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  • 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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Questions (4)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.MC.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? Review Topic

QID: 104991
FIGURES:
1

Sulfadiazine

38%

(41/108)

2

Metronidazole

6%

(6/108)

3

Oxycodone

9%

(10/108)

4

Lisinopril

19%

(20/108)

5

Atorvastatin

15%

(16/108)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(M1.MC.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? Review Topic

QID: 100968
1

Initial administration of glucocorticoids

3%

(7/262)

2

Monitoring of drug levels

2%

(6/262)

3

Obtaining a thorough history of patient allergies

1%

(3/262)

4

Adequate initial hydration

75%

(196/262)

5

Initial administration of allopurinol

18%

(47/262)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 4
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