Antifungal Therapy Flashcards

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1
Q

Amphotericin B

mechanism

A

Amphotericin “tears” holes

  • binds ergosterol
  • forms membrane pores
  • allows leakage of electrolytes
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2
Q

Amphotericin B

clinical use

A
  • serious, systemic mycoses
  • Cryptococcus
  • Blastomyces
  • Coccidioides
  • Histoplasma
  • Candida
  • Mucor
  • intrathecally for fungal meningitis
  • supplement K+ & M2+(altered renal tubule permeability)
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3
Q

Amphotericin B

toxicity

A
  • fever/chills (“shake & bake”)
  • hypotension
  • nephrotoxicity
  • arrhythmias
  • anemia
  • IV phlebitis
  • hydration decreases nephrotoxicity
  • liposomal amphotericin decreases toxicity
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4
Q

Nystatin

mechanism

A
  • same as amphotericin B
  • topical form
  • too toxic for systemic use
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5
Q

Nystatin

clinical use

A
  • “swish & swallow” for oral candidiasis (thrush)
  • topical for diaper rash or vaginal candidiasis
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6
Q

Azoles

A
  • fluconazole
  • ketoconazole
  • clotrimazole
  • miconazole
  • itraconazole
  • voriconazole
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7
Q

Azoles

mechanism

A
  • inhibit fungal sterol (ergosterol) synthesis
  • inhibit CYP450 enzyme that converts lanosterol to ergosterol
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8
Q

Azoles

clinical use

A
  • local & less serious systemic mycoses
  • fluconazole - chronic suppression of cryptococcal meningitis in AIDS patients & candidal infections of all types
  • itraconazole - Blastomyces, Coccidioides, Histoplasma
  • clotrimazole & miconazole - topical fungal infections
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9
Q

Azoles

toxicity

A
  • testosterone synthesis inhibition
    • gynecomastia (ketoconazole)
  • liver dysfunction
    • inhibits CYP450
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10
Q

Flucytosine

mechanism

A
  • inhibits DNA & RNA biosynthesis
  • conversion to 5-FU by cytosine deaminase
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11
Q

Flucytosine

clinical use

toxicity

A
  • systemic fungal infections
  • combination w/ amphotericin B
  • bone marrow suppression
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12
Q

Echinocandins

A
  • caspofungin
  • micafungin
  • anidulafungin
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13
Q

Echinocandins

mechanism

A

inhibits cell wall synthesis

inhibits synthesis of ß-glucan

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14
Q

Echinocandins

clinical use

toxicity

A
  • invasive aspergillosis, Candida
  • GI upset, flushing (histamine release)
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15
Q

Terbinafine

mechanism

A

inhibits the fungal enzyme squalene epoxidase

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16
Q

Terbinafine

clinical use

toxicity

A
  • dermatophytoses
  • GI upset, headaches, hepatotoxicity, taste disturbance
17
Q

Griseofulvin

mechanism

A
  • interferes w/ MT function
  • disrupts mitosis
  • deposits in keratin-containing tissues (nails)
18
Q

Griseofulvin

clinical use

A
  • oral treatment of superficial infections
  • inhibits growth of dermatophytes
    • tinea, ringworm
19
Q

Griseofulvin

toxicity

A
  • teratogenic
  • carcinogenic
  • confusion
  • headaches
  • increased P450 & warfarin metabolism
20
Q

Antiprotozoan therapy

  • Toxoplasmosis
  • Trypanosoma brucei
  • T. cruzi
  • Leishmaniasis
A
  • Toxoplasmosis
    • pyrimethamine
  • Trypanosoma brucei
    • suramin
    • melarsoprol
  • T. cruzi
    • nifurtimox
  • Leishmaniasis
    • sodium stibogluconate
21
Q

Chloroquine

mechanism

A
  • blocks detoxification of heme into hemozoin
  • heme accumulates & is toxic to plasmodia
22
Q

Chloroquine

clinical use

A
  • **treatment of plasmodial species other than P. falciparum **
  • resistance due to membrane pump (decreases intracellular conc of drug)
  • treat P. falciparum w/ artemether/lumefantrine or atovaquone/proguanil
  • life threatening malaria: quinidine
23
Q

Chloroquine

toxicity

A
  • retinopathy
  • pruritis (esp dark skinned individuals)
24
Q

antihelminthic therapy

A
  • mebendazole, pyrantel pamoate, ivermectin, diethylcarbamazine, praziquantel (immobilize helminths)
  • flukes (schistosoma): praziquantal