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.pharmocology > Antifungal Agents > Flashcards

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
Q

Allylamines

A

Synergistic drugs: Terbinafine and naftifine
More effective than griseofluvin

25
Q

Flucytosine drug rx

A

Synergistic with Amphotericin and Ketoconazole
Combo reduces resistance development

25
Q

Flucytosine uses

A

Fungistatic
Candida, crytococcus, Aspergillus
Systemic fungi and dermatophytes resistant

25
Q

Allylamines MOA

A

Block conversion: squalene → lanosterol

26
Q

Allylamines uses

A

Fungicial against dermatophytes
Fungistatic against yeast

27
Q

Terbinafine adverse

A

Good tolerance
Mild elevation of hepatic enzyme
Won’t cause drug interaction or inhibit steroid synthesis

28
Q

Benzimidazoles

A

Thiabendazole
Binds B-tubulin of microtubule→ develops resistance

29
Q

Iodides

A

Rapid and complete oral absorption: concentrate in the thyroid
Topical use for fungal rhinitis

30
Q

Clioquinol

A

Antibacterial and anti-fungal properties
Tx: superficial dermatophytosis + bacterial infection

31
Q

Enilconazole

A

Topical
Poultry hatcheries to control Aspergillus in facilities and equipment

32
Q

Clotrimazole

A

Topical
Otitis externa caused by Malassezia pachydermatitis

33
Q

Miconazole

A

2% creamor 1% spray or lotion for tx of dermatophytosis in dogs and cats

34
Q

Which regards to Amphotericin B, which statement is most accurate?

A

Nephrotoxicity is most serious side effect and is predictable and dose related

35
Q

Which of the following statement is most accurate with respect to anti0fungals and their effect on steroid biosynthesis?

A

Ketoconazole is used to treat hyperadrenocorticism

.pharmocology (21 decks)

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