Antimycobacterial agents

Question 1

RIPE therapy

Answer 1

TB drugs. All associated with hepatotoxicity; should do 2 phases of treatment for TB: phase 1: 4 drugs for 2 months; phase 2: 2 drugs for 4 months.

Question 2

rifampin

Answer 2

activates CytP450 and binds DNA dependent RNA pol to inhibit RNA synthesis. Causes orange bodily secretions - i.e. urine.
Can be hepatotoxic especially in combination. Can be nephrotoxic. Can cause flu-like illness when intermittently taken.

Rapid resistance in monotherapy for TB.
Can be used for monotherapy prophylaxis in close contacts of H. influenzae and N. meningitidis patients.

Question 3

isoniazid (INH)

Answer 3

“lone ranger,” blocks production of mycolic acids at the mycobacteria cell surface. Active only against dividing cells.

INH inhibits CytP450 which causes transient increases of ALT/ liver function tests.
INH = “injury to nerves and hepatocytes” (peripheral neuropathy, seizures, hepatotoxicity)

Can be used for monotherapy in latent TB infections, but most be combined for active therapy.

Question 4

PZA (pyrazinamide)

Answer 4

“pyro tech knitter,” pro drug, converted to active form in cytoplasm. Blocks alanine synthesis which prevent Vit B6 from activating co-A. Decreased co-A = decreased ATP = cell death. Active against non-dividing and dividing organisms in contrast to INH.

Can cause hyperuricemia and gout. Hepatotoxic.

Question 5

ethambutol

Answer 5

“Ethel the horse whisperer,” blocks the transferase enzymes that add arabinose sugars to the cell wall’s lipoarabinomannan and arabinogalactin.
Bacteriostatic - does not kill directly but inhibits replication/proliferation.

Side effect: optic neuritis, red and green colorblindness

Question 6

aminoglycosides/ streptomycin

Answer 6

first anti-TB drugs; binds the 30s ribosome subunit inhibiting proper translation of the bacterium’s proteins = lethal. Resistance emerged. Also caused toxicity to cranial nerve 8 = hearing issues, balance issues.

Question 7

bedaquiline

Answer 7

binds and inhibits mycobacterial ATP synthase (preferentially over euk version- so we good), which causes mycobacterial cell death due to lack of energy and lack of ability to regulate ion concentrations.

Toxicity: prolonged QT interval, chest pain, hemoptysis, hepatitis

Question 8

clofazimine

Answer 8

highly lipophilic dye / oxidizing agent that disrupts the cell membrane in mycobacteria, pulling away e- from ETC and thus increasing antibacterial ROS. Used in combo with dapsone and rifampin for leprosy.

Can also be used for MDR Tb therapy.

Toxicity: GI upset, brownish black skin discoloration