Anti-mycobacerial drugs

Question 1

the following treatment is used for

Rifampin, Isoniazid, Pyrazinamide, Ethambutol (RIPE for treatment)

• What bacterium
• Define the prophylaxis

Answer 1

• Mycobacterium tuberculosis
• Isoniazid

Question 2

the following treatment is used for

More drug resistance M. tuberculosis, Azithromycin or clarithromycin + ethamutol. can add rifanbutin or ciprofloxacin.

• What bacterium
• Define the prophylaxis

Answer 2

• MAC; M. avium-intracellulare
• Azithromycin, rifabutin

Question 3

the following treatment is used for

Long term treatment w/dapsone and rifampin for tuberculoid form.

Add clofazimine for lepromatous form.

• What bacterium
• Define the prophylaxis

Answer 3

• M. leprae
• N/A

Question 4

Clincial use

Mycobacterium tuberculosis. The only agent used as a solo prophylaxis against TB.

MOA, Toxicity

Answer 4

• INH (isoniazid)
• MOA
  
  • Dec synthesis of mycolic acid. Bacterial catalase-peroxidase (encoded by KatG) needed to convert INh to active metabolite
• Toxicity: INH (injures, neurons, hepatocytes)
  
  • Neurotoxicity, hepatotoxicity. Pyridoxine (Vit B6) can prevent neurotoxicity, lupus.

Question 5

mRNA inhibitor

Clincial use

Mycobacterium tuberculosis, delays resistances to dapsone when used for leprosy.

Used for meningococcal prophylaxis and chemoprophylaxis in contacts of children with Haemophilus influenzae type B.

MOA, Toxicity

Answer 5

• Rifamycins
  
  • rifampin, rifabutin
• MOA
  
  • inhibits DNA dependent RNA polymerase
• Toxicity
  
  • Minor hepatotoxicity and drug interactions (inc P-450); orange body fluids (nonhazardous side effect).
  • Rifabutin favored over rifampin in pts w/HIV infection due to less cytochrome P-450 stimulation.

Question 6

What are Rifampin’s 4 R?

Answer 6

• RNA polymerase inhibitor
• Ramps up microsomal cytochrome P450
• Red/orange body fluids
• Rapid resistance if used alone

Rifampin ramps up cytochrome p-450 but rifabutin does not.

Question 7

Clincial use

Mycobacterium tuberculosis (starts with P)

MOA, Toxicity

Answer 7

• Pyrazinamide
• MOA:
  
  • ?, thought to acidify intracellular environment via conversion to pyrazinoic acid. Effective in acidic pH of phagolysosomes, where TB engulfed by macrophages is found.
• Toxicity
  
  • Hyperuricemia, hepatotoxicity

Question 8

Clincial use

Mycobacterium tuberculosis (starts with E)

MOA, Toxicity

Answer 8

• Ethambutol
• MOA
  
  • dec carbohydrate polymerization of mycobacteriumd cell wall by blocking arabinosyltransferase.
• Toxicity:
  
  • Optic neuropathy (red-green color blindness)