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Introduction
  • Drugs (all systemic unless otherwise noted)
    • amphotericin B
    • nystatin
      • topical formulation only
    • terbinafine
      • topical or systemic
    • echinocandins
      • anidulafungin
      • caspofungin
      • micafungin
    • azoles
      • topical formulations (too toxic for systemic use)
        • clotrimazole
        • miconazole
        • econazole
      • systemic
        • itraconazole
        • fluconazole
        • isavuconazole
        • ketoconazole (can also be topical)
        • voriconazole
    • griseofulvin
    • flucytosine
    • selenium sulfide
      • topical formulation only
  • Clinical use
    • fungal infections
 
Anti-Fungal Medications
Drug Mechanism of Action
Adverse Effects of Systemic Treatment
Indications
Amphotericin B
  • Binds to ergosterol in the membrane that is unique to fungi, forming membrane pores through which electrolytes and other cell content leak 
  • Can be fungistatic or fungicidal
  • Fevers, chills, and flu-like reaction
  • Renal toxicity
    • hydrate
    • supplement potassium and magnesium
  • Arrhythmias
  • Anemia
  • IV phlebitis
  • Systemic mycoses
    • Cryptococcus
    • Blastomyces
    • Coccidioides
    • Histoplasma
    • Candida
    • Mucor
Nystatin
  • Binds to ergosterol
  • Can be fungistatic or fungicidal
  • Topical formulation only
    • adverse effects are too toxic for systemic use
  • Oral candidiasis
  • Topical yeast infection
    • diaper rash
    • vaginal candidiasis
    • intertrigo
Terbinafine
  • Inhibits squalene epoxidase, an enzyme in fungi that is key in lanosterol synthesis
  • Fungicidal
  • Gastrointestinal upset
  • Liver toxicity (rarely, can cause fulminant liver failure requiring liver transplant)
  • Taste disturbance
  • Widespread dermatophyte infections
  • Onychomycosis
Echinocandins
  • Disrupts cell wall synthesis by inhibiting beta-glucan synthesis
  • Can be fungistatic or fungicidal
  • Gastrointestinal upset
  • Flushing
    • mediated by histamine
  • Aspergillosis
  • Candida
Azoles
  • Inhibits 14-alpha-demethylase, which is key in ergosterol synthesis in fungi
  • Fungistatic
  • Anti-androgen effects via inhibiting testosterone synthesis
    • gynecomastia (in particular, ketoconazole)
  • Inhibits cytochrome P450
  • Local mycoses
  • Mild systemic mycoses
  • Specific indications
    • fluconazole
      • chronic suppression of Cryptococcus in immunosuppressed patients
    • itraconazole
      • Blastomyces
      • Coccidioides
      • Histoplasma
    • voriconazole
      • Aspergillus
      • Candida
    • isavuconazole
      • Aspergillus
      • Mucor
Griseofulvin
  • Disrupts mitosis via microtubule dysfunction
  • Especially targets keratin-containing tissues such as nails
  • Fungistatic
  • Teratogenic
  • Disulfiram-like reaction
  • Neurologic symptoms
    • confusion
    • headaches
  • Induces cytochrome P450
  • Superficial infections
  • Dermatophytes
    • inhibits growth
Flucytosine
  • Converted by fungal enzyme cytosine deaminase to 5-fluorouracil, which then inhibits nucleic acid synthesis
  • Can be fungistatic or fungicidal
  • Bone marrow suppression
  • Systemic mycoses
    • Cryptococcus
Selenium sulfide
  • Disrupts mitosis, resulting in decreased turnover of epidermal cells and decreased flaking
  • Also has mild antibacterial and antifungal activity
-
  • Seborrheic dermatitis
  • Pityriasis versicolor
 

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Questions (1)
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.15.75) A 57-year-old florist presents to his family physician with nodular lesions on his right hand and forearm. He explains that he got pricked by a rose thorn on his right "pointer finger" where the first lesions appeared, and the other lesions then began to appear in an ascending manner. The physician prescribed a medication and warned him of gynecomastia as a side effect if taken for long periods of time. Which of the following is the mechanism of action of the medication? Review Topic | Tested Concept

QID: 106869
1

Inhibits ergosterol synthesis

61%

(95/157)

2

Binds to ergosterol, forming destructive pores in cell membrane

17%

(27/157)

3

Inhibits squalene epoxidase

11%

(18/157)

4

Inhibits formation of beta glucan

3%

(5/157)

5

Disrupts microtubule function

6%

(10/157)

L 1 D

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