Antifungal Agents

Front 1

Allyamines and azoles target what part of fungal lifescycle?

Back 1

Synthesis, as opposed to other drugs which effect ergosterol or enzymes

Front 2

Amphotericin B- MOA, Class

Back 2

Class: Polyene Antifungal Agent
MOA: amphotericin B is structurally sim to membrane sterol and will be incorporated into the cell membrane. This disrupts membrane permeability leading to cell death.

Front 3

Amphotericin B- General Toxicity

Back 3

- Although has greater affinity for ergosterol, cellular sterols are sometimes also targeted and especially KIDNEY CELL MEMBRANES leading to renal problems (thus must moniter kidney function)--Epo effected leading to Anemia
- fever, IV site clot

Front 4

Amphotericin B- Class, PK

Back 4

Class: Polyene Antifungal Agent
PK: Insoluble, complexed w/ bile salt deoxycholate- IV. HIGHLY protein bound (must think about drug interactions). Has longg half life (24-48hrs, can dose every other day)

Front 5

AmFOtericin B- Class, Use

Back 5

Class: polyene antifungal
Use: Broad spectrum--cryptococcosis, histoplasmosis, coccidiodomycosis, aspergillosis

Front 6

AmFOtericin B- Class, Toxicity

Back 6

Class: Polyene Antifungal
Toxicity: Fever

Thrombophlebitis at the site of infusion
Chronic adverse effects: anemia (due to suppression EPO), RENAL DYSFUNCTION

Front 7

Nystatin- MOA, Class

Back 7

Class: Polyene Antifungal
MOA: create pores in the membrane (similar to amphotericin B)

Front 8

Nyastatin- PK, Use

Back 8

PK- not absorbed orally, used for only for topical and mucus membrane formulations
Use: skin, oral, GI, and vaginal candidiasis

Front 9

Nyastatin- Tox

Back 9

Tox: Not much b/c NOT absorbed systemically

Front 10

Flucytosine- Class, MOA

Back 10

Class: Pyrimidine antifungal
MOA: cytosine analog, Metabolized by fungal enzyme cytosine deaminase, incorporated into RNA
Thymidylate synthetase stops fungal DNA synthesis.
Humans do not possess the enzyme, cytosine deaminase

Front 11

FLucytosine- Class, PK

Back 11

Class- Pyrimidine antifungal
PK: must be given with amphotericin B--up to 200 hrs in RENAL failure-- DOSING MUST BE CHANGED if pt has renal complications

Front 12

Flucytosine- Class, Resistance, Use

Back 12

Class: pyrimidine Antifungal
Resistance: develops rapidly due to loss of deaminase
Use: in combo with amphotericin B for cytptococcal meningitis

Front 13

Flucytosine: Class, Toxicity

Back 13

Class: Pyrimidine Antifungal
TOxicity: bone marrow suppression (leukopenia and thrombocytopenia), severe enterocolitis. Temp increase in LFTs

Front 14

Imidazole and Triazole- Class, General MOA

Back 14

Class: Azole antifungals
MOA- impairs biosynthesis of ergosterol by inhibiting sterol 14 a demethylase.
- 14 a demethylase is part of microsomal cytochrome p450 depedant enzyme syst. Also this enzyme is part of the sterol hormone synthesis pathway- thus can see hormonal side effects

Front 15

Ketoconazole- PK, Toxicity

Back 15

PK- ACIDIC env
Toxicity: hormonal, LFTs

Front 16

Ketoconazole- drug interactions, use

Back 16

Drug interactions: P450 enzyme inhibitor, increased plasma levels of cyclosporine, midazolam, triazolam, indinavir, and phenytoin and decreased levels of ketoconazole by rifampin, , isoniazid, H2 blockers, PPI, sulcrafate, phenytoin
Use: candida but NOT aspergillus

Front 17

Itraconazole-class, PK

Back 17

Class: Azole,
PK: oral and IV, highly protein bound, metabolized by liver (CYP3A4)-- potent enzyme inhibitor, half life 30-40 hrs

Front 18

Itracanozole- Tox, Class

Back 18

Class: Azole
Tox: hypertriglyceridemia, hypokalemia, increased LFTs
Potential adverse effects resulting from interaction with other drugs
Although use same pathway as ketoconazole, does not cause hormonal changes

Front 19

Itraconazole- Drug interactions

Back 19

POTEnt CYP3A4 inhibitor , protein bound-- LOTS of drug interactions

Front 20

Itraconazole- uses

Back 20

Candidas, aspergillus

Front 21

Fluconazole- PK, Class

Back 21

Class: Azole
PK: CYP34 CYPA219 inhibitor

Front 22

Fluconazole: Use

Back 22

Use: similar to ketoconazole (CANDIDA but NOT aspergillus), has good CNS penetration (also can easily cross placental barrier)

Front 23

Fluconazole-Tox

Back 23

Tox: ABSOLUTE CONTRAINDICATION in pregnancy (b/c can cross BBB and placental barrier), elevated LFTs, rare hepatic failure

Front 24

Fluconazole- Pk

Back 24

Longish half life

Front 25

Voriconazole- PK, Class

Back 25

Class: Azole
PK: inhibitor of CYP3A4 enzymes
Nonlinear kinetics, depends on the dose
At lower dose may still follow linear kinetics so will try to keep lower dose
Adjust dose for renal compromised patients

Front 26

Voriconazole-use

Back 26

Candida and aspergillus

Front 27

Voriconazole- Tox

Back 27

Tox: visual changes - 15-30%, cardiovasc, CNS (fever, rash hallucinations), hepatotoxiicty

Front 28

Voriconazole- drug interactions

Back 28

Hepatic enzyme inhibitors, lots of drug interactions (sim to itraconazole)

Front 29

Posaconazole- PK, Use

Back 29

PK: highly protein bound,CYP3A4 inhibitor, half life= >30 hrs
Broad Spectrum: candida, aspergillus, zygomycoses

Front 30

Posaconazole- Use

Back 30

Broad spectrum use--aspergillus, candida, zygomycetes

Front 31

Posaconazole- Tox, Drug interactions

Back 31

Tox: cardiac, hypokalemia,
Drug interactions: mod inhibitor of enzymes CYP3A4

Front 32

Name some topical azole agents.

Back 32

Clotrimazole, miconazole, terconazole, butoconazole, tioconazole, oxiconazole

Front 33

What use do topical azoles have?

Back 33

effective for topical infections--Dermatophytosis (ringworm), candidiasis, tinea versicolor, piedra, tinea nigra, and fungal keratitis but NOT EFFECTIVE for nails or hair

Front 34

Name the echinocandins.MOA

Back 34

Caspofungin, micafungin, anidulafungin.
MOA: while most antifungals work on cell membrane, fungins inhibit synthesis of cell WALL

Front 35

Caspofungin, micafungin, anidulafungin- Class, PK

Back 35

Class: Echinocandins
PK: IV, Protein bound, Minimal CNS penetration

Front 36

Fungins- Tox

Back 36

Tox: Fever (20%), HA, Hepatotoxicity, hist mediated symptoms at IV site

Front 37

Echinocandins (fungins)- PK, use

Back 37

PK: Protein bound, IV
Use: systemic fungal infections- aspergillus and candida species

Front 38

Griseofulvin- MOA, PK

Back 38

MOA: inhibits fungal cell mitosis, binds to human keritin and makes resistant to fungal infection-- new growth of hair or nails are free of disease
PK: poor absorption (eat with fatty meal to improve absorption)

Front 39

Griseofulvin- Tox, Drug interactions

Back 39

HA, CNS (periph neuritis, fatigue, syncope), hepatotoxicity, hematologic effects (leukopenia, neutropenia, nasophilia), albuminuria
DI: Hep enzyme inducers-- warfarin, OCP

Front 40

Griseofulvin- use, class

Back 40

Mycotic disease of skin, hair (and also nails but not as much)
Class: benzofucan cyclohexane

Front 41

Terbinafine: MOA, PK

Back 41

Inhibits squalene epoxidase and leads to a deficiency in ergosterol in fungal cell wall
PK: well absorbed, highly protein bound, builds up in skin, nails, fat (has half life up to 200 hrs), renal excretion. Pulse therapy works well

Front 42

Terbinafine: class, uses

Back 42

class:allylamine
Terbinafine accumulates in skin, nails, and fat and releases slowly from skin and adipose tissues. Useful for nail infections. Ringworm

Front 43

Terbinafine: TOx

Back 43

Very well tolerated, minimal GI effects
Uncommon hepatoxicity, severe neutropenia, stevens-johnson syndrome may occur