3B : ANTI-MYCOBACTERIUM Flashcards
exerts its effects by reversibly inhibiting DNA-dependent RNA polymerase, which
further inhibits bacterial protein synthesis and transcription.
Rifampin
a pro-drug that is converted to its active form metabolite by catalase-peroxidase
and exerts its action by further inhibiting the biosynthesis of mycolic acid.
Isoniazid
converted to its active form and exerts its effect by inhibiting
trans-translation and possibly coenzyme A synthesis needed for the bacteria to survive.
Pyrazinamide
inhibits the enzyme arabinosyltransferases and prevents the biosynthesis of the
mycobacterial cell wall.
Ethambutol
binding to the 30S subunit of ribosomes and inhibiting the protein synthesis of the mycobacteria.
Aminoglycosides (Streptomycin, Kanamycin, Amikacin)
inhibiting DNA gyrase and topoisomerase IV, further inhibiting DNA synthesis within the bacteria.
Fluoroquinolones (Levofloxacin, Moxifloxacin, Gatifloxacin)
ADMINISTRATION
oral
Rifampin, Isoniazid, Pyrazinamide, and Ethambutol
Fluoroquinolones such as moxifloxacin, gatifloxacin, and levofloxacin
ADMINISTRATION
parenteral
Streptomycin is usually administered daily as a single intramuscular injection
Aminoglycosides are usually administered by intravenous infusion or intramuscular
injection
Adverse Effects
Rifampin:
- Hepatotoxicity,
- Thrombocytopenia,
- Neutropenia,
-
Orange/Red discoloration of bodily
fluids, - CYP450 Inducer
Adverse Effects
Isoniazid:
- Hepatotoxicity,
- Vitamin B6 deficiency,
- Peripheral Neuropathy
Isoniazid can interfere with the activity of vitamin B6. Vitamin B6 supplementation
is recommended, especially in people with poor nutritional status, to prevent the
development of isoniazid-induced peripheral neuritis (inflamed nerves).
INH metabolites directly attach to and inactivate pyridoxine species. The
combination of isoniazid and pyridoxine form a hydrazone which is excreted in
the urine.
INH inhibits the enzyme pyridoxine phosphokinase; this enzyme is necessary
to activate pyridoxine to pyridoxal 5’ phosphate, the cofactor in many
“pyridoxine-dependent” reactions
adverse effect
Pyrazinamide:
- Hepatotoxicity,
- Hyperuricemia,
- Arthralgia
ADVERSE EFFECT
Ethambutol:
- Optic neuropathy,
- Hepatotoxicity
ADVERSE EFFECT
Aminoglycosides (Streptomycin, Kanamycin, Amikacin):
- Ototoxicity,
- Nephrotoxicity
ADVERSE EFFECT
Fluoroquinolones (Levofloxacin, Moxifloxacin, Gatifloxacin):
- Tendonitis,
- Tendon rupture,
- Arthropathy
During pregnancy, all anti-tubercular medications are useful for treatment except for
AMINOGLYCOSIDES.
Aminoglycosides such as streptomycin, amikacin, and kanamycin may
exhibit ototoxic effects on the developing fetus