Tuberculosis  Complete DRUGS –

• ATT (ANTITUBERCULAR TREATMENT)  TREATMENT with Resistant and MDR Tubercular Treatment In All Cases

Complete RUGS – ATT (ANTITUBERCULAR TREATMENT)  TREATMENT

Case definitions:

• 1. Tuberculosis suspect : Any person with symp­toms or signs suggestive of tuberculosis like cough more than 2 weeks.
• 2. Case of tuberculosis: A patient in whom tuber­culosis is confirmed bacteriologically
• 3. Definite case of tuberculosis : A patient with positive culture for M. tuberculosis complex or patient with 2 sputum smears showing AFB

History of treatment – Definitions for diagnosis:

• 1. New -A patient who has never taken antituber­cular treatment or taken for less than a month.
• 2. Relapse -A patient treated for TB and declared cured, or full treatment taken but smear or cul­ture for tuberculosis is positive.
• 3. Treatment after failure – A patient given An again, after failed previous treatment
• 4. Treatment after default – If a patient, bacterio­logically positive, interrupts treatment for 2 moths or more and starts An again.
• 5. Transfer in – A patient transferred from another TB centre for continuation of treatment.
• 6. Other – Any other case like chronic case, spu­tum positive at the end of repeat treatment.
• Sometimes pulmonary and extra pulmonary relapse cases may be smear-negative.

RUGS – ATT (ANTITUBERCULAR TREATMENT) There are 3 main properties of antituberculous drugs:

• 1. Bactericidal action
• 2 Sterilizing activity
• 3-To prevent resistance.

The first line agents consist of Isoniazid, Rifampin, Pyrazinamide, Ethambutol.

• These drugs are given orally, once a day.
• Peak level is at 4 hours and effect lasts for 24 hours. Second line drugs have lower efficacy and more toxicity. These are streptomycin, kanamycin, amikacin, capreomycin, ethionamide, cycloserine, and PAS(Paraamino salicylic acid).
• Other drugs are Ofloxacin, Levofloxacin, Gatifloxacin, Moxifloxacin, Clofazimine, thiacetazone, amoxycillin and linezolid.
• Isoniazid and Rifampicin are strong bactericidal drugs. Pyrazinamide and streptomycin are also bactericidal Streptomycin is bactericidal against rapidly multiply­ing tubercle bacilli.
• Rifampicin is the most potent sterilizing drug. Ethambutol and thiocetazone prevent resistance to drugs.

Standard Treatment Regimens: Treatment is started with:

• 1 st–  intensive phase for 2 months and
• 2 nd– continuation phase for 4 – 6 months.

Intensive phase consists of Isoniazid, Rifampicin, Pyrazinamide, and EthambutoL.

This intensive phase results in rapid killing of tubercle bacilli.

• In two weeks the infectious patient becomes non­infectious, symptoms subside.
• If patient is smear positive he becomes smear nega­tive in two months.

Continuation phase consists of lesser drugs for longer time.

• This makes the patient disease-free and prevents re­sistance and relapse.
• Patients with large bacillary load (which means smear­positive or HIV-infected patients),’ are given short course chemotherapy with four drugs during initial phase and two drugs during continuation.
• Patients negative for HIV and smear negative tuber­culosis are given rifampicin, isonex, pyrazinamide and ethambutol.
• Ethambutol may not be given in young children and primary tuberculosis.

Retreatment Regimen:

• For patients with smear or culture positive tuberculo­sis, 5 drugs in initial phase and 3 drugs in continua­tion phase should be given.
• Rifampicin, Isonex, Ethambutol are given throughout the treatment.

Standard code for Anti- TB regimens  :

• Each antitubercular drug has an abbreviation as fol­lows:
• Rifampicin – R
• Isoniazid – H
• Pyrazinamide – Z
• Streptomycin – S
• Ethambutol – E
• Thioacetazone – T.

Any regimen consists of :

1. Initial phase
2. Continuation phase

• The number before a phase is duration of that phase in months.
• Letters in brackets indicate the names of drugs.
• A subscript after the letters in brackets indicates num­ber of doses per week. Eg. 2 (HRZE) / 4 (HR)3
• This means that initial phase of 2 months consists of Isoniazid, Rifampicin, Pyrazinamide, Ethambutol. The

TB Diagnostic TB Patients Category

• New smear positive patients; New smear negative PTB with extensive parenchymal involvement;
• Severe concomitant HIV disease or severe forms of EPTB
• Previously treated sputum smear-positive PTB :
• – relapse;

treatment after interruption; treatment failure

• New smear negative PTB (other than in Category I); Less severe forms of EPTB
• Chronic and MDR – TB cases (still sputum positive after supervised re-treatment)

Treatment Regimen in Special Conditions  Pregnancy:

• Streptomycin is unsafe. It is hepatotoxic to fetus and so should not be used in pregnancy.

Breastfeeding :

• All drugs are safe. Baby can be given Isoniazid during infectious stage of mother and for 3 months after that.

Oral contraception:

• Rifampicin interacts with oral contraceptives and de­creases their efficacy.

Liver disease:

• Isoniazid, Rifampicin and Pyrazinamide can cause hepatitis.
• Rifampicin is least toxic, but can cause cholestatic jaundice.
• Pyrazinamide is most hepatotoxic.
• Patients with chronic liver disease should not take Pyrazinamide.
• In chronic liver disease patient can take isoniazid and rifampicin with streptomycin and etham­butol for 8 months.
• In acute he(?atitis, treatment should be delayed till hepatitis resolves otherwise streptomycin and etham-
• continuation phase is of 4 months consisting of Iso­niazid and Rifampicin given 3 times / week.

TB treatment regimens

1. Initial phase (Daily Continuation phase
2. or 3 times weekly) (Daily or 3 times weekly)a

• Specially designed standardized or individualized regimens are suggested for this category
• ethambutol can be given for 3 months and when hepatitis is resolved, isoniazid and rifampicin may be given.
• If acute hepatitis does not resolve for many months then only Streptomycin and Ethambutol should be continued for 12 months.

Renal Failure:

• In renal failure, Isoniazid, Rifampicin and Pyrazina­mide can be given in normal doses.
• Pyridoxin should be given with Isoniazid to prevent peripheral neuropathy if renal failure patients.
• Streptomycin and Ethambutol are avoided or given in low doses.
• Thiocetazone should not be used.
• Patients with renal failure should be on 2 HRZ / 4 HR.

HIV infected patients:

• Thiocetazone is not given. Rest of the drugs can be given.

Chronic and MDR (Mutli-Drug Resistant) TB :

• Chronic tuberculosis is a patient with tuberculosis who. is sputum-positive after standard treatment with es­sential drugs given for complete duration.
• MDR TB is a patient who is Multi-Drug Resistant, i.e. who has active tuberculosis with bacilli resistant to at least Rifampicin and Isoniazid.

Minor

• Anorexia, nausea, abdominal pain Joint pains.
• Burning sensation in the feet
• Orange j red urine
• Pyrazinamide Isoniazid

Major

• Itching, skin rash Deafness (no wax on auroscopy) Dizziness (vertigo and nystagmus) Jaundice (other causes excluded) hepatitis
• Confusion (suspect drug induced acute liver failure if jaundice present)
• Visual impairment (other causes excluded)
• Shock, purpura, acute renal failure
• Thioacetazone (SHRZ) Streptomycin
• Isoniazid, Pyrazinamide, rifampicin
• Reserved drugs for tuberculosis are Amikacin, Kapriomycin, Ciprofloxacin, Cycloserine, Ethionamide, Kanamycin, Ofloxacin, p-aminosalycilic acid.

Management

• Continue anti-TB drugs, check drug doses Give drugs with small meals or last thing at night
• Aspirin
• Pyridoxine 100 mg daily
• Reassurance, Patients should be told when starting treatment that this commonly happens and is normal.

Stop responsible drug(s) Stop anti-TB drugs

• Stop streptomycin use ethambutol
• Stop anti-TB drugs
• Urgent liver function tests and prothrombin time

Management of Drug Induced Hepatitis:

• Isoniazid, Pyrazinamide, Rifampicin, and rarely Etham­butol can damage the liver.
• When a patient develops hepatitis during tubercular treatment, all An should be stopped till liver func­tion tests become normal, or An is not given for 2 weeks after jaundice has disappeared. Rifampicin can give rise to jaundice without hepatitis and symptoms.
• For patients with drug-induced hepatitis Streptomy­cin, and Ethambutol may be given.

Anti Tuburculous Drug Isoniazid

• • Highly bactericidal
• · Given orally (1M also available)
• · Dose 5 mgjkg or 300 mgjday
• · Preventive dose 300 mgjday for 6 months
• · Contraindications – Active liver disease,

Hypersensitivity.

• In malnutrition, alcoholics, and diabetics, patient should be given pyridoxine 10 mgjday with Isoniazid.

Adverse Effects :

• Peripheral neu ropathy Optic neuritis
• Toxic psychosis Generalized convulsions Hepatitis.

Side effects :

• Nausea
• Vomiting Dizziness
• Blurred vision Slurring of speech Seizures.

Rifampicin —

• Strong bactericidal drug
• Should be given 30 minutes before meals Dose is 10 m k or 150 – 600 mg daily
• The drug causes red coloration of urine, tears, saliva, sweat, sputum and contact lenses. Contraindications:
• Hypersensitivity Liver dysfunction.

Adverse effects :

• Gastro-intestinal disturbances Fever
• Flu-like syndrome Thrombocytopenia Skin rashes Exfoliative dermatitis Oliguria
• Dyspnoea
• Hemolytic anaemia
• Hepatitis (which may be fatal).

Pyrazinamide

• Weak bactericidal, potent sterilizing activity. Dose – 30 mgLkgLQay.

Contraindications :

• Hypersensitivity Hepatic impairment.

Adverse effects :

• Gastrointestinal disturbances Increased serum transaminases Hyperuricemia
• Gout
• Arthralgia.

Streptomycin It is bactericidal.

• Given by deep intramuscular injection.
• Dose – 15 mg/kg/day or 750 mg – 1 gm /day. Contraindications :
• Hypersensitivity Auditory nerve deafness Myasthenia gravis
• Should not be used in pregnancy as it causes deafness and nephrotoxicity in the fetus.

Adverse effects :

• Injection abscess Hypersensitivity
• Impairment of vestibular function – Headache, vomiting, vertigo and tinnitus
• Nephrotoxicity
• Hemolytic anaemia
• Aplastic anaemia
• Agranulocytosis
• Thrombocytopenia
• Streptomycin should not be given to patients who are to receive neuromuscular blocking agents during anaesthesia.

Ethambutol —

• Its role is to prevent emergence of resistant strains. Dose – 15 mgLl<g/daL

Contraindication:

• . Hypersensitivity
• .• Optic neuritis
• Creatinine clearance < 50 ml/min.

Adverse effects :

• Optic neuritis – Visual impairment and loss of colour vision
• Blindness
• Peripheral neuritis