Antitubercular drugs
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Transcript of Antitubercular drugs
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ANTI-TUBERCULAR DRUGS
Yogapriya.vB.Opt(IIIyr)
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INTRODUCTION
• Tuberculosis is an infectious disease caused by the mycobacteria M.tuberculosis
• It was once considered to be an incurable disease
• But now,effective chemotherapeutic agents are available for its treatment
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CLASSIFICATION OF DRUGS
PRIMARY OR STANDARD DRUGS
SECONDARY OR RESERVE DRUGS
i) BACTERICIDAL• Isonicotinic acid hydrazide• Rifampicin• Streptomycin• pyrazinamide
i) BACTERICIDAL• Capreomycin• kanamycin
ii) BACTERIOSTATIC• Ethambutol• Para aminosalicylic acid• thiacetazone
ii) BACTERIOSTATIC• Ethionamide• cycloserine
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PRIMARY OR STANDARD DRUGS(bactericidal)
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ISONICOTINIC ACID HYDRAZIDE (INH)
• It is the mosteffective drug used in the treatment of tuberculosis• It is a tuberculocidal drug
Mechanism of action • INH acts by inhibiting the synthesis of mycolic acid• It is an unique fatty acid component of mycobacterial cellwall
Absorption,fate and excretion• INH is well absorbed on both oral and parenteral administration• It is distributed in all body tissues and fluids including CSF• It is mainly metabolized in liver by acetylation• It is almost completely excreted in urine within 24 hours
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Adverse reaction• Intolerence like fever,malaise or jaundice• Peripheral neuritis due to pyridoxine deficiency is an important toxicity• CNS effects like convulsion and psychosis• Epigastric distress,dryness of mouth and urinary retention
Preparation and doseIsoniazid tablet-300mg daily by oral route
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RIFAMPICIN
• It is a semisynthetic derivative of rifamycin B(isolated from Streptomyces mediteranei)
• It is bactericidal and it acts by inhibiting DNA dependent RNA polymerase• It is well absorbed on oral administration• It is widely distributed in tissues• It is metabolized to desacetyl rifampicin• This metabolite is equally tuberculocidal and undergoes enterohepatic circulation
Adverse reaction• Hepatitis is the major adverse effect• Also it produces skin rashes,eosinophilia and leucopenia• Rifampicin imparts an orange red color to urine,sweat,tear and other secretion
Dose450 mg daily by mouth
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PRIMARY OR STANDARD DRUGS (bacteriostatic)
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ETHAMBUTOL
• It is a bacteriostatic drug• It is used with other bactericidal drug as a substitute for PAS• It is effective against mycobacteria resistant to INH,PAS and streptomycin• It is absorbed after oral administration
Adverse reactionOptic neuritis and peripheral neuritis
Dose800 mg per day by oral route
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PARA AMINOSALICYLIC ACID(PAS)
• It is a synthetic compound which is less potent than streptomycin or INH
Dose• Dose is high =10-15 g daily• So it is rarely used now
THIACETAZONE• It is a thiosmicarbazone derivative• It is used with INH or as a substitute for PAS• It is absorbed orally• It crosess placenta and also secreted in milk
Adverse reactionDrug fever,skin rashes,anemia,liver and kidney damage
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SECONDARY OR RESERVE DRUGS
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CAPREOMYCIN• It is a polypeptide antibiotic obtained from Streptomyces capreolus• it is inactivated in the gastrointestinal tract• So it is administered by parenteral route• It is effective against mycobacteria resistant to drug of first choice
Adverse effectsAllergy,renal disturbances and 8th nerve damage
KANAMYCIN• It is an aminoglycoside antibiotic obtained from Streptomyces kanamyceticus• it is effective against mycobacteria resistant todrug of first choice• It is completely absorbed from the gut
Adverse effectNephrotoxicity and 8th nerve damage
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ETHIONAMIDE
• It is chemically related to INH• It is effective against tubercle bacilli resistant to other drugs• It act by inhibiting protein synthesis• It is rapidly absorbed from gastrointestinal tract• A significant concentration is present in CSF
Adverse reactionAllergic reactions,gastrointestinal symptoms and neurological disturbances
CYCLOSERINE
• It is an antibiotic having tuberculostatis effect• It is well absorbed from the gut• Significant concentration is present in CSF
Adverse effects• Neurologic and psychic effets
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NEWER DRUGS
• Fluoroquinalones like ciprofloxacin and ofloxacin• Macrolids like clarithromycin and azithromycin• Rifabutin which is related to rifampicin• They are used in multi-drug resistant tuberculosis in combination with
other drugs
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Followed by (for 4 months)
SHORT TREM REGIMEN FOR TUBERCULOSIS ( for 2 months)
INH 300 mgRIFAMPICIN 450 mgETHAMBUTOL 800 mgPYRAZINAMIDE 1.5 g
INH 300 mgRIFAMPICIN 450 mg
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