2. Antimycobacterial drugs

Question 1

1st line Tuberculosis treatment

Answer 1

**“RIPE” - “4 FOR 2 AND 2 FOR 4”

R**
ifampin
Isoniazide
Pyrazinamide
Ethambutol

Question 2

Rifampin

Answer 2

• rifampin activated CYP P450
• rifampin bind to bacterial DNA dependent RNA polymerase deactivates it - this is where resistance will develop if used alone.
• Rifampin prophylactic monotherapy in close contacts of H. FLU and N. Meningitides
• Hepatotoxic in RIPE therapy
• Rifampin may produce orange body fluids

Question 3

Isoniazide

Answer 3

• INH inhibits cytochrome P450
• primary TB (often presents as middle lobe cavity)
• INH can be used alone to treat latent TB infections
• administration of INH and pyridoxine (vitB6) prevents peripheral neuropathy

-INH is activated by catalase-peroxidase (KatG)
(tail makes a G Shape)

• resistance to INH by downregulating KatG
• INH works at the bacterial cell wall inhibiting mycolic acid production

Question 4

Isoniazide

side effects

Answer 4

• INH promotes excretion of Vit B6 causing peripheral Neuropathy is caused by a Vit B6 deficiency
• INH may cause seizures
• hepatotoxicity associated with all RIPE therapy drugs
• INH causes an asymptomatic rise in aminotransferases
• INH may cause drug induced lupus
• INH may cause anion gap metabolic acidosis
• INH metabolized by the liver enzyme N acetyltransferase – slow acetylators have higher risk of side effects

Question 5

Ethambutol

Answer 5

• blocks arabinosyl transferase, inhibiting carbohydrate formation at the cell wall
• ethambutol is bacteriostatic
• optic neuritis (red -green blindness)

Question 6

Pyrazinamide

Answer 6

• moa same as Isoniazide
• pyrazinamide may cause hyperuricemia and needle shaped uric acid crystal formation

Yell ball on toe: pyrazinamide may precipitate gout attacks

• can be hepatotoxic

Question 7

2nd line treatment

Answer 7

**“C-PEARL” (F)

C**
ycloserine

• *P**as ( para amino salicylic acid)
• *E**thionamide
• *A**mikacin
• *R**ifabutin
• *L**inezolid

Fluoroquinolones

Question 8

Mycobacterium avium treatment

Answer 8

• a macrolide (azithromycin or clarithromycin) combined with ethambutol for MAC infections
• MAC is a common cause of disseminated disease in AIDS patients
• macrolide prophylaxis for MAC when CD4 <50

-Rifabutin
(may be added as a third agent to combat MAC infections)

• rifampin and rifabutin activate CYP450

Question 9

Mycobacterium Leprae - LEPROSY

Answer 9

Dapsone
Rifampin
Clofazamine
——————————————————————————-
- agranulocytosis

• hemolytic anemia in G6PD deficiency
• bite cells and Heinz bodies seen in RBC’s
• leonine facies seen in lepromatous leprosy