Anti-fungals Flashcards
How do fungi grow?
As single celled (yeasts) or filamentous multicellular aggregates (molds)
How do yeastlike fungi reproduce?
Budding
What does dimorphic fungi mean?
Fungi can grow as yeasts or as molds
Dimorphic fungi grow as what in host at what in room temp?
Yeast in host
Mold at room temp
Fungi that are pathogenic in humans are what?
Nonmotile and have a rigid cell well
The cell wall in pathogenic fungi are composed of what?
Chitin and polysaccharides
Fungi that are transmissible?
Ringworm of the scalp
Thrush in newborns
What are dermatomycoses?
Filamentous fungi that live on keratinized tissue
Onychomycoses?
Fungal infection of the nail
How does Tolnaftate function?
Inhibits fungal squalene epoxidase resulting in decreased ergosterol
What does ergosterol do in fungi?
Steroid in fungal cell membranes
Why does Tolnaftate not affect humans?
We use cholesterol as steroid in membranes
How does Clotrimazole work?
Inhibit CYP450 which catalyzes 14a-demethylation of lanosterol to ergosterol
How do azaleas affect humans?
They have a greater affinity for fungal CYP450s but still get humans so they can interfere with drug metabolism
Griseofulvin natural product of whaT?
Penicillium griseofulvin
How does Griseofulvin work?
Disrupts mitotic spindle by binding to polymerized microtubules to inhibit mitosis
Griseofulvin treats what?
Fungal nail infections, treatment can last a year, taken with high fat diet
Amphotericin B is amphoteric, what does that mean?
Has both acidic and basic groups
How do you give Ampho B?
IV due to poor GI absorption due to poor water solubility
How does Ampho B work?
Binding to ergosterol in membranes, pores open, ions and organic molecules leak out
How does 5-Fluorocytosine work?
Fungi convert 5-Fluorocytosine to 5-fluorouracil which is converted into 5-fluorodeoxyuridine monophosphate which inhibits thymidylate synthase
What does inhibiting thymidylate synthase do?
Inhibits DNA synthesis
In addition to DNA synthesis what else does 5-fluorouracil inhibit?
protein synthesis via incorporation into RNA in place of uracil due to van der Waals radius similarity to hydrogen
If used in humans by itself what is 5-fluorouracil used as?
Anticancer agent
Why doesn’t 5-fluorouracil harm humans?
Human cells have little or no cytosine deaminase activity
5-fluorocytosine used with what can treat systemic Candida and Cryptococcus neoformans meningitis?
Ampho B
What is 5-fluorocytosine combined with to kill resistant strains
Ampho B
How does the combo of 5-Fluorocytosine and Ampho B work?
Ampho B enhances uptake of 5-fluorocytosine
Danger of 5-fluorocytosine?
Depresses bone marrow function so don’t give to people with bone marrow depression or bad kidneys due to renal excretion
Anti fungal used for systemic infections but weaker than Ampho B?
Ketaconazole
Distinguishing point about Fluconazole?
3 nitrogen in rings
Use for Fluconazole?
Treatment of meningitis from fungi
Biggest danger of Fluconazole
Hepatotoxicity
Distinguishing feature of Itraconazole?
1:1:1:1 racemic mixture of four diastereomers
3 nitrogen rings
What do you use Itraconazole for?
Histoplasmosis
Danger of Itraconazole?
Heart failure so don’t give to cardiac patients
Liver failure
Itraconazole will interact with what other drugs?
Those metabolizes by CYP450
How do Echinocandins work?
Inhibit 1,3-B glucan synthesis in fungal cell walls via noncompetitive inhibition of 1,3-B-glucan synthase
Why do Echinocandins not harm humans?
Mammalian cells lack 1,3B-glucan synthase
Cross resistance of Echinocandins?
None
What does Echinocandins synergistic with?
Voriconazole and ampho B
