Pharmacology: Test 4: Mycobacterial Infection Lec 75

Front 1

First line agents: IREP

Back 1

Isoniazid, rifampin, ethambutol, pyrazinamide

Front 2

Isoniazid (INH)

Back 2

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.

Front 3

INH Pharmacology and clinical use

Back 3

inactivated by acetylation which has genetic heterogencity and might influence individual sensitivities.

For tx of dz in combo

prophylaxis in PPD pos. pts.

Front 4

INH adverse rxns

Back 4

peripheral and central NEUROTOXICITY, hepatotoxicity, allergic rxn

INH inhibits parahydroxylation of PHENYTOIN (tox in 30% pts on both drugs).

Front 5

INH bacterial resistance

Back 5

INH activated by CATALASE PEROXIDASE encoded by KatG gene, in which a mutation can lead to resistance.

Front 6

Rifampin

Back 6

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

Front 7

Rifampin: clinical use and adv. rxns

Back 7

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.

Front 8

Rifampin: Drug Interactions

Back 8

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

Front 9

Rifapentine

Back 9

a long-acting drug similar action to rifampin.

DO NOT USE IN PREGNANT WOMEN OR HIV POS PTS.

Front 10

Ethambutol

Back 10

relatively LOW TOXICITY.

MOA: inhibits synthesis of ARABINOGALACTAN.

BACTERIOSTATIC for mycobacteria with no effect on other bacteria.

Front 11

Ethambutol: pharm., adv rxns

Back 11

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.

Front 12

Pyrazinamide

Back 12

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.

Front 13

Use of second line agents in TB

Back 13

Fluoroquinolones (levofloxacin, moxifloxacin, ofloxacin), streptomycin, ethonamide, aminosalicylic acid (PAS) and cylcoserine

Used only when:

resistant
response to first line fails
expertise avail. to deal with toxic side effects

Front 14

Fluoroquinolones (levofloxacin, moxifloxacin, ofloxacin)

Back 14

tx of MDR-TB

Front 15

streptomycin

Back 15

does not enter cell readily, so doesn't kill intracellular microbes.

Used only in severe cases in combo.

Adv rxn: OTOTOXICITY, NEPHROTOXICITY

Front 16

Ethonamide

Back 16

mech similar to INH. poorly tolerated due to gastric irritation, metallic taste and neurologic sxs.

Front 17

Aminosalicylic Acid (PAS)

Back 17

mech similar to sulfonamides. Bacteriostatic for mycobacterial

High conc. reaches urine, so crystalluria prevented by keeping urine alkaline.

Front 18

Cycloserine

Back 18

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)

Front 19

Drugs for Mycobacterium Avium Complex (MAC)

Back 19

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.

Front 20

Rx in Tx of Hansen's Dz (Leprosy)

Back 20

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.

Front 21

Rx for PB

Back 21

single dose tx with Rifampin, minocycline and ofloxacin

Front 22

Rx for MB

Back 22

use Dapsone +Rifampin + Clofazimine

Front 23

Dapsone

Back 23

mech same as sulfonamides (inhibits folate synthesis). Bacteriostatic.

adv. rxn: hemolysis, erythema nodosum leprosum

Front 24

Clofazamine

Back 24

ACTS VERY SLOWLY, may take 50 days after therapy is started.

Mech unknown.

adv rxn: skin red discoloration

Front 25

Thalidomide

Back 25

causes SEVERE BIRTH DEFECTS. Pt must be on MANDATORY use of two forms of contraceptives and MONTHLY PREGNANCY TESTS.