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38 Cards in this Set
- Front
- Back
What are the different anti-fungal drugs available? |
Polyenes: Amphotericin B, Nystatin Azoles: Imidazoles- Clotrimazole, miconazole; Triazoles- Itraconazole, Voriconazole, Fluconazole Echinocandins: Caspofungin Pyramidine analogue: Flucytosine Topical meds: Terbinafine, clotrimazole, miconazole |
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What is the mode of action of amphotericin B? |
Binds to ergosterol, destroying integrity of fungal cell membrane |
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How do fungi gain resistance to amphotericin B? |
- Modify ergosterol to decrease binding affinity - Decrease membrane concentration of ergosterol |
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Describe the pharmacokinetics of amphotericin B. |
A: Poor oral bioavailability, administer by IV, eye drops, intra-articular way D: Widely distributed but poor CSF entry M: Metabolised by unknown pathway E: Excreted in urine over several days (Slow excretion) |
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Give the clinical uses of amphotericin B. |
- As eye drops: To treat fungal keratitis - As intra-articular administration: to treat fungal arthritis - As intrathecal administration: To treat fungal meningitis - Used for invasive aspergillosis, systemic candidiasis and histoplasmosis |
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List the toxicity effects of amphotericin B. |
- Nephrotoxicity *** - Hypokalemia - Reduced erythropoietin production -> normochromic normocytic anaemia - Thrombophlebitis *** - Fever, chills, vomitting - Bone marrow suppression |
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What is the precaution to take note of when giving IV amphotericin B? |
- Start with small dose of 1mg/50ml dextrose first - If no adverse reaction, infuse slowly over 2-4h |
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What are the important drug interactions to take note of when using amphotericin B? |
- Digoxin. (due to hypokalemia as a result of amphotericin B) - Other nephrotoxic drugs like aminoglycosides, NSAIDs, cyclosporine |
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What is the mode of action of nystatin? |
Binds to ergosterol, forming pores in fungal cell membrane |
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What are the clinical uses of nystatin? |
CANDIDIASIS! - Oral (by gargle) - Vaginal (by pessary) |
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What is the mode of action of azoles? |
Binds to lanosin-a-demethylase, to inhibit demethylation of lanosterol to ergosterol -> affects cell wall synthesis |
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What is the spectrum of activity of itraconazole? |
Systemic fungi: Aspergillus, candida, histoplasma, blastomyces, trichophyton |
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Describe the pharmacokinetics of itraconazole. |
A: Oral route, lowest bioavailability of all the azoles, best absorbed with food D: Poor entry into CSF M: Extensive hepatic metabolism E: Urinary excretion |
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What are the clinical uses of itraconazole? |
Superficial infections: - For dermatophytosis and onychomycosis (trichophyton, epidermophyton) Subcutaneous infections: - For sporotrichosis (sporothrix schenckii) Systemic infections: - For candida, aspergillus, blastomyces, histoplasma |
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What are the toxicity effects of using itraconazole? |
- GIT disturbances - Rashes - Headache - Cardiac suppression - Hepatotoxicity |
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What are the significant drug interactions with itraconazole? |
- itself is a CYP inhibitor - Proton pump inhibitors, antacids, H2 antagonists cause decrease absorption of itraconazole |
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Describe the pharmacokinetics of voriconazole. |
A: Good oral bioavailability, can be administered by IV also D: Enters CSF well M: Extensively metabolised by liver E: Excreted in urine |
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What are the clinical uses of voriconazole? |
- Candidemia - Invasive aspergillosis |
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What are the toxicity effects of voriconazole? |
- GIT disturbances - Rash - Hepatitis - Acute transient visual disturbances (eg changes in colour perception, blur vision, photophobia) |
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What is the contraindication of using voriconazole? |
Cannot be used for pregnant women |
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What are the important drug interactions with voriconazole? |
- Itself is CYP inhibitor, avoid with use of other powerful CYP inducers |
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What are the clinical uses of fluconazole? |
- Candidemia -> IV route - Oral candidiasis -> Oral route - Cryptococcal meningitis |
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Describe the pharmacokinetics of fluconazole. |
A: Good oral bioavailability, administered by IV route also D: Widely distributed, enters CSF well M: Minimal metabolism by liver E: Excreted in urine |
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List the toxicity effects of fluconazole. |
- GIT disturbances - Rashes (Stevens-Johnson Syndrome) - Headache |
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What are the important drug interactions with fluconazole? |
It is a CYP inhibitor itself, interacts with other drugs (cause their plasma conc to rise) |
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What is the mode of action of caspofungin? |
Inhibits B-glucan synthase |
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Describe the pharmacokinetics of caspofungin. |
A: IV only due to poor oral bioavailability D: Widely distributed but cannot enter CSF M: Gradual metabolism over time E: Excreted in urine and bile |
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What are the clinical uses of caspofungin? |
- Used in invasive aspergillosis as salvage treatment if amphotericin B fails - Candidemia/candidiasis in immunocompromised patients |
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List the toxicity effects of caspofungin. |
Generally well-tolerated. - GIT disturbances (vomitting) - Fever - Rashes - Histamine-like reactions (flushing) - Thrombophlebitis |
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What are the important drug interactions with caspofungin? |
- Cyclosporine: can increase risk of hepatotoxicity - Interaction with CYP inducers reduces plasma levels of caspofungin |
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What is the mode of action of flucytosine? |
A pyrimidine analogue. 1. Converted by cytosine deaminase to form 5-fluorouracil 2. 5-fluorouracil converted to 5-fluoro-dUMP -> inhibits thymidylate synthase -> inhibits DNA synthesis 3. 5-fluoro-dUMP converted to 5-fluoro-dUTP -> inhibits RNA processing and translation |
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Describe the pharmacokinetics of flucytosine. |
A: Good oral bioavailability, only oral administration D: Widely distributed, enters CSF well E: 90% excreted renally |
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What are the clinical uses of flucytosine? |
Can be combined with amphotericin B to treat candida/cryptococcal meningitis. --> therefore dose for amphotericin B can be reduced, so reduce nephrotoxicity |
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List the toxicity effects of flucytosine. |
- Myelosuppression - Hepatotoxicity |
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What are the important drug interactions with flucytosine? |
- Use with nephrotoxic drugs (e.g. amphotericin B) - Flucytosine itself is CYP inhibitor |
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What is the mode of action of terbinafine? |
Inhibits squalene epoxidase so that squalene accumulates, which is fungicidal |
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What are the clinical uses of terbinafine? |
For dermatophytic infections. |
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What are the clinical uses of clotrimazole and miconazole? |
- Clotrimazole: For skin and vulvovaginal infections - Miconazole: For oral thrush, vulvovaginal candidiasis, tinea infections. |