many are rapid and they distribute in body water of all tissues

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many are hepatically metabolized to an innactive metabolite via acetylation, but renally excreted unchanged

they are folate inhibitors and do so by being an analog of PABA, which is vital to the folate synthesis pathway.

Nearly all sulfonamides compete with dihydropteroate synthase which is ONLY present in bacteria, and this competition prevents changing PABA to dihydrofolic acid

later down the chain, trimethoprim is capable of inhibiting DHFR which reduces dihydrofolic which is necessary to make components for DNA synthesis

all components alone are bacteriostatic, but together they are bacteriocidal

G pos aerobics, stepto, pneumo, caMRSA

G neg aerobes and some enterococci (e. coli)

some protozoans

NOT FOR ANAEROBES, SPIROCHETES, PSEUDO, ATYPICALS

an antifungal which is adminstered IV or IT

wide distribution in kidney, spleen, liver and lung

biphasic so can have relatively short to extremely long 1/2 life (up to 15 days)

trimetoprim with sulfamethoxazole (TMP-SMX)

hemolytic anemia, especially in patients with G6PD.  Important to note prior to prescribing

Kernicteris which is the displacement of bilirubin from albumin sites which can potentially lead to encephalopathy

sulfa drugs are contraindicated in children younger than 2 years and for women who are nursing

rapid and complete GI absorption

the majority are renally excreted, therefore, dosing interval needs to be increased for patients with renal impairment

they inhibit DNA gyrase and topoisomerase

-does so by forming a DNA ternary complex when DNA separates and inhibits resealing resulting in breakage

**resistance to this bacteria would likely be conferred by bacterial chromosome mutations to the topoisomerase IV and gyrase genes

ciprofloxacin and norfloxacin

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-limited against strepto and entero

-good for G neg and pseudo (cipro is best)

-good for atypicals (myco, ricketssia)

-MSSA

moxifloxacin

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essentially same as 2nd and 3rd, but i with reduced efficacy against G neg compared to CIPRO

-hypersensitivity rxns

-tendon rupture when used with steroids

-abnormal glucose regulation

-increased QTc interval (especially when used with macrolides)

-when used with theophylline, the plasma conc. of theophylline can be increased by cipro and become toxic -->> leads to siezure bc of competition at CYP1A2

associates with ergosterol in the cell wall of a fungus.  creates a pore so that molecules and ions can leak out

**there may be some binding of the drug to the cholesterol of human cells

a broad spectrum anti-fungal against many of the opportunistic fungi and systemic fungi

major toxicity is a concern (nephro is the biggie), so the infections it is used for have to be severe (ie. crytococcal meningitis in an AIDS patient)

***can cause anemia due to supression of erythropoietin

-oral, rapid, with good absorption

-penetrates CSF

-renal elimination unchanged, therefore, be  careful if there is renal impairment

fungal cells take up cytosine deaminase.  this converts flucytosine (a pyramidine analog) to 5-FU which is a toxic chemotherapeutic agent

further down the line, 5-FU makes other molecules which can effectively block DNA and RNA synthesis when its by products get incorperated into growing strands

it has a narrow spectrum of activity which includes:

-crytococcus neoformans

-candida species

-molds causing chromoblastomycosis

**often used with amphotericin

Resistance:

has a narrow therapeutic window

-bone marrow supression of all lineages (can even be irreversible)

-increase in hepatic transferases leading to toxicity (can be reversible)

-toxicities may be enhanced when used with amphotericin due to its effects on renal function

theses are all do 5-FU being produced.  even though only microorganisms have cytosine deaminase, our normal flora have it and 5-FU will get into the system little by little

-high prevalance of drug interactions (since they are substrates and powerful inhibitors of CYP3A4)

-all are hepatically eliminated except one=fluconazole; interactions are fewer and it is renally eliminated

blocks ergosterol biosynthesis by blocking:

14-alpha sterol demethylase

through blocking the conversion of lanosterol to ergosterol, membrane-bound protein's functions are affected

echinocandin facts

MOA?

-IV only

-heavily plasma protein-bound

-poor pentration to CSF

-lack of renal clearance of active drug

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inhibits synthesis of B-1,3-D-glucan on cell well - destroys cell wall (narrow spectrum, just for candida and aspergillus)

the echinocandin

used for candida infection and aspergillus infections which have proven to be refractory to treatments by voriconazole and amphotericin

Griseofulvin

antifungal for systemic mucocutaneous infections

poor oral bioavailabilty, extensively metabolized through oxidative hepatic

deposits in keratin cells and makes them resistent to fungal infections

-binds to tubulin thus inhibiting fungal mitosis

-fungistatic

TINEA infections, dermatophytoses

Terbinafine

MOA

antifungal for systemic mucocutaneous infections

oral

well absorbed, but 99% protein bound

-extensive first pass hepatic metab, 40%

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works through inhibiting fungal sqalene epoxidase (needed in sterol biosynthesis).  squalene accumulates which is toxic

fungicidal

DERMATOPHYTE infections, onychomycosis