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Tb treatment


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Tb treatment

  1. 1. By the pharmacist Ayia nazum kamal بسم الله الرحمن الرحيم
  2. 2. Tuberculosis treatment
  3. 3. Tuberculosis treatment <ul><li>refers to the medical treatment of the infectious disease tuberculosis(TB). Active tuberculosis will kill about 2 of every 3 people affected if left untreated. Treated tuberculosis has a mortality rate of less than 5%. </li></ul><ul><li>The standard &quot;short&quot; course treatment for TB is isoniazid , rifampicin , pyrazinamid e and ethambuto l for 2 months, then isoniazid and rifampicin alone for a further 4 months. The patient is considered cured at six months (although there is still a relapse rate of 2 to 3%). </li></ul>
  4. 4. <ul><li>For latent tuberculosis , </li></ul><ul><li>the standard treatment is six to </li></ul><ul><li>nine months of isoniazid alone. </li></ul><ul><li>If the organism is known to be fully </li></ul><ul><li>sensitive, then treatment is with isoniazid , rifampicin and pyrazinamide for two months, followed by isoniazid and rifampicin for four months. Ethambutol need not be used </li></ul>
  5. 5. Drugs <ul><li>First line </li></ul><ul><li>Ethambutol </li></ul><ul><li>isoniazid </li></ul><ul><li>pyrazinamide </li></ul><ul><li>rifampicin </li></ul><ul><li>streptomycin </li></ul>
  6. 6. Drug regimens : <ul><li>2HREZ/4HR3 </li></ul><ul><li>means isoniazid, rifampicin, ethambutol, pyrazinamide daily for two months, followed by four months of isoniazid and rifampicin given three times a week. </li></ul>
  7. 7. Second line <ul><li>There are six classes of second-line drugs (SLDs) used for the treatment of TB. A drug may be classed as second-line instead of first-line for one of three possible reasons : </li></ul><ul><li>* it may be less effective than the first-line drugs </li></ul><ul><li>(e.g., p -aminosalicylic acid) </li></ul><ul><li>or </li></ul><ul><li>* it may have toxic side-effects (e.g., cycloserine) </li></ul><ul><li>or </li></ul><ul><li>* it may be unavailable in many developing countries (e.g., fluoroquinolones) </li></ul>
  8. 8. <ul><li>* aminoglycosides : e.g .amikacin, kanamycin </li></ul><ul><li>* polypeptides : e.g .capreomycin, viomycin, enviomycin </li></ul><ul><li>* Fluoroquinolones : e.g .ciprofloxacin, levofloxacin, moxifloxacin </li></ul><ul><li>* Thioamides e: e.g .ethionamide,prothionamide </li></ul><ul><li>* cycloserine </li></ul><ul><li>* p -aminosalicylic acid </li></ul>
  9. 9. Third line <ul><li>Other drugs that may be useful, but are not on the WHO list of SLDs: </li></ul><ul><li>rifabutin </li></ul><ul><li>macrolides e.g .clarithromycin </li></ul><ul><li>linezolid </li></ul><ul><li>thioacetazone </li></ul><ul><li>thioridazine </li></ul><ul><li>arginine </li></ul><ul><li>These drugs may be considered &quot;third-line drugs&quot; and are listed here either because they are not very effective (e.g., clarithromycin) or because their efficacy has not been proven (e.g., linezolid). Rifabutin is effective, but is not included on the WHO list because for most developing countries, it is impractically expensive </li></ul>
  10. 10. Mode of action & Recommended dose mg/kg 45 30 15 bacteriostatic Ethambutol 15 15 15 bactericidal streptomyicin 50 35 25 bactericidal pyrazinamide 10 10 10 bactericidal Rifampicin 15 10 5 bactericidal INH Twice/wk 3times/wk Daily dose mg/kg Mode of action Essential anti-tuberculosis drug
  11. 11. Pharmacokinetic renal Without hepatic metabolism 5-6hr streptomycin renal liver 9-10hr pyrazinamide renal liver 3-4 hr (increased in impaired renal function) Ethambutol urine (primarily), feces liver 0.5-1.6h (fast acetylators), 2-5h (slow acetylators) INH renal 15to 030% Faecal 60% Hepatic and intestinal wall 6 to 7 hours rifampicin Excretion Metabolism Half-life Drugs name
  12. 12. Adverse effect, caution ,contraindication & interaction of Essential anti-tuberculosis drugs
  13. 13. ↑ toxicity of these drugs ↑ INH hepatotoxicity INH effects ↓ *Carbamazepine & phynetoin *Carbamazepine *Antacids drug-induced liver disease *hepatic impairmet *renal impairment *epilepsy *alcohol dependence *breast-feeding *Nausea *vomiting *peripheral neuritis *Convulsion *psychotic episodes *allergic reactions *blood dyscrasias INH Results interaction contraindications cautions Adverse effects Drugs names
  14. 14. ↓ Effects of these drugs Phenytoin Digoxin Theophylline Oral anticoagulant Contraceptive b-blockers Sulphonylureas jaundice *hepatic impairment *pregnancy & breast-feeding, advise patients on hormonal contraceptive to use additional means, *discolours soft contact lenses GI disturbance, liver damage , influenza-like syndrome some times with thrombocytopenia, haemolytic anaemia, shock and renal failure (particularly with intermittent therapy) may coloure skin, urine, saliva & terars orange-red Rifampicin Results interaction contraindications cautions Adverse effects Drugs names
  15. 15. ↓ effect of Ethambutol Almunium hydroxide optic neuritis, poor vision reduce dose in renal impairment and if creatinine clearance less than 30 mL/minut *children under 6 years optic neuritis, red/green colour blindness, peripheral neuritis, rarely rash, pruritus, urticaria, thrombocytopenia Ethambutol Results interaction contraindications cautions Adverse effects Drugs names
  16. 16. antagonize effects of these drugs Probenecid Sulfinpyrazone Liver damage * diabetes *gout *renal dysfunction Liver damage, hyperuricemia, *GI disturbance, arthralgia, rash and occasionally photosensitivity pyrazinamide result interaction contraindications cautions Adverse effects Drugs names
  17. 17. ↑ nephrotoxicty ↑ ototoxicity ↑ skletal muscle paralysis *Cephalosprins,cycloserine, vancomycin, amphotericin, furosemide *Loop diuretic ,vancomycin, neuromascular blockers *pregnancy myasthenia gravis ↑ dose interval in renal dysfunction <ul><li>*ototoxicity </li></ul><ul><li>reversible nephrotoxicty </li></ul><ul><li>neuromascular blockade with apnea </li></ul>streptomycin Results interaction contraindications cautions Adverse effects Drugs names
  18. 18. Tuberculosis and other conditions
  19. 19. <ul><li>Pregnancy and breast - feeding </li></ul><ul><li>The standard regimen may be used during pregnancy and breast - feeding </li></ul><ul><li>Streptomycin which is ototoxic to fetus should not given in pregnancy </li></ul>
  20. 20. <ul><li>Liver disease </li></ul><ul><li>patients with established chronic liver disease should not recived pyrazinamide </li></ul><ul><li>recommended regimens are; </li></ul><ul><li>2SHRE/6HR OR 2SHE/10HE </li></ul>
  21. 21. Epilepsy <ul><li>INH may be associated with an increased risk of seizures. </li></ul><ul><li>Pyridoxine 10 mg daily should be given to all epileptics taking INH. </li></ul><ul><li>There is no evidence that INH causes seizures in patients who are not epileptic. </li></ul>
  22. 22. <ul><li>TB treatment involves numerous drug interactions with anti-epileptic drugs and serum drug levels should be closely monitored. </li></ul><ul><li>There are serious interactions between rifampicin and carbamazepine, rifampicin and phenytoin, and rifampicin and sodium valproate. </li></ul>
  23. 23. Kidney disease <ul><li>* Isoniazid , rifampicin and pyrazinamide are either eliminated almost entierly by biliary excretion or metabolized into non toxic substance . </li></ul><ul><li>*these drugs may be given in normal dosage to patients with renal dysfunction. </li></ul><ul><li>*In sever renal failure patients should recived pyridoxine with isoniazid in order to prevent peripheral neuropathy. </li></ul>
  24. 24. <ul><li>* Streptomycin & Ethambutol can given in reduced dose under close monitoring of renal function (since these drugs are excreted by the kidney). </li></ul><ul><li>* Thiocetazone , which is partially in urine, but has a narrow margin of safety , should be avoided in patients with renal failure </li></ul>
  25. 25. <ul><li>* When using 2HRZ/4HR in patients on dialysis, the drugs should be given daily during the initial high-intensity phase. </li></ul><ul><li>*In the continuation phase, the drugs should be given at the end of each haemodialysis session and no dose should be taken on non-dialysis days. </li></ul>