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Chemotherapy of Tuberculosis

Chemotherapy of Tuberculosis. By Prof. Azza El-Medany. Tuberculosis. Common sites of infections : 1-Apical areas of lung 2- Renal parenchyma 3- Growing ends of bones Where oxygen tension is high. Transmission. Through inanimate جامده objects

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Chemotherapy of Tuberculosis

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  1. Chemotherapy of Tuberculosis By Prof. Azza El-Medany

  2. Tuberculosis • Common sites of infections : • 1-Apical areas of lung • 2- Renal parenchyma • 3- Growing ends of bones Where oxygen tension is high

  3. Transmission • Through inanimate جامده objects • Through air ( air borne transmission )

  4. Treatment Of Tuberculosis • Tuberculosis remains the primary cause ofdeath due to infectious disease. • Periods of treatment ( minimum 6 months) مهمه • Drugs are divided into two groups: • First line • Second line

  5. Antimycobacterial drugs • First line of drugs: • Isoniazid (INH) • Rifampin • Ethambutol • Streptomycin • Pyrazinamide

  6. Never use a single drug therapy • Isoniazid –rifampin combination administered for 9 months will cure 95-98% of cases . • Addition of pyrazinamide for this combination for the first 2 months allows total duration to be reduced to 6 months.

  7. : اولاIsoniazid • Bacteriostatic for resting bacilli. • مهمهBactericidal قاتل للبكتيريا for rapidly dividing bacilli. • Is effective against intracellular as well as extracellular bacilli لانها تخترق المايكروفيج

  8. Mechanism Of Action • Is a prodrug دواء غير نشط قبل التناول يحول للشكل النشط بعد تنشيطه بواسطه بعض الانزيمات بالجسم او من البكتيريا نفسها, activated by mycobacterial enzyme • Inhibits synthesis of mycolic acid---- ( component of mycobacterial cell wall). مهمه جدا جدا

  9. Clinical uses مهمه • Mycobacterial infections . • Latent tuberculosis in patients with positive tuberculin skin test • Prophylaxis وقائي against active TB in individuals who are in great risk .

  10. Adverse effects • Peripheral neuritis التهاب الاعصاب بالاطراف • يحدث هذا بسبب نقص • Optic neuritis &atrophy. نفس السبب العلاج(Pyridoxine should be given ) • Allergic reactions • systemiclupus erythematosus ( SLE) • Hepatitis من علاماتها ( )مهمه جدا Pyridoxin (vitamine B6) gondes صفار ناتج عن مرض الكبد

  11. Drug Interactions دواء يحظر عمل دواء اخر of INH Cont . تحدث الاعراض الجانبيه غالبا للمرضى الذين : It is more likely to occur in slow acetylators and patients with malnutrition, alcoholism, diabetes and AIDS • Inhibits the hepatic microsomal enzymes, cytochrome P450 . • ..مما يقلل عمليهmetabolize of other drugs

  12. ثانيا : Rifampin • Bactericidal قاتل للبكتيريا • MOA : مهمهInhibits RNA synthesis. بالتاثير على الانزيمات كما شرح بالاسفل • : شرحRifampin binds to the β subunit of bacterial DNA – dependent RNA polymerase اسم الانزيمand thereby inhibits RNA synthesis. • 2nd chioce after INH and do not used alone

  13. Site of Action • Intracellular bacilli • Extracellular bacilli

  14. Clinical uses • Mycobacterial infections • Prophylaxis وقائي of active tuberculosis. • Treatment of serious staphylococcal infections. • Meningitis مهمه by highly resistant penicillin pneumococci • . Atypical mycobacterial infections. • As alternative of isoniazid in prophylaxis of latent tuberculosis

  15. Adverse effects • Harmless red-orange discoloration of body secretions . مثل البول والدم • Hepatitis • Flu-like syndrome • Hemolytic anemia • Thrombocytopenia

  16. Drug Interactions • Potent قوي inducer منشط – عكس الدواء السابق of hepatic microsomal enzymes مهمه جدا جدا ( cytochrome P450) • ..مما يزيد عمليهmetabolize of other drugs مما يعطل عملها Rimpfin excreted by Bile from live as fesses Liver >> bile >> fesses مهمه

  17. : ثالثا Ethambutol • Bacteriostaticمهمه جدا عكس السابق – يقلل تكاثر البكتيريا • مهمه جداInhibits mycobacterialarabinoglycan a component of mycobacterial cell wall لذلك يمنع تكوين الجدار الخلوي

  18. Site Of Action • Intracellular & Extracellular bacilli

  19. Clinical uses • Treatment of tuberculosis in combination with other drugs. الاستخدام الوحيد له

  20. Adverse effects • Optic neuritis مهمه جدا causing loss of visual acuity • red-green color blindness. (Relatively contraindicated in children under 5 years). • Hyperuricemia

  21. Contraindication موانع الاستخدام • It is relatively contraindicated in children too young to permit assessment of visual acuity and red green color discrimination

  22. Pyrazinamide • Prodrug يتحول للشكل النشط عند درجه حامضيه منخفضه • يتحول للشكل النشط كما يلي : • Pyrazinamide >> يتحول الى pyrizenic acid at PH= 5.5 • Bactericidal • Mechanism of action is unknown . Pharmacodinamic : 1- widley disturputed 2- orally and well absorbed in GIT 3- pass through 1st pass metabolism in liver then excreted through kidney Half time = 8-11 H

  23. Site Of Action • Active against Intracellular Bacilli

  24. Clinical uses • Mycobacterial infections mainly in multidrug resistance cases. • It is important in short –course (6 months) regimen. • Prophylaxis وقائي of TB .

  25. Adverse effects • Hepatotoxicity • Hyperuricemia >> cause GOUTY نقرس ARTHRIETS مهمه جدا ( سؤال ) • Drug fever & skin rash

  26. : رابعا Streptomycin • Bactericidal • Inhibitors of protein synthesis by binding to 30 S ribosomal subunits. • Active mainly on extracellular bacilli يعتبر كبديل لل في الخطه العلاجيه given by injection الوحيد الذي يعطى عبر الحقن عكس كل السابق الذي يعطى عبر الفم erythrobutile

  27. Clinical uses • Severe , life-threating form of T.B. as meningitisمهمه, disseminated disease.

  28. Adverse Effects • Ototoxicityمهمه • Nephrotoxicity تسمم الكليه • Neuromuscular block

  29. Indication of 2nd line treatment • Resistance to the drugs of 1st line. • Failure of clinical response • There is contraindication for first line drugs. • Patient is not tolerating the drugs first line drugs.

  30. اولا Ethionamide • Inhibits the synthesis of mycolic acid هذا الدواء له نفس ميكانيكيه INH ويعتبر شبيه له

  31. Clinical uses • As a secondary line agent.

  32. Adverse Effects Poorly tolerated Because of : مهمه • Severe gastric irritation & • Neurological manifestations

  33. ثانيا : CAPREOMYCIN • يعطى عبر العضل ولذلك من اعراضه الجانبيه • Local pain & sterile abscesses due to injection. • ومن اثاره الجانبيه : • Nepherotoxicity

  34. : ثالثا Cycloserine • Inhibitor of cell wall synthesis by inhipite formation of peptiesdoglycan • The most serious side effects are peripheralneuropathy and CNS dysfunction مهمه. • Pyridoxineshould be given. • Contraindicated in epileptic صرع patients.

  35. : رابعا Fluoroquinolones (Ciprofloxacin &Levofloxacin ) • Effective against multidrug- resistant tuberculosis. • Block DNA bacterial synthesis • يستخدم ضد الجرام السالبه

  36. Adverse effects • Nausea , vomiting , diarrhea • Prolong QT interval • Damage growing cartilage ( arthropathy) مهمه لذلك لا يعطى للاطفال والحوامل والمرضعات

  37. خامسا : Rifabutin rifampin • RNA inhibitor. شبيه ال • Cross –resistance with rifampin is complete. • Enzyme inducer for P450 (hepatic enzymes).

  38. Clinical uses • Effective in prevention &treatment of T.B. in AIDS patients.

  39. Adverse Effects • GIT intolerance • Orange-red discoloration of body secretions.

  40. سادسا : Aminosalicylic Acid (PAS). • قليل الاستخدام هذه الايام بسبب كثره الاعراض الجانبيه • Bacteriostatic • Inhibits Folic acid synthesis.

  41. Clinical uses • AS a second line agent is used in the treatment of pulmonary & other forms of tuberculosis.

  42. Adverse effects • GIT upset ( anorexia, nausea, diarrhea, epigastric pain ). • Hypersensitivity reactions • Crystalluria

  43. TB & Pregnancy • Untreated TB represents a great risk to the pregnant woman & her fetus than the treatment itself. • First line drugs are given for 9 months in normal doses • Streptomycin is the last alternative in treatment

  44. TB & Breast Feeding • It is not a contraindication to receive drugs , but caution is recommended شكر خااااص لـ غالي عبد الرحمن فهد المطيري ناصر العبيداء

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