Antifungals

Question 1

Moa of amphotericin B

Answer 1

Amphotericin B binds to ergosterol in the plasma membranes of sensitive fungal cells -form pores - pores disrupt membrane function, allowing electrolytes (particularly potassium) and small molecules to leak from the cell, resulting in cell death

Question 2

Antifungal spectrum of amphotericin B

Answer 2

effective against a wide range of fungi: Candida albicans
 Histoplasma  capsulatum
Cryptococcus  neoformans
Coccidioides  immitis
Blastomyces  dermatitidis
and many strains of  Aspergillus
protozoal infection leishmaniasis

Question 3

Elimination of amphotericinB

Answer 3

Some via bile

Some in urine

Question 4

Csf penetration of amphotericin B

Answer 4

Minimal penetration in CSF

Question 5

Method of administration of amphotericin

Answer 5

topical

IV-
conventional( soadium deoxycholate)

Liposomal preparation( less infusion and renal toxicity)

Question 6

adverse effects of amphotericin

Answer 6

ACUTE
Fever and chills
Thrombophlebitis

CHRONIC
Renal impairment: more if given with other nephrotoxic drugs
Hypokalemia: caution in digoxin
Anemia: BM depression

Question 7

Moa of flucytosine

Answer 7

Combined with amphotericjn which increases its entry into cell by making it more permeable.

Flucyosine- 5 florouracil - 5 FdUMP which inhibits thymidylate synthase depriving the cell of nucleotide

Question 8

Adr of flucytosine

Answer 8

BM depression

Hepatic dysfxn

Git: n/v/d

Question 9

Excretion of 5FC

Answer 9

Urine

Question 10

2 different classes of azole antifungals

Answer 10

Imidazoles : cutaneous ds

Troazoles : cutaneous and systemic ds

Question 11

Moa of azoles

Answer 11

block the demethylation of lanosterol to ergosterol, the principal sterol of fungal membranes disrupting membrane structure and function.

Question 12

All azoles _____ hepatic CYP450 3A4 isoenzymes to varying degrees

Answer 12

INHIBIT

Question 13

CI of azoles

Answer 13

Pregnancy: teratogenic

Question 14

Fluconazole use

Answer 14

CRYPTOCOCCUS NEOFORMANS

CANDIDA

Question 15

Adr of fluconazole

Answer 15

n/v ,headache, and skin rashes Hepatotoxicity

Question 16

Adr of itraconazole

Answer 16

n/v,  rash
hypokalemia
hypertension
edema, headache
Hepatotoxicity 
Itraconazole  has a negative inotropic effect  and  should  be  avoided  in  patients  with  evidence  of  ventricular dysfunction, such as heart failure.

Question 17

Itraconazole use

Answer 17

Broad spectrum
drug of choice for the treatment of blastomycosis
sporotrichosis
paracoccidioidomycosis
 histoplasmosis

Question 18

Hepatoxicity os common to which class of antifungals

Answer 18

Azoles

Question 19

Posaconazole use

Answer 19

Candida
Aspergillus
Zygomycetes

Question 20

Voriconazole use

Answer 20

Broad spectrum

Doc for invasive Aspergillosis

Question 21

All azole inhibit CYP 450 isoenzymes

All azole are hepatotoxic

Answer 21

Yes

Yes

Question 22

Primary route of elimination of 
Flu
Itra
Vori
Posa

Answer 22

Renal

Rest Hepatic

Question 23

Echinocandins

Answer 23

Moa: interfere with synthesis of fungal cell wall leading to lysis of cell

Use: candida , aspergillus (little against others)

Eg: caspofungin , micafungin , anidulafungin

Question 24

Antifungal for Tinea capitis and unguim

Oral / topical

Answer 24

Oral

Question 25

Moa of squalene oxidase inhibitors

Answer 25

These agents act by inhibiting squalene epoxidase, thereby blocking the biosynthesis of ergosterol, an essential component of the fungal cell membrane

Question 26

Squalene oxidase inhibitors eg

Answer 26

Terbrnafine Naftifine Butenafine

Question 27

Kinetics of terbenafine

Answer 27

Oral terbinafine is extensively metabolized by several CYP450 isoenzymes and is excreted mainly via the urine . The drug should be avoided in patients with moderate to severe renal impairment or hepatic dysfunction.

Question 28

Adberse effects of terbenafine

Answer 28

gastrointestinal disturbances (diarrhea, dyspepsia, and nausea), headache, and rash. Taste and visual disturbances transient elevations in serum hepatic transaminases. Terbinafine is an inhibitor of the CYP450 2D6 isoenzyme, and concomitant use with substrates of that isoenzyme may result in an increased risk of adverse effects with those agents.

Question 29

Moa of griseofulvin

Answer 29

causes disruption of the mitotic spindle and inhibition of fungal mitosis

Question 30

Polyene antifungals

Answer 30

Amphotericin B | Nystatin

Question 31

Use of nystatin

Answer 31

cutaneous and oral Candida infections. The drug is negligibly absorbed from the gastrointestinal tract, and it is not used parenterally. It is administered as an oral agent for the treatment of oropharyngeal candidiasis (thrush), intravaginally for vulvovaginal candidiasis, or topically for cutaneous candidiasis.

Question 32

Imidazoles

Answer 32

``` butoconazole clotrimazole econazole ketoconazole miconazole oxiconazole sertaconazole sulconazole ```

Question 33

Moa of various antifungals

Answer 33

Echinocandins: inhibit cell wall Azoles : inhibit cell membrane Polyenes : inhibit cell membrane Griseofulvin : mitotic spindle hence mitosos Flucytosine: DNA synthsis