Fungal Pharmacology

Question 1

What are the three species of fungi that cause human infection?

Answer 1

Trichophyton, Microsporum, Epidermophyton

Question 2

What are the topical azole antifungals?

Answer 2

Clotrimazole (Lotrimin) ointment; (Desenex) powder, Miconazole (Micatin, Monostat Derm), Ketoconazole (Nizoral)

Question 3

What are the indications for topical azole antifungals?

Answer 3

Tinea corporis, tinea cruris, tinea pedis, cutaneous candidiasis.

Question 4

What are CI of topical azole antifungals?

Answer 4

Pregnancy, lactation. Use with caution in liver failure. Ketoconazole not for use in asthma patients or history of sulfa allergy

Question 5

What are indications and CI of clotrimazole?

Answer 5

Cutaneous candidiasis (topical), Vulvovaginal candidiasis (topical), Oropharyngeal candidiasis (oral). CI: Hypersensitivity

Question 6

What are adverse effects of clotrimazole?

Answer 6

Topical: vulvovaginal burning. Oral: Abnormal LFTs, Pruritus, N/V

Question 7

What are indications/CI of mycostatin?

Answer 7

Cutaneous and mucocutaneous infections caused by Candidia. Oral and intestinal Candidia infections. CI: Hypersensitivity to mycostatin

Question 8

What are adverse effects of mycostatin?

Answer 8

Contact dermatitis. Stevens-Johnson syndrome. Oral: N/V, diarrhea

Question 9

What are the systemic azole antifungals?

Answer 9

Ketoconazole (Nizoral), Itraconazole (Sporanox), Fluconazole (Diflucan)

Question 10

Why is ketoconazole restricted to treatment of life threatening fungal infections?

Answer 10

hepatotoxicity, decreased adrenal corticosteroid secretion, QT prolongation, inhibitor of CYP450 (many drug interactions)

Question 11

What potential life threatening infections could ketoconazole be used for if all other options failed?

Answer 11

Blastomycosis, coccidiomycosis, histoplasmosis, chromomycosis, paracoccidioiodmycosis. Should NOT be used for candida or dermatophyte infections

Question 12

What are indications for Itraconazole (Sporanox)?

Answer 12

Aspergillosis, Blastomycosis, Esophageal and oropharyngeal candidiasis (oral soln), Coccidioidomycosis, Histoplasmosis, Onychomycosis

Question 13

What are CI to itraconazole (Sporanox)?

Answer 13

Hypersensitivity. Use of other drugs that need CYP450 system. Ventricular dysfunction (negative inotrope): will further reduce ejection fraction
CHF. Pregnancy or intend to become pregnant

Question 14

What are the pharmacodynamics of itraconazole?

Answer 14

Requires gastric acidity. Better absorbed with food (capsule). Solution better absorbed on an empty stomach. 99.8% protein bound. Half life is about 21 hours

Question 15

What are adverse effects of itraconazole?

Answer 15

Nausea, diarrhea, Edema, Headache, Rash, Abnormal LFTs, Heart failure, Arrhythmia, Hearing loss

Question 16

What monitoring is needed with itraconazole?

Answer 16

Baseline liver function tests. Monthly LFTs. Serum concentrations to assure therapeutic levels after 2 weeks of therapy

Question 17

What are indications for Fluconazole (Diflucan)?

Answer 17

Blastomycosis-CNS. Candidiasis-Candidemia, endocarditis, oropharyngeal, prophylaxis, vaginal.
Coccidioidomycosis-Meningitis, pneumonia, prophylaxis. Crypococcosis-Meningitis, pneumonia

Question 18

What are CI to fluconazole?

Answer 18

Hypersensitivity. Coadministration of CYP3A4 substrates which may lead to QT prolongation (cisapride, primozide or quinidine)

Question 19

What are the pharmacokinetics/dynamics of fluconazole?

Answer 19

Good penetration into CSF, eye, peritoneal fluid, sputum, skin and urine. Half life is 30 hours

Question 20

What are some commonly used drugs the fluconazole interacts with?

Answer 20

statins, viagra, warfarin, sulfonylureas, PPIs, antihypertensives, benzos, macrolides, fentanyl

Question 21

What are adverse effects of fluconazole?

Answer 21

Pregnancy category C/D, Headache, dizziness, N/V, diarrhea, Elevated LFTs, QT prolongation

Question 22

What monitoring needs to be done with fluconazole?

Answer 22

Baseline liver function tests. Periodic liver function, renal function, and potassium

Question 23

What are indications for Terbinafine (Lamisil)?

Answer 23

Oral/systemic formulation-Oncychomycosis, Tinea capitis. Topical-Tinea pedis, Tinea cruris, Tinea corporis

Question 24

What are the pharmacodynamics/kinetics of Terbinafine (Lamisil)?

Answer 24

half life 36 h. Distribution to the sebum and skin. 99% plasma bound. Hepatic metabolizm

Question 25

What are some significant drug interactions with terbinafine (Lamisil)?

Answer 25

for the oral formulation it interferes with metroprolol and tramadol

Question 26

What are SE of Terbinafine (Lamisil)?

Answer 26

ORAL-Headache, Diarrhea, Elevated LFTs. TOPICAL-Burning, Contact dermatitis, Dryness, Pruritus, Rash

Question 27

What are indications of Griseofulvin?

Answer 27

Most commonly used for tinea capitis. Also used for tinea infections of the skin, hair and nails

Question 28

How should griseofulvin be administered?

Answer 28

Fatty meal (peanut butter or icecream) can increase GI absorption. With food or milk to decrease GI upset

Question 29

What are CI of Griseofulvin?

Answer 29

Liver failure, Porphyria, Pregnancy (category X). penicillin allergy has potential for cross reactivity. Breast feeding not recommended

Question 30

What monitoring needs to be done with Griseofulvin?

Answer 30

Renal fxn, liver fxn, CBC to watch for granulocytopenia

Question 31

What are potential drug interactions of Griseofulvin?

Answer 31

Warfarin, oral contraceptives, barbiturates, cyclosporine. If taken w/alcohol can cause N/V, dizziness, palpitations

Question 32

What are the indications for amphotericin B?

Answer 32

severe systemic and CNS infections that are progressive and potentially life threatening

Question 33

What are SE of amphotericin B?

Answer 33

Anaphylaxis, infusion reaction, leukoencephalopathy (damage to brain white matter), nephrotoxicity

Question 34

What needs to be monitored with amphotericin B?

Answer 34

renal and liver function, electrolytes, PT/PTT, CBC

Question 35

What are drug interactions with amphotericin B?

Answer 35

aminoglycosides, antifungal agents, corticosteroids, cyclosporine