antifungal and antiprotozoal Flashcards
what can anti fungal drugs be split into? what kind of drugs are there
- For subcutaneous and systemic mycotic infections
a. Amphotericin B
b. Antimetabolites antifungals like flucytosine
c. Echinocandins
i. Caspofungin
d. Azole antifungals
i. triazoles- For cutaneous mycotic infections
a. Nystatin
b. Squalene epoxidase inhibitors
i. Terbinafine
c. Azole antifungals
Imidazoles
- For cutaneous mycotic infections
What is amphotericin B
○ A naturally occurring polyene antifungal
Produced by streptomyces nodosus
what does amphotericin do
○ Binds to ergosterol in plasma membranes of sensitive fungal cells to form pores
○ Pores disrupts membrane function
§ Allows electrolytes and small molecules to leak from the cell and resulting in cell death
what is amphotericin active against
candida albicans
cryptococcus neoformans
many strains of aspergillus
How as amphotericin B administered
topical or slow IV
why must amphotericin B coformulated with sodium deoxycholate
because they are insoluble in water, can coformulate to form liposomes
How is the CSF penetration of amphotericin B
poor CSF penetration, increases with inflammation
how is amphotericin B excreted
low level of drugs and metabolite appear in urine over a long period of time, some eliminated in bile.
What are the adverse reactions of amphotericin B
fever and chills
nephrotoxicity (most important)
- can cause renal vasoconstriction, can reduce glomerular filtration rate by more than half. Need hydrate patients adequately
hypotension, shock like fall in blood pressure
What is 5- flucytosine
○ Is a water soluble fluorinated pyrimidine analogue
What does 5-FC do
interferes with fungi DNA synthesis and protein synthesis
is 5-FC fungistatic or fungicidal
fungistatic
What is 5-FC usually paired with
amphotericin B, which allows 5-Fc to penetrate the cell
what is the pk of 5-FC
○ Well absorbed orally
○ Penetrates into CSF
○ 80% of given dose excreted unchanged in urine
Dose must be adjusted in patients with compromised renal function
What are the adverse effects of 5-FC
GI effects
Bone marrow suppression which is the most serious
hepatotoxicity
Cat C in pregnancy
What is the mechanism for echinocandins
○ Inhibits the activity of glucan synthase complex, resulting in loss of structural integrity of cell wall
what is the distribution of echinocandin
○ Undergo extensive protein binding unable to penetrate into CSF
what antifungal activity does caspofungin have
§ Good first line option for patients with invasive candidiasis including candidemia
§ Second line option for invasive aspergillosis in patients with who cannot take or failed amphotericin B
what are some adverse effets
GIT related symptoms like fever, chills, rashes, skin flushing, thrombocytopenia
What is the mechanism of triazole
○ Inhibit C-14 a-demethylase ( a CYP450 enzyme). Blocks the demethylation of lanosterol to ergosterol
○ Inhibition of ergosterol biosynthesis disrupts membrane structure and function
§ Inhibits fungal cell growth
What are the adverse effects of itraconazole and voriconazole
itraconazole associated with cardiotoxicity
voriconazole associated with neurotoxicity
What kind of resistance could happen to triazoles
○ Mutations in the C-14 a-demethylase gene that lead to decreased azole binding
○ Some strains of fungi have developed efflux pumps that pump the azole out of the cell
What are some adverse effects of triazoles
nausea, vomiting, headache, skin rashes, hepatotoxicity, Interferes with CYP450 enzymes resulting in drug drug interactions
What are the contraindications for triazoles
azoles are considered teratogenic, should be avoided in pregnancy unless benefits outweigh risk
