medication-related (Correct Answer)
C. Alcohol use
D. Congenital anomaly of the pancreas
E. Metformin
Explanation: ***HIV medication-related***
- The patient's recent **HIV diagnosis** and presentation with **acute pancreatitis** (elevated amylase/lipase, epigastric pain radiating to the back, imaging findings) strongly suggest drug-induced pancreatitis.
- Many **antiretroviral drugs**, particularly nucleoside reverse transcriptase inhibitors (NRTIs) like didanosine (ddI) and stavudine (d4T), are known to cause pancreatitis as a serious side effect.
*Abdominal trauma*
- The patient **denies any history of trauma**, and there are no external signs or specific imaging findings suggestive of blunt abdominal injury.
- While trauma can cause pancreatitis, it is typically associated with a direct injury to the abdomen, which is absent here.
*Alcohol use*
- Although alcohol is a common cause of pancreatitis, the patient reports only **moderate social alcohol use**, which typically does not lead to acute pancreatitis in the absence of chronic heavy use.
- The acute onset in a patient with recent HIV diagnosis and new medications makes drug-induced pancreatitis a more probable cause.
*Congenital anomaly of the pancreas*
- Conditions like **pancreas divisum** can predispose to recurrent pancreatitis, but there's no mention of a history of recurrent episodes in this patient.
- Imaging (CT) would usually reveal anatomical abnormalities if present, but the report only mentions an edematous pancreas and peripancreatic fluid, not a congenital anomaly.
*Metformin*
- While metformin can cause various gastrointestinal side effects (e.g., nausea, diarrhea), it is **not generally associated with acute pancreatitis**.
- Its mechanism of action does not involve direct pancreatic damage or inflammation.