ANTIFUNGALS

Question 1

Systemic mycoses

Answer 1

Involve various internal organs; difficult to treat

Question 2

Superficial mycoses (yeast)

Answer 2

Involve skin, nails or mucous membrane

Question 3

Opportunistic mycoses

Answer 3

Primarily in debilitated or immunocompromised patients (AIDS, leukemia)

Question 4

Endemic mycoses

Answer 4

Non opportunistic

Caused by various pathogens distributed unevenly around the world, can occur in

Question 5

Two major drug classes for antifungals

Answer 5

1. Polyene Antibiotics (amphotericin B, nystatin)

2. Azoles

Question 6

Amphotericin B

Answer 6

• Used to treat deep systemic mycoses
• MOA: opens a channel in fungal cell to let the components leak out so the cell dies
• Cautions: highly toxic, effective against some protozoa, infusion reaction and renal damage occurs in ALL patients to varying degrees

Question 7

Administration of Amphotericin B

Answer 7

• Absorbed poorly from GI tract (oral admin no work)
• Administer via slow infusion 2-6 hours everyday or every other day
• Infusion reactions: fever, chills, rigors, nausea, headache, can cause bone marrow suppression and hypokalemia

Question 8

Nystatin

Answer 8

Useful in treatment of superficial mycoses of candidacies (skin, mouth, esophagus, vagina) used orally
Topical Nystatin drug of choice for candidal infections of the oral cavity
Same MOA as amphotericin
adverse: diarrhea, nausea, vomiting, upset stomach

Question 9

AZOLES

Answer 9

• Broad spectrum synthetic compounds for treating systemic mycoses
• Less toxic than amphotericin B, given orally
  MOA: inhibits enzyme involved in the synthesis of fungal ergosterol; inhibits P 450 enzymes
  DISadvantages: Inhibits P450 drug metabolizing enzymes and can increase levels of other drugs
  ITRACONAZOLE, FLUCONAZOLE, KETOCONAZOLE

Question 10

Itraconazole

Answer 10

• Broader spectrum than other azoles
• Well absorbed in GI when given w meals
• Mostly metabolized by the liver
  Adverse: cardio suppression, hepatotoxicity, hypokalemia, hypertension

Question 11

Fluconazole

Answer 11

• Well absorbed from GI tract through entire body including CNS
• Effective in immunocompromised patients
• Used for: cryptococcal meningitis, blastomycosis and mucosal candidiasis
• Adverse: GI disturbances, birth defects if given during pregnancy, headaches, rashes, seizures, dermatitis

Question 12

Ketoconazole

Answer 12

• Can’t take antacids or antihistamines
• Toxicity: Less toxic than amphotericin, severe hepatotoxicity in approx 0.01% of individuals
• Inhibits synthesis of testosterone and estradiol causing menstrual irregularities, gynecomastia

Question 13

Onychomycosis

Answer 13

Fungal infection of the nails

Question 14

Tinea corporis

Answer 14

Ringworm of the body

Question 15

Tolnaftate

Answer 15

• Superficial mycoses coverage
• Tinea pedis, tinea cruris
• Ineffective against yeast (Candida)
• Adverse: allergic contant dermatitis possibly teratogenic

Question 16

Tinea cruris

Answer 16

Ringworm of the groin

Question 17

Clotrimazole

Answer 17

• Used for various mucosal and cutaneous infections (athletes foot cream)
• Spectrum and MOA similar to other azoles
• Restricted to topical use

Question 18

Miconazole

Answer 18

No longer used systemically
- 2% miconazole nitrate cream used for cutaneous vaginal Candida albicans infections (think Monistat use)
May cause burning, redness, itching