TUBERCULOSIS

Tuberculosis is a chronic granulomatous disease and is one of the world’s most widespread and deadly illness. It is commonly called as Consumption or Wasting disease or White plague

RISK FACTORS AND ETIOLOGY 1. TB is a weakly gram positive, non motile, rod-shaped bacterium 2. Acid fast bacilli that grows at 37C TB occurs disproportionately among dis-advantages population such as Mal nutrition Homeless those living with over crowded and substandard housing and also other under laying like children 65 years Immuno-Suppression (renal failure, cancer) HIV positive

PATHOGENESIS

CLINICAL PRESENTATION Signs and symptoms Malaise, Anorexia, Weight loss, fever, Night sweats, Chronic cough, Frank Hemoptysis Physical Examination: Dullness, Malnourished, Rales, Increased vocalfremitus on ausculation Laboratory Test: Moderate elevation of WBC count Others include Acid fast bacilli light microscopy Myco bacterial growth detection Identification of myco bacterium TB complex by DNA probe First line drug susceptibility testing

Special Examination: Latent TB infection is done if person is suspected to be present with TB Tuberculin skin test or Montoux test: A 48 to 74 hours when a Tuberculin test is positive then

TREATMENT Desire out comes: 1. Rapid identification of a new TB case. 2. Isolation of the patient with active disease to prevent spread of disease. 3. Initiation of specific treatment 4. Prompt resolution of Signs and syptoms. 5. Adherence to treatment regimen. 6. Cure of the patient as quickly as possible.

NON-PHARMACOLOGICAL TREATMENT : Prevents spread of infection Replenish the weakened patient to normal PHARMACOLOGICAL TREATMENT: First Line: High anti tubercular efficacy and low toxicity 1. Isoniazid (H) 2. Rifampin (R) 3. Pyrazinamide (P) 4. Ethambutol (E) 5. Streptomycin (S)

Second Line: Either low anti TB efficacy or high toxicity or both and are used under special circumstances. 1. PAS 2. Ethionamide 3. Kanamycin 4. Amikacin 5. Ciprofloxacin 6. Ofloxacin 7. Clarithromycin 8. Azithromycin 9. Rifabutin

ISONIAZID: Dose: 5mg/kg MOA: Inhibits enzymes Resulting inhibits synthesis of mycolic Acid ADME: A: Impaired Acid food M: Chronic Liver Disease dose is reduced E: Urine ADR’s: Peripheral neuropathy hepatitis, rash DI: Phenytoin

ETHAMBUTOL: Dose: 5-25mg/kg MOA: Inhibit arabinogalatan transferase resulting in interference with mycolic acid synthesis ADME: Absorbed orally metabalized in Liver excreted in Urine. Caution: Dose adjustment in renal disease. ADR’s: Optic neuritis, Red-Green color blindness.

RIFAMPIN: Dose: 10mg/kg MOA: Inhibits RNA synthesis ADME: A: Oral M: Enterohepatic cycling E: Bile, feaces, Urine ADR’s: Hepatitis, Red colour Urine, Fever, Rash, Respiratory syndrome DI: Inhibits effect of oral contraceptive, Corticosteriods, Warfarin, Digoxin, Oralhypoglycemic.

PYRAZINAMIDE : Dose: 15-30mg/kg MOA: Exact MOA unknown but resemble INH, it inhibits mycolic acid synthesis. ADME: Oral, metabolized in liver, excreted in Urine. CI: Liver disease. ADR’s: Hyperuricemia, Hepatotoxicity, Rash, Loss of diabetic control. DI: Rare

Other class of drugs as flouroquinolones (Cipro, Ofl, Moxi) used in combination regement against MDR TB Drugs stopped due to hepatotoxicity Macrolides (CLA, AZI)

 DOTS: A total of either a 6 months or 9 months regimen. Initial phase of 6 months regimen—2 months of daily H+R+P+E space followed by 2 nd phase of therapy consists of H+R for minimum 4 months If DOT is used medication may be given intermittently using one of 3 regimen 1. Daily H+R+P+E ……..2 Months H+R 2 or 3 times a week …… 4 months 2. Daily H+R+P+E …….. 2 weeks H+R+P+E twice a week …… 6 weeks H+R twice each week for 4 months 3. H+R+P+E thrice in a week for 6 months

 CATEGORY WISE TREATMENT REGIMEN: Category 1: New smear positive TB New smear negative TB with extensive Phrenchymal involvment New cases extra pulmonary TB IP: HRPE: Thrice weekly …. 2 months CP: HR …. 4 months or HE ….. 6 months and is extended 6 to 7 months in TB mengitis, miliary and spinal disease. Category 2: Smear positive failure, relapse, interrupted treatment cases IP: SHREP ….. 2 Months HRZE ……. 4 months CP: HRE ….. 5 months thrice weekly

Category: 3 Smear negative pulmonary TB with less severe form of extra pulmonary TB i.e., Bone, Unilateral Pleural Effusion, Peripheral joint or skin TB HRE …..2 months CP…..Similar to category 1 Category: 4 Chronic cases who has remained or have become smear positive after completing fully supervised re-treatment. MDR TB for H resistance – RZE for…..12 months for H+R resistance-ZE+S+Cipro+Etm could be used.

TUBERCULOSIS IN PREGNANT WOMEN: Standard 6 months regimen of 2 HRZ+4HR Streptomycin is contra indicated In India Z is not advised, so the regimen is 2HRE+7HR TUBERCULOSIS IN BREAST FEEDING WOMEN: All 4 drugs are safe during breast feeding, but the baby has to be vaccinated with BCG and Isoniazid prophylaxis. TUBERCULOSIS IN AIDS PATIENT: The approach to HIV positive patient has additional consideration of 1. Longer duration of therapy … 2 months HRZE is started immediately on the diagnosis of TB followed by continues phase of 7 months HR. Alternatively HRE are given for 4 months in continues phase. Pyridoxine mg/per day is routinely given.

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