Antifungals

Question 1

The antifungal ___ is taken up thru cytosine permease >> enters cells and heads to nucleus >> inhbits RNA synthesis by blocking thymidylate synthase

Answer 1

5FC (5 fluorouracil)

Question 2

Which antifungal is used in conjuction with Amphotericin B to treat Crytpococcus?

Answer 2

5FC

(5FC and Amp B, kill the CryptoC!!)

Question 3

Cryptococcus infections can be treated by the combination of which 2 antifungals?

Answer 3

Amphotericin B and 5FC

Question 4

The primary treatment for Cryptococcal meningitis is ___ and ___

Answer 4

Amphotericin B + 5FC

(5FC + AmpB kill CryptoC)

Question 5

The use of 5FC is conc dependent because much like 5FU (used for cancer pts), it can cause ___

Name 2 other toxicities that 5FC has

Answer 5

5FC use is concentration dependent because much like 5FU (used for cancer pts), it can cause bone marrow suppression (pancytopenia)

Hepatic (elevates AST and ALT liver enzymes), and CNS toxicities

Question 6

What is the primary target of most antifungals?

Answer 6

Ergosterol!!

(real barrier between fungus and environment is the cell membrane, made of ergosterol)

Question 7

There are generally 3 classes of antifungals that all target Ergosterol. Name them

Answer 7

Polyenes: AmpB (polyene like amphoteriCENE)

Azoles: triazoles and imidazoles

Allylamines: terbanifine

Question 8

___directly binds ergosterol and forms pores in the membrane, and causes oxidative damage

Answer 8

amp B (see image below)

Question 9

Describe the function of azoles in antifungal therapy

Answer 9

Azoles: inhibit ergosterol synthesis by inhibiting 14-alpha-demethylase (CP450 enzyme, converts lanosterol to ergosterol)

Question 10

___ inhibit squalene epoxidase (blocks conversion of squalene to squalene epoxide

Answer 10

Allylamines: inhibit squalene epoxidase (blocks conversion of squalene to squalene epoxide

Question 11

Amp B can cause renal toxicity. What is the main way to mitigate this?

Answer 11

Using a lipid formulation

**

Ways in which AmpB causes nephrotoxicity: direct toxicity on the glomerulus, and effects on the renal tubule (results in elevated serum creatinine – independent predictor for mortality)

Question 12

What are the two lipid formulations of AmpB?

Answer 12

2 formulations of AmpB: AmpB lipid complex, and liposomal ampB

Question 13

Which drug is mainly used for treating dermatophyte infections?

Answer 13

Terbinafine

Question 14

Azoles are more commonly used for ___ infections

Answer 14

Azoles are more commonly used for systemic infections

Question 15

Which 3 azole drugs have imidazole rings?

Answer 15

Clotrimazole, Miconazole and Ketoconazole: have imidazole rings

Question 16

Which drug is used for oropharyngeal and vaginal candidiasis, also sometimes used for diaper dermatitis?

Miconazole is used for __ infections

___is orally absorbable but too toxic. Used only if there’s no other option

Answer 16

Clotrimazole: used for oropharyngeal and vaginal candidiasis, also sometimes used for diaper dermatitis

Miconazole: topical dermatophyte infections

Ketoconazole: orally absorbable but too toxic. Used only if there’s no other option

Question 17

Which azole is a triazole with long hydrophobic tail?(molecule can incorporate into the 14 alpha demethylase enzyme; covers Aspergillus infections (as well as other infections covered by the other azoles))

Answer 17

Itraconazole

Question 18

___ is a bistriazole; has narrow spectrum that covers Candida and Crypto; available IV and oral

Answer 18

FluConazole (fluConazole can’t stand candida and crypto)

Question 19

Which 3 drugs are the primary therapy for Aspergillus?

Answer 19

Voriconazole and Isavuconazole are the 2 main drugs for anti-Aspergillus therapy

Posaconazole also covers Aspergillus and is used for prophylaxis

**Aspergillus is a VIP so he needs three bouncers to protect him as he goes into the club**

Question 20

The presence of 1, 3 beta D glucan and Mannans is useful for the detection of which fungal spp?

Answer 20

The presence of 1, 3 beta D glucan and Mannans is useful for the detection of Candida spp (note that the glucans can also be used to detect other fungi)

Question 21

Galactomannan is used as a marker for which fungal spp?

Answer 21

Aspergillus

Question 22

Which class of drugs targets the fungal cell wall?

Answer 22

Echinocandins (as in they candindly like the cell wall of the fungus)

Question 23

Echinocandins target 3 components of the fungal cell wall, namely ___

Answer 23

Beta glucans (1,3)

Mannans

Galactomannan (so you know they work against aspergillus)

Question 24

Which 2 fungal species do echinocandins work against?

Answer 24

EchinoCANDINs: works against Candida an Aspergillus

Question 25

Which 3 drugs make up the class of Echinocandins?

Answer 25

Anidulafungin

Caspofungin

Micafungin

(A nid a dula to deliver the birth of Caspo, the cousin of Mica from the Fungin world)