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Antitubercular drugs-MDR TB
First-line oral antituberculosis agents Isoniazid Rifampicin Ethambutol Pyrazinamide (H) (R) (E) (Z)
Viomycin [Vi]
[Doubtful efficacy]
Ethionamide: ( Etm )
It is bacteriostatic. It acts on both extracellular and intracellular bacilli also effective against atypical mycobacteria. It blocks the synthesis of mycolic acid.
Adverse effects: Hepatotoxicity, gastric irritation, peripheral neuritis. Dose: 1 gm/day orally.(500mg 750mg/day).
Thiacetazone: ( Tzn )
It was once used as a first line drug. It is a tuberculostatic drug. Usually combined with INH.
Adverse effects: Hepatitis, Exfoliative dermatitis, StevensJohnson syndrome. Contraindicated in HIV positive cases. Dose: 150 mg/day.
Adverse effects: Git symptoms, fever, goiter,liver dysfunction and blood dyscrasias Dose: 1012gms (200 mg/day) in
Cycloserine ( Cys ):
It is a tuberculostatic drug which inhibits cell wall synthesis. Rapidly absorbed from gut and achieves good concentration in the CSF when meninges are inflamed.
Capreomycin:
It is a polypeptide obtained from Streptomyces capreolus. It is similar to Streptomycin.
Dose: 15 20 mg per kg IM for 60 days and then twice weekly for 18 months. Clarithromycin and Azithromycin.
Fluoroquinolones
Ciprofloxacin, Ofloxacin, Moxifloxacin and
Sparfloxacin.
They are active against M.tuberculosis and some atypical mycobacteria. They are also effective in killing the bacilli lodged in the macrophages.
Aminoglycosides:
Kanamycin and Amikacin. They are used in resistant cases and against atypical mycobacteria.
Rifabutin:
Action is similar to Rifampicin. More active against MAC.
Adverse effects: Neutropenia, Myalgia, Impairment of taste Uses:1. Treatment and prophylaxis of Pulmonary MAC. 2. Pulmonary Tuberculosis.
RNTCP
National programme
DOTS
Implimentation
Sub-populations
Goals of therapy
Kill dividing bacilli Non contagious
[Multiple drugs]
Categorization of Patients
Classified into two groups based on H/o previous treatment
New cases [CAT I]: All new pulmonary (sputum positive and negative) and extra pulmonary TB patients Previously treated cases [CAT II]: Patients who have more than one month Anti TB Rx previously (default, failure and relapse)
Characteristics All new cases sputum +ve or negative Patients who have more than one month Anti TB Rx previously (default, failure and relapse)
[II]
If sputum is + ve at the end of two months, IP is continued for another one month (12 doses) CP is for 4 months
Intensive Phase
1.Aims for a rapid killing of bacilli 2.A state of non-infectiousness achieved within a short period 2/52 3.Quick relief of symptoms 4.Smear negativity by 2/12 5.Prevent development of drug resistance
Continuation Phase
Aims to eliminate remaining bacilli Killing of persisters prevents relapses
DOTS
All drugs can be given as a single daily dose. Direct observation is recommended for all patients Particularly essential when intermittent regimens are used.
Principles DOTS
Sputum microscopy Domiciliary treatment Short course chemotherapy Intermittent chemotherapy Directly observed treatment
t least 1/3 of patients on self-administered Rx fail to adhere to Rx to predict which patients will take
Impossible
medicines
DOT
Benefits of DOTS
Produces cure rates of up to 95 % Prevents new infections Prevents the development of MDR-TB Cost effective
Multi-drug resistant and Extensively drug resistant TB MDR-TB Defined as resistance to Isoniazid and Rifampicin XDR-TB Defined as resistance to at least Isoniazid and Rifampicin (i.e. MDR-TB) PLUS resistance to any of the Fluoroquinolones and any one of the second-line injectable drugs (Amikacin, Kanamycin, or
RNTCP CATEGORY MDR REGIMEN: 6 (9) Km Ofx (Lvx) Eto Cs Z E / 18 Ofx (Lvx)Eto Cs E 6 Drugs for intensive phase [6-9 Months] 4 Drugs for intensive phase [18 Months]
Chemoprophylaxis-Primary
To prevent latentActive 1. Contacts of open cases-recent Mx conversion 2. Children with +ve Mx with contacts 3. Neonates of tubercular mother 4. DM, HIV, Leukemia with contactsMx+ve 5. Who received inadequate therapy
Drugs used are: INH 300mg for 6 12 months OR INH ( 5mg/kg ) + Rifampicin ( 10 mg/kg ) for 6 months OR INH + Rifampicin + Pyrazinamide for 2 3 months.
Glucocorticoids in Tuberculosis:
Glucocorticoids must never be used without cover of effective antitubercular chemotherapy.
The indications for steroids are: 1.Miliary or severe pulmonary TB. 2.Hypersensitive reactions to anti TB drugs. 3.Meningeal and Renal TB. 4.Pleural and Pericardial effusion. 5.Rapidly enlarging mediastinal lymph node. 6.To prevent fibrosis in ocular & genitourinary TB.
Tt not to be with held Initial phase H R [Z] E for 2 months. Continuation phase H R for 7 months. [Ethambutol not added during early pregnancy] All drugs can be given to the mother during breast feeding
TB in pregnant women:
Clarithromycin + Ethambutol Azithromycin + Ethambutol Clarithromycin + Ethambutol + Ciprofloxacin OR Rifabutin Azithromycin + Ethambutol + Ciprofloxacin OR Rifabutin