Exam 4 - Antifungals & Antivirals & Cannabinoids Flashcards
describe how the allylamines target cell membrane synthesis or structure in fungal cells
fungicidal
inhibit squalene epoxidase which inhibits ergosterol synthesis
describe how the azoles target cell membrane synthesis or structure in fungal cells
fungistatic
inhibit ergosterol synthesis
describe how the polyenes target cell membrane synthesis or structure in fungal cells
fungicidal by binding to ergosterol
How do the pharmacokinetics of amphotericin B dictate its use? How is this compound normally formulated and how can this alter its distribution?
colloidal dispersion (oily) OR lipid-complex formulations which allows it to bind to cell membranes & lipoproteins
not absorbed from GI so IV only
distributes to CNS,eye, bone
accumulates in liver,kidney,lung
synergistic with flucytosine
why there is some selection for fungal as opposed to animal cells.
Ergosterol is on the cell membrane of fungal cells, NOT animal cells
What is the primary adverse event associated with amphotericin B use?
what form is safer?
nephrotoxicity
hypokalemia
lipid formulations are safer due to taken up by mononuclear phagocytes with lower renal accumulation
why is Amphotericin B the most toxic of the clinically useful antifungals in vetmed?
binding of mammalian cell cholesterol
PK of Fluconazole (oral)
only one excreted in urine as active drug making it useful for fungal cystitis
PK of ketoconzaole (oral)
decrease in gastric acidity reduced bioavailability
adverse endocrine effects – suppression of adrenal or gonadal steroids, lightening of hair coat coloration and hepatotoxicity in cats
Why are some azole drugs associated with drug interactions and what is the biochemical basis of this interaction?
Imidazoles & Triazoles target the fungal cytochrome P450-Cyp51p (or Erg11p) which can affect mammalian P450s
Why is griseofulvin indicated for use against dermatophytes but is dosed systemically?
inhibits fungal mitosis
distributes to keratin precursor cells of skin, hair shafts, nails
clinical concerns of griseofulvin
leukopenia/anemia in kittens
teratongenic
altered spermatogenesis
only FDA approved anti-fungal for ophthalmic use
Natamycin
What unique features of viral replication and spread are targeted by anti-viral agents?
Block viral attachment to cells/fusion inhibitors
Block uncoating of virus/anti membrane drugs
Inhibit viral DNA/RNA synthesis (nucleoside analogs)
Inhibit specific viral enzymes necessary for assembly, release, etc. (protease inhibitors)
Amantadine & Rimantadine inhibit what virus
influenza A & C
Sendai virus
