- OFLOXACIN (used in “Middle Path Regime” by Dr. Tully)
>is the hydrazide of isonicotinic acid.
>is the primary drug for the chemotherapy of tuberculosis.
>is bacteriostatic for “resting” bacilli, but is bactericidal for rapidly dividing bacteria.
>Mechanism of Action: inhibition of mycolic acid biosynthesis of the mycobacterial cell-wall.
>Dose : 5mg/kg/day( usual adult dose 300mg daily); 600mg thrice a week in DOTS.
>COMPLICATION: Most important complication- neurotoxic effects due to depletion of pyridoxine causing peripheral neuropathy, muscular twitching, paraesthesiae & psychological disturbances (psychosis, depression, memory impairment)- can be treated by giving 10-50mg of Pyridoxine daily.Other complications: Hepatitis, dizziness, encephalopathy, anorexia, agranulocytosis, gynecomastia etc.
>Pregnancy Risk factor:- CAT C
- Rifampicin: is considered as the primary drug for treatment of tuberculosis. It is bacteriocidal, & also acts on most Gram positive & many Gram negative bacteria.
>Mechanism of Action: It inhibits bacterial RNA synthesis by binding to the β-subunit of DNA-dependent RNA polymerase, blocking RNA transcription.
>Dose: 10mg/kg/day; maximum 600mg daily, usual adult dose 450mg/day, should be increased to 600mg/day for pt > 60 kg. DOTS dose- 450 mg (10mg/kg, maximum 600mg) thrice a week.
>COMPLICATION: Rash, fever, G I disturbances (nausea, vomiting etc.), rarely, hepatitis or shock-like syndrome with hepatic involvement and deaths due to liver failure; flu like syndrome with fever, chills, and myalgias & may include eosinophilia, interstitial nephritis, acute tubular necrosis, thrombocytopenia, hemolytic anemia, and shock; red-brown discolouration of bodu fluids like sweat, tears, urine, faeces etc; if used IV, may cause thrombophlebitis
>Pregnancy Risk factor:- CAT C
- Pyrazinamide: is the synthetic pyrazine analog of nicotinamide & especially bactericidal to mycobacteria multiplying intracellularly at low pH.
>Mechnism of action: acts by inhibition of mycolic acid synthesis by interacting with gene of fatty acid synthesis.
>Dose: 15-30 mg/kg/day; Pt. 40-55kg: 1000mg/day, 56-75kg: 1500mg, 76-90 kg: 2000mg (maximum daily dose); DOTS dose: thrice a week, pt. 40-55kg- 1500mg, 56-75kg: 2500mg.
>COMLICATION: Injury to the liver is the most serious complication of pyrazinamide causing jaundice & rarely death due to hepatic necrosis. The drug inhibits excretion of urate, resulting in hyperuricemia in nearly all patients, can lead to acute episodes of gout. Other complications include arthralgias, anorexia, nausea and vomiting, dysuria, malaise, and fever.
- Ethambutol: It suppresses the growth of most isoniazid- and streptomycin-resistant tubercle bacilli.
>Mechanism of action: Ethambutol inhibits arabinosyl transferases involved in cell wall biosynthesis Ethambutol interferes with RNA synthesis, causing suppression of Mycobacteria multiplication; also act as bacteriostatic by acting on rapidly growing as well on slow-growing pathogens.
>Dose: 15mg/kg/day; (some prefer 25 mg/kg per day for the first 60 days and then to reduce the dose to 15 mg/kg per day, particularly for those who have received previous therapy); dose-adjustment necessary in renal impairment; not recommended for children below 5 years of age, main concern inability to test their visual acuity; Children from ages 6 to 12 years should receive 10 to 15 mg/kg per day.
>COMPLICATION: The most important complication is optic neuritis (retrobulbar neuritis), resulting in decreased visual acuity and loss of ability to differentiate red from green-green-red colour blindness, constriction of visual field, central/peripheral scotoma, retinal haemorrhage(rare), reduced renal clearance of urates- acute gout, G I disturbances, jaundice, thrombocytopenia, pulmonary infiltrates etc.
- Streptomycin: is an aminoglycosidde having antibiotic & anti-tubercular activities.
>Mechanism of action: inhibits bacterial protein synthesis by binding to the 30s ribosomal subunits leading to faulty peptide sequence.
>Dose: For tuberculosis: 15mg/kg/day (maximum: 1g); DOTS dose: 25-30mg (maximum: 1.5g) thrice a wk. Children:20 to 40 mg/kg/day in divided doses every 12 to 24 hours (maximum1 g/day).
>COMPLICATION: Giddiness, vertigo, tinnitus, ataxia, ototoxicity & nephrotoxicity, hypersensitivity reaction; Fatal complication-Anaphylactic shock, aplastic anaemia & agranulocytosis, Stevens-Johnson syndrome & Toxic Epidermal Necrolysis.
> Different Regime for Tuberculosis of Spine:
- Middle Path regime (By Dr. Tully): a.Rest, b. Drugs- Intensive Phase: HRO (5-6 months); Continuation Phase: HZ (3-4 months) + HR (4-5 months); Prophylactic Phase: HE (4-5 months), c. Radioogical Follow-up(x-ray, MRI), d. Gradual Mobilisation +/- Spinal braces, e. Management of Abscess/Sinuses, f. Management of Neurological complications, g. Surgey(Excisional surgery; Definitive Surgery: Indication of Surgery in Pott’s spine), h. Post-operative care
- HRZE4 + HRE/HRZ3 + HR11