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mrts > C4 > Flashcards

C4 Flashcards

1
Q

Antifungal drugs?

9

A
  • Clot.RimaZol (ريما)
  • Fluconazol
  • Itraconazol
  • Voriconazol
  • Caspofungin (فنجان)
  • Flucytosin
  • Terbinafine
  • Nystatin
  • Amphotericin B
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2
Q

what about Amphotericin B?

A

Amphotericin B is a polyene Abx related to nystatin

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3
Q

Amphotericin B PharmacoKinetix?

A
  • dministered I.V. in 3 forms poorly (absorbed from G.I.T):
    1. nonlipid colloidal suspension
    2. lipid complex
    3. liposomal formulation
  • distribution: all tissues (except CNS)
  • Elimination: slow hepatic metabolism
    ( a bit in urine)
  • 1/2 life: ± weeks

-

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4
Q

Amphotericin MOA?

A
  • fungicidal
  • affect the permeability and transport
    properties of fungal membranes
  • bind to Ergosterol (cell membranes)
    –> artificial pores
  • Resistance: uncommon, occurs if membrane ergosterol level or structure decrease
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5
Q

Amphotericin B Clinical uses?

A
  • treatment of systemic mycoses
  • used for initial induction regimens before Azole
  • widest Antifungal spectrum
  • drug of choice, or codrug of choice, for most systemic infections caused by (Aspergillus, C.Albicans, Cryptococcus)
  • given by slow I.V.
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6
Q

Amphotericin Toxicity?

A

infusion related

doe limiting

Neurotoxicity

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7
Q

Amphotericin B I.V. Infusion related toxicity?

A
  • fever
  • chills
  • muscle spasms
  • vomiting
  • shock-like fall in blood pressure
  • effects can be attenuated by: slow infusion rate and premedication with antihistamines, antipyretics, glucocorticoids*
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8
Q

Amphotericin B dose limiting toxicity?

A
  • decreases the glomerular filtration rate + renal tubular acidosis (with magnesium and potassium wasting)
  • Anemia: decrease of erythropoietin formation
  • Liposomal formulations have reduced nephrotoxic effects
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9
Q

Amphotericin B Neurotoxicity toxicity?

A

Intrathecal administration –> seizures and neurologic damage

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10
Q

what about Flucytosine?

A

pyrimidine antimetabolite related to the anticancer 5-FU

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11
Q

Flucytosin PharmacoKinetix?

A
  • Bioavailability: effective orally
  • distribution: most body (also CNS)
  • Elemination: intact in the urine
    (dose must be reduced in patients with renal impairment)
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12
Q

Flucytosine MOA?

A
  • membrane permease –> accumulate the drug in fungal cells –> cytosine deaminase –> 5-FU –> inhibits thymidylate synthase
  • Resistance can occur rapidly if flucytosine is used alone
  • When 5-FC is given with amphotericin B/ itraconazole –> emergence of resistance is decreased and synergistic antifungal effects may occur
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13
Q

Flucytosine clinical uses?

A
  • antifungal spectrum of 5-FC is narrow
  • limited to the treatment in combination with amphotericin B / itraconazole
  • used against:
    1. Cryptococcus neoformans
    2. molds (for chromoblastomycosis)
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14
Q

Flucytosine Toxicity?

A
  • Prolonged high plasma LvLs:
    1. reversible bone marrow depression
    2. alopecia
    3. liver dysfunction.
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15
Q

Azole Antifungal agents?

FIV(5)

A
  • Fluconazol
  • Itraconazol
  • Voriconazol
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16
Q

Azoles MOA

A
  • inhibit ergosterol synthesis –> interfere with membrane permeability
  • resistance: with increasing use of azoles (long-term prophylaxis in immunocompromised and neutropenics)
17
Q

Azoles PharmacoKinetix?

A
  • Bioavailability: orally absorbed
  • distribution: most body tissues
  • metabolism and elimination:
  • -> Liver for Itra and Vori
  • -> kidney for Fluco (unchanged)
18
Q

Fluconazole clinical uses?

A
  • Esophageal and Oropharyngeal candidiasis and most infections by Coccidioides
  • A single oral dose usually eradicates vaginal candidiasis
  • treatment and secondary prophylaxis against cryptococcal meningitis
  • alternative drug (with amphotericin B) in active Cryptococcus neoformans
19
Q

Itraconazole clinical uses?

A
  • systemic infections caused by Blastomyces and Sporothrix
  • subcutaneous chromoblastomycosis
  • alternative agent against Aspergillus, Coccidioides, Cryptococcus
  • Esophageal candidiasis
  • used in dermatophytoses (especially onychomycosis)
20
Q

Voriconazole clinical uses?

A
  • wider spectrum than itraconazole
  • against invasive aspergillosis
  • alternative drug in candidemia
  • in AIDS patients: candidal esophagitis and stomatitis
21
Q

Azoles Toxicity?

A
  • vomiting
  • diarrhea
  • rash
  • hepatotoxicity (preexisting liver dysfunction)|
  • Voriconazole causes immediate but transient visual disturbances including blurring of vision of unknown cause in more than 30% of patients
22
Q

Echinocandins example?

A

Caspofungin

23
Q

what about Caspofungin ?

A

echinocandin

24
Q

Caspofungin pharmacoKinetix?

A
  • Bioavailability: I.V.
  • distribution: widely to the tissues
  • elimination: hepatic metabolism
  • 1/2 life: 9–12h
25
Q

Caspofungin MOA?

A
  • fungicidal

- inhibits the synthesis of beta-Glucan (cell walls)

26
Q

Caspofungin Clinical uses?

A
  • used for disseminated and mucocutaneous Candida infections
  • mucormycosis
  • used after fail to respond to amphotericin B*
27
Q

caspofungin Toxicity?

A
  • well tolerated
  • Infusion-related:
    1. headache
    2. G.I.T distress
    3. fever
    4. rash
    5. flushing (histamine release)

Combined use of echinocandins with cyclosporine may elevate liver transaminases

28
Q

Terbinafine MOA?

A
  • fungicidal

- inhibit squalene epoxidase –> accumulation of toxic levels of squalene–> interfere with ergosterol synthesis

29
Q

Terbinafine Clinical uses?

A
  • oral / topical
  • accumulates in keratin
  • effective in onychomycosis
30
Q

Terbinafine Toxicity?

A
  • G.I.T. upsets
  • rash
  • headache
  • taste disturbances
31
Q

Topical Antifungal?

A

Nystatin

32
Q

what about Nystatin?

A
  • polyene antibiotic

- used topically for superficial infections caused by C.albicans and dermatophytes

33
Q

Nystatin MOA?

A

disrupts fungal membranes by binding to ergosterol

34
Q

Nystatin MOA?

A

disrupts fungal membranes by binding to ergosterol

35
Q

Nystatin clinical uses?

A
  • topically: suppresses local Candida infections

- orally: eradicates GI fungi (if impaired defense)

35
Q

Nystatin clinical uses?

A
  • topically: suppresses local Candida infections

- orally: eradicates GI fungi (if impaired defense)

mrts (19 decks)

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