Tuberculosis
-M. tuberculosis
1st line therapy:
Isoniazide Pyrazinamide
Rifamycins Ethambutol
2nd line therapy
Aminoglycoside (streptomycin, kanamycin, Amikacin)
Capreomycin (inject able)
Ciprofloxacin, Moxifloxacin, levofloxacin
cycloserin
Macrolids (Azithromycin, clarithromycin)
*2nd line used in infection resistant to 1st line drug
Or patient sensitive to 1st line drug
*Rx 6 month – 2 year
*Multidrug therapy used due to resistance
Initial phase : for 2 months
Isoniazide + refampin + ethambutol +pyrazinamide
Continual phase: for 4 months
Isoniazide + rifampin
Isoniazide (INH)
-static for resting M & cidal for dividing M
-inhibit the synthesis of mycolic acid (important component in cell wall of M
-decrease absorption with food
-widely distributed in body tissue, CSF, penetrate caseous Tb lesion (necrotic tissue)
-infected tissue retain the drug longer
SE:
-Paresthesia of hand & feet (due vit B6 deficiency)
-Hepatotoxicity due to toxic metabolite
-mental abnormalities
DIA:
Inhibit the metabolism of phenytoin
Rifamycins
Rifampin, Rifabutin, Rifapentine
Rifampin:
-block the transcription by inhibiting DNA-dependant RNA polymerase so inhibit mRNA synthesis
-cidal
-orally, well distributed
-undergo enterohepatic circulation
-enzyme inducer so shorten itself t 1/2
-orange staining of saliva, sputum, tears, urine
SE:
-Hepatic dysfunction
-Flu like symptom, myalgia
-Hemolytic anemia
DIA:
- Enzyme inducer so decrease t1/2 of warfarin , propranolol, oral contraceptive, prednisone
Rifabutin
-Used in TB with HIV patient because it less enzyme inducer
-Cause hyperpigmentation & neutropenia as SE
Rifapentine
-Longer t1/2
-Given twice weekly in initial phase therapy for TB
-Once weekly in continuous phase
Pyrazinamide
-Cidal
-Unknown mechanism
-The metabolite is the active form
-Effective against bacilli in acidic PH
-Cause urate retention producing gouty attack
Ethambutol
-Static
-Act by Inhibiting enzyme essential in cell wall synthesis
-Penetrate CNS
SE:
Optic neuritis : dose related (visual disturbances, red – green color blindness)
Decrease urate excretion (gout attack)
Capreomycin
-Inhibit Pr. synthesis
-Parenteral
-Used for multiple drug resistant TB
-Cause nephrotoxicity & ototoxicity
Cycloserine:
-Inhibit cell wall synthesis
- Cause CNS disturbances, epileptic seizure
-also Peripheral neuropathy ( so pyridoxine used)
Ethionamide
-Analogue of isoniazide
SE:
-Cause gastric irritation
-Hepatotoxicity
-Peripheral neuropathy ( so pyridoxine used)