Anti-TB Drugs

Question 1

Isoniazid

Answer 1

M: effect ability to make mycolic acid, enters through passive diffusion, prodrug converted by KatG enzyme, spontaneous reaction with NAD or NADP creates a reactive adduct which inhibits mycolic acid for cell wall and DHFR for nucleic acid synthesis.
P: only active on actively growing bacilli, oral admin, 9-6 months, daily, can get inside the cells
S: specific for TB since humans don’t have mycolic acid,
C: prophylaxis and treatment of TB, give with Vitamin B6
SE: neurotoxicity bcz of less Vitamin B6, hepatotoxicity, inhibits phenytoin metabolism

Question 2

Rifampin/Rifabutin

Answer 2

M: bactericidal, block DNA dependent RNA polymerase, can get into intraceulluar organisms (abcesses)
C: treat TB, ppl with latent TB, (older ppl, isonazid resistant strain) only works on bacilli with spurts of metabolism
P: orally admin, 4 months, daily
SE: hepatotoxicity, possible drug interactions

Question 3

Ethambutol

Answer 3

M: bacteriostatic, effect ability to make arabinogalactan, usually will be used in combination with other drugs. blocks cell wall synthesis. Inhibits arabinosyl transferase.
P: Oral admin,
SE: optic neuritis so lose red/green differentiation

Question 4

Pyrazinamide

Answer 4

M: effect ability to make fatty acid precursors which messes up mycolic acid synthesis, pH reeducation, or cell membrane disruption
used in combination, pro-drug, needs to be in acidic environment, intracellular infections, activated by pyrazinamidase enzyme in bacteria
C: Only use against bacilli in acid pH for intracellular infection
SE: hepatotoxicity

Question 5

Streptomycin

Answer 5

M: block protein synthesis by binding to 30S subunit, bactericidal since causes misreading of the mRNA
P: injectable drug
SE: ototoxicity and nephrotoxicity

Question 6

Ethionamide

Answer 6

M: blocks mycolic acid synthesis but different target so no cross resitance to INH, similar to INH
SE: GI, metallic taste, neurological symptoms
P: orally available

Question 7

Capreomycin

Answer 7

M: peptide protein synthesis inhibitor
P: injectable and metabolized by live
SE:nephrotoxicity, ototoxicity

Question 8

Cycloserine

Answer 8

M: structural analog of D-alanine which inhibits cell wall synthesis by blocking D-ala incorporation
P: orally, excreted unmetabolized in the urine
SE: CNS toxicity
R: competed out by D-alanine racemase enzyme which is the other substrate

Question 9

PAS

Answer 9

M: similar mechanism to sulfonamides where blocks dihyropropertic synthase in nucleic acid synthesis
P: orally available, to keep drug from crystalizing in the urine keep it alkaline
SE: GI symptoms
R: mutation in thymidylate synthase A

Question 10

Dapsone

Answer 10

C: used to treat leprosy
M: similar to that of sulfonamides where inhibits folate synthesis. is both bacteriostatic and bactericidal
P: orally available
R: overproduce PABA or decreased sensitivity in the folate syn enzyme
SE: hemolysis develops with high doses especially with G6PD deficiency, erythema nodosum

Question 11

Clofazamine

Answer 11

M: ? binds preferentially to mycobacterial DNA and may inhibit template function of DNA
P: GI absorption, sometimes has slow absorption
C: treats leprosy
SE: GI intolerance, red discoloration of skin