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Antifungal drugs Flashcards

1
Q

Cutaneous mycoses - types

A
  1. tinea capitis (dermatophytoses)
  2. tinea corporis (dermatophytoses)
  3. tinea cruris (dermatophytoses)
  4. tinea pedis (dermatophytoses)
  5. tinea unguium (dermatophytoses)
  6. Tinea versicolor
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2
Q

fungal cell - erogsterol synthesis - pathway and enzymes

A

Squalene –> Squalene epoxide (Squalene epoxidase)(LANOSTEROL SYNTHESIS)
Squalene epoxide –> Lanosterol
Lanosterol –> Ergosterol (14-α-demethylase)
ertosterol –> cell membrane

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3
Q

fungal cell - cell ergosterol synthesis - pathway and enzymes - lanosterol synthesis

A

Squalene –> Squalene epoxide (Squalene epoxidase) –> Lanosterol

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4
Q

fungal cell - ergosterol synthesis - pathway and enzymes - Ergosterol synthesis

A

Lanosterol –> Ergosterol (14-α-demethylase)

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5
Q

drugs that interrupt cell ergosterol synthesis pathway in fungus (and enzymes affected)

A
  1. Terbinafine block Squalene epoxidase (Lanosterol synthesis)
  2. Azoles blocks 14-α-deamethylase (Cytochrome P-450 that converts lanesterol to ergosterol) (Ergosterol syntehsis)
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6
Q

Antifungul drugs - group according to action (not the names of the drugs)

A
  1. Lanosterol synthesis inhibitor
  2. Ergosterol synthesis inhibitor
  3. Cell wall synthesis inhibitor
  4. Nucleic acid synthesis inhibitor
  5. Membrane pores formers
  6. Griseofulvin
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7
Q

Membrane pores formers - drugs

A

polyenes

  1. Amphotericin B
  2. Nystatin
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8
Q

Membrane pores formers - drugs - and mechasnim of action

A
  1. Amphotericin B 2. Nystatin

Binds to ergosterol (unique to fungi) –> membranes pores that allow leakage of electrolytes

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9
Q

Membrane pores former drugs - harmless for host cell - why

A

Because ergosterol is UNIQUE TO FUNGI

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10
Q

Amphotericin B - clinical use

A
  1. SERIOUS SYSTEMIC MYCOTIC INFECTIONS : Histoplasmosis, Blastomycosis, Coccidioidomycosis, Mucor, Candida, Cryptococcus
  2. Naegleria Fowleri
  3. Leismania Donovani
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11
Q

Amphotericin B - meningitis

A
  • with/without flucytosine for cryptococcal meningitis

- Intrathecally for fungal meningitis

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12
Q

Amphotericin B - administrate with (and why)

A

supplement K+ and Mg2+ because of altered renal tubule permeability

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13
Q

Amphotericin B - toxicity

A
  1. fever/chills (shake and bake)
  2. Hypotenesion
  3. nephrotoxicity
  4. arrhythmias
  5. anemia
  6. IV phlebitis
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14
Q

Amphotericin B - solution of toxicity

A
  1. Hydration decreases nephrotoxicity

2. Liposomal amphotericin –> decreased toxicity

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15
Q

Nystatin - clinical use

A

TOPICAL USE ONLY (TOO TOXIC FOR SYSTEMIC USE)

  1. oral candidiasis (swish and swallow)
  2. topical for diaper rash or vaginal candidiasis
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16
Q

Antifungul drugs - Nucleic acid synthesis inhibitor

A

Flucytosine

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17
Q

Flucytosine - mechanism of action

A

Inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil by cytosine deaminase –> inhibits thymidylate synthetase

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18
Q

Flucytosine - clinical use

A

Systemic fungal infections (esp meningitis caused by Cryptococcus) in combination with amphotericin B

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19
Q

Flucytosine - toxicity

A

Bone marrow suppression

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20
Q

Antifungul drugs - Ergosterol synthesis inhibitor - drugs

A

-AZOLE

clotrimazole, fluconazole, intraconazole, ketoconazole, miconazole, voriconazole

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21
Q

azoles - mechanism of action

A

inhibit fungal stero (ergosterol) synthesis by inhibiting the cytochrome P-450 enzyme that converts lanosterol to ergosterol (14-α-demethylase)

22
Q

azoles - clinical use

A

Local and less serious systemic mycoses:

  • Fluconazole: chronic suppression of cryptococcal meningitis in AIDS patients, all types of candidal infections, LOCAL systemic mycoses
  • Intraconazole: (LOCAL systemic mycoses) Blastomyces, Coccidioides, Histoplasma
  • Clotrimazole, miconazole: topical fungal infection
23
Q

Fluconazole - clinical use

A
  • chronic suppression of cryptococcal meningitis in AIDS patients,
  • all types of candidal infections
  • LOCAL systemic mycoses
24
Q

Intraconazole - clinical use

A

(LOCAL systemic mycoses) Blastomyces, Coccidioides, Histoplasma

25
Clotrimazole, miconazole - clinical use
topical fungal infection
26
Azoles - toxicity
1. testosterone synthesis inhibition --> gynecomastia (esp ketoconazole) 2. liver dysfunction (inhibits P450)
27
fungus - Lanosterol synthesis inhibitor - drugs
Terbinafine
28
Terbinafine - mechanism of action
inhibits the fungal enzyme squalene epoxidase (Lanosterol synthesis inhibitor)
29
Terbinafine - clinical use
Dermathophytes (esp onychomycoses)
30
Terbinafine - toxicity
1. GI upset 2. headaches 3. hepatotoxicity 4. Taste disturbance
31
Antifungul drugs - Cell wall synthesis inhibitor - drugs
Echinocandins --> 1. Anidulafungin 2. caspofungin | 3. micafungin
32
Echinocandins - drugs
1. Anidulafungin 2. caspofungin 3. micafungin
33
Echinocandins - drugs and mechanism of action
Echinocandins --> 1. Anidulafungin 2. caspofungin 3. micafungin inhibit cell wall synthesis by inhibiting synthesis of β-glucan
34
Echinocandins - inhibit cell wall synthesis by inhibiting synthesis of
β-glucan
35
Echinocandins - clinical use
1. invasive aspergilosis | 2. Candida
36
Echinocandins - drugs and toxicity
Echinocandins --> 1. Anidulafungin 2. caspofungin 3. micafungin GI upset, flushing (by histamine release)
37
Griseofulvin - mechanism of action
interferes with microtubule formation --> disrupts mitosis | DEPOSITIS IN KERATIN-CONTAINING TISSUES (EG. NAILS)
38
Griseofulvin - clinical use
1. oral treatment of superficial infections | 2. inhibits growth of dermatophytes (tinea, ringworm)
39
Griseofulvin - toxicity
1. teratogenic 2. carcinogenic 3. confusion 4. headaches 5. increased cytochrome P-450 and warfarin metabolism
40
Tinea versicolor - treatment
1. topical and/oral antifungul medication | 2. selenium sulfate
41
Candida ablicans - treatment
topical azole for vagina nystatin, fluconazole or caspofungin for oral/esophageal caspofungin, fluconazole or amphotericin B for systemic
42
Mucormycosis treatment
1. surgical debridement | 2. amphotericin B
43
Pneumocystis jirevecii - Treatment/prophylaxis/start prophylaxis when
1. TMP-SMX 2. Pentamidine 3. dapsone (only prophylaxis) 4. atovaquone CD4 cound drops under 2 hundred cells/mm3 in HIV patients
44
Sporothrix schenckii - treatment
intraconazole or potassium iodide
45
terbinafine - toxicity
1. GI upset 2. headaches 3. hepatotoxicity 4. Taste disturbance
46
Echinocandins - drugs and toxicity
Echinocandins --> 1. Anidulafungin 2. caspofungin 3. micafungin GI upset, flushing (by histamine release)
47
griseofulvin - toxicity
1. teratogenic 2. carcinogenic 3. confusion 4. headaches 5. increased cytochrome P-450 and warfarin metabolism
48
invasive aspergilosis - treatment
echinocandins
49
antifungal drugs - P450
Griseofulvin --> induces | Azoles --> inhibits
50
antimycobacterial drgus - P450
Rifampin --> induces | isoniazid --> inhibits

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