Antifungal medications

Question 1

What is the MoA of Amphotericin B?

Answer 1

Binds to ergosterol of fungal PM and alters membrane permeability, causing cell lysis

Can be fungistatic or fungicidal

Question 2

How is Amphotericin B distributed?

Answer 2

Has poor CSF penetration

Question 3

What are the ADRs of amphotericin B?

Answer 3

Nephrotoxicity

Anemia

Systemic: shaking, chills, fever, myalgias

Question 4

What is the potential benefit of Amphotericin Lipid formulations?

Answer 4

Lower incidence of nephrotoxicity

Question 5

What is the MoA of 5-Fluocytosine?

Answer 5

Penetrates fungal cell where it is deaminated by a fungus specifi enzyme

Inhibits pyrimidine metabolism an ultimately RNA and protein synthesis

Question 6

How does FLuorocytosine distribute?

Answer 6

60-100% CSF penetration

Question 7

What are the ADRs of 5-Fluocytosine?

Answer 7

Bone marrow hypoplasia

More common in prolonged therapy

Question 8

What is the MoA of Azole products?

Answer 8

Interfere with fungal cytochrome P450 enzymes responsible for ergosterol production

Fungistatic or fungicidal

Question 9

What are the ADRs of azole antifungals?

Answer 9

N/V

Hepatitis

Increases aminotransferases

Question 10

What ADR is specific to Ketoconazole?

Answer 10

Dose dependent depression of serum testosterone and ACH

Question 11

What are the drug interactions for azole antifungals?

Answer 11

Antacids, PPIs and H2 antagonists

Cyclosporin

Warfarin

Question 12

Describe the absorption of Ketoconazole.

Answer 12

Rapidly absorbed from GI tract

pH dependent bioavailability (increased pH, decreased absorption)

Question 13

Describe the absorption and distribution of Fluconazole.

Answer 13

Rapidly absorbed from GI tract

Widely distributed, readily into CSF

Question 14

How is Fluconazole eliminated?

Answer 14

Renal, 60-80% unchanged in urine

Question 15

How is Itraconazole distributed?

Answer 15

Widely distributed

Poorly into CSF

Question 16

How is Itraconazole used in therapy?

Answer 16

Effective for oral therapy of histo/blasto

Useful for aspergillosis

Question 17

How is Voriconazole absorbed and distributed?

Answer 17

GI, decreased by high fat meals

40-70% in CSF

Question 18

How is voriconazole eliminated?

Answer 18

Metabolized in liver

Interacts with CYP3A4

Question 19

How is voriconazole used in therapy?

Answer 19

Invasive aspergillosis and Fusarium spp.

Candidiasis

Question 20

What is the use of Posaconazole?

Answer 20

Candida and Aspergillus infection in immunocompromised patients

Inhibits CYP3A4

Question 21

What is the MoA of Caspofungin acetate?

Answer 21

Echinocandin - blockes fungal cell wall synthesis

Glucan synthesis inhibitor

Question 22

What is Caspofungin acetate used for?

Answer 22

Candidiasis

Invasive aspergillosis

Question 23

What are the ADRs of Caspofungin acetate?

Answer 23

Phlebitis, headache, fever

Increased LFTs, SrCr

Question 24

What is the MoA of Griseofulvin?

Answer 24

Disrupts the cells mitotic spindle structure

Question 25

What is the use of Griseofulvin?

Answer 25

Dermatophytosis

Question 26

What are the ADRs of Griseofulvin?

Answer 26

NVD Hypersensitivity Hepato/Nephrotoxicity Headace CYP3A4 inducer

Question 27

What is the MoA of Terbinafine?

Answer 27

Synthetic allylamine derivative Inhibits squalene epoxidase

Question 28

What are the ADRs of Terbinafine?

Answer 28

Hypersensitivity/Rash - erythema multiforme, toxic epidermal necrolysis Liver enzyme abnormalities Headache

Question 29

What are the drug interactions with Terbinafine?

Answer 29

Cimetidine - T clearance decreased Rifampin - T clearance increased Cyclosporin - increased clearance Warfarin

Question 30

What is Terbinafine used for?

Answer 30

Onychomycosis Consider ADRs

Question 31

What are the treatments of oral candidiasis?

Answer 31

Nystatin - oral suspension Clotrimazole troches Amphotericin B