Test-2-Antifungal Agents Flashcards
OXAZOLADINONES: LINEZOLID
Mech of Action: The binding site of the drug in a pocket in the a site where the amino acid moiety in aminoacyl trna normally binds.
NYSTATIN
POLYENE (Cell membrane) ANTI – FUNGAL AGENT
Mechanism of Action: Increase PERMEABILITY OF MEMBRANE -> Loss of small molecules.
Uses: Only topical.
_Binds to Ergosterol to make holes in the membrane. _
*NO ANTIBACTERIAL ACTIVITY
AMPHOTERICIN B
POLYENE ANTIBIOTIC
Uses: CRYPTOCOCCAL MENINGITIS (only serious stuff) - Broad Spectrum
- FUNGAL PNEUMONIA, BONE INFECTIONS, DISSEMINATED FUNGAL INFECTIONS, FUNGAL MENINGITIS
Mech of Action: Binds to Ergosterol just like Nystatin. Works on Lysosomal Membranes
Admin: Usually IV as Oral is poorly absorbed.
Toxicities:
- ANEMIA (75%) results in a decrease in RBC proteins.
- ***RENAL (DO NOT EXCEED 4grams TOTAL): So start with low dose.
Additional Uses:
POTENTIATION OF THE ANTIFUNGAL EFFECTS OF OTHER DRUGS BY AMPHOTERICIN B - Low dose of Amp B helps to get drug A into the cell.
AZOLES
All end in “azole.”
KETOCONAZOLE
Oral antifungal agent. First line for many serious infections.
*M.O.A.: INHIBITS ERGOSTEROL SYNTHESIS
Toxicity:
*GI (N, V, D)
*LIVER
***INHIBITS CYTOCHROME P450 (PROBLEM)
ITRACONAZOLE
Similar to Ketaconazole only fewer P450 interactions, so becoming more popular.
VORICONAZOLE
Same as Ketoconazole
*LOW P450 INHIBITION (STILL PROBLEM)
*EFFECTIVE FOR ASPERGILLOSIS
FLUCONAZOLE
Can be used prophylactically, *RESISTANCE MAY BE PROBLEM.
Increases levels of other drugs (PHENYTOIN, SULFONYLUREAS, WARFARIN, CYCLOSPORIN).
AIDS PATIENTS DO NOT TOLERATE WELL.
Uses:
- CRYPTOCOCCAL MENINGITIS RELAPSE AFTER AMP B (AIDS)
GRISEOFULVIN
Mech of Action: INHIBITS FUNGAL MITOSIS
Uses:
- Dermatophytes, Ringworm (MICROSPORUM, TRICHOPHYTON, EPIDERMOPHYTON)
Absorption: *ORAL, ABSORPTION increases with FATTY MEAL
Toxicity:
- *HEADACHE
- *TERATOGENIC / CARCINOGENIC (ANIMALS)
5 - FLUOROCYTOSINE
Mech of Action: Inhibits DNA synthesis by conversion of 5 - FLUOROCYTOSINE by cutosine deaminase. Inhibits dUMP.
- A lethal synthesis occurs in a fungus, making the active drug from the pro-drug. This does not occur in humans.
Uses:
**CRYPTOCOCCUS SPECIES (used with Amp B)
****RESISTANCE: HIGH (COMBINE WITH AMP B)
Toxicity:
**SERIOUS BONE MARROW DEPRESSION
ALLYLAMINES - TERBINAFINE
M.O.A.: INHIBITS SQUALENE EPOXIDASE (SQUALENE EPOXIDE IS A NECESSARY COMPONENT OF ERGOSTEROL)
Side Effects:
*CHANGES IN TASTE PATTERNS (MAY LAST FOR WEEKS AFTER STOPPING DRUG)
GLUCAN SYNTHESIS INHIBITORS
*BLOCK CELL WALL SYNTHESIS
*INHIBIT: 1,3- β – GLUCAN SYNTHASE
Example: CASPOFUNGIN
USE: INVASIVE ASPERGILLOSIS (AMP B FAILURES)
CANDIDAL BLOODSTREAM INFECTIONS
Drug Interactions:
**GRISEOFULVIN INDUCES MICROSOMAL ENZYMES (WARFARIN decreases)
**GRIESOFULVIN INDUCES δ - AMINOLEVULINIC ACID SYNTHETASE (PORPHYRIA)
