Name Target Organism Mechanism Side effects Absortion !"cretion #esistance ANT$% T&'!#(&)OS $S -Mycobacterium tubercolosis -Other Mycobacteria - -Hepatotoxicity is a major concern -Need to rule out hepatitis viruses and liver toxins (including alcohol) - - -Common i only one drug is used #ifamin *#$+, -'road% sectrum -!hould be used in a coc"tail #henever possible in H$%- associated Mycobacterium tuberculosis inection -&ctive against dividing and semi-dormant Mycobacterium tuberculosis -'acterio($-A) -$nhibits 'N&-dependent (N& polymerase in bacterial cells by binding its beta-subunit) prevents transcription -.eatoto"icity almost never seen #hen used alone but *+,- ris" #hen used #ith $NH and .+.- ris" #ith other -/ruritis (itching) /0- rash in 12- -/ermanent orange staining3 small amount enters tears) saliva) and urine #ith staining o contacts / clothing -Se0ere immunologic reactions3 (are cause o acute renal ailure) thrombocytopenia) hemolytic anemia) thrombotic thrombocytopenia purpura (445)+ 6ach in 78+.- patients -9ood CN! penetration since it is lipophilic -6xcreted in liver0bile -/120 is induced by drug so enhanced clearance over time - Oral contraceptives) methadone) NN(4is) #ararin -:pregulates cytosolic drug- metaboli;ing en;ymes including glcuronosyl transferase that metaboli;es <idovudine (&<4) = Chloramphenicol -Can be used #ith 6aviren; (NN(4$) most N(4$ NO4 &<4 - $sonia3id *$N., -T'%secific -Mycobacterium tuberculosis $ncluded in all regimens -Can be used as monotherapy or 55'-positive persons in absence o ongoing disease (latent) -$nhibits mycolic acid synth -'acterio($-A) against actively-replicating bacteria -Not very eective against slo#ly-replicating -.eatoto"icity (lo# ris" 78+*- i used alone but ris" increases #ith age) $ncrease i underlying disease but can be used i stable -+atal heatitis i in presence o clinical hepatitis -/eriheral neuroathy- increase ris" in nutritional deiciency) H$%) renal ailure) pregnancy) breast eeding -6specially in slo#-acetylators (psych disturbances too) -Many adverse reactions are reduced by daily yrido"ine *4itamine '5, -)uus%like syndrome3 *8- patients develop &N&) .- develop lupus (stop drug) -.yersensiti0ity) monoamine (histamine0tyramine) poisoning ater cheeses and beers generali;ed lushing -9ood CN! penetration -6xcreted in urine as unchanged and acetyl orm -Need catalase3peroxidas e to transorm it to active orm -$ catalse gene absent (katG) or transport gene mutated (inhA) resistant /yra3inami de */6A, -T'%secific -'acterioSTAT$( on dormant 0 semi-dormant in >phages or in acidic casous oci -7(idal on active-replicating -NO acti0ity at alkaline8neutral . -Converted to pyra;inoic acid by deaminase #hich inhibits atty acid synthase -The most heatoto"ic) #orst at high dose .- ris" in absence o preexisting liver disease -/olyarthralgia (non-gouty) ?8- o patients @ aspirin (x -Asymtomatic hyeruricemia9 transient rash Common but not problematic -/hotosensiti0e dermatitis Occasional - -$nactivated by the liver -6xcreted by the "idney Monitoring needed in renal disease -M. bovis is resistant since its deaminase has single-base mutation !thambutol *!M', -T' : Some others -'acterioSTAT$( -$nhibits arabinosyltransferase (needed or cell #all0outer -NOT .!/ATOTO;$( @ sae to use #0liver disease -#etinobulbar neurotis #orst at high dose or renal dis - -Cleared by "idneys (dose needs adjustment or renal d) - layer arabinogalactan) -'ecrease in visual acuity -'ecrease in red-green color discrimination (Not advised in children #here vis testing cant be done unless $NH0($F resistance is "no#n0li"ely) -(utaneous reactions @ reAuire discontinuation in 8+B- Antimycobacterials !econd-line drugs 2009 Mark Tuttle Name Target Organism Mechanism Side effects Absortion !"cretion #esistance Stretomyc in (&minoglycocid e) -Formerly used as a 4C drug) no# 4C is resistant -Mainly #or"s on extracellular organisms -&cts #ell in neutral and al"aline environments can be used #ith 5<& (only #or"s at acid pH) - -NOT .!/ATO;$( -Neurotoxicity (especially CN %$$$) -Ototoxic -Circumoral parasthesias -Not used in pregnancy to avoid etal hearing loss -Dess eective at penetrating inlammatory oci so does not sterili;e inections - -Fairly common Other !econd-line 'rugs3 (:sed #hen drug resistance is a problem) 4hiaceta;one p-aminosalicylic acid (5&C&) 6thionamide and prothionamide Capreomycin %iomycin Cycloserine FluorAuinolones (levoloxacin) moniloxacin) gatiloxacin) !treptomycin (&minoglycosides) &mi"acin Eanamycin (&minoglycoside) ANT$%)!/#OS< = Need multidrug therapy -asone - -+olate inhibitor -$nflammatory reaction *!rythema nodosum lerosum, -Thalidomide (teratogenic) and steroids - - - #ifamin - - - - - - (lofa3imine - - - - - - Others - - - - - - ANT$% MYCOBACTERIUM AVIUM = in &$'!) Fe# anti-Mycobacterium tuberculosis drugs #or" -&;ythromicin/ 6MC (/ Ciproloxacin) - - - - - -Clarithromycin / 6MC / Ciproloxacin - - - - - Nucleic Acid Synthesis $nhibitors F*88G Mar" 4uttle Name Target Organism Mechanism Side effects Absortion !"cretion S&)+ONAM$-!S -!ome stimulate Rickettsia gro#th -(esistance is becoming #idespread including E. coli -9ram / and 9ram @ -Nocardia -Chlamydia -!ome proto;oa -5oor activity against anaerobes /yrimethamine%sulfonamide= -4oxoplasmosis -Malaria -5yrimethamine is a dihydroolate reductase inhibitor !ulomamide alone is NO4 recommended in any case #here systemic disease is being treated (including uncomplicated :4$s) -(educed toxicity -H days 4M5-!MI is eAuivalent to B-.8 !MI -. day 4M5-!MI - H days !MI -Folate synth inhibitor -!tructural analogue o p- aminoben;oic acid (5&C&) -$nhibits dihydropteroa te synthetase in early step o 4HF acid synthesis - -&llergies -5hotosensitivity -Nausea and diarrhea -Fever and s"in rashes) exoliative dermatitis -!teven-Johnson syndrome (7.-) @ &utoimmune #0 rashes -Crystalluria) hematuria (drugs precipitate at acid pH) -Hematopoietic reactions - Hemolytic anemia or aplastic anemia - 9ranulocytopenia) thrombocytopenia) leu"emoid (KCC L) - $n late pregnancy - Eernicterus (brain damage rom jaundice) - 5roblems in toxoplasmosis treatment Oral absorbable3 -has various hal-lie Oral non-absorbable3 -!ulasala;ine (used or ulcerative colitis) 4opical3 -!odium !ulacetamine (ophthalmic @ trachoma) -!ilver suladia;ine -%aries) usually urine T#$M!T.O/#$M Trimethorim%sulfametho"a3ole *TM/%SM6, -5rophylaxis against pneumocystis pneumonia in H$% -H days or uncomplicated :4$ (Cystitis) typically caused by E. Coli -Salmonella, Shigella, E. Coli, ibro cholera, but Auinolones are usually the irst choice -Folate synth inhibitor -'ihydroolate reductase inhibitor Occasional (4rimethoprim by itsel) -Megaloblastic anemia -9ranulocytopenia -Deu"openia -&lso has the typical side eects o !ulomamides #hen used in combination -More severe toxicity in elderly) especially #hen less good renal unction and #hen treatment periods are long -9ood absorption orally -Dipid solubility enhances its distribution ( M sulamethoxa;ole) including C!F -4M5-!M< .3B ratio reaches .3*8 in plasma -(oncentrates in rostatic and 0aginal fluids -Mainly in urine >&$NO)ON!S - -$nterere #ith 'N& gyrase and 'N& topoisomeras e $% -Nausea @ vomiting @diarrhea -!ome cause >%T inter0al rolongation -May damage gro#ing cartilage (not recommended or ppl under .N especially in long-term use) -6x+ 'onOt use or 5seudomonas in CF -4endinitis @ rare in adults) main M B8 :sually &chilles) can lead to rupture Oral administration -:pta"e $ n habited up to N8- by coadministration #ith &l and Mg-containing antacids -!ome inhibition by Ca and Fe $% administration -%ariable +luoro?uinolo ne 'erivative o nalidixic acid (#as or :4$) -6xcellent against 9ram neg -Dess activity against 9ram pos -(4$s3 may need in combination #ith C-lactam or severe pneumonia or !seudomonas -9astrointestinal inection3 Shigella, (resistance) Salmonella, E. coli, cholera, Campylobacter -CacterioC$'& D -Have post- antibiotic eect 9enitourinary systems -C-lactam resistant gonococcus (. dose) -Cystitis (#here 4M5-!MI not useul) -Complicated ascending :4$ -5rostatitis (drugs concentrate in prostate) -5elvic $nlammatory 'isease (5$') -%ariable -:rine3 Oxaloxacin) levoloxacin (iroflo"acin -Cetter against 9ram pos - - -B8- urine (& luoroAuinolone) -6specially or C. anthracis -B8- Diver orms inactive glucuronides M!T#ON$-A6O) ! *+lagil, -Obligate anaerobic bacteria (Clostridium di""icille, Gardnerella vaginallis) -NO4 Actinomyces, !roprionibacteria -&naerobic proto;oa (4richomonas) 9iardia) 6ntamoeba) -5roduces ree radicals #hich ragment 'N& -(eduction o NO* group -&ctivated by being reduced by erredoxin -&erobic bact donOt have lo# enough redox potential -No net charge at phys pH -6nters cells #ell) good bioavail -Can be given orally -%ariable