Test-2-Anti-TB Agents

Question 1

ISONIAZID

Answer 1

Mech of Action: Binds to NADH and inhibits ability to break down H2O2 AND decreaes **Mycolic Acid (cell wall synthesis)

Induces a lag of growth that lasts longer than exposure - > Don’t have to treat every day, results in compliance issues.

Only drug used prophylactically.

RESISTANT MUTANTS READILY SELECTED
2 - 3 WEEKS:

• **CATALASE – PEROXIDASE MUTATION
• *MYCOLIC ACID BIOSYNTHESIS IS ALTERED (LESS INHIBITION)

Absorbed well, but **INACTIVATED BY METABOLISM (acetylation) (said this twice). - > _slow and fast (__INUIT (ALASKA), __JAPANESE - ASIANS)__acetylators in the population. _

• Slow Acetylators: *PYRIDOXINE DEFICIENCY (B6)

Toxicity:

**HEPATIC TOXICITY: ~1% Hepatitis.

*LIVER FUNCTION TESTS SHOULD BE MONITORED (ESP. IN CHILDREN) IF ALSO TAKING RIFAMPIN.

Question 2

ETHAMBUTOL

Answer 2

Mech of Action: INHIBITS ARABINOSYL TRANSFERASE (CELL WALL INHIBITOR).

TB only, NO ANTIBACTERIAL ACTION.

Toxicity:

*RETROBULBAR NEURITIS – HIGH DOSES. LOSS OF VISUAL ACUITY,_ RED - GREEN COLOR BLINDNESS_

Question 3

RIFAMPIN

Answer 3

Mech of Action: Inhibits DNA-dependent RNA polymerase (**BLOCKS INITIATION OF RNA SYNTHESIS)

*NEVER USE ALONE – RESISTANCE DEVELOPS

**NO EFFECT ON MAMMALIAN DNA-DEPENDENT RNA POLYMERASE

USES:
**SYSTEMIC TB
**TB MENINGITIS
**ERADICATION OF MENINGOCOCCAL CARRIER STATE (prophylaxis)

TOXICITY ( VERY LOW):
***HEPATITIS (RARE): 1 DEATH / 30,000
**ORANGE STAIN (ONLY NUISANCE)
**FLU - LIKE SYMPTOMS

*POTENT INDUCER OF LIVER MICROSOMAL ENZYMES (decreases half life of *ORAL CONTRACEPTIVES)

*RESISTANCE:
MUTATION IN RNA POLYMERASE

Question 4

PYRAZINAMIDE

Answer 4

TOXICITY:
*HEPATIC – CHECK LIVER FUNCTION (**TOXICITY TOLERABLE FOR SHORT DURATIONS)

Question 5

CYCLOSERINE

Answer 5

Toxicities:

*PERIPHERAL NEUROPATHY
*CENTRAL NERVOUS SYSTEM DYSFUNCTION

*GRAND MAL / PETIT MAL CONVULSIONS

Treatment:

GIVE WITH PYRIDOXINE (B6), (AMELIORATES NEUROLOGIC TOXICITY)

Question 6

ETHIONAMIDE

Answer 6

*GI PROBLEMS

*MENTAL DEPRESSION

*NEUROLOGICAL: BLURRED VISION, DIPLOPIA,

DIZZINESS, PARESTHESIAS, HEADACHE

Question 7

AMINOSALICYLIC ACID (PAS)

Answer 7

***GI PROBLEMS

*HYPERSENSITIVITY

***COMPLIANCE due to the GI problems.

*MECHANISM OF ACTION:
INHIBITS COUPLING ENZYME – FOLIC ACID synthesis

Question 8

ANTI - LEPROSY - DAPSONE (SULFONE)

Answer 8

Mech of action: INHIBIT FOLIC ACID SYNTHESIS – COMPETITION WITH PABA

TOXICITIES:
*GI
*BLOOD DYSCRASIAS (ANEMIA, METHEMOGLOBINEMIA, Fe+++)