Synthesis of Certain Derivatives of Schiffbases of Isoniazid and Its in-Vitro Assay Against Tuberculosis - Multi and Extremely Drug Resistance Strains

Topics: Tuberculosis, Isoniazid, Mycobacterium Pages: 7 (2145 words) Published: August 10, 2011
Microbiological Studies
A definitive diagnosis of tuberculosis can only be made my culturing Mycobacterium tuberculosis organisms from a specimen taken from the patient (Most often sputum, but may also include pus, cerebero spinal fluid (CSF)), biopsied tissue, etc. Sputum smears and cultures should be done for acid-fast bacilli. The preferred method for the identification is fluorescence microscopy which is more sensitive than conventional Ziehl- Neelson staining denoted by Steingart et al., 2006 6. If sputum is not produced, specimens can be obtained by gastric washings, an laryngeal swab, bronchoscopy with broncho alveolar lavage or fine needle aspiration of a collection. A comparative study found that inducing three sputum samples is more sensitive than three gastric washings. Many types of culture media are available. Traditionally Lowenstein –Jensen (LJ), Kirchner or Middle Brook media (7H9, 7H10, 7H11 and 7H12) are used for cultivating of Mycobacterial species. A culture of the acid-fast bacilli distinguishes the various forms of Mycobacteria. New automated systems that are faster include BACTEC 460 TB, BACTEC 9000 and the Mycobacterial growth Indicator tube (MGIT). The microscopic observation drug susceptibility assay (MODS) culture may be faster and more accurate method.

Drugs Used In Tuberculosis in the current scenario
Active tuberculosis will kill about two of every three people affected if left untreated. Treated tuberculosis if taken up early has a mortality rate of less than 5%.The standard short course treatment for tuberculosis comprises of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol for two months, then Isoniazid and Rifampicin alone for a further four months. For latent tuberculosis, the standard treatment is six to nine months of Isoniazid alone. Drug regimens are abbreviated in a standardized manner. a). Streptomycin is STM or S

b) Isoniazid is INH or H
c) Rifampicin is RMP or R
d) Ethambutol is EMB or E
e) Pyrazinamide is PZA or Z.
a)According to WHO norms, there are six classes of second line drugs that are used for the treatment of tuberculosis. A drug may be classified as second line instead of first line for one of two possible reasons; it may be less effective than the first line drugs or it may produce toxic side –effects. They are classified based on their chemical nucleus: Aminoglycosides – Amikacin and Kanamycin b)Polypeptides – Capreomycin

c)Fluoroquinolones – Ciprofloxacin
d)Thioamides – Ethionamide, Prothionamide and Cycloserine. e)Para-amino Salicylic acid.
Tuberculosis has been treated by combination therapy over fifty years. Single drug treatment is ineffective and regimens that use only single drugs result in the rapid development of resistance and thus treatment results in failure.The rationale for using multiple drugs to treat tuberculosis is based on simple probability. The frequency of spontaneous mutations that confer resistance to an individual drug is well known: 1 in 10 7 for Ethambutol (EMB); 1 in 108 for streptomycin (STM) and Isoniazid (INH); 1 in 10 10 for Rifampicin (RMP). A patient with extensive pulmonary tuberculosis has approximately 10 12 bacteria in his body and therefore will probably be harbouring approximately 10 5 Ethambutol resistant bacteria, 10 4 Streptomycin resistant bacteria, 104 Isoniazid resistant bacteria and 102 Rifampicin resistant bacteria respectively. DOTS stands for ‘Directly Observed Therapy, Short - course’ and is a major plank in the WHO global tuberculosis eradication programme. The WHO advises that all tuberculosis patients should have atleast the first two months of their drug therapy should be observed with the aid of observer within that society. DOTS is used with intermittent dosing – Thrice weekly (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide) or twice weekly.The relative incidence of major adverse effects has been carefully described . a)Isoniazid – Hepatitis, Neuropathy – 0.49%.

b)Rifampicin – Skin...
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