ANTI-TUBERCULAR DRUGS

Yogapriya.vB.Opt(IIIyr)

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

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

PRIMARY OR STANDARD DRUGS(bactericidal)

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

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

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

PRIMARY OR STANDARD DRUGS (bacteriostatic)

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

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

SECONDARY OR RESERVE DRUGS

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

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

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

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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