C-2 : Antimycobacterials

Question 1

Microbiology of Mycobacteria

Answer 1

Slow growing aerobic, non-motile rods with resistant lipid rich wall They are facultative intracellular pathogens that can remain dormant

Question 2

Anti tuberculosis Drug Distribution Considerations:

Answer 2

in younger well vascularized, cellular granulomas, anti TB drugs must enter the interstitium and penetrate immune cells to enter phagolysosomes where bacteria are in necrotic granulomas, drugs must diffuse through the caseated material to reach extracellular pathogens

Question 3

First line agents anti TB (names)

Answer 3

RIPE regimen - Rifampin (RA), isoniazid (INH), pyrazinamide (PZA) and ethambutol (ETB)

Question 4

First line agents anti TB dosage

Answer 4

give all 4 for first 2 months then just RA and INH for 4 more months after that (RI of the RIPE)

Question 5

Isoniazid MOA

Answer 5

active metabolites block mycolic acid synthesis via enzyme/carrier protein inhibition

bactericidal in actively growing microbes, -static in dormant

mycobacterium specific catalsae G enzymes create active metabolites within the micobes

Question 6

isoniazid kinetics

Answer 6

prodrug given orally

distributes well even in cns and granulomas

metabolized in the liver by acetylation + eliminated in urine

Question 7

isoniazid side effects

Answer 7

Hepatotoxic - worse w/ alcohol or rapid acetylators

Peripheral neuropathy - parestesias (sometimes cns effects: headache, memory loss, seizure)

• via b6 deficiency caused by INH-pyridoxine binding
• worse in slow acetylators + reversible with b6 supplementation muscle

muscle cramps, fever, rash

Drug induced Lupus, anion- gap acidoses and CYP 450 inh

Question 8

Rifampin MOA

Answer 8

Inhibits RNA poylemerase

bactericidal effect, especially dormant microbes with a long post antibiotic effect

Question 9

Rifampin

Spectrum

Answer 9

m ost Mycobacteria (incl. leprae) plus N. meningitidis and H. flu (as prophylactic monotherapy), and Pox viruses

Good for highly resistant Staph endocarditis/osteomyelitis with ciprofloxacin

Question 10

Rifampicin

kinetics

Answer 10

Good oral absorption + distribution (phagocytes, abcess/cavity, csf)

accelerates its own hepatic metabolism (CYP inducer, incl 3A4)

hepatic and renal elimination

Question 11

Rifampin

Side effects

Answer 11

Hepatotoxic- increases ezymes, rarely hepatitis

Orange discoloration - urine, sweat, tears

(rare neuro issues)

Question 12

pyrazinamide

MOA

Answer 12

forms pyrazinoic acid in microbe membrane/metabolism disruption

has a bactericidal effect esp in dormant mycobacteria

Question 13

Pyrazinamide

Spectrum

Answer 13

Only for M.tuberculosis

good sybstitute for INH in case of resistance

Question 14

Pyramidazine kinetics

Answer 14

Good oral absorption and good distribution (penetrates BBB)

liver metabolism and urine excretion

Question 15

Pyramidazine side effects

Answer 15

Hepatotoxicity - as severe as liver necrosis

Hyperuricemia - can precipitate gout attacks; but rifampin decreases uric acid

Question 16

Ethambutol moa

Answer 16

inhibits arabinogalactan formation by blocking arabinosyl transferases has a bacteriostatic effect

Question 17

Ethambutol spectrum

Answer 17

M. tuberculosis, kanasii and some avium

Question 18

Ethambutol kinetics

Answer 18

Good oral absorption but decreased by alcohol and macrophage penetration CNS

excreted unchanged in urine

Question 19

Ethambutol Side effects

Answer 19

Retrobulbar neuritis - decreases visual acuity, red-green color blindness and scotomas (check vision monthly)

rarely nausea, joint pain, headache and allergy

Question 20

Streptomycin

Answer 20

ripes?

-first line anti TB drug but not part of the classic combination