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Pharmacology > Antifungals > Flashcards

Antifungals Flashcards

1
Q

what layer do superficial, subcutaneous, and systemic mycoses affect

A

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

systemic - internal organs

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2
Q

antifungals that affect cell membrane permeability

A

polyenes - amphotericin B and nyostatin

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

allylamines - terbinafine

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3
Q

antifungal that blocks nucleic acid synthesis

A

flucytosine

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4
Q

antifungal that disrupts microtubule function

A

Griseofulvin

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5
Q

antifungal that disrupts the fungal cell wall

A

echinocandins: caspofungin

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6
Q

what are the antifungal systemic drugs for subcutaneous and systemic mycoses

A

Flucytosine

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

Polyenes: amphotericin B

Echinocandins: Caspofungin

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7
Q

what are the systemic antifungals for superficial mycoses

A

GAA

Griseofulvin

Allylamines: Terbinafine

Azoles: FIK – fluconazole, itraconazole, ketoconazole

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8
Q

what are the topical antifungals for superficial mycoses

A

Polyenes: amphotericin B and Nystatin

Allylamines: Terbinafine

Azoles: CMK – clotrimazole, miconazole, ketoconazole

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9
Q

mechanism of amphoTEARricin B

A

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

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10
Q

drug of use for deep fungal infections during pregnancy

A

amphotericin B

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11
Q

what phase is amphotericin B used in and why?

A

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

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12
Q

conditions amphotericin B commonly used in

A

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

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13
Q

what is usually given before treatment of amphotericin B

A

saline solution to keep the electrolytes balanced

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14
Q

common adverse effects of amphotericin B

A

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

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15
Q

what steps have been taken to reduce nephrotoxicity with amphotericin B

A

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

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16
Q

mechanism of flucystosine

A

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

fluorouridine triphosphate also formed –> blocks protein synthesis

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17
Q

what two antifungals are usually used synergistically in the induction phase

A

amphotericin B and flucystosine

18
Q

what are amphotericin B and flucytosine used synergistically to treat

A

Candida and Cryptococcus

19
Q

adverse effects of flucytosine

A

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

BLT

20
Q

what are the imidazoles

A

Clotrimazole
Miconazole
Ketoconazole

21
Q

what are the triazoles

A 
F VIP
Fluconazole
Voriconazole
Itraconazole
Posaconazole
22
Q

mechanism of the azoles

A

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

23
Q

what interferes with absorption of ketoconazole

A

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

ketoconazole absorbed best at low pH

24
Q

adverse effects of ketoconazole

A

decreases testosterone –> gynecomastia

inhibits adrenal steroid synthesis –> decreases plasma cortisol conc

25
Q

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

A

cryptococcus meningitis

26
Q

effective against aspergillus

A

Voriconazole

27
Q

adverse effect of Voriconazole

A

visual disturbances including blurring and changes in color vision or brightness

28
Q

effective against Zygomycetes such as Mucor

A

Posaconazole

29
Q

what antifungal drugs is an echinocandins and what is its mechanism

A

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

30
Q

use of Griseofulvin

A

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

31
Q

mechanism of Griseofulvin

A

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

32
Q

Griseofulvin has been replaced with what antifungals

A

Itraconazole and Terbinafine

33
Q

adverse of Griseofulvin

A

induces liver P450 enzymes –> increasing metabolism of warfarin

34
Q

mechanism of terbinafine

A

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

35
Q

mechanism of nystatin

A

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

36
Q

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

A

candidiasis

bitter taste in mouth

37
Q

two azoles most commonly used topically

A

clotrimazole and miconazole

38
Q

what type of microorganism is pneumocystis jirovecii

A

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

39
Q

first line therapy for treatment of pneumocystis pneumonia

A

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

40
Q

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

A

corticosteroid preferably prednisone if P02 is less than 70

41
Q

alternative therapies for PCP

A

Clindamycin + Primaquine
Dapsone + Trimethoprim
Atovaquone
Pentamidine

CP DAP

Pharmacology (79 decks)

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