Primary "First Line" TB drug

Use: TB prophylaxis; Latent TB (alone); Active TB (w/ rifampin, ethambutol and pyrazinamide)

Mechanism: inhibits biosynthesis of mycolic acid; prodrug that requires KatG; can reach intracellular bacillia; bactericidal if actively growing, bacteristatic in latent or dormant infections

Mech of Resistance: mutations in katG, inhA or ndh; develops quickly when given alone. 

Adverse rxn: Hepatitis (must monitor monthly), CNS stim, peripheral neuritis (pyridoxine aka B12 antagonizes), hemolysis; lupus like syndrom

PHK: oral, metabolism (acetylation) inactivates drug (rapid vs slow metabolizer problem)

Tox: liver damage

Primary "First line" Anti TB dx

Use: Latent TB (alone); Active TB (w/ Isoniazide, ethambutol and pyrazinamide); almost as effective as Isoniazid; leprosy, N. meningitidis (meningitis only), inhibits growth of most G+ cocci and some G- microbes (e.coli, pseudomonas, proteus, klebsiella), chlamydia, pox virus

Mechanism: inhibits DNA dependent RNA polymerase (rpoB subunit)

Mech of Resistance: rpoB mutation

Adverse rxn: orange urine, sweat, tears, contact lenses;  induces P450 system (dx interactions in HIV pts! Rifabutin used here); decreases effectiveness of oral contraceptives

PHK: oral, distrubutes throughout the body (CSF included); eliminated through bile; 

Primary "First line" anti Tb dx

Use: Active TB (w/ isonizid, rifampin and pyrazinamide)

Mechanism: inhibits arabinosyl transferases (embCAB) involved in the synthesis of arabinogalactan (AG); bacteriostatic

Mech of Resistance: embCAB mutation

Adverse rxn: relatively low Tox; decreased visual acuity and loss of green-red perception suggesting retrobulbar neuritis; numbness, joint pain, peripheral neuritis, renal insufficiency, allergy, GI distress

PHK: oral, 50% unchanged appears in urine, also found in feces

Primary "First line" anti TB dx

Use: Active TB (w/ isoniazide, rifampin and ethambutol); bacteriostatic and bacteriocidal but greates activity against dormant organisms; reduced therapy to current standarad of 6 months!

Mechanism: unknown; active at acidic pH

Mech of Resistance: pncA mutation (converts pyrazinamide to active pyraxinoic acid)

Adverse rxn: hepatic dysfunction, hyperuricemia, non gouty polyarthralgia, myalgia, GI irritation, porphyria, photosensitivity

PHK: oral, 

Primary "First line" anti TB

Use: Primary M. avium complex prophylaxis in HIV pts (instead of clarithromycin and azithromycin); Rifampin alternative in TB (fewer dx interactions

Mechanism: inhibits DNA-dependent RNA polymerase

Spectrum: M. avium-intracellulare, M. tuberculosis, M. leprae. G+ and G- organisms

Secondary anti TB dx

Tox: anorexia, nausea, diarrhea, epigastric pain, PUD, hemorrhage, kidney/liver damage, thyroid injury, drug fever, joint pain, skin rasehs, granulocytopenia, neuro problems

Secondary anti TB dx

Tox: GI irritation, neuro complications

Secondary anti TB dx

Tox: ?

Secondary anti TB dx

Tox: Kidney damage, nitrogen retention, 8th nerve damage, deafness and vestibular distrubances

Secondary anti TB Dx

Tox: 

Secondary anti TB dx

Tox: 

Other drugs: Levofloxacin (Levaquin) Ofloxacin (Floxin)

Secondary anti TB dx

Tox: 

Leprosy Dx

Mechanism: similar to sulfonamides, interference with M. leprae nutrition (folic acid)

Adverse Rxn: nasal obstruction for 3-6 months: Dose related hemolysis, nausea vomiting, headache, dizziness, methemoglobinemia, leukopenia, agranulocytosis, allergic dermatitis, exfoliative dermatitis, liver damage, fever, peripheral neuritis

PHK: Oral, GI absorption is almost complete and rapid; excretion is slow

Leprosy Dx; phenazine dye

Use: anti-leprosy and antiinflammatory

Mechanism: Bactericidal against M. tuberculosis and M. marinum, slowly bactericidal against M. leprae

Adverse Rxn: GI, hepatitis, crystaline deposits, skin discoloration

PHK: slowley and incompletely absorbed in GI, 30 days to reach steady state

Leprosy Dx

Use: moderate to severe ENL (erythema nodosum leprosum); increases LBM in AIDS pts w/ wasting; reactional lepramatous leprosy

Mechanism: unknown BUT reduces levels of tumor necrosis factor alpha (TNF-a) by accelerating the degradation of TNF-a mRNA

Adverse Rxn: human teratogenesis; most heavily regulated dx in US; drowsiness, somnolence, peripheralneuropathy, constipation, rash immune complex mediated rxn (presents as multiple erythematous tender nodules

PHK: Oral, slowly absorbed