Antibiotics: Antifungals

Question 1

Morphological classifications of yeast:

Answer 1

Molds
Yeasts
Dimorphic (yeast at body temperature, mold in the environment)

Question 2

Fungal cell wall:

Answer 2

Antigenic in nature
Multi-layered, consisting of polysaccharides, proteins, and glycoproteins.
Target of ECHINOCANDINS.

Question 3

Fungal cell membrane:

Answer 3

Deep to the cell wall.
Composed of phospholipid and ERGOSTEROL.
Facilitates capsule and cell wall synthesis.
Ergosterol is the target of the AZOLES and POLYENES.

Question 4

Azoles:

Answer 4

Inhibit rate-limiting step of ergosterol synthesis.
Potent CYP450 INHIBITOR.
Side effects: GI upset, hepatitis, rash, headache

Question 5

Fluconazole:

Answer 5

IV or oral.
EXCELLENT GI ABSORPTION AND CNS PENETRATION.
Fewest interactions of any azole.
Used against: CANDIDA, mild to moderate efficacy against cryptococcus. No activity against molds.

Question 6

Itraconazole:

Answer 6

IV or oral.
Poor GI absorption and CNS penetration.
Most drug interactions of any azole.
Toxicity: usual azole side effects plus adrenal insufficiency, impotence, gynecomastia, rarely hepatitis and CHF.
Used against: HISTOPLASMA. Treats most yeasts, most dimorphics, many molds.

Question 7

Voriconazole:

Answer 7

Most activity against MOLDS of all azoles.
Excellent GI absorption (100% bioavailability) and CNS penetration.
Toxicity: VISUAL DISTURBANCES, hepatitis, rash
Used against: INVASIVE ASPERGILLOSIS, prophylaxis during neutropenia and GVHD.

Question 8

Posaconazole:

Answer 8

Drug of choice against MUCORMYCOSIS.

Question 9

Polyenes (amphotericin B) mechanism of action:

Answer 9

Binds to ergosterol in cell membrane, forming pores and leakage of cellular components.

Question 10

Amphotericin B uses:

Answer 10

Candida, Cryptococcus, dimorphics, Aspergillus, mucormycosis

Question 11

Amphotericin B pharmacokinetics/toxicity:

Answer 11

Highly nephrotoxic (constricts afferent arterioles, damages distal tubules).
Causes infusion reactions (rigors and fever), and anemia.
Poor CNS penetration (highly plasma protein bound).
Avoid other nephrotoxic drugs.
Fever can be treated with acetaminophen, chills/rigor with diphenhydramine.

Question 12

Lipid-based amphotericin B:

Answer 12

Same spectrum of action, fewer ADRs. Requires higher doses to achieve same therapeutic effects.

Question 13

Echinocandin (caspofungin) mechanism of action:

Answer 13

Inhibition of 1,3-D-glucan synthesis in the fungal cell wall.

Question 14

Caspofungin uses:

Answer 14

CANDIDA (azole resistant or pt. is azole intolerant) and ASPERGILLUS (third line therapy)

Question 15

Caspofungin adverse reactions:

Answer 15

Fever, rash, phlebitis, hepatitis.

Hepatically cleared.