Pharm Test 3: Antifungal Drugs
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Amphtericin B, Nyastatin
Binds sterole moiety (primarily ergosterol)
Forms pores/ channels that increase membrane permeability
Causes leakage of intracellular molecules
Polyenes (Amp B, Nyastatin)
Mechanism of Resistance to Polyenes (Amp B)
Species with notable resistance?
- Bacteria replaces ergosterol w/ precursor sterols
- Candida lusitaniae
- Aspergillus nidulans
Which drug is dosed only topically to treat Candida (folds of obese patients with fungal infxns)
Amp B is used to treat
Candida, Aspergillus, Coccidoides, Rhisopus, Cryptococcus, Blastomyces, Histoplasma
Amp B: Fungistatic of Fungicidal?
Clinical roles of Amp B?
Meningitis, mucormycosis, neutropenic fever
Toxicity of AmpB (3)
- Infusion-related rxns (Worst with ABCD)
- Azotemia (Treat w/ K+, Mg2+)
- Anemia (Decreased productionof erythropoietin)
Name 4 azoles
What drugs work by inhibiting 14-a-sterole demethylase?
Azoles work by inhibiting (2 things)
14-a-sterol demethylase, impairs biosynthesis of ergosterol
Resistance to the Azoles is by accumulation of mutations in
(Protects heme in enzyme pocket from binding)
Azoles: Fungistatic or Fungicidal?
What is the spectrum of action of azoles?
Candida, Blastomyces, Histoplasma, Coccidiodes
What drug interacts with the CYP450 pathway? (not other drug friendly)
Which azole must have the stomach acidity to be absorbed?
- (If they're on an H2 antagonist or PPI, they shouldn't take itraconazole)
Itraconazole is PO only. What forms? Are these interchangeable?
Capsule and liquid, the dosing levels are different so very hard to interchange
Adverse effect of Itraconazole?
CHF (also contraindicated in pregnancy)
Tx of Cryptococcus meningitis or transplant prophylaxis?
What does Fluconazole treat?
Cryptococcus meningitis, transplant prophylaxis, candidiasis
Why is SBECD required with Voriconazole?
It is necessary for absorption of the drug
Who can't receive Voriconazole? Why?
Pts. w/ decreased renal function because SBECD (which is required for Voriconazole absorption) causes nephrotoxicity
SBECD is necessary for absorption of?
Why is Posaconazole not really clinically useful?
Very difficult to reach therapeutic levels, the drug is cleared too rapidly.
Which azole causes visual side effects/ hallucinations?
N/V/D, Hepatotoxicity, abdominal paint, QT prolongation are adverse effects of what class of drugs?
Echnocandins inhibit cell wall synthesis by inhbiting
- 1,3-B-D-glucan synthase
- (Reduces structural integrity, fungal cell wall--> osmotic instability, death)
Which class of drugs inhibits cell wall synthesis by inhibiting 1,3-B-D-glucan synthase?
Mechanism of resistance to Echnocandins is a mutation in
Fks1p (subunit of glucan synthase)
Echnocandins: Fungistatic or Fungicidal?
1) Oral bioavailability?
2) Protein bound?
3) Cleared by?
- 1) Not orally bioavailable
- 2) Highly protein bound
- 3) Hepatic clearance
Treat deeply invasive candidiasis
Don't give pts. w:
- Renal impairment- Voriconazole
- Hepatic impairment- Caspfungin
Treat deeply invasive candidiasis, esophageal candidiasis, prophylaxis HSCT
Treat candidemia, esophageal candidiasis
Which class of drugs acts on RNA and is the only antifunga that can have synergy w/ other antifungals?
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