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•
• Substance abuse
• Recent TB infection
• Prolonged therapy with
corticosteroids and other
immunosuppressive
therapy, such as prednisone
and tumor necrosis factor-
alpha [TNF-α] antagonists
• Diabetes mellitus
• Severe kidney disease
• Certain types of cancer
• Certain intestinal conditions
• Low body weight
Some conditions increase probability of LTBI
progressing to TB disease
Infection with HIV • Organ transplant
Chest x-ray findings • Silicosis
suggestive of previous TB
Progression to TB Disease](https://image.slidesharecdn.com/tuberculosis2dr-180808143038/85/Tuberculosis-2-dr-noha-21-320.jpg)
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Tuberculosis (2)dr.noha
This document provides information on the diagnosis and treatment of tuberculosis (TB). It defines TB as a contagious lung infection caused most commonly by Mycobacterium tuberculosis. TB can be classified as pulmonary or extra-pulmonary depending on the affected area. Diagnosis involves tests such as sputum smears, culture, chest x-ray, and tuberculin skin test. Standard treatment is a 6 month regimen including isoniazid, rifampin, pyrazinamide, and ethambutol. Directly observed therapy is recommended to monitor patient compliance. Common adverse effects and interactions of anti-TB drugs are also outlined.
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Tuberculosis (2)dr.noha
- 1.
- 2. Clinical Pharmacist Dept. OfNephrology M. N. G. Hospital TUBERCULOSIS TREATMENT
- 3. Definition Tuberculosis (TB)is a potentially fatal contagious disease that can affect almost any part of the body but is mainly an infection of the lungs. Neo-latin word : - Round nodule/Swelling - Condition “Tubercle” “Osis”
- 4.
- 5. Other causative organisms Mycobacterium africanum Mycobacterium microti Non-Mycobacterium Genus Mycobacterium leprae Mycobacterium avium Mycobacteriumasiaticum M. africanum M. Bovis M. Canetti M. microti M. tuberculosis complex
- 6. Discovered in1882 by RobertKoch.
- 8. Classification Pulmonary TB - PrimaryDisease - Secondary Disease Extra pulmonary i. Lymph node TB ii. Pleural TB iii. TB of upper airways iv. Skeletal TB v. Genitourinary TB vi. Miliary TB vii. Pericardial TB viii. Gastrointestinal TB ix. Tuberculous Meningitis x. Less common forms
- 9. Based on typesof TB
- 10. Severe Symptoms Persistentcough Chest pain Coughingwith bloodysputum Shortness of breath Urine discoloration Cloudy & reddish urine Fever with chills. Fatigue
- 11.
- 12. TB Transmission • Probabilitythat TB will be transmitted depends on: – Infectiousness of person with TB disease – Environment in which exposure occurred – Length of exposure – Virulence (strength) of the tubercle bacilli • The best way to stop transmission is to: – Isolate infectious persons – Provide effective treatment to infectious persons as soon as possible
- 13. Preventive measures 1) Mask 2)BCG vaccine 3) Regular medical follow up 4) Isolation of Patient 5) Ventilation 6) Natural sunlight 7) UV germicidal irradiation
- 15. Diagnosis 1.Bacteriological test: a. Zeihl-Neelsenstain b. Auramine stain(fluorescence microscopy) 2. Sputum culturetest: a. Lowenstein –Jensen(LJ) solid medium: 4-18 weeks b. Liquid medium : 8-14 days c. Agar medium : 7 to 14days
- 16. 3.Radiography: Chest X-Ray(CXR) 4.Nucleic acidamplification: Species identification ; several hours Low sensitivity, high cost Most useful for the rapid confirmation of tuberculosis in persons with AFB-positive sputa
- 17. 5.Tuberculin skin test(PPD) Injection of fluid into the skin of the lower arm. 48-72 hours later – checked for a reaction. Diagnosis is based on the size of the wheal. 1 dose = 0.1 ml contains0.04µg Tuberculin PPD.
- 18.
- 19. BCG vaccine BacilleCalmette Guerin(BCG). First used in 1921. Onlyvaccine available today forprotectionagainst tuberculosis. It is mosteffective in protecting children from thedisease. Given 0.1 ml intradermally. Duration of Protection 15 to 20years Efficacy 0 to80%. Should begiven toall healthy infantsas soonas possibleafterbirth unless thechild presented with symptomatic HIV infection.
- 20. LTBI vs. TBDisease Latent TB Infection (LTBI) TB Disease (in the lungs) Inactive, contained tubercle bacilli in the body TST or blood test results usually positive Chest x-ray usually normal Sputum smears and cultures negative No symptoms Not infectious Not a case of TB Active, multiplying tubercle bacilli in the body TST or blood test results usually positive Chest x-ray usually abnormal Sputum smears and cultures may be positive Symptoms such as cough, fever, weight loss Often infectious before treatment A case of TB
- 21. • • • Substance abuse •Recent TB infection • Prolonged therapy with corticosteroids and other immunosuppressive therapy, such as prednisone and tumor necrosis factor- alpha [TNF-α] antagonists • Diabetes mellitus • Severe kidney disease • Certain types of cancer • Certain intestinal conditions • Low body weight Some conditions increase probability of LTBI progressing to TB disease Infection with HIV • Organ transplant Chest x-ray findings • Silicosis suggestive of previous TB Progression to TB Disease
- 22. Tuberculosis Treatment • refersto 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%. • The standard "short" course treatment for TB is isoniazid, rifampicin, pyrazinamideand ethambutol 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%).
- 23. • For latenttuberculosis, • the standard treatment is six to • nine months of isoniazid alone.
- 24. • Ethambutol • isoniazid •pyrazinamide • rifampicin First line Drugs
- 25. Drug regimens: • 2HREZ/4HR3 •means isoniazid, rifampicin, ethambutol, pyrazinamide daily for two months, followed by four months of isoniazid and rifampicin given three times a week.
- 26. Dosage regimen Intensivephase + continuationphase HREZ (2 months) + HRE (4 months)
- 27. Second line • Thereare 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: • *it may be less effective than the first-line drugs • (e.g., p-aminosalicylic acid) • or •*it may have toxic side-effects (e.g., cycloserine) or • *it may be unavailable in many developing countries (e.g., fluoroquinolones)
- 28. Third line • Otherdrugs that may be useful, but are not on the WHO list of SLDs: • rifabutin • macrolides e.g.clarithromycin • linezolid • thioacetazone • thioridazine • arginine • These drugs may be considered "third-line drugs" 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
- 29. Drugs MOA Diagram IsoniazidInhibits mycolic acidsynthesis. RIFAMPICIN Blocks RNA synthesis by blocking DNA dependent RNA polymerase PYRAZINAMIDE •Bactericidal-slowly metabolizing organism within acidic environment of Phagocyte or caseous granuloma.
- 30. Drugs MOA Diagram ETHAMBUTOL•Bacteriostatic •Inhibition of Arabinosyl Transferase STREPTOMYCIN •Inhibition of Protein synthesis by disruption of ribosomal function
- 31. Mode of action& Recommended dose mg/kg Essential anti- tuberculosis drug Mode of action Daily dose mg/ kg 3times/ week Twice/ week NH bactericidal 5 10 15 Rifampicin bactericidal 10 10 10 pyrazinamide bactericidal 25 35 50 streptomyicin bactericidal 15 15 15 Ethambutol bacteriostatic 15 30 45
- 32. Pharmacokinetic Drugs name Half-lifeMetabolism Excretion rifampicin 6 to 7 hours Hepatic and intestinal wall renal 15to 030% Faecal 60% INH 0.5-1.6h (fast acetylators), 2-5h (slow acetylators) liver urine (primarily), feces Ethambutol 3-4 hr (increased in impaired renal function) liver renal pyrazinamide 9-10hr liver renal streptomycin 5-6hr Without hepatic metabolism renal
- 33.
- 34. Drug name Adverse effects cautions contrai ndicati ons Interaction Results INH*Nausea *vomiting *peripheral neuritis *hepatic impairmet *renal drug- induced liver disease *Carbamazepine & phynetoin ↑toxicity of these drugs ↑INH hepatoto xicity INH effects↓ *Convulsion impairment *Carbamazepine *psychotic *epilepsy episodes *alcohol *allergic dependence reactions *Antacids *blood dyscrasias *breast- feeding
- 35. Drugs names Adverse effects cautionscontrai ndicati ons interaction Result s Rifampici n GI disturbance, liver damage , influenza-like syndrome some times with thrombocytopen ia, haemolytic anaemia, shock and renal failure (particularly with intermittent therapy) *hepatic impairme nt *pregnancy & breast- feeding, advise patients on hormonal contraceptive to use additional means, jaundice Phenytoin Digoxin Theophylline Oral anticoagulant Contraceptive b-blockers ↓ Effects of these drugs may coloure skin, urine, *discolours soft contact Sulphonylureas
- 36. Drugs names Adverse effects cautions contrain dication s interactio n Results Ethambut ol optic neuritis, red/green colour blindness, peripheral neuritis, rarelyrash, pruritus, urticaria, thrombocytope nia reduce dose in renal impairment and if creatinine clearance less than 30 mL/minut *children under 6 years optic neuritis, poor vision Almunium hydroxide ↓effect of Ethambutol
- 37. Drugs names Adverse effects cautions contra indicat ions interaction result pyrazinami de Liverdamage, hyperuricemia, *diabetes *gout Liver damage Probenecid antagonize effects of these drugs *GI disturbance, arthralgia, rash *renal dysfunctio n Sulfinpyrazone and occasionally photosensitivity
- 38. Drugs names Adverse effects cautions contrain dications interaction Results streptomyci n *ototoxicity •reversible nephrotoxicty neuromascular blockadewith apnea ↑dose interval in renal dysfunction *pregnancy *Cephalosprins ,cycloserine, vancomycin, ↑nephrotox icty ↑ ototoxicity ↑skletal muscle paralysis amphotericin, myasthenia gravis furosemide *Loop diuretic ,vancomycin, neuromascular blockers
- 39. Kidney disease • *Isoniazid,rifampicin and pyrazinamide are either eliminated almost entierly by biliary excretion or metabolized into non toxic substance . • *these drugs may be given in normal dosage to patients with renal dysfunction. • *In sever renal failure patients should recived pyridoxine with isoniazid in order to prevent peripheral neuropathy.
- 40. • *Streptomycin &Ethambutol can given in reduced dose under close monitoring of renal function (since these drugs are excreted by the kidney). • *Thiocetazone, which is partially in urine, but has a narrow margin of safety , should be avoided in patients with renal failure
- 41. • *When using2HRZ/4HR in patients on dialysis, the drugs should be given daily during the initial high-intensity phase. • *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.
- 42. DOTS DOTS - Directlyobserved treatment,short-course DOT means that a trained health care worker or other designated individual provides the prescribed TB drugsand watches the patient swallow everydose.
- 43. • Lewis, S.Heitkemper, M., Dirksen, S., O’Brien, P.,& Bucher, L. (2011). Medical –Surgical Nursing Assessment and Management of Clinical Problems (8th ed.), volume 1, Philadelphia, PA,: Mosby Elsevier • CDC - Tuberculosis (TB) • www.cdc.gov/tb/ Jun 30, 2018 - Centers for Disease Control and Prevention, Division of Tuberculosis Elimination. • Lippincott’s Mannual • Saunder’s Theory 4th edition • www.seha-elibrary.com REFERENCE