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Antimycobacterials First-line drugs 2009 Mark TuttleName Target

OrganismMechanism 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#heneverpossible in H$%-associatedMycobacteriumtuberculosisinection

-&ctive against dividing andsemi-dormantMycobacterium

tuberculosis-'acterio($-A)-$nhibits 'N&-dependentN& polymerase inbacterial cells by binding itsbeta-subunit preventstranscription

-.eatoto"icityalmost never seen #hen usedalone but *+, ris" #hen used #ith $NH and .+.ris" #ith other

-/ruritis (itching) /0- rash in 12-/ermanent orange staining3 small amountenters tears saliva and urine #ith staining ocontacts / clothing

-Seere immunologic reactions3 are cause oacute renal ailure thrombocytopenia hemolyticanemia thrombotic thrombocytopenia purpura(445)+

6ach in 78+. patients

-9ood CN!penetrationsince it is

lipophilic

-6xcreted in liver0bile-/10isinducedby drug soenhanced clearance over

time- Oral contraceptives

methadone NN4is#ararin

-:pregulates cytosolic drug-metaboli;ing en;ymesincluding glcuronosyltransferasethat

metaboli;es phages or in acidiccasousoci

-7(idalon active-replicating-NO actiity atalkaline8neutral .

-Converted to pyra;inoicacid by deaminase#hichinhibits 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 hyeruricemia transient rashCommon but not problematic

-/hotosensitie dermatitisOccasional

- - $nactivated by the liver-6xcreted by the "idneyMonitoring needed in renaldisease

-M. bovisis resistantsince its deaminasehas single-basemutation

!thambutol*!M',

-T' : Someothers -'acterioSTAT$(-$nhibits

arabinosyltransferase(needed or cell #all0outer

-NOT .!/ATOTO;$(@ sae to use #0liverdisease

-#etinobulbar neurotis#orst at high dose orrenal dis

- -Cleared by "idneys (doseneeds adjustment or renal

d)

-

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layer arabinogalactan) -'ecrease in visual acuity-'ecrease in red-green color discrimination(Not advised in children #here vis testing cant bedone unless $NH0$F resistance is "no#n0li"ely)

-(utaneous reactions@ reAuire discontinuation in8+B

Antimycobacterials !econd-line drugs 2009 Mark TuttleName Target Organism Mechanism Side effects Absortion !"cretion #esistance

Stretomyc

in(&minoglycocide)

-Formerly used as a 4

drug no# 4 is resistant-Mainly #or"s onextracellular organisms

-&cts #ell in neutral and

al"aline environmentscan be used #ith 5

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Nucleic Acid Synthesis $nhibitors *88G Mar" 4uttleName Target Organism Mechanism Side effects Absortion !"cretion

S&)+ONAM$-!S

-!ome stimulateRickettsiagro#th

-esistance isbecoming#idespreadincluding E. coli

-9ram / and 9ram @-Nocardia-Chlamydia-!ome proto;oa-5oor activity against anaerobes/yrimethamine%sulfonamide=-4oxoplasmosis-Malaria-5yrimethamine is a dihydroolate reductaseinhibitor

!ulomamide alone is NO4 recommended in anycase #here systemic disease is being treated

(including uncomplicated :4$s)-educed toxicity

- days 4M5-!MI is eAuivalent to B-.8 !MI-. day 4M5-!MI - days !MI

-Folate synthinhibitor

-!tructuralanalogue op-aminoben;oicacid (5&&)

-$nhibitsdihydropteroate synthetasein early stepo 4HF acid

synthesis-

-&llergies-5hotosensitivity-Nausea and diarrhea-Fever and s"in rashes exoliativedermatitis

-!teven-Johnson syndrome (7.) @&utoimmune #0 rashes

-Crystalluria hematuria (drugs precipitate atacid pH)

-Hematopoietic reactions- Hemolytic anemia or aplastic anemia- 9ranulocytopenia thrombocytopenia

leu"emoid (KC L)- $n late pregnancy

- Eernicterus (brain damage romjaundice)

- 5roblems in toxoplasmosistreatment

Oral absorbable3-has various hal-lieOral non-absorbable3-!ulasala;ine(used or ulcerative colitis)

4opical3-!odium !ulacetamine(ophthalmic @ trachoma)

-!ilver suladia;ine

-%aries usuallyurine

T#$M!T.O/#$M Trimethorim%sulfametho"a3ole *TM/%SM6,-5rophylaxis against pneumocystis pneumonia inH$%

- days or uncomplicated :4$ (Cystitis) typicallycaused by E. Coli

-Salmonella, Shigella, E. Coli, ibro cholera, butAuinolones are usually the irst choice

-Folate synth

inhibitor-'ihydroolate

reductaseinhibitor

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 itsdistribution

( sulamethoxa;ole)including C!F

-4M5-!M< .3B ratio reaches.3*8 in plasma

-(oncentrates in rostatic

and aginal fluids

-Mainly in urine

>&$NO)ON!S - -$nterere #ith'N& gyraseand 'N&topoisomerase $%

-Nausea @ vomiting @diarrhea

-!ome cause >%T interal rolongation-May damage gro#ing cartilage (notrecommended or ppl under . especiallyin long-term use)

-6x+ 'ont use or 5seudomonas in CF-4endinitis @ rare in adults main B8:sually &chilles can lead to rupture

Oral administration

-:pta"e $ n habited up to 8by coadministration #ith &land Mg-containing antacids

-!ome inhibition by Ca and Fe$% administration

-%ariable

+luoro?uinolone'erivative onalidixic acid(#as or :4$)

-6xcellent against 9ram neg-Dess activity against 9ram pos-4$s3 may need in combination #ith -lactam orsevere pneumonia or !seudomonas

-9astrointestinal inection3 Shigella, (resistance)Salmonella, E. coli, cholera, Campylobacter

-acterioC$'&D

-Have post-antibiotic

eect

9enitourinary systems--lactam resistant gonococcus (. dose)-Cystitis (#here 4M5-!MI not useul)-Complicated ascending :4$

-5rostatitis (drugs concentrate in prostate)-5elvic $nlammatory 'isease (5$')

-%ariable-:rine3Oxaloxacinlevoloxacin

(iroflo"acin -etter against 9ram pos - - -B8 urine

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(& luoroAuinolone) -6specially or C. anthracis -B8 Diver ormsinactiveglucuronides

M!T#ON$-A6O)!*+lagil,

-Obligate anaerobic bacteria (Clostridium di""icille,Gardnerella vaginallis)

-NO4Actinomyces, !roprionibacteria-&naerobic proto;oa (4richomonas 9iardia6ntamoeba)

-5roduces reeradicals #hichragment 'N&

-eduction oNO*group

-&ctivated by being reduced by erredoxin-&erobic bact dont have lo# enough redoxpotential

-No net charge at phys pH-6nters cells #ell goodbioavail

-Can be given orally

-%ariable