Antifungals

Question 1

what layer do superficial, subcutaneous, and systemic mycoses affect

Answer 1

superficial: outermost layers of skin, nails, hair, mucous membranes
subcutaneous: dermis, subcutaneous tissue, and adjacent bone

systemic - internal organs

Question 2

antifungals that affect cell membrane permeability

Answer 2

polyenes - amphotericin B and nyostatin

azoles: ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, clotrimazole, miconazole

allylamines - terbinafine

Question 3

antifungal that blocks nucleic acid synthesis

Answer 3

flucytosine

Question 4

antifungal that disrupts microtubule function

Answer 4

Griseofulvin

Question 5

antifungal that disrupts the fungal cell wall

Answer 5

echinocandins: caspofungin

Question 6

what are the antifungal systemic drugs for subcutaneous and systemic mycoses

Answer 6

Flucytosine

Azoles: PFVIK – posaconazole, fluconazole, voriconazole, itraconazole, ketoconazole

Polyenes: amphotericin B

Echinocandins: Caspofungin

Question 7

what are the systemic antifungals for superficial mycoses

Answer 7

GAA

Griseofulvin

Allylamines: Terbinafine

Azoles: FIK – fluconazole, itraconazole, ketoconazole

Question 8

what are the topical antifungals for superficial mycoses

Answer 8

Polyenes: amphotericin B and Nystatin

Allylamines: Terbinafine

Azoles: CMK – clotrimazole, miconazole, ketoconazole

Question 9

mechanism of amphoTEARricin B

Answer 9

bind to ergosterol and TEARS a hole/form pores in cell membrane –> leakage of intracellular ions and macromolecules –> cell death

Question 10

drug of use for deep fungal infections during pregnancy

Answer 10

amphotericin B

Question 11

what phase is amphotericin B used in and why?

Answer 11

it is usually used in the induction phase to rapidly reduce fungal burden then replaced with an azole for chronic use

Question 12

conditions amphotericin B commonly used in

Answer 12

mucormycosis, cryptococcal meningitis, histoplasmosis, blastomycosis, coccidiodomycosis, extracutaneous sporotrichosis, fusariosis, and other systemic fungal infections

Question 13

what is usually given before treatment of amphotericin B

Answer 13

saline solution to keep the electrolytes balanced

Question 14

common adverse effects of amphotericin B

Answer 14

RENAL TOXICITY due to amphotericin B binding to cholesterol in mammalian cell membrane and forming pores

magnesium and potassium wasting hence why saline is given

Question 15

what steps have been taken to reduce nephrotoxicity with amphotericin B

Answer 15

formulation of lipid amphotericin B such as
Liposomal Amphotericin B (L-AMB)
Amphotericin B Lipid Complex (ABLC)
Amphotericin B Colloid Complex (ABCC)

they all decrease drug exposure to proximal tubule of the nephron

Question 16

mechanism of flucystosine

Answer 16

converted to 5-fluorouracil –> 5 fluorodeoxyuridine –> inhibits thymidylate sythetase –> blocks synthesis of

fluorouridine triphosphate also formed –> blocks protein synthesis

Question 17

what two antifungals are usually used synergistically in the induction phase

Answer 17

amphotericin B and flucystosine

Question 18

what are amphotericin B and flucytosine used synergistically to treat

Answer 18

Candida and Cryptococcus

Question 19

adverse effects of flucytosine

Answer 19

due to toxic fluorouracil –>
Bone marrow toxicity with anemia
Leukopenia
Thrombocytopenia

BLT

Question 20

what are the imidazoles

Answer 20

Clotrimazole
Miconazole
Ketoconazole

Question 21

what are the triazoles

Answer 21

F VIP
Fluconazole
Voriconazole
Itraconazole
Posaconazole

Question 22

mechanism of the azoles

Answer 22

inhibits CYP450 enzyme 14α-sterol demethylase which converts lanesterol to ergosterol which is needed for cell membrane of the fungus

Question 23

what interferes with absorption of ketoconazole

Answer 23

antacids, H2 blocker, PPI –> since they all increased pH

ketoconazole absorbed best at low pH

Question 24

adverse effects of ketoconazole

Answer 24

decreases testosterone –> gynecomastia

inhibits adrenal steroid synthesis –> decreases plasma cortisol conc

Question 25

what condition is fluconazole used in especially if amphotericin B is not available

Answer 25

cryptococcus meningitis

Question 26

effective against aspergillus

Answer 26

Voriconazole

Question 27

adverse effect of Voriconazole

Answer 27

visual disturbances including blurring and changes in color vision or brightness

Question 28

effective against Zygomycetes such as Mucor

Answer 28

Posaconazole

Question 29

what antifungal drugs is an echinocandins and what is its mechanism

Answer 29

Caspofungin --> inhibits synthesis of β(1-3)-D-glucans in the fungal cell wall --> disruption of fungal cell wall --> cell death

Question 30

use of Griseofulvin

Answer 30

only used for treatment of dermatophytosis - skin, hair, nails

Question 31

mechanism of Griseofulvin

Answer 31

interacts with microtubules of fungus to disrupt mitotic spindle and inhibit mitosis

Question 32

Griseofulvin has been replaced with what antifungals

Answer 32

Itraconazole and Terbinafine

Question 33

adverse of Griseofulvin

Answer 33

induces liver P450 enzymes --> increasing metabolism of warfarin

Question 34

mechanism of terbinafine

Answer 34

inhibits squalene epoxidase which turn squalene to lanesterol which is need to turn to ergosterol for fungal cell membrane

Question 35

mechanism of nystatin

Answer 35

structurally similar to amphotericin B and has same mechanism where it makes pores in the cell membrane --> leaky --> cell death

Question 36

what is nystatin used only to treat and what is adverse effect

Answer 36

candidiasis bitter taste in mouth

Question 37

two azoles most commonly used topically

Answer 37

clotrimazole and miconazole

Question 38

what type of microorganism is pneumocystis jirovecii

Answer 38

now recognized as a fungus but responds to antiprotozoals and not antifungals

Question 39

first line therapy for treatment of pneumocystis pneumonia

Answer 39

TMP-SMX (trimethoprim-sulfamethoxazole) aka co-trimoxazole

Question 40

what other medication can be given in combination with TMP-SMX and for what reason

Answer 40

corticosteroid preferably prednisone if P02 is less than 70

Question 41

alternative therapies for PCP

Answer 41

Clindamycin + Primaquine Dapsone + Trimethoprim Atovaquone Pentamidine CP DAP