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Anti TB drugs
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BACILLARY POPULATION (IN LUNG FIELDS) • population A – bacilli lining the cavity wall – rapid growth and multiplication due to abundant supply of O2 – reside in neutral or slightly alkaline [pH] environment – source of infectiousness, communicability, and resistant mutants • population B (Persisters) – bacilli in caseous nodules and inner linings of cavitary lesions – slow or intermittent metabolism [persisters] – environment contains little O2 and pH is slightly acidic – source of relapse à difficult to eradicate • population C (Intracellular Bacilli) – bacilli inside macrophages [intracellular population] – slow metabolizers [persisters] – environment is poorly oxygenated and frankly acidic – source of relapse S**M Pop.A INH RFP PZA Pop.B Pop.C active Second m ostactive M ostactive M ostactive W eakly active M ostactive Lessactive than R FP 2 nd m ostactive Streptomycin (O ldest, 1944) 2 ETHAMBUTOL • Bacteriostatic to populations A and C • Inhibits the growth of mutants resistant to INH and RFP • Not hepatotoxic but causes optic neuritis, give to adults only, not in children. • Hepatotoxic: – Isoniazid – Pyrazinamide ß Causes gout – Rifampicin SHORT COURSE THERAPY OR SHORT COURSE CHEMOTHERAPY [AUGUST 19, 1986] Given for the first 2 months - Intesnsive – INH [Isoniazid] 300 mg PO daily – PZA [Pyrazinamide] 500 mg PO daily – RFP [Rifampicin] 450 mg PO AC OD Given for the next 4 months – Maintenance – INH – RFP Same dose as mentioned above • Total number of Rx= 6 months CONTRAINDICATIONS TO SCC • History of liver disease (SGPT, SGOT, alcoholics) • History of chronic and acute renal disease • History of gout or predisposition to gout (PZA) • Patients taking steroids for more than 6 months – Immunosuppression VITAL FACTORS IN THE CHEMOTHERAPY OF TB • Correct dosage • Regularity of administration • Adequate duration • Proper drug combination PRIMARY HEALTH CARE [PHILIPPINES] • For 2 months daily Rx -intensive – Rifampicin 450mg – INH 300mg – Pyrazinamide 1000mg to 15000mg • For 4 months -maintenance – Rifampicin 450mg – INH 300mg • Pyrazinamide 500mg/ tab (aka Para amino salicylic acid) • Above 50 kilos – 3tabs (1,500 mg) • 50 kilos and below – 2tabs (1,000 mg) • Rifater, Pyrina – RNZ (Rifampicin, INH, PZA) – For 2 months • Rifinah – RN (Rifampicin, and INH) – For 4 months REASONS FOR RX FAILURE 1. Non-observance of vital factors of Rx by either physician or px 2. Very extensive disease 3. Uncontrolled DM and alcoholism 4. Primary resistance to drugs 5. Inherent of cellular immunity in the px ADVERSE DRUG REACTIONS [ADR] – 1ST MONTH • Loss of appetite and tiredness without reason - INH • Unexplained nausea and vomiting, collapse - INH • Rash and persistent itchiness - INH • Yellowish discolorations of skin and eyeballs - Rifamp • Flu-like syndrome- fever, chills, pain • When R is given intermittently in high dose - Rifamp • Tingling and burning sensation of hands and feet • Swelling and generalized edema • Shortness of breath - INH • Petechiae and ecchymoses – Rifampicin • Advice- stop medication for few days and do desensitization
Transcript of Anti TB drugs
BACILLARY POPULATION (IN LUNG FIELDS)
• population A– bacilli lining the cavity wall– rapid growth and multiplication due to abundant
supply of O2– reside in neutral or slightly alkaline [pH] environment– source of infectiousness, communicability, and
resistant mutants • population B (Persisters)
– bacilli in caseous nodules and inner linings of cavitary lesions
– slow or intermittent metabolism [persisters] – environment contains little O2 and pH is slightly
acidic– source of relapse à difficult to eradicate
• population C (Intracellular Bacilli)– bacilli inside macrophages [intracellular population]– slow metabolizers [persisters]– environment is poorly oxygenated and frankly acidic– source of relapse
S**M
Pop. A
INH RFP
PZA
Pop. B
Pop. C
active
Second most activeMost active
Most activeWeakly active
Most active
Less active than RFP 2ndmost active
Streptomycin (Oldest, 1944)
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ETHAMBUTOL• Bacteriostatic to populations A and C• Inhibits the growth of mutants resistant to INH and RFP• Not hepatotoxic but causes optic neuritis, give to adults
only, not in children.• Hepatotoxic:
– Isoniazid– Pyrazinamide ß Causes gout– Rifampicin
SHORT COURSE THERAPY OR SHORT COURSE CHEMOTHERAPY [AUGUST 19, 1986]
Given for the first 2 months - Intesnsive– INH [Isoniazid] 300 mg PO daily– PZA [Pyrazinamide] 500 mg PO daily– RFP [Rifampicin] 450 mg PO AC OD
Given for the next 4 months – Maintenance– INH– RFP Same dose as mentioned above
• Total number of Rx= 6 months
CONTRAINDICATIONS TO SCC• History of liver disease (SGPT, SGOT, alcoholics)• History of chronic and acute renal disease• History of gout or predisposition to gout (PZA)• Patients taking steroids for more than 6 months –
Immunosuppression
VITAL FACTORS IN THE CHEMOTHERAPY OF TB• Correct dosage• Regularity of administration• Adequate duration• Proper drug combination
PRIMARY HEALTH CARE [PHILIPPINES]• For 2 months daily Rx -intensive
– Rifampicin 450mg– INH 300mg– Pyrazinamide 1000mg to 15000mg
• For 4 months -maintenance– Rifampicin 450mg– INH 300mg
• Pyrazinamide 500mg/ tab (aka Para amino salicylic acid)• Above 50 kilos – 3tabs (1,500 mg)• 50 kilos and below – 2tabs (1,000 mg)• Rifater, Pyrina – RNZ (Rifampicin, INH, PZA)– For 2 months
• Rifinah – RN (Rifampicin, and INH)– For 4 months
REASONS FOR RX FAILURE1. Non-observance of vital factors of Rx by either physician
or px2. Very extensive disease3. Uncontrolled DM and alcoholism4. Primary resistance to drugs5. Inherent of cellular immunity in the px
ADVERSE DRUG REACTIONS [ADR] – 1ST MONTH• Loss of appetite and tiredness without reason - INH• Unexplained nausea and vomiting, collapse - INH• Rash and persistent itchiness - INH• Yellowish discolorations of skin and eyeballs - Rifamp• Flu-like syndrome- fever, chills, pain• When R is given intermittently in high dose - Rifamp• Tingling and burning sensation of hands and feet• Swelling and generalized edema• Shortness of breath - INH• Petechiae and ecchymoses – Rifampicin
• Advice- stop medication for few days and do desensitization
– Dose- 1/10, ¼, ½ à average dose
DRUG DOSE ADJUSTMENT• INH – 5-10mg/kg, up to 400mg/ day• Rifampicin – 10mg/kg, up to 600mg/day• Pyrazinamide – 25-35 mg/kg, not to exceed 2grams
daily• irrespective of serum uric and level for as long as px is
asymptomatic• Ethambutol – 25mg/ kg/ day for 1st 2 months– 15mg/ kg for next 4 months
• Streptomycin – 15-20mg/ kg up to 1 gram daily by IM
INH PROPHYLACTIC USE– Infants and children up to 6 years who converts to [+]
PPD [without previous BCG]– PPD [–] medical personnel and students who are in close
contact with active cases in wards– Recent tuberculin converters in close contact with open
cases of TB– Px on corticosteroid, anti-metabolite therapy with
previous TB history • dose- 10mg/kg/ day
- 300-400mg daily
Best recommended Rx regimen for pulmonary TB [MDRTB ?]
– RHZE or RHZS daily [2 months]– RH [4 months] daily
• Chemoprophylaxis of adult patient [13-35 years]– INH + Ethambutol daily for 6 months;– Or INH + Rifampicin daily for 4 months
• 4 drugs given initially [2 months]– Big bacillary population especially cavitary lesion– Previous use of anti-TB drugs– High primary resistance to H ?– Close contact with resistant source case
MDT FOR LEPROSY [WHO]Disease Paucibacillary Multibacillary
Other Name Tuberculoid, Indeterminate type
Lepromatous, mid borderline (Serious, fingerless)
Rx Rifampicin 600mg once a month, Dapsone 100 mg 1-2 mg/kg/d
-Same
-Same-Clofazimine(Lamprene) 300mg once a month AND 50 mg/d
Rx duration 6 months 2 years or until skin smears are negative
Surveillance after Rx completion
Annual exams for at least 2 years
Annual exams for at least 5 years
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SIDE NOTES• Give Vitamin B complex (Pyridoxine) to prevent INH (Isoniazid H) toxicity• DOT – Direct Observance Therapy• Streptomycin – Only anti TB drug administered IM• Increased dose in INH causes convulsions• 2 months is INTENSIVE, 4 months is MAINTENANCE• Myrin P – Combination of the following drugs, 2 months: (INTENSIVE)
– R = Rifampicin– I = Isoniazid– P = Pyrazinamide– E = Ethambutol
• Myrin (4 months), only R I E• Rifampicin has PAE against leprosy, it is leprocidal• PHILCAT – Philippine Coalition Against tuberculosis
Rx regimenI. 2 HRZE (2 RIPE) / 4HR (4 RI)
I. New pulmonary smear (+) casesII. New seriously ill pulmonary smear negative
cases with parenchymal involvementIII. New seriously ill extrapulmonary TB cases
II. 2 HRZES (2 RIPES) / 1 HREZ (1 RIPE) / 5 HRE (5 RIE)I. Failure casesII. Relapse casesIII. X-ray smear (+)
III. 2 HRZ (2 RIP) / 4 HR (4 RI) I. New cases, smear (--) but with minimal pulmonary TB on x-ray confirmed by medical officer
II. New extrapulmonary TB (Not serious)
• H = Isoniazid H• R = Rifampicin• Z = Pyrazinamide• E = Ethambutol
• INH & rifampicin- hepatotoxic• Streptomycin & ethambutol- parenteral route• Rifampicin- nephrotoxic• Pyrazinamide- increase uric acid- gout• Ethambutol- cause optic neuritis in chidren
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