Antifungal Drugs

Question 1

Naturally Occurring Antifungals

Answer 1

Amphotericin , Griseofulvin , Caspofungin
(N:AG C)

Question 2

Synthetic Drugs

Answer 2

Clotrimazole/fluconazole , Flucytosine , Terbinafine (Clot = flu = Ter)

Question 3

PolYEne

Answer 3

Derived from StREPtomyces
Amphotericin B , Nystatin ( ye sin nye)

Question 4

Polyene MOA

Answer 4

binds to ergosterol = pore formation = cell death

Question 5

Amphotericin PK

Answer 5

Insoluble in water ( w/ SODIUM DEOXYCHOLATE / LIPOSOMES: reduce renal toxicity)
narrow therapeutic index , slow IV , passes CSF , Vitreous humor , amniotic fluid , placenta.

Question 6

Amphotericin Adverse Effects

Answer 6

Nephrotoxicity , hypotension , thrombophlebitis , anemia , neurotoxicity (intrathecal)

Question 7

Amphotericin Uses

Answer 7

Opportunistic (ye): Candida Albicans , Aspergillus

Question 8

Nystatin Uses (TOXIC)

Answer 8

Orally ; Candida : skin , mucus , intestinal , anal

Question 9

Polyenes CI

Answer 9

Pregnancy , renal dysfunctions , electrolyte disturbances

Question 10

Azoles

Answer 10

Triazole ex: fluconazole (try flu) ; Imidazole ex: ketoconazole & Clotrimazole ( I’m low keto)

Question 11

Azoles MOA

Answer 11

Inhibit lanosine 14a demethylase (depletion of ergosterol = fluidity alteration = enzymes alteration = cell death) + inhibit candidal yeast to hyphae formation .

Question 12

Azoles Uses

Answer 12

athlete’s foot , onychomycosis , ringworm (ring on nail)

Question 13

Clotrimazole Uses

Answer 13

(topical) Diaper rash , vaginal infections

Question 14

Ketoconazole Uses

Answer 14

(Oral) Systemic fungal infections

Question 15

Fluconazole Uses

Answer 15

(oral + IV) fungal meningitis

Question 16

Echinocandins

Answer 16

synthetic modification of echinocandin B ( asp.) = fungistatic to Asp. , Fungicidal to Candida
Ex: Caspofungin (Ekin Cas): IV

Question 17

Echinocandins MOA

Answer 17

inhibit 1.3 B glucan synthesis ( cell wall loses integrity = lysis )

Question 18

Echinocandins Adverse

Answer 18

Hepatotoxicity , flushing , GI upset , hypotension , phlebitis , fever , shivering

Question 19

Benzofurans

Answer 19

Narrow spectrum Ex: Griseofulvin from Penicillium Griseofulvum (grease=benzene)

Question 20

Benzofurans MOA

Answer 20

binds to keratin precursors = interfere w/ microtubules = no mitosis = cell death

Question 21

Griseofulvin PK

Answer 21

oral , poor water solubility , concentrated in keratin , T1/2= 24hr , induces CYP

Question 22

Griseofulvin Adverse

Answer 22

Photosensitivity , GI upset , Headache , Allergic Reactions

Question 23

Griseofulvin Uses

Answer 23

Dermatophytes (Tinea pedis) , ringworm , jock itch

Question 24

Griseofulvin CI

Answer 24

Hepatic failure , pregnancy/breastfeeding

Question 25

Allylamines

Answer 25

Fungicidal Ex: Naftifine , terbinafine (ally tifter)

Question 26

Allylamines MOA

Answer 26

inhibit squalene epoxidase ( ergosterol inhibition) = accumulation of squalene = cell death

Question 27

Allylamines Uses

Answer 27

Skin & Nail Dermatophytosis

Question 28

Antimetabolites

Answer 28

Ex: flucytosine IV

Question 29

Flucytosine MOA

Answer 29

gets converted to 5-fluorouracil by fungal cytosine deaminase which inhibits thymidylate synthetase = inhibits DNA & RNA = cell death

Question 30

Flucytosine Uses

Answer 30

Monotherapy: genitourinary candida (2nd line)
Combination Therapy : w/amphotericin for candidiasis & cryptococcal meningitis

Question 31

Flucytosine Adverse

Answer 31

BM depression , alopecia , enterocolitis , hepatitis