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Pharm 46 Sulfas, TMP, Fluoroquinolones
Terms in this set (38)
what is the basic chemistry of sulfonamides? excretion?
weakly acidic, common chemical nucleus resembling PABA
-solubility may be dec in acidic urine, resulting in precipitation-use combo of 3 separate drugs to combat this
what is the mechanism of sulfonamides?
bacteriostatic inhibitors of folic acid synthesis
-antimetabolites of PABA- competitive inhibitors of dihydropteroate synthase, or substrate for it- nonfunctional folic acid
what is the mechanism of trimethoprim?
selective inhibitor of bacterial dihydrofolate reductase that prevents formation of the active tetrahydro form of folic acid
-more sensitive to inhibition than mammalian
what is the mechanism of trimethoprim plus sulfamethoxazole (TMP-SMZ)
antimicrobial synergy from sequential blockade of folate synthesis
what are the mechanisms of resistance against the sulfonamides?
may be plasmid mediated
-dec intracellular accumulation
-inc production of PABA by bacterial
-dec in sensitivit of dihydrofolate reductase for drug
what are the uses for sulfonamides?
-G (+) and G (-), Chlamydia, Nocardia
-UTI- oral (triple sulfa, sulfisoxazole)
-ocular ifxn- topical- sulfacetamide
-burn ifxns- topical- mafenide, silver sulfadiazine
-ulcerative colitis, RA- oral - sulfasalazine
-toxoplasmosis- oral sulfadiazine plus pyrimethamine plus folinic acid
what are the uses for TMP-SMZ?
respiratory, ear, sinus ifxn by Haemophilus influenzae and Moraxella catarrhalis
-immunocompromised pt- Aeromonas hydrophila
-DOC preventing pneumocystis pneumonia
-IV for severe pneumocystis and G (-) sepsis
-alt for cholera, typhoid fever, shigellosis, methacillin resistant Listeria monocytogens
what are the toxicities of the sulfonamides?
-hypersensitivity- allergic rxn, skin rash, fever, cross allergenicity btw drugs and oral hypoglycemics, thiazides
-exfoliative dermatitis, polyarteritis nodosa, Stevens Johnson syndrome
-nausea, vomiting, diarrhea, mild hepatic dysfxn
-hematotox- rare- granulocytopenia, thrombocytopenia, aplastic anemia, hemolysis in G6PS deficient pts
-may precipitate in acidic urine- crystalluria, hematuria
what are the drug interactions of the sulfonamindes?
competition with warfarin and methotrexate for plasma protein binding transiently inc plasma levels of these drugs
-can displace bilirubin from plasma proteins, kernicterus in newborn if used in 3rd trimester
what are the toxicities of trimethoprim? TMP-SMZ? in AIDS pts?
megaloblastic anemia, leukopenia, grnaulocytopenia
-supplement w/folinic acid to ameliorate
-combo TMP-SMZ same as sulfonamides
-AIDS pts w/TMP-SMZ high incidence of fever, rashes, leukopenia, diarrhea
what is topoisomerase IV?
bacterial topoisomerase initiating decatenation, 2 daughter DNA molecules are separated at the end of replication
which 1st generation fluoroquinolone has activity against common UTI pathogens?
Against which groups of pathogens are second generation fluoroquinolones active (ciprofloxacin and ofloxacin)?
greater activity against G (-)
G (+) cocci
agents of atypical pneumonia (Mycoplasma pneumoniae, Chlamydophila pneumoniae)
Against which groups of pathogens are third generation fluoroquinolones active (levofloxacin, gemifloxacin, moxifloxacin)?
slightly less active against G (-)
greater activity against G (+) cocci (S pneumoniae, MRSA, some enterococci)
which are the newest fluoroquinolones? what is their activity?
gemifloxacin and moxifloxacin
enhanced activity against anaerobes
which generation of fluoroquinolones are commonly referred to as respiratory fluoroquinolones?
which fluoroquinolone does not have good systemic activity?
what drug can be given with fluoroquinolone to block active tubular secretion by the kidneys?
which fluoroquinolone is eliminated by hepatic metabolism in addition to elimination by the kidneys?
which fluoroquinolone is not recommended for UTIs?
what substances may interfere with absorption of fluoroquinolones?
antacids with multivalent cations
what is topoisomerase II?
responsible for negative supercoiling of dsDNA that balances the positive supercoiling of DNA replication
what is the mechanism of the fluoroquinolones?
inhibit DNA gyrase (esp in G (-)) and topoisomerase IV (esp in G(+))
block relaxation of supercoiled DNA catalyzed by DNA gyrase
inhibition of topo IV interferes with separation of replicated chromosomal DNA during cell division
Are fluoroquinolones bactericidal or bacteriostatic?
continue to inhibit growth even after plasma concentration has fallen below MIC
what are the mechanisms of resistance to fluoroquinolones?
2nd gen- Campylobacter jejuni, gonococci, G (+) cocci (MRSA), Pseudomonas aeruginosa, Serratia
-dec intracellular accumulation via efflux pumps or changes in porin structure (G -)
-changes in sensitivity of target enzymes via point mutations in Abx binding regions
what species produce efflux pumps as a means of resistance to fluoroquinolones?
what is the mechanism of resistance to fluoroquinolones in gonococci?
mutation in the fluoroquinolone resistance determining region of gyrA gene that encodes DNA gyrase
what are the clinical uses of fluoroquinolones?
GU and GI by G -
-gonococci, E coli, Klebsiella pneumoniae, C jejuni, enterobacter, P aeruginosa, Salmonella, Shigella
-respiratory tract, skin, soft tissue- effectiveness variable
-meningococcal carrier state, TB, prophylactic management of neutropenic pts
which fluoroquinolone is used for Tx Chlamydia?
ofloxacin (7d course reqd)
which fluoroquinolone is used for community acquired pneumonias?
- chlamydiae, mycoplasma, legionella
Toxicities of fluoroquinolones?
GI distress most common
-skin rashes, headache, dizziness, insomnia, abn LFTs, phototoxicity, tendinitis and tendon rupture
contraindications for fluoroquinolones? why?
preggo and kids
-may damage growing cartilage and cause arthropathy
which drugs are affected by fluoroquinolones?
may inc plasma levels of theophylline and other methylxanthines, enhancing their tox
which fluoroquinolones prolong the QTc interval?
gemifloxacin, levofloxacin, moxofloxacin
which fluoroquinolone was withdrawn from use in the US due to serious cardiotoxicity?
toxicities of sulfas
hemolysis if G6PD deficient
kernicterus in infants
displace other drugs from albumin (ie warfarin)
tox of TMP
clinical uses of TMP
combo TMP-SMZ for UTI
P jirovecii (Tx and prophylaxis)
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