Antimycobacterial Drugs

Question 1

Treatment: M. tuberculosis

Answer 1

Rifampin

Isoniazid

Pyrazinamide

Ethambutol

(RIPE)

Question 2

Treatment: M. leprae

(lepromatous form)

Answer 2

Long-term Dapson + Rifampin

+ Clofazimine

Question 3

Prophylaxis: M. avium-intracellulare

Answer 3

Azithromycin

Rifabutin

Question 4

Clinical use: Ethambutol

Answer 4

1. Mycobacterium tuberculosis

Question 5

Treatment: M. leprae

(tuberculoid form)

Answer 5

Long-term Dapson + Rifampin

Question 6

Clinical use: Rifamycins

Rifampin

Rifabutin

Answer 6

1. Mycobacterium tuberculosis
2. Leprosy: Delays resistance to Dapsone
3. Prophylaxis:
   
   • N. meningitidis (meningitis)
   • Haemophilus influenza type B (meningitis)
4. Rifabutin favored over Rifampin in HIV due to less P-450 stimulation (reduces protease inhibitor concentrations)

Question 7

Mechanism: Rifamycins

Rifampin

Rifabutin

Answer 7

RNA synthesis inhibitor:

Inhibit DNA-dependent RNA polymerase → inhibiting bacterial RNA synthesis

Question 8

Mechanism: Isoniazid (INH)

Answer 8

• Decrease synthesis of mycolic acids
  
  • Bacterial catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolite

Question 9

Mechanism: Pyrazinamide

Answer 9

Uncertain

Prodrug that is converted to the active compound pyrazinoic acid

Works best at acidic pH (e.g., host phagolysosomes)

Question 10

Adverse effects: Rifamycins

Rifampin

Rifabutin

Answer 10

1. Minor hepatotoxicity
2. Drug interactions (P-450 inducer)
3. Orange body fluids (nonhazardous)

Question 11

Resistance: Isoniazid

Answer 11

Mutations leading to underexpression of KatG

(encodes bacterial catalase peroxidase)

Question 12

Clinical use: Streptomycin

Answer 12

1. Mycobacterium tuberculosis (2nd line)

Question 13

Prophylaxis: M. tuberculosis

Answer 13

Isoniazid (INH)

Question 14

Adverse effects: Streptomycin

Answer 14

1. Nephrotoxicity
2. Tinnitus
3. Vertigo
4. Ataxia

Question 15

Adverse effects: Pyrazinamide

Answer 15

1. Hyperuricemia
2. Hepatotoxicity

Question 16

Adverse effects: Isoniazid

Answer 16

1. Hepatoxocity
2. P-450 inhibition (vs Rifampin)
3. Drug-induced SLE
4. Anion gap metabolic acidosis
5. Vitamin B₆ deficiency → peripheral neuropathy, sideroblastic anemia (administer with pyridoxine)

Question 17

Treatment: M. avium-intracellulare

Answer 17

More drug resistant than M. tuberculosis

Macrolide + Ethanbutol

Can add Rifabutin or Ciprofloxacin

Question 18

Clinical use: Pyrazinamide

Answer 18

1. Mycobacterium tuberculosis

Question 19

Note that Isoniazid half-lives vary based on whether the patient is a fast or slow ___.

Answer 19

Acetylator

(N-acetyltransferase)

Question 20

Mechanism: Streptomycin

Answer 20

Aminoglycoside

Interferes with 30S component of ribosome

Question 21

Resistance: Rifamycins

Rifampin

Rifabutin

Answer 21

Mutations reduce drug binding to RNA polymerase (necessary for RNA synthesis)

Monotherapy rapidly leads to resistance

Question 22

Adverse effects: Ethambutol

Answer 22

1. Optic neuropathy (red-green color blindness)

Question 23

Mechanism: Ethambutol

Answer 23

Arabinogalactan synthesis inhibitor:

Decrease carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyl transferase

Question 24

Clinical use: Isoniazid

Answer 24

1. Mycobacterium tuberculosis
2. The only agent used as solo prophylaxis to TB
3. Monotherapy for latent TB