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Derm ex2
folate inhibs/antifungals
31
Medical
Professional
12/12/2011

Additional Medical Flashcards

 


 

Cards

Term
general PK of most sulfonamides?  PD?
Definition

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

Term
sulfonamide MOA
Definition

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

Term
bacterial species that sulfonamides are good for?
Definition

G pos aerobics, stepto, pneumo, caMRSA

 

G neg aerobes and some enterococci (e. coli)

 

some protozoans

 

NOT FOR ANAEROBES, SPIROCHETES, PSEUDO, ATYPICALS

Term
amphoteracin B PK
Definition

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)

Term
what's a good sulfonamide for uncomplicated UTIs, MRSA, toxoplasmosis, and pneumo. jiroveci?
Definition

trimetoprim with sulfamethoxazole (TMP-SMX)

 

 

Term
some major adverse effects of sulfa drugs?
Definition

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

Term
fluroquinalone PK
Definition

rapid and complete GI absorption

 

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

Term
fluroquinalones MOA
Definition

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

 
 
—DNA gyrase inhibition prevents relaxation of positively supercoiled DNA
—Topoisomerase IV inhibition interferes with separation of replicated chromosomal DNA into the respective daughter cells
Term
second gen fluroquinalones
Definition

ciprofloxacin and norfloxacin

--------------------------------

-limited against strepto and entero

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

-good for atypicals (myco, ricketssia)

-MSSA

Term
3rd gen fluroquinolone
Definition

levofloxacin

--------------------------------

-better coverage against strepto and entero, and staph pneumo over 2nds

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

-good for atypicals (myco, ricketssia)

-MSSA

Term
4th gen fluroquinolone
Definition

moxifloxacin

-------------------

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

Term
risk of treating traveller's diarrhea with a fluroquinolone if it is caused by a specific e. coli strain?
Definition
hemolytic-uremic syndrome
Term
important adverse effects of fluroquinolone use?
Definition

-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

Term
amphoteracin B MOA
Definition

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

Term

amphoteracin B is most effect against/as

 

cautions?

Definition

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

Term
flucytosine PK
Definition

-oral, rapid, with good absorption

-penetrates CSF

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

Term

flucytosine MOA

Definition

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

Term
flucytosine activity and resistance
Definition

it has a narrow spectrum of activity which includes:

-crytococcus neoformans

-candida species

-molds causing chromoblastomycosis

 

**often used with amphotericin

 

Resistance:

}Loss of cytosine permease transporter
}¯cytosine deaminase or uridinephosphoribosyltransferase  activity
Term
flurocyosine toxicities
Definition

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

Term
azole antifungals facts
Definition

-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

Term
azole antifungal MOA
Definition

blocks ergosterol biosynthesis by blocking:

14-alpha sterol demethylase


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

Term
what is itraconazole the drug of choice for?
Definition
Treatment of indolent nonmeningeal infections
DOC: blastomycosis; sporotrichosis; paracoccidioidomycosis; histoplasmosis
Onychomycosis
Term
what is fluconazole the drug of choice for?
Definition
cryptococcal meningitis, prophylaxis for a BMT
Term
what is voriconazole the drug of choice for?
Definition
invasive aspergillosis
Term
fluconazole advantages
Definition
}I.V. ; oral with bioavailability >90%
}Not dependent on acidic pH for absorption
}Minimal plasma proteins binding
}Excellent penetration into CSF
}Renal elimination
}Long t½
}Does not cause endocrine dysfunction
Term
which azole has had reports of stevens-johnson's syndrome?
Definition
fluconazole
Term

echinocandin facts

 

MOA?

Definition

-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)

Term
uses for caspofungin
Definition

the echinocandin

 

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

Term

Griseofulvin

Definition

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

Term

Terbinafine

 

MOA

 

Definition

antifungal for systemic mucocutaneous infections

 

oral

 

well absorbed, but 99% protein bound

-extensive first pass hepatic metab, 40%

-------------------------

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

fungicidal

 

DERMATOPHYTE infections, onychomycosis

Term
the combination of itraconazole and simvastatin increase the risk of?
Definition
rhabdomyolysis
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