TB drugs

Question 1

Where does TB reside?

Answer 1

In the apex of the lung and in macrophages

Question 2

Treatment of TB is with what drugs? (4)

Answer 2

RIPE: Rifampin, isonazid, pyrazinamide, ethambutol

Question 3

Do you ever give a single agent for treatment of TB?

Answer 3

Hell no!

Question 4

MOA for rifampin?

Answer 4

Inhibits bacterial DNA dependent RNA polymerase–> bacteriocidal
Think “R” for Rifampin and RNA polymerase

Question 5

ADE for rifampin?

Answer 5

Discoloration of body fluids, Hepatotoxicity (contraindicated in ppl with liver dz), CYP inhibitor (can effect drugs that treat HIV)
Think “R” for Really weird colored body fluids

Question 6

How does TB acquire resistance to rifampin?

Answer 6

Alter RNA polymerase

Question 7

MOA of isonazid?

Answer 7

Inhibits mycolic acid synthesis in MTB cell wall. Bacteriostatic for closed caseous lesions. Bacteriocidal for fast-dividing extracellular MTB
Think “I” for Isonazid and Inhibition of Micolic acid synthesis

Question 8

Distribution of isonazid?

Answer 8

Everywhere (including CSF, placenta)

Question 9

Excretion of isonazid?

Answer 9

Urine (however, you do NOT have to adjust the dose for kidney disease/renal failure)

Question 10

ADE of isonazid?

Answer 10

Peripheral neuropathy, hepatotoxicity (because isonazid is metabolized into a toxic metabolite when it is aceltylated in the liver)
Think “I’ for Isonazid and “I have tingling toes and a shitty liver”

Question 11

Drug interactions with isonazid?

Answer 11

Decreased absorption with antacids, and decreased efficacy with corticosteroids

Question 12

MOA of pyrozinamide?

Answer 12

MTB converts PZA –> pyrazinoic acid –> decreases the pH in TB’s environment –> slows growth (static/cidal is dose dependent)
Think “P” for pyrozinamide and decreased pH

Question 13

Is PZA effective against intracellular or extracellular TB?

Answer 13

intracellular (TB within macrophages)

Question 14

ADE of PZA?

Answer 14

Hepatotoxicity (increases AST), hyperuricemia –> gout, Polyarthralgia
Think “P” for hePatotoxicity, hyPeruricemia–>gout, Polyarthralgia

Question 15

MOA of ethambutol (EMB)?

Answer 15

Inhibits arabinosyl transferase, the enzyme used to attach mycolic acids to D-arabinose residues of arabinogalactan in peptidoglycan wall (only works in rapidly dividing cells)
Think “E” for Ethambutol and Enzyme arabinosyl transferase

Question 16

ADE of EMB?

Answer 16

1. Optic neuritis–> decreased visual acuity, color discrimination, visual fields
2. Hyperuricemia
   Think “E” for Eyes

Question 17

Contraindication for EMB? (Hint: this decreases absorption)

Answer 17

Antacids like Aluminum decrease the absorption of EMB

Question 18

MOA for Cycloserine?

Answer 18

Analog for D-alanine; tricks L-alanine racemase and D-alanine synthetase. It is incorporated into the cell wall and causes cell lysis
Think “C” for Cycloserine and Cell wall lysis (as a D-alanine analog)

Question 19

ADE of Cycloserine?

Answer 19

CNS problems:
1. Seizures
2. Suicidal ideation
Think “C” for Cycloserine and CNS (Ceizures, Cuicide)