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Snapshot
  • A 36-year-old man presents to the emergency department with lethargy and confusion. His symptoms began approximately 2 days ago when he experienced a headache, memory impairment, vomiting, and fever. His temperature is 101°F (38.3°C), blood pressure is 144/95 mmHg, pulse is 104/min, and respirations are 18/min. The patient has an altered level of consciousness on the physical exam. A non-contrast CT scan of the head is unremarkable. A lumbar puncture is performed and the patient is started on antibiotics. Cerebrospinal fluids results return with a mononuclear pleocytosis, elevated red blood cells and protein, and normal glucose. A polymerase chain reaction (PCR) is positive for herpes simplex virus 2. The patient's empiric treatment has been narrowed to acyclovir. (Herpes simplex encephalitis)
Introduction
  • Mechanism of action
    • acyclovir is phosphorylated by a virally-encoded thymidine kinase 
      • acyclovir triphosphate acts as a guanosine analog, which impairs viral DNA polymerase, impairing viral DNA synthesis 
        • acyclovir is not phosphorylated in uninfected cells, resulting in a favorable adverse effect profile
  • Mechanism of resistance
    • altered virally-encoded thymidine kinase 
    • altered viral DNA polymerase
  • Clinical use
    • herpes simplex virus 1 and 2 infection
    • varicella-zoster virus
  • Adverse effects
    • acute renal failure 
      • acyclovir can precipitate into crystals in the renal tubules  
        • slow drug infusion and pre-hydration decreases this risk 
 

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(M1.MC.14.106) A 69-year-old female with acute myelogenous leukemia is admitted for bone marrow transplant. Her initial course is uncomplicated. On day 10, she becomes profoundly ill and is diagnosed with disseminated herpes simplex virus. The resident discovers that acyclovir prophylaxis was omitted from her daily orders. She is immediately treated with high-dose intravenous acyclovir and her symptoms resolve. In the midst of receiving this therapy, her creatinine triples from her baseline and her potassium rises above the normal range. Urinalysis shows the following seen in Figure A. Which of the following drugs might result in a similar complication? Tested Concept

QID: 104991
FIGURES:
1

Sulfadiazine

47%

(84/177)

2

Metronidazole

6%

(10/177)

3

Oxycodone

10%

(17/177)

4

Lisinopril

14%

(25/177)

5

Atorvastatin

12%

(22/177)

L 4 D

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(M1.MC.14.14) A 35-year-old man with a past medical history of HIV is hospitalized with a disseminated zoster infection and treated with IV acyclovir. His course of illness worsens on the 4th day after admission and his creatinine level increases to 4.2 mg/dL. Urinalysis shows birefringent needle-shaped crystals. What could have prevented this deterioration in the patient's renal function? Tested Concept

QID: 100968
1

Initial administration of glucocorticoids

4%

(11/313)

2

Monitoring of drug levels

3%

(10/313)

3

Obtaining a thorough history of patient allergies

1%

(4/313)

4

Adequate initial hydration

73%

(227/313)

5

Initial administration of allopurinol

19%

(58/313)

L 3 D

Select Answer to see Preferred Response

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