ID 18 Flashcards
Sulfonamides
Sulfamethoxazole
Sulfisoxazole
Sulfadiazine
Dihydropteroate synthase action
PABA + Pteridine –> Dihydropteroic acid
dihyrofolate reductase action
Dihydrofolic acid –> tetrahydrofolic acid
sulfonamide MOA
Inhibit dihyropteroate synthase
sulfonamide uses
nocardia
chlmaydia
nephrotoxic mechanism of sulfonamides
tubulointerstitial nephritis
sulfonamide MOA of resistance
1) Altered enzyme (bacterial dihydropteroate synthase)
2) decrease uptake
3) Increase PABA synthesis
Dapsone mechanism
similar to sulfonamides but structurally distinct; inhibits dihydropteroate synthase
trimethoprim MOA
Inhibits bacterial dihydrofolate reductase.
trimethoprim uses
1) UTIs
2) shigella
3) salmonella
4) pneumocystis jirovecii
5) pneumonia treatment and prophylaxis
6) toxoplasmosis prophylaxis
TMP AE’s
1) megaloblastic anemia
2) leukopenia
3) granulocytopenia
fluoroquinolone mechanism
inhibit topo II and IV
topo II
DNA gyrase
fluoroquinolones AE’s
1) GI upset
2) superinfection
3) skin rashes
4) headache
5) dizziness
6) leg cramps and myalgia
7) QT prolongation
fluoroquinolone contraindications
pregnant or nursing
kids under 18
patients taking prednisone
tendonitis or tendon rupture in people over 60
fluoroquinolone resistance AE
1) *chromosome encoded mutation in DNA gyrate
2) plasmid-mediated resistance
3) efflux pumps
daptomycin mechanism/structure
lipopeptide that disrupts cell membrane
daptomycin use
S aureus skin infections (especially MRSA)
bacteremia
endocarditis
VRE
caveat about daptomycin
can’t use it for pneumonia because it binds to and is inactivated by surfactant.
disulfiram-like reaction presentation
severe flushing
tachycardia
hypotension
metronidazole uses
Guardia Entamoeba Trichomonas Gardnerella vaginalis Anaerobes (bactericides, C diff)
other drug that can be used as prophylaxis for m avium
rifabutin
m avium treatment
azithromycin or clarithromycin + ethambutol. Can add rifabutin or ciprofloxacin
Structure of mycobacterial cell
FA 179
Rifamycins
Rifampin
Rifabutin
rifampin/rifabutin MOA
inhibit DNA-dependent RNA polymerase
Why is rifampin used for leprosy?
Delays resistance to dapsone
Why is rifabutin used in patients with HIV infection rather than rifampin?
less CYP-450 stimulation
MOA of resistance to rifampin?
Mutations reduce drug binding to RNA polymerase.
enzyme required to activate isoniazid…
catalase peroxidase (encoded by KatG)
acetylation point with isoniazid
different INH half-lives in fast vs slow acetylators
treatment for latent TB?
INH can be used as monotherapy
isoniazid MOA of resistance
mutations leading to under expression of KatG
pyrazinamide caveats
1) prodrug (active compound = pyrazinoic acid)
2) works best at acidic pH (eg, in host phagolysosomes)
2nd line for TB?
streptomycin
streptomycin AE’s
Tinnitus
Vertigo
Ataxia
Nephrotoxicity
strep viridan’s prophylaxis
amoxicillin
Prophylaxis of strep pharyngitis in child with prior rheumatic fever
Benzathine penicillin G or oral penicillin V
Drugs covering MRSA
Vancomycin Daptomycin Linezolid Tigecycline Ceftaroline
Drugs covering VRE
Linezolid
streptogramins (quinupristin, dalfopristin)
Drugs for multidrug-resistant P aeruginosa or acinetobacter baumannii?
polymyxins B and E (colistin)
Squalene epoxidase action
squalene –> squalene epoxide
14 alpha-demethylase action
lanosterol –> ergosterol
caveat about administering amphotericin
Need to supplement K and Mg because of altered renal tubule permeability.
amphotericin AE’s
1) fever/chills
2) hypotension
3) nephrotoxicity
4) arrhythmias
5) anemia
6) IV phlebitis
How do you decrease toxicity of amphotericin?
Hydration
Liposomal amphotericin
nystatin caveat
can only be used topically since too toxic
flucytosine MOA
Inhibits DNA and RNA biosynthesis by conversion to 5-FU by cytosine deaminase.
azole mechanism
Inhibit ergosterol synthesis by inhibiting CYP450 enzyme that converts lanoserol to ergosterol.
Fluconazole use..
Chronic suppression of cryptococcal meningitis in AIDS patients and candidal infections.
Azoles for use in topical fungal infections?
Clotrimazole
Miconazole
azoles and CYP450?
Inhibit
terbinafine AE’s
GI upset
headaches
hepatotoxic
taste disturbance
echinocandins AE’s
GI upset + flushing (histamine release)
colistin
Polymyxin E
polymyxins
o Coded character: Polly Nichols, as a DJ having a dance party in her kitchen: she’s pouring laundry detergent over everyone/MOA: bind to gram-negative bacterial cell membrane phospholipids and destroy the membrane by acting like a detergent. Monsterous green Ozed/used to treat severe gram-negative infections that are resistant to less toxic antimicrobials, such as multi-drug resistant pseudomonas meningitis. Her arms and legs are ice cubes + giraffe in the corner + she has stag antlers on her head (nystagmus code) + motorcycle goggles on/toxicity = numbness of the extremities + nephrotoxicity + nystagmus + blurred vision. J. Cole rapping to the left of Polly/colistin is polymixin E. Huge Giorgio armanii in left corner/also use for multidrug-resistant Acinetobacter baumannii.
o Location: Nichol’s kitchen
pyrimethamine MOA and usage
1) t gondii
2) inhibits dihydrofolate reductase
