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Antifungal Agents Flashcards

1
Q

Fungi

A

Eukaryotes
Rigid cell wall (lipid bilayer with erogosterol)

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2
Q

Antifungal targets

A

Cell wall
Cytoplasmic membrane
Nucleic acid synthesis
Nuclear division

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3
Q

Griseofulvin (heterocyclic benzofurans) MOA

A

Entry by energy-dependent transport system
Interacts with polymerized microtubules (disrupts mitotic spindles) → arrests fungal mitosis

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4
Q

Griseofulvin uses

A

Dermatophytes (ring worm)

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5
Q

Griseofulvin PK

A

Fatty food ↑ absorption
Concentrate in keratin precursor cells
Metabolized in liver

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6
Q

Adverse effects of Griseofulvin

A

Cats: leukopenia, anemia, ↑ hepatic enzyme activity and neurotoxicosis
GI disturbance, teratogenic and carcinogenic effects (high doses)

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7
Q

Polyenes (Amphotericin B)

A

Produced by Streptomyces
Most effective antifungals
Use limited by host toxicity

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8
Q

Polyenes (Amphotericin B) MOA

A

Bind to ergosterol of fungal cell mem. → leakage of cellular components → K+ efflux and hydrogen influx (fungal inhibition)
Immuomodulator

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9
Q

Amphotericin B uses

A

Aspergillosis, candidiasis, coccidiodal meningitis, pythiosis
Histoplasmosis, blastomycosis, cryptococcosis, coccidioidomysis

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10
Q

Amphotericin B formational

A

Not soluble in water
Parenteral IV prep: Lipid complexes will ↓ nephrotoxicity
Ointment or local injection

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11
Q

Amphotericin B PK

A

No oral bioavailability
Binds to cholesteral

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12
Q

Amphotericin B drug interactions

A

Synergestic action with Rifampin and 5-flucytosine

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13
Q

Amphotericin B drug interaction toxicity

A

Aminoglucoside + cyclosporin: nephrotoxicity
Digitalis: Cardiotox
Curariform: NM block
Mineralocorticoids: Hypokalemia
Thiazide diuretics: Hypokalemia and hyponatremia
Antineoplastic: cytotoxic
Amphotericin: neophrotoxic

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14
Q

Side effects of Amphotericin B

A

First: renal vasoconstriction
Second: PU, concentration defects, nephrocalcinosis acification abnormalities, renal tubular acidosis → metabolic acidosis
Precipitation of Ca in acid environment

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15
Q

Azole antifungals

A

Synthetic drugs
Safety profile more
Broad spectrum
Topical, oral and IV

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16
Q

Imidazoles

A

Affect mammal steroid synthesis
Topical: clotrimazole
Systemic: ketoconazole

17
Q

Triazoles

A

Less effect on mammal steroid synthesis, longer elimination
Itraconazlole
Second gen: voriconazole and posaconazole

18
Q

Azole MOA

A

Blocks synthesis of ergosterol and inhibits fungal cytochrome P450 enzyme
Inhibits mammalian P450 enzymes

19
Q

Azole uses

A

Dermatophytes
Candida
Yeast, nocardia, some G+ bacteria
Aspergillosis, Leishmania, Chaga’s

20
Q

Ketoconzaole PK

A

Low oral bioavailability (soluble in acid)
Distribute throughout the skin and SQ tissue
Hepatic metabolism

21
Q

Azole adverse effects

A

GI and hepatoxicities (keta in cats)
Inhibits cytochrome P450 enzyme system (metabolism of other drugs inhibited)

22
Q

Itraconazole

A

5-100x better potency than ketoconazole
Better distribution to tough tissues

23
Q

Itraconazole uses

A

Aspergillus sp.
Meningeal cryptococcosis

24
Q

Flucytosine MOA

A

Converts 5-fluorouracil in fungal cell → interferes with pyrimidine metabolism and RNA protein synthesis

25
Allylamines
Synergistic drugs: Terbinafine and naftifine More effective than griseofluvin
25
Flucytosine drug rx
Synergistic with Amphotericin and Ketoconazole Combo reduces resistance development
25
Flucytosine uses
Fungistatic Candida, crytococcus, Aspergillus Systemic fungi and dermatophytes resistant
25
Allylamines MOA
Block conversion: squalene → lanosterol
26
Allylamines uses
Fungicial against dermatophytes Fungistatic against yeast
27
Terbinafine adverse
Good tolerance Mild elevation of hepatic enzyme Won't cause drug interaction or inhibit steroid synthesis
28
Benzimidazoles
Thiabendazole Binds B-tubulin of microtubule→ develops resistance
29
Iodides
Rapid and complete oral absorption: concentrate in the thyroid Topical use for fungal rhinitis
30
Clioquinol
Antibacterial and anti-fungal properties Tx: superficial dermatophytosis + bacterial infection
31
Enilconazole
Topical Poultry hatcheries to control Aspergillus in facilities and equipment
32
Clotrimazole
Topical Otitis externa caused by Malassezia pachydermatitis
33
Miconazole
2% creamor 1% spray or lotion for tx of dermatophytosis in dogs and cats
34
Which regards to Amphotericin B, which statement is most accurate?
Nephrotoxicity is most serious side effect and is predictable and dose related
35
Which of the following statement is most accurate with respect to anti0fungals and their effect on steroid biosynthesis?
Ketoconazole is used to treat hyperadrenocorticism

.pharmocology (21 decks)

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