chemotherapy of tuberculosis by prof. azza el-medany
TRANSCRIPT
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 Through air ( air borne transmission )
Treatment Of Tuberculosis
Tuberculosis remains the primary cause of death due to infectious disease.
Periods of treatment ( minimum 6 months) مهمه
Drugs are divided into two groups:First lineSecond line
Antimycobacterial drugs
First line of drugs:Isoniazid (INH)RifampinEthambutolStreptomycinPyrazinamide
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.
Isoniazidاوال :
Bacteriostatic for resting bacilli. مهمهBactericidal للبكتيريا قاتل
for rapidly dividing bacilli.Is effective against intracellular as
well as extracellular bacilli النهاالمايكروفيج تخترق
Mechanism Of Action
Is a prodrug التناول قبل نشط غير دواءبواسطه تنشيطه بعد النشط للشكل يحولالبكتيريا من او بالجسم بعضاالنزيماتactivated by mycobacterial enzyme ,نفسها
Inhibits synthesis of mycolic acid----
( component of mycobacterial cell wall). جدا جدا مهمه
Clinical uses مهمهMycobacterial infections .Latent tuberculosis in patients with positive
tuberculin skin test
Prophylaxis وقائي against active TB in individuals who are in great risk .
Adverse effectsPeripheral neuritis باالطراف االعصاب التهاب بسببنقص هذا يحدثOptic neuritis &atrophy. نفسالسبب
( Pyridoxine should be given)العالجAllergic reactionssystemic lupus erythematosus ( SLE)Hepatitis ( ) عالماتها جدا من مهمه
Pyridoxin (vitamine B6)
gondes
مرضالكبد عن ناتج صفار
Drug Interactions اخر دواء عمل يحظر of INH دواءInhibits the hepatic microsomal enzymes,
cytochrome P450 . .. عمليه يقلل metabolize of otherمما
drugs
Cont .الذين للمرضى غالبا االعراضالجانبيه : تحدث
It is more likely to occur in slow acetylators and patients with malnutrition, alcoholism, diabetes and AIDS
Rifampin : ثانيا
Bactericidal للبكتيريا قاتلMOA : مهمهInhibits RNA synthesis.
باالسفل شرح كما االنزيمات على بالتاثير : شرحRifampin binds to the β subunit of
bacterial DNA – dependent RNA polymerase االنزيم .and thereby inhibits RNA synthesis اسم
2nd chioce after INH and do not used alone
Site of Action
Intracellular bacilliExtracellular bacilli
Clinical usesMycobacterial infectionsProphylaxis 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
Adverse effects
Harmless red-orange discoloration of body secretions . والدم البول مثل
HepatitisFlu-like syndromeHemolytic anemiaThrombocytopenia
Drug Interactions
Potent قوي inducer عكس – منشطالسابق of hepatic microsomal الدواء
enzymes جدا جدا cytochrome ) مهمهP450)
.. عمليه يزيد metabolize of otherمماdrugs عملها يعطل Rimpfin excreted byمما
Bile from live as fessesLiver >> bile >> fesses
مهمه
Ethambutol ثالثا :
Bacteriostatic – عكسالسابق جدا مهمهالبكتيريا تكاثر يقلل
جدا Inhibits mycobacterialمهمهarabinoglycan a component of mycobacterial cell wall تكوين يمنع لذلك
الخلوي الجدار
Site Of Action
Intracellular & Extracellular bacilli
Clinical uses
Treatment of tuberculosis in combination with other drugs. له الوحيد االستخدام
Adverse effects
Optic neuritis جدا causing loss of مهمهvisual acuity
red-green color blindness.(Relatively contraindicated in
children under 5 years).
Hyperuricemia
Contraindication االستخدام موانع It is relatively contraindicated in children too
young to permit assessment of visual acuity and red green color discrimination
PyrazinamideProdrug درجه عند النشط للشكل يتحول حامضيه
منخفضه يلي كما النشط للشكل : يتحول Pyrazinamide >> الى pyrizenic acid at PH= 5.5 يتحول
Bactericidal Mechanism of action is unknown .
Pharmacodinamic : 1- widley disturputed 2- orally and well absorbed in GIT3- pass through 1st pass metabolism in liver then excreted through kidney
Half time = 8-11 H
Site Of Action
Active against Intracellular Bacilli
Clinical uses
Mycobacterial infections mainly in multidrug resistance cases.
It is important in short –course (6 months) regimen.
Prophylaxis وقائي of TB .
Adverse effects
Hepatotoxicity
Hyperuricemia >> cause GOUTY نقرس ARTHRIETS ( ) سؤال جدا مهمه
Drug fever & skin rash
Streptomycin رابعا :
BactericidalInhibitors of protein synthesis by binding to 30 S
ribosomal subunits. Active mainly on extracellular bacilli
العالجيه الخطه في لل كبديل يعتبر given by injection عبر يعطى الذي الوحيدعبر يعطى الذي السابق عكسكل الحقنالفم
erythrobutile
Clinical uses
Severe , life-threating form of T.B. as meningitis مهمه, disseminated disease.
Adverse Effects
Ototoxicityمهمه Nephrotoxicity الكليه تسممNeuromuscular block
Indication of 2nd line treatment
Resistance to the drugs of 1st line.Failure of clinical responseThere is contraindication for first line
drugs.Patient is not tolerating the drugs first
line drugs.
Ethionamide اوال
Inhibits the synthesis of mycolic acid
نفسميكانيكيه له الدواء هذا INH
له شبيه ويعتبر
Clinical uses
As a secondary line agent.
Adverse Effects
Poorly tolerated
Because of : مهمهSevere gastric irritation &Neurological manifestations
CAPREOMYCIN : ثانيا
الجانبيه اعراضه من ولذلك العضل عبر يعطى Local pain & sterile abscesses due to injection. الجانبيه اثاره : ومن Nepherotoxicity
Cycloserine ثالثا :
Inhibitor of cell wall synthesis by inhipite formation of peptiesdoglycan
The most serious side effects are peripheral
neuropathy and CNS dysfunction مهمه.
Pyridoxine should be given. Contraindicated in epileptic صرع patients.
Fluoroquinolones رابعا : (Ciprofloxacin &Levofloxacin )
Effective against multidrug- resistant tuberculosis.
Block DNA bacterial synthesis السالبه الجرام ضد يستخدم
Adverse effects
Nausea , vomiting , diarrhea Prolong QT interval Damage growing cartilage ( arthropathy) مهمه
والمرضعات والحوامل لالطفال يعطى ال لذلك
Rifabutin : خامسا
RNA inhibitor. ال شبيهCross –resistance with rifampin is
complete.Enzyme inducer for P450 (hepatic
enzymes).
rifampin
Clinical uses
Effective in prevention &treatment of T.B. in AIDS patients.
Adverse Effects
GIT intolerance
Orange-red discoloration of body secretions.
Aminosalicylic Acid : سادسا(PAS).
كثره بسبب االيام هذه االستخدام قليل االعراضالجانبيه
Bacteriostatic
Inhibits Folic acid synthesis.
Clinical uses
AS a second line agent is used in the treatment of pulmonary & other forms of tuberculosis.
Adverse effects
GIT upset ( anorexia, nausea, diarrhea, epigastric pain ).
Hypersensitivity reactions
Crystalluria
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
TB & Breast Feeding
It is not a contraindication to receive drugs , but caution is recommended
خااااصلـ شكرالرحمن عبد غالي
المطيري فهدالعبيداء ناصر