Antifungal, Antituberculosis, Herpes Flashcards
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Amphotericin B
Antifungal
MOA: Combination of the polyene with cytoplasmic sterols, mainly ergosterols, results in increased cell permeability and death of the fungi.
-does not effect synthesis of ergosterols
MOR: Alteration of sterols for decreased affinity and decreased sterol concentrations in cell membranes.
Nystatin
Antifungal
MOA: Combination of the polyene with cytoplasmic sterols, mainly ergosterols, results in increased cell permeability and death of the fungi.
-does not effect synthesis of ergosterols
MOR: Alteration of sterols for decreased affinity and decreased sterol concentrations in cell membranes.
AE: -Nephrotoxicity is the major side effect.
● Adequate hydration status may decrease toxicity.
-Idiosyncratic hypotension and arrhythmias
● Test doses
-Electrolyte disturbances
● K+ , Mg++
-Fever, chills, and rigors
Clinical use: -Systemic fungal infections
Fluconazole & voriconazole
Antifungal
Azole
MOA: inhibit ergosterol synthesis;
Fluconzaole:
Drug interactions occur
Active against candida albicans
Voriconazole:
Major drug interactions through inhibition of mammalian cytochrome p450
● This is also the case with Itraconazole
Aspergillus- active against
- Very potent inhibitor of cytochrome p450
Capsofungin
Antifungal
Class: Echinocandins
MOA: beta-(1,3)-glucan inhibitor. Beta-(1,3)-glucan is an integral part of the fungal cell wall
Terbinafine
Antifungal
AE: Liver function abnormalities, hepatitis
Isoniazid (INH)
Antituberculosis
MOA: Inhibition of synthesis of mycolic acid in cell wall
INH is a prodrug
- Catalase/peroxidase enzyme (katG) metabolizes isoniazid to active form in cell
- Strains which fail to metabolize isoniazid due to defective catalase/peroxidase are resistant to isoniazid
Metabolism:
◦ Metabolized in the liver by N-acetyl transferase. Rate of acetylation is genetically determined as an autosomal recessive trait. Does not alter therapy clinically except for weekly administration schedules.
Clinical use:
1) Treatment of latent tuberculosis (positive PPD without active disease)
2) Combination therapy for active TB at any stage
AE:
Hepatitis
◦ Can occur at any time but peak incidence is within the first 4-8 weeks. Hepatic failure can ensue and lead to death if drug is continued.
Neurotoxicity
◦ is mediated by increased excretion of pyridoxine and concomitant administration of B6 is always given when INH is used
Rifampin
Antituberculosis
MOA: Inhibits DNA dependent RNA polymerase of mycobacterial cells. Human enzyme is insensitive to effects of the drug.
(RNA-DNA polymerase= RNA reverse transcriptase)
MOR: Alteration of DNA-dependent, RNA polymerase, (rpoB).
Absorption:
◦ Excellent oral absorption; wide distribution, including CNS.
Metabolism
◦ Hepatic via cytochrome P-450 (deacylation). Induces its own increased metabolism.
AE:
Hepatotoxicity generally manifests as cholestatic changes ( increased Alk. Phos., increased bili) but can also be necroinflammatory with elevated transaminases. INH and rifampin may potentiate hepatotoxicity of the other agent.
Major major drug interactions!!!
Increased metabolism of coumarin, oral contraceptives, and phenytoin may occur. Interaction with verapamil causes marked reduction in verapamil levels.
Pyrazinamide
Antituberculosis
MOA: Inhibition of fatty acid synthesis
-prodrug
MOR: unknown
AE:
Hepatotoxicity / Hepatitis
Gout - drug can cause elevated uric acid levels causing gout
Ethambutol
Antituberculosis
MOA:
Possibly interferes with arabinosyl transferase, an enzyme that polymerizes arabinose into arabinan
MOR:
Mutations in the gene cluster but not a specific target identified
AE: Retrobulbar neuritis(optic neuritis) ◦ Usually develops as decreased acuity and change in color vision (yellow and green).
Associated with high doses.
Peripheral neuropathy can also occur.
Acyclovir
Antivirals: Herpes
MOA:
Chain termination: removal of acyclovir triphosphate addition
-Acyclovir triphosphate is present in 40-100 fold higher concentrations in HSV infected cells. The triphosphate form inhibits DNA polymerase and is incorporated into viral DNA as function as a chain terminator.
Most commonly used:
Valacyclovir
