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TUBERCULOSIS

TUBERCULOSIS. Tuberculosis. Tuberculosis is a contagious bacterial disease that primarily involves the lungs, but can occur in other tissues (lymph, CNS, pericardium, liver, etc.)

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TUBERCULOSIS

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  1. TUBERCULOSIS

  2. Tuberculosis • Tuberculosis is a contagious bacterial disease that primarily involves the lungs, but can occur in other tissues (lymph, CNS, pericardium, liver, etc.) • The World Health Organization (WHO) estimates that 1.6 million deaths resulted from TB in 2005, and more than 2 million deaths are expected this year. • Opportunistic tuberculosis has also become a significant problem in immunocompromised patients. • Mycobacteria tuberculosis • M. tuberculosis is an obligate gram-positive, non-motile, rod aerobe mycobacterium that divides every 15 to 20 hours.

  3. TUBERCULOSIS – A GLOBAL EMERGENCY? • NEARLY ONE – THIRD OF THE WORLD’S POPULATION IS INFECTED WITH TUBERCLE BACILLUS • CAUSES 3 MILLION DEATHS EACH YEAR • A LEADING CAUSE OF DEATH IN HIV POSITIVE PEOPLE. • RISE IN THE NUMBER OF CASES REPORTING EACH YEAR

  4. Who are likely to be infected with Tuberculosis? • Close contacts with sputum smear positive people • Persons infected with HIV • Alcoholics • Renal Failure Patients, Diabetic Patients • People who are on Prolonged Corticosteroids

  5. ANTITUBERCULOSIS DRUGS A. First – Line Drugs DrugsDosage Isoniazid Adult - 5 mg/Kg/day or 300mg/day Children - 10 mg/Kg/Day or 300 mg/day Intermittent Therapy - 15 mg/Kg 3 times a week or 600 mg To be taken 30 minutes before food.

  6. DrugsDosage Rifampicin 10 mg/Kg/Day or 450 mg < 50 Kg 600 mg > 50 Kg To be taken 30’ before food

  7. DrugsDosage Ethambutol15 – 25mg/Kg/day or 1200 mg < 50 Kg 1600 mg > 50 Kg (Food - not interfere its absorption) Pyrazinamide 20 – 25 mg /Kg/day or 1000 mg < 50 Kg 1500 mg > 50 Kg Streptomycin Inj. 15 mg/Kg /day or 750 mg < 50 Kg 1000 mg > Kg

  8. B. Second – Line Drugs DrugsDosage Aminosalicylic Acid 8 – 12 g/day in divided dose Ethionamide 500 – 750 mg / day Cycloserine 10 mg/Kg/Day or 200 mg twice daily Capreomycin Inj. 1 g / day Clofazimine 200 mg/day Ciprofloxacin 1500 mg in two divided dose Levofloxacin 500 mg / day Ritabutin 500 mg / day Rifapantine 600 mg /day

  9. Treatment Regimens A. Short Course Regimen ( 6 – 9 months) Initial Phase Continuous Phase (2 months) (4 months) HRZE HR OR HRE ( 2 months) HR (28 weeks)

  10. B. DOT’S REGIMEN (Directly observed therapy) • Mandatory when drugs prescribed less often than daily. • All drugs are administered thrice a week. • Direct observation of consumption of every dose in the initial phase. • Direct observation of first dose of the week in the continuation phase.

  11. DOT REGIMENS CategoriesPatient TypeRegimenDuration I - Sputum Positive H2R2Z2E2 6 months - Serious extra + H4R4 pulmonary II - Sputum Positive relapse H2R2Z2E2S2 8 months - Sputum Positive failure + H1R1Z1E1 - Sputum Positive default + H5R5E5 III Not serious extrapulmonary H2R2Z2 6 months + H4R4

  12. Why to use combination of drugs in Tuberculosis ? • Mycobacterium is slow growing organism. • Mycobacterium can remain dormant. • Their response to chemotherapy is slow. • Mycobacterium is inaccessible to drug action. • Develop resistance rapidly when used alone.

  13. Characteristics of First Line Drugs -ISONIAZID • Mechanismof Action • Bactericidal. Extra & Intracellular organism. • Inhibits synthesis of Mycolic Acid - Isoniazid activated by mycobacterial catalase peroxidase. The activated form of Isoniazid form a covalent complex with carrier protein – Blocks Mycolic Acid Synthesis • Kinetics • Above 20% of serum conc. with inflammed meninges. • Metabolized by Acetylation. • Reduce the dose in renal impairment

  14. Common Side effects • Peripheral neuritis - The incidence of this side effects are more in alcoholics, diabetics, hepatitic patients) • Liver toxicity - Increased incidence in aged patients. • CNS effects – Psychosis, seizures. • Interaction • Inhibits metabolism of Carbamazepine, Phenytoin. • Rifampin and INH cause additive hepatic toxicity. • Precaution • Test for Hepatitis – AST & ALT • Pyridoxine 10 mg daily as prophylactic against Neuritis.

  15. RIFAMPICIN • Spectrum & Mechanism • Bactericidal. Intra, Extra & dormant Tubercle Bacilli. • Active against Gram +ve and Gram –ve cocci. Enteric bacteria, chlamydia. • Binds to Bacterial DNA dependent RNA polymerase, thereby inhibits RNA synthesis • Kinetics • Above 30% of serum level are in inflammed meninges. • Active metabolite formed in the liver by deacetylation . Undergo Enterohepatic circulation. • 50 – 60% Excreted in the feces.

  16. Common sideEffects • G. I Disturbances • Liver toxicity • Respiratory syndrome • Flu like syndrome • Abdominal syndrome • Cutaneous syndrome • Drug Interaction • Potent inducer of hepatic microsomal enzymes • ↓ Efficacy of O.C, Warfarin, Steroids

  17. Caution • Test for subclinical hepatitis – AST, ALT, Platelet count . • Warn about Orange/Red colour of body fluids • ↓ dose in hepatic impaired patients. • Clinical uses • Meningococcal carrier – 600 mg twice daily x 2 days • Prophylaxis against H. influenzae • Treatment of staphylococcal osteomylitis with Vancomycin / Ceftriaxone

  18. ETHAMBUTOL SITE & MECHANISM OF ACTION: • Bacteriostatic both intra and extracellular • Inhibit development of resistant mutants. • Inhibit mycobacterial arabinosyl transferase which involved in polymerazation of Arabinoglycan - a component of Mycobacterial cell wall. KINETICS : • Up to 54% of serum levels are in inflammed maninges. • > 50% Excreted in urine as unchanged form.

  19. TOXIC EFFECTS: • Ocular toxicity • Precipitate Gout CAUTION: • Test for visual Acuity and colour vision. • Not recommended in children < 3 years • ↓ dose in Renal impairment

  20. PYRAZINAMIDE SITE & MECHANISM • Bactericidal in acidic pH. Active against Intracellular and dormant bacilli. • Inhibits mycolic acid synthesis KINETICS • Upto 100% serum levels achieved in inflammed meninges. • Metabolized and inactive metabolite is excreted.

  21. TOXICITIES: • Hepatotoxic • Hyperglycaemia • Rashes and G.I Upset CAUTION: • Reduce Dose in Renal and hepatic impaired Patients

  22. PRINCIPLE ADVERSE EFFECTS OF SECOND LINE DRUGS • Ethionamide Oral G.I Upset,Hepatotoxic, Hypotension, Hypoglycaemia, Neuropathy, Alopecia • Cycloserine Oral CNS – Drowsiness Vertigo confusion, disorientation

  23. Capreomycin I.M Ototoxic and Nephrotoxic ↓ dose > 40 years and Renal impairment • Clofazimine Oral Brown discolouration of skin

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