Anti tubular drugs Flashcards
First line of Anti tubular drugs- M tuberculosis
RIPES
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
Streptomycin (Nephrotoxicity and ototoxicity)
Second line drug of anti tubular drugs
Fluoroquinilones
Amikacin, Capreomycin
EThionamide
PAS, Cycloserine and Thiacetazone
Isoniazid
Inhibits the Mycolic acid
Prodrug active by bacterial catalase peroxidase (KatG)
Any mutation in KatG causes resistance
Adverse effects:
- Hepatitis, Hepatotoxicity
- Drug indice SLE
- Vitamin B6 (pyridoxin) deficiency- competes with Vitamin 6. Causes peripheral Neuropathy
- Sideroblastic anemia- administer pyridoxine B6
Clinical
1. Only agent used solo prophylaxis against TB
2. Also used as mono therapy for latent TB
Ethambutol
Inhibits synthesis of arabinogalactan
Inhibits carbohydrate polymerization of mycobacterial cell wall by blocking arabinosyltransferase.
Resistance:
Mutation resulting in over expression of gene for arabinosyl transferases
Adverse effect:
1. Opic neuritis- Red green color blindness.
E for Eye
Rifampin
Inhibits mRNA synthesis (DNA dependent RNA polymerase) by binding to the B subunit of bacterial DNA dependent
Mechanism of resistance
Point mutation in the gene for the Beta subunit of RNA polymerase
Reduced binding of rifampin to the beta subunit
Monotherapy rapidly leads to resistance
Is a stronger inducer of P450 isoforms
Ribabutin is prefer over rifampin in patients with HIV because of the P450
Adverse effects:
Orange body fluid- Tears, urine, sweat (NORMAL)
minor hepatotoxicity
Flu like syndrome
acute tubular necrosis
Uses:
1. Bactericidal for both extra and intra cellular
2. Used for meningococcal prophylaxis in contact of children with H influenza type B
3. Active against gram pos and neg
4. Against m. Leprae
Pyrazinamide
Highly effective on intracellular mycobacteria
Prodrug that is converted to the active compound pyrazinoic acid
Pyrazinoic acid disrupts mycobacterial cell membrane metabolism and transport functions
Work best at acid pH
Resistance:
1. Impaired uptake of pyrazinamide
2. mutations in pyrazinamidase that impair conversion of PZA to its active form.
Adverse effect:
1. Hepatotoxicity
2. Hyperuricemia: contraindication for Gout.
streptomycin
Inhibits 30S
Ototoxicity
Nephrotoxic
teratogenic
Cycloserien
Rarely use as secondary because of Psych
inhibits cell wall synthesis
Rifabutin
Bacterial RNA polymerase inhibitor
Inducer of cytochrome P450
Les potent than rifampin
Often for patients in TB and have HIV
Rifapentine
Potent inducer of P450
combined with isoniazid
