C/4. Antifungal Agents

Question 1

Drugs need to know in this topic (9)

Answer 1

Amphotericin B
Nystatin
Clotrimazole
Fluconazole
Itraconazole
Voriconazole
Flucytosine (5-FC)
Caspofungin
Terbinafine

Question 2

Amphotericin B

Answer 2

Both polar and nonpolar structures
Interacts with ergosterol in fungal membrane and form pores which disrupt membrane permeability
Fungicidal effect

Broadest antifungal spectrum
Systemic fungal infection: Against aspergillus, Blastomyces, Candida, Cryptococcus, Histoplasma, Mucor, Sporothrix

Oral(poor bioavailability)
IV
Topical
Poor CNS penetration (intrathecal injection is required against Cryptococcal or Candida meningitis)
Clearance via hepatic metabolism and renal elimination

Fever, chill, muscle spasm
Dose dependent : nephrotoxicity, CNS toxicity, Anemia

Question 3

Nystatin

Answer 3

Both polar and nonpolar structures
Interacts with ergosterol in fungal membrane and form pores which disrupt membrane permeability
Fungicidal effect

Topical for Candidiasis

Question 4

Clotrimazole

Answer 4

Tx for dermatophytes, superficial candidiasis, vaginal candidiasis
OTC drug

Can cross BBB(ketoconazole can’t penetrate)
Hepatic metabolism
Renal elimination
Inhibitors of CYP450 enzymes

GI symptom, skin rash
Decreased synthesis of steroid hormones(mainly cortisol and testosteron): decreased libido, gynecomasia, menstrual irregularity
Visual disturbances

Question 5

Fluconazole

Answer 5

Oropharyngeal, genital candidiasis
Coccidiodes infection
Cryptococcus meningitis

Hepato metabolism
Renal elimination
Inhibitor of CYP450 enzymes

GI symptom, skin rash
Decreased synthesis of steroid hormones(mainly cortisol and testosteron): decreased libido, gynecomasia, menstrual irregularity
Visual disturbances

Question 6

Itraconazole

Answer 6

Balstomyces and sporothrix infections
2nd line agent for Aspergillus, coccidiodes, Cryptococcus, Histoplasma

Hepato metabolism
Renal elimination
Inhibitor of CYP450 enzymes

GI symptom, skin rash
Decreased synthesis of steroid hormones(mainly cortisol and testosteron): decreased libido, gynecomasia, menstrual irregularity
Visual disturbances

Question 7

Voriconazole

Answer 7

2nd generation
Against Aspergillus, invasice candida infection

Hepato metabolism
Renal elimination
Inhibitor of CYP450 enzymes

GI symptom, skin rash
Decreased synthesis of steroid hormones(mainly cortisol and testosteron): decreased libido, gynecomasia, menstrual irregularity
Visual disturbances

Question 8

Flucytosine (5-FC)

Answer 8

Activated by fungal cytosine deaminase to 5-FU which incoporates into fungal RNA
Inhibits DNA synthesis

Narrow spectrum
Combination with amphtericin B or triazole to tx Cryptococcal meningitis and invasive candidiasis

Oral
Can penetrate BBB
Renal elimination

BM suppression
Alopecia
Liver dysfunction

Question 9

Caspofungin

Answer 9

Inhibits the synthesis of beta(1-3)-glucan, a critical component of fungal cell wall

Candida infections failed to respond to amphotericin B
Mucar infeciton
Aspergillus infection

IV
Hepatic metalism

GI distress
Fever, Headache, skin rash

Question 10

Terbinafine

Answer 10

Inhibits squalene epoxidase, interfering with ergosterol synthesis
Fungicidal effect

Systemic drigs for Superficial fungal infections
Onychomycosis
Dermatophytosis ofr the skin hair

Topical (OTC drug)
Oral(prescription drug)

GI distress
Headache, rash