Antifungal agents

Question 1

fungal infections- Dermatophytes are restricted to what?

Answer 1

restricted to the keratinized layers of the integument

Question 2

Treatment for fungal infections- Dermatophytes

Answer 2

Treatment is usually conservative with use of topical antifungal agents

1. Clotrimazole
2. Terbinafine

Question 3

Nail infection (onychomychosis) TX

Answer 3

This usually requires systemic Tx for weeks to 6 months

1. Itraconazole
2. Terbinafine

Topical therapy can be ciclopirox

Question 4

Fungal infections- Candida Tx

Answer 4

Topical Tx: Clotrimazole

can use nystatin for mucocandidiasis

Question 5

If someone tried using clotrimazole or nystatin for their candida infections what medicine can they try?

Answer 5

Flucanozole via systemic (oral)

Question 6

Describe the organisms for systemic fungal infections

Answer 6

Causative organism are inherently virulent and cause disease in HEALTHY humans

Question 7

Tx for systemic fungal infectons?

Answer 7

Amphotericin B infusions

Question 8

Some with a BLASTOMYCOSIS systemic fungal infection needs to be Tx with what?

Answer 8

Amphotericin B then Itraconazole then fluconazole.

Question 9

Tx for coccidiodomycosis systemic fungal infection?

Answer 9

Amphotericin B then maintenance with fluconazole or itraconazole

Question 10

Tx for cryptococcosis systemic fungal Tx

Answer 10

Amphotericin B plus fluconazole

Question 11

Tx for histoplasmosis systemic fungal infection

Answer 11

Amphotericin B or itraconazole

Question 12

Tx for disseminated candidiasis

Answer 12

Fluconazole

Question 13

Tx for aspergillosis opportunistic systemic fungal infection?

Answer 13

Amphotericin B, casopfungin, itraconazole

Question 14

Tx for pnuemocystis pneumonia?

Answer 14

TMP-SMX (bactrim)

Question 15

Amphotericin B pharmokinetics

Answer 15

rapidly sequestered in tissues then slowly released

Question 16

Amphotericin B adverse reactions

Answer 16

Nephrotoxicity-major dose limiting factor
Infusion related toxicities
Anemia

Liposomal preps may reduce renal and infusion toxicities
The lipid vehicle serves as Amphotericin B reservoir reducing non-specific binding to human cell membranes

Question 17

is Nystatin absorbed by GI tract

Answer 17

no

Question 18

What limits nystatin use?

Answer 18

Toxicity limits systemic use

Question 19

What is Nystatin safe and effective for?

Answer 19

Safe and effective for topical tx of candidal infections

Question 20

MOA of Fluconazole - Itraconazole

Answer 20

selective inhibition of fungal cytochrome P450 (static-Cidal)

Question 21

Clinical use of Fluconazole?

Answer 21

Vaginal Candidiasis- if topical tx fails taken orally

Oropharyngeal and esophageal Candidiasis- systemic

Question 22

Pharmacokinetics of fluconazole?

Answer 22

cleared primarily by the kidneys so renal dosing adjustment if impaired- has the least effect on liver compared to other azoles

Readily enters CNS

Question 23

Pharmacokinetics of itraconazole

Answer 23

Eliminated by the hepatic metabolism

Question 24

What are the imidazoles?

Answer 24

Ketoconazole
Clotrimazole
Miconazole

Question 25

MOA of imidazoles?

Answer 25

inhibit P450-dependent enzyme (fungicidal)

Question 26

Imidazoles clinical uses?

Answer 26

• there is a decline in systemic use of ketoconazole
• Chronic mucocutaneous candidiasis
• ORAL AND VAGINAL CANDIDIASIS (CLOTRIMAZOLE TOPICALLY)

Question 27

Imidazoles pharmacokinetics

Answer 27

• only ketoconazole has been used systemically (oral and IV)
• Eliminated by hepatic metabolism (CYP450 oxidation)
• Excreted in breast milk

Question 28

Ketoconazole (can be used systemically) which causes what adverse reactions

Answer 28

Hepatotoxicity- generally avoid if liver dysfunction

Remember this one: CAN INHIBIT MAMMALIAN TESTOSTERONE SYNTHESIS CAUSING DECREASED LIBIDO AND GYNECOMASTIA

Question 29

Is terbinafine bactericidal or static

Answer 29

Its CIDAL

it inhibits squalene oxidase

Question 30

What is the agent of choice for toe/finger nail infections caused by onychomycosis?

Answer 30

Terbinafine- its a once daily oral dose

Available TOPICALLY for ATHLETES FOOT

Question 31

What are the adverse reactions of Terbinafine?

Answer 31

Inhibition of CYP450 drug metabolism