anti fungal historical and nucleic acid synthesis inhibitors

Question 1

historically what was used to treat mucocutaneous sporotrichosis

Answer 1

Potassium Iodide

Question 2

How does KI work?
How is it administered?
Toxicity?

Answer 2

KI mechanism unknown but probably by iodination of proteins in fungal cell wall and membrane
administered orally
excreted by kidneys and low toxicity of acne, nausea, diarrhea
NOT really used!!

Question 3

what is a drug that inhibits mitosis (cell division) and is produced by Penicillin Griseofulvin?
fungistactic or cidal?
how does it work?

Answer 3

Griseofulvin- fungistatic but can be cidal in large quantities
Griseofulvin works by binding to tubulin dimers and preventing polymerization into microtubules leading to metaphase arrest

Question 4

what is Griseofulvin used for? long or short term tx?

Answer 4

Griseofulvin is used against dermatophytes, hair, nails, and skin. fungi are lost as they grow out.
USED LONG Term, better TX available today

Question 5

absorption of Griseofulvin? take with what?
Distribution?
Metabolism?
Toxicity?

Answer 5

orally poor absorption, TAKE W FATTY MEAL!
distrib: keratinocytes
Metab: liver demethylation, out in feces
Tox: low, long term can produce headaches, memory lapse, photosensitivity, porphyria,

Question 6

Griseofulvin is concerning bc it is possibly what?

Answer 6

carcinogenic and teratogenic

Question 7

what is a synthetic analog of cytosine that is static and cidal?

Answer 7

Flucytosine

Question 8

What is flucytosine effective against

Answer 8

aspergillus, candida, cryptococcus

Question 9

what is used together to treat cryptococcal meningitis?

Answer 9

flu cytosine with amphotericin B

also combine with azoles to treat pts w AIDS

Question 10

Flucytosine is a prodrug what does this mean

Answer 10

must be changed to its active form inside the cell

Question 11

MoA of flucytosine

Answer 11

inhibition of RNA/ DNA synthesis

Question 12

why is their a selective action of flucytosine

Answer 12

bc humans have low level of cytosine deaminase which is responsible for changing flucytosine into its active form of 5-FU

Question 13

Flucytosine
absorption:
cross into CNS?
metabolism/ excretion:
toxicitity:
warning about drug?

Answer 13

flucytosine
well absorbed orally, crosses into CNS
not metabolized, excreted in urine
toxicity: BONE MARROW DEPRESSION, neutropenia, thrombocytopenia
BE careful to monitor pts with renal deficiency and AIDS pts on AZT

Question 14

what can flucytosine cause?

Answer 14

BONE MARROW DEPRESSION!
Thrombocytopenia
and neutropenia

Question 15

describe the drug resistance of flucytosine

Answer 15

drug resistance is high due to transport alterations, cytosine deaminase alterations, and alteration of anabolic enzymes

Question 16

what is the synergy component of flucytosine

Answer 16

use flucytosine with amphotericin B and inc accumulation of 5-FC through membrane holes created by amphotericin B

Question 17

Basic summary of flucytosine

Answer 17

narrow spectrum, good pharmacokinetics, INC resistance and high side effects need close monitoring