pharmacology: tuberculosis drugs

the pharm lecture on the conventional treatment for TB. first a few facts: over one third of the world is exposed to TB, 90% of which are asymptomatic-- yet 50% of untreated cases are fatal. the pathognomonic signs are "rust colored sputum" and microscopically, the "red snapper" sign. the 4 drugs used in combination to treat TB are rifampin, isoniazid, pyrazinamide, and ethambutol. isoniazid, a drug activated by catalase, acts to prevent mycolic acid synthesis in the mycobacterial cell wall. side effects include rash, hepatitis, CNS effects, peripheral neuropathy (caused by deficiency of pyridoxine, the synthesis of which is blocked by isoniazid), as well as sideroblastic anemia.

the three other drugs used to treat TB: rifampin is a drug that inhibits RNA polymerase, preventing protein translation within mycobacterial cells. it is used both in TB as well as MRSA. its unique side effect is that it turns urine and tears a yellow color, and might cause fever / GI upset / rash / hepatotoxicity. pyrazinamide is a nicotinamide analog, and ethambutol works via the same mechanism as isoniazid. for a strain of TB to be labeled as "resistant", it must be resistant to at least isoniazid and rifampin. MDR-TB, or multidrug resistant tuberculosis is currently treated with a 7 drug protocol which might be modified after sensitivity testing is performed.


questions
1. how much of the world's population has been exposed to TB bacterium?
2. what percentage of people infected with TB are asymptomatic?
3. death rate for untreated TB cases?
4. pathognomonic morphological sign?
5. what are the 4 drugs used as standard treatment for TB?
6. which antibiotics are ineffective against the "resistant" strains?

isoniazid...
7. activation?X
8. mechanism?X
9. contraindicated in what patients?X
10. side effects?
11. effect on blood?
12. competes with which enzyme to produce which side effect?
13. what measures should be taken to combat [12]?

rifampin...
14. indications?
15. mechanism?
16. characteristics?
17. side effects?

misc...
18. pyrazinamide is an analog of...
19. ethambutol mechanism?
20. drugs used for TB can also be used for what other condition?

MDR-TB...
21. defined as...
22. standard CDC treatment?

answers
1. over one third.
2. 90%.
3. 50%.
4. red snapper.
5. RIPE:
rifampin
isoniazid
pyrazinamide
ethambutol
6. rifampin and isoniazid.

7. prodrug activated by catalase.
8. INH inhibits mycolic acid synthesis in cell wall.
9. liver disease due to load on the liver.
10. rash
hepatitis
CNS effects
peripheral neuropathy
11. sideroblastic anemia.
12. competes with an enzyme that produces pyridoxine, responsible for peripheral neuropathy.
13. pyridoxine supplementation.

14. tuberculosis
MRSA
n. meningitides
15. inhibits RNA polymerase which prevents protein translation.
16. causes body urine and tears to become yellow.
17. fever
GI upset / N / V
rash
hepatotoxicity

18. nicotinamide.
19. same as isoniazid.
20. leprosy.

21. TB that is resistant to at least isoniazid and rifampin.
22. 7 drug treatment: SHREZ MC
streptomycin
hydrazine
rifampin
ethambutol
pyrazinamide
moxifloxacin
cycloserine