Antifungal Drugs

Front 1

i. What is the clinical use for amphotericin B?

Back 1

1. Broad-spectrum antifungal drug
2. Effective for most fungal infections
3. Used for serious and progressive infections

Front 2

ii. What are the adverse effects of amphotericin B?

Back 2

1. NEPHROTOXIC

Front 3

iii. What are the four formulations of amphotericin B?

Back 3

1. Amphotericin B deoxycholate
2. Amphotericin B lipid complex (ABLC)
3. Amphotericin B cholesteryl sulfate complex (ABCD)
4. Liposomal formulaton of amphotericin B

Front 4

What is the advantage of lipid formulations of amphotericin B over deoxycholate?

Back 4

Less nephrotoxic

Front 5

What is the MOA of amphotericin B?

Back 5

1. Binds to ergosterol
2. Causes pore formation

Front 6

What is the bioavailability of amphotericin B?

Back 6

1. Poor
2. Poor absorption

Front 7

How is amphotericin B administered?

Back 7

IV

Front 8

Why is amphotericin B so effective?

Back 8

Liposomal formulations transfer amphotericin B to fungal membranes and less to human membranes

Front 9

What drug interactions should you be wary of with amphotericin B?

Back 9

1. Other nephrotoxic drugs
2. Amphotericin B + Flucytosine

Front 10

What does amphotericin B+Flucytosine yield?

Back 10

They potentiate one another so are more toxic when used together and the dosage should be reduced

Front 11

What are the benefits of combination use?

Back 11

1. Decreased resistance
2. Drug A can kill things that Drug B cannot

Front 12

What are the clinical uses of Azole and itraconazole?

Back 12

Broad-spectrum antifungal agents

Front 13

What do imidazoles and triazoles bind in their MOA?

Back 13

1. P450 enzymes (fungi version preferentially)
2. Inhibit ergosterol synthesis

Front 14

Which is safer, amphotericin B or itraconazole?

Back 14

Itraconazole

Front 15

What is the route of administration for itraconazole?

Back 15

Oral

Front 16

What are the adverse effects of itraconazole?

Back 16

1. Liver toxicity
2. Cardiosuppression (H+ inhibitor)

Front 17

Ketoconazole is not used very much. Why?

Back 17

High hepatotoxicity

Front 18

What is the clinical use of ketoconazole?

Back 18

Broad spectrum anti fungal agent.
Safer than amphotericin B

Front 19

What is the administration of ketoconazole?

Back 19

Oral

Front 20

What are the adverse effects of ketoconazole? How do you combat these effects?

Back 20

1. Hepatotoxicity
2. Monitor liver function before and during treatment

Front 21

What is the MOA for azoles?

Back 21

1. Inhibit ergosterol synthesis
2. Bind to cytochrome P450 enzymes

Front 22

Why are triazoles a “good azole”?

Back 22

1. Fewer side effects
2. Better absorption
3. Better drug distribution
4. Fewer drug interactions

Front 23

What do itraconazole and ketoconazole inhibit?

Back 23

1. CYP3A4 (450)

Front 24

What decreases the absorption of itraconazole?

Back 24

1. Drugs that raise gastric pH
2. H2 antagonists
3. Proton pump inhibitors

Front 25

What is the MOA of fluconazole?

Back 25

Inhibits cytochrome P450 syndrome

Front 26

What does fluconazole inhibit?

Back 26

Cytochrome P450 CYP3A4

Front 27

What are the adverse effects of fluconazole?

Back 27

1. Some Nausea, but generally well tolerated
3. Rare hepatotoxicity
4. May be associated with Stevens-Johnson syndrome
5. May be teratogenic

Front 28

What is flucytosine converted to, and where does it take place?

Back 28

5-FU, in Fungal cells

Front 29

After flucytosine is converted to 5-FU, what is 5-FU converted to?

Back 29

1. FdUMP→ inhibits DNA synthesis

Front 30

What is the MOA of echinocandins?

Back 30

1. Inhibit synthesis of beta-1,3-D-glucan
2. Block synthesis of cell wall components in fungal membranes

Front 31

What is the administration of echinocandins?

Back 31

IV

Front 32

What are echinocandins approved for?

Back 32

1. Aspergillosis in patients unresponsive or intolerant to other drugs
2. Systemic Candida infections

Front 33

What are the four classes of drugs used for superficial mycoses?

Back 33

i. Azoles
ii. Griseofulvin
iii. Polyene antibiotics
iv. Allyamines

Front 34

How are azoles formulated for superficial mycoses?

Back 34

1. Topical
2. Oral

Front 35

What is the most effective formulation of clotrimazole?

Back 35

1. Topical
2. Tinea pedis….

Front 36

What can clotrimazole be used for? In what parts of the body?

Back 36

1. Dermatophytic infections and candidiasis
2. Skin, mouth, and vagina

Front 37

What are the adverse effects of Clotrimazole? (skin and intravaginal)

Back 37

1. Skin→ stinging, erythema, edema
2. Intravaginal→ burning and lower abdominal cramps

Front 38

Against what type of infection is Griseofulvin active? Inactive?

Back 38

1. Active against superficial dermatophytic infections
2. Inactive against candidiasis and systemic infections

Front 39

What is the MOA of Griseofulvin?

Back 39

1. Deposited in keratin of skin, hair, and nails
2. Inhibits fungal mitosis by binding components of mcirotubules

Front 40

What is the availability of Griseofulvin?

Back 40

Oral

Front 41

What are the polyene antibiotics?

Back 41

i. Amphotericin B
ii. Nystatin

Front 42

What is the clinical use of nystatin?

Back 42

Topical for candidiasis

Front 43

What is the MOA of Nystatin?

Back 43

Binds ergosterol

Front 44

What is the availability of nystatin?

Back 44

Oral and topical

Front 45

What is the toxicity of nystatin?

Back 45

i. Very low only when used topically
ii. Too toxic by parenteral injections

Front 46

What is the clinical use of naftifine?

Back 46

Topical treatment of dermatophyte infections

Front 47

What is the MOA of naftifine?

Back 47

i. Inhibits the enzyme squalene epoxidase
ii. Decreases ergosterol
iii. Fungicidal

Front 48

What is ciclopirox used for?

Back 48

i. Broad spectrum
ii. Skin and nail infections?

Front 49

What is the MOA of ciclopirox?

Back 49

Chelates iron and aluminum

Front 50

What is tolnaftate used for?

Back 50

i. Dermatophytes, not Candida
ii. Treatment of tinea pedis, tinea cruris, tinea corporis

Front 51

What is the MOA of tolnaftate?

Back 51

Unknown

Front 52

Why may systemic formulation be favored over topical formulation?

Back 52

a. Systemic may be more effective because it can cover disseminated systemic infections

Front 53

What are some general drawbacks of systemic formulations?

Back 53

a. Antifungals have toxicity issues

Front 54

Why might topical be better than systemic formulation?

Back 54

a. Topical reduces adverse effects and may be effective

Front 55

A patient undergoes a round of an azole and hasn’t completely responded. What drug should they switch to?

Back 55

Echinocandins

Front 56

What drug has negative inotropic action?

Back 56

Itraconazole

Front 57

Is resistance to flucytosine common?

Back 57

Yes

Front 58

What drug can decrease levels of immunosuppresant drugs?

Back 58

Caspofungin