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25 Cards in this Set

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First line agents: IREP
Isoniazid, rifampin, ethambutol, pyrazinamide
Isoniazid (INH)
Primary drug for TB.

MOA: inhibits synthesis of MYCOLIC ACIDS, which is needed for cell wall.

bacteriostatic for resting and -cidal for dividing organism

same extra and intra-cellular levels are similar, so kills bacteria in macrophages.
INH Pharmacology and clinical use
inactivated by acetylation which has genetic heterogencity and might influence individual sensitivities.

For tx of dz in combo

prophylaxis in PPD pos. pts.
INH adverse rxns
peripheral and central NEUROTOXICITY, hepatotoxicity, allergic rxn

INH inhibits parahydroxylation of PHENYTOIN (tox in 30% pts on both drugs).
INH bacterial resistance
INH activated by CATALASE PEROXIDASE encoded by KatG gene, in which a mutation can lead to resistance.
given in combo with INH as first line.

MOA: binds and inhibits RNA polymerase. BACTERIOCIDAL for mycobacteria. Gets into cells and kills bacteria in phagocytes.

ORANGE-RED urinary color
Rifampin: clinical use and adv. rxns
used in combo with INH and other drugs. Other uses: menigococcal dz and meningitis due to H. influeza, also endocarditis, osteomyelitis, nasopharyngeal infections.

adv rxns: jaundice, rashes, nephritis, flu-like sxs.
Rifampin: Drug Interactions
induces many hepatic enzymes: incl. Oral contraceptives, and [Protease Inhibitors] in HIV pts. Also, reduces half-lives of other drugs.

Resistance: mutation in bacterial RNA polymerase
a long-acting drug similar action to rifampin.

relatively LOW TOXICITY.

MOA: inhibits synthesis of ARABINOGALACTAN.

BACTERIOSTATIC for mycobacteria with no effect on other bacteria.
Ethambutol: pharm., adv rxns
does not cross BBB except in meningitis.

adv rxn: few side effects, mostly OPTIC NEURITIS leading to decrease visual acuity. AVOID IN CHILDREN.

resistance when used in monotherapy.
Inhibits MYCOBACTERIAL FATTY ACID SYNTHASE I gene involved in mycolic acid biosyntheis.. readily enters cells.

Contraindication in pts with severe liver dz, or GOUT.

Resistance: must be activated by PYRAZINAMIDASE, who's mutation can lead to resistance.
Use of second line agents in TB
Fluoroquinolones (levofloxacin, moxifloxacin, ofloxacin), streptomycin, ethonamide, aminosalicylic acid (PAS) and cylcoserine

Used only when:

response to first line fails
expertise avail. to deal with toxic side effects
Fluoroquinolones (levofloxacin, moxifloxacin, ofloxacin)
tx of MDR-TB
does not enter cell readily, so doesn't kill intracellular microbes.

Used only in severe cases in combo.

mech similar to INH. poorly tolerated due to gastric irritation, metallic taste and neurologic sxs.
Aminosalicylic Acid (PAS)
mech similar to sulfonamides. Bacteriostatic for mycobacterial

High conc. reaches urine, so crystalluria prevented by keeping urine alkaline.
Irreversible inhibitor of ALANINE RACEMASE, and D-Ala-D-Ala synthetase which are involved in wall synthesis

Adv rxn: CNS dysfunction, psychotic reaction (25% of pts)
Drugs for Mycobacterium Avium Complex (MAC)
MAC common in AIDS pts

Macrolides (clarithromycin or azithromycin) with ethambutol

Sometimes Rifabutin (a deriv of rifamycin) can be added. Also Clofazimine or quinolone may be added.
Rx in Tx of Hansen's Dz (Leprosy)
PB (Paucibacillary): 5 of fewer lesions w/ absence of organisms on smear.

Multibacillary (MB): 6 or more lesions with possible visualization of bacilli on smear.
Rx for PB
single dose tx with Rifampin, minocycline and ofloxacin
Rx for MB
use Dapsone +Rifampin + Clofazimine
mech same as sulfonamides (inhibits folate synthesis). Bacteriostatic.

adv. rxn: hemolysis, erythema nodosum leprosum
ACTS VERY SLOWLY, may take 50 days after therapy is started.

Mech unknown.

adv rxn: skin red discoloration
causes SEVERE BIRTH DEFECTS. Pt must be on MANDATORY use of two forms of contraceptives and MONTHLY PREGNANCY TESTS.