Pharm 46 Sulfonamides, Trimethorprim, & Quinolones By Tracy-Jo

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efflux mechanisms are responsible for resistance in strains of

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M tuberculosis, S aureus, and S pneumoniae

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mutations in what gene is responsible for resistance in gonococci

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the quinolone resistance-determining region of the gyrA gene that encodes for DNA gyrase

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what organisms causing urogenital and gastrointestinal tract infections are effectively treated with fluoroquinolones

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gram -: gonococci, Ecoli, Klebsiella, campylobacter, enterobacter, psuedomonas, salmonella and shigella

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ciprofloxacin and ofloxacin are alternatives to what class of drugs for the treatment of gonorrhea

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third generation cephalosporins

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levofloxacin has activity against most organisms associated with community-aquired

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pneumonia (including chlamydiae, mycoplasma and legionella species)

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which fluoroquinolone has the widest spectrum of activity (both gram + and -, atypical pneumonia agents and some anaerobes)

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gemifloxacin and moxifloxacin

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fluoroquinolones have been used in the meningococcal carrier state in the treatment of

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TB and in the prophylactic mgmt of neutropenic pts

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what is most common side effect of fluoros

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GI distress; may cause rashes, headache, dizziness, insomnia, abn liver test, phototoxicity, tendinitis

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fluoroquinolones are contraindicated in

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pregnancy and in children (cartilage problems in developing animals)

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fluoroquinolones may increase plasma levels of_________ and other ________ enhancing their toxicity

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theophylline, methylxanthines

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what do newer fluoroquinolones prolong

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QT interval; should be avoided in pts with known QT prolongation and on certain antiarrythmic drugs

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what are the newer fluoros

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gemifloxacin, levofloxacin, moxifloxacin

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what is the prototypical oral sulfonamide

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sulfisoxazole (other signif agent: sulfadiazine)

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what is the prototypical local sulfonamide

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sulfacetamide (other signif agent: silver sulfadiazine)

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what is the prototypical combination drug

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Trimethoprim-sulfamethoxazole (TMP-SMX)

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what is prototypical folate reductase inhibitor

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Trimethoprim (other signif agent: pyrimethamine)

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what is prototypical first gen fluoroquinolone

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norfloxacin

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what is prototypical 2nd gen fluoroquinolone

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ciprofloxacin (other signif agent: ofloxacin)

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what is prototypical 3rd gen fluoroquinolone

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levofloxacin

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what is prototypical 4th gen fluoroquinolone

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moxifloxacin (other signif agent: gemifloxacin)

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Reason fluoroquinolones are contraindicated in children and pregnancy

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cartilage damage

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previously untreated UTIs respond to

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sulfisoxazole (E coli, proteus); chronic UTI use TMP-SMX

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sulfanomades are bacteriocidal or static

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static

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forms of resistance

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altered enzyme (mutations), decreased uptake, inc PABA synthesis (more substrate)

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what sulfa used for IBD

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sulfasalazine

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what sulfa usedfor salmonella and shigella

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succinylsulfathiazole

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bc of risk of sensitization, sulfas not usually applied

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topically; but in burns use mafenide acetate or silver sulfadiazine

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sulfas can be administered oral, IV or

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suppository

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sulfas can pass into

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CSF, placental barrier and breast milk

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sulfas acetylated in liver and can precipitate at neutral or acidic pH causing

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crystalluria (stone formation); newer agents less likely to cause this - sulfisoxazole and sulfamthoxazole

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elimination of sulfas is by

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glomerular filtration

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SE for sulfas

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hypersensitivity - rashes, stevens johnson; hemolytic anemia if G6PD def; kernicterus, drug potentiation - warfarin, tolbutamide, methotrexate

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sulfas contraindicated in

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newborns and infants < 2 mos as well as pregnant women; also methenamine for UTIs

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MOA for trimethoprim

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dihydrofolate reductase

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what is another folate reductase inhibitor used with sulfonamides in parasitic infections

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pyrimethamine

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trimethoprim is 20-50 times more potent than the sulfonamide, used in

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UTIs and prostatis (although fluoros preferred

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what are adverse effects of trimethoprim

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folate def -megalo, leukopenia, granulocytopenia; simult administer folinic acid

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trimethoprim most often compounded with sulfamethoxazole (co-trimoxaxole) example of

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synergistic effect - blocks folate synthesis at two steps

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TMP-SMX active against what protozoa

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PCP (mild in infants, opportunistic in AIDs)

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TMP-SMX also active against what resp infections

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H. influenzae, streptococcus pneum; alt treat for legionella (gram - bacilli)

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TMP-SMX active against what GI infections

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shigellosis, salmonella; Ecoli, proteus; chronic and recurrent UTIs - gram - enteric rods

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TMP-SMX useful in treatment of what genital infections

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gonococcal urethritis; oropharyngeal gonorrhea

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TMP-SMX usually given orally except

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IV for severe PCP in pts cant take orally

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trimethoprim concentrates in acidic millieu of

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prostatic and vaginal fluids

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both agents in TMP-SMX are excreted in the

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urine

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what are adverse effects of TMP-SMX

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skin, NV, glossitis, stomatitis; megalo, hemolytic with G6PD def

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what are drug interactions of TMP-SMX

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prolonged PT in pts on warfarin, halflife inc in phenytoin, methotrexate may rise due to displacement from albumin

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sulfonamides most useful in treating

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UTIs

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trimethoprim ______ the ratio of tetrahydrofolate to folate in the organism

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lowers

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sulfonamides potentiates the anticoagulant effect of

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warfarin and bis-hydroxycoumarin