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
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•
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
Pop. A Weakly active
INH
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
Second most active
Most active
Pop. B
RFP 2nd most active
Less active than RFP
Pop. C Most active 2
PZA 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
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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
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
active
Most active
PRIMARY HEALTH CARE [PHILIPPINES] • For 2 months daily Rx -intensive – Rifampicin 450mg – INH 300mg – Pyrazinamide 1000mg to 15000mg
•
Streptomycin (Oldest, 1944)
S**M
VITAL FACTORS IN THE CHEMOTHERAPY OF TB • Correct dosage • Regularity of administration • Adequate duration • Proper drug combination
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– •
History of gout or predisposition to gout (PZA) Patients taking steroids for more than 6 months – Immunosuppression
• •
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
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Advice- stop medication for few days and do desensitization
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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
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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
II. III.
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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
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4 drugs given initially [2 months] – Big bacillary population especially cavitary lesion – Previous use of anti-TB drugs
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High primary resistance to H ? Close contact with resistant source case
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MDT FOR LEPROSY [WHO] Disease Other Name
Rx
Rx duration Surveillance after Rx completion
Paucibacillary Tuberculoid, Indeterminate type
Multibacillary Lepromatous, mid borderline (Serious, fingerless)
Rifampicin 600mg once -Same a month, Dapsone 100 mg 1-2 mg/kg/d -Same -Clofazimine (Lamprene) 300mg once a month AND 50 mg/d 6 months
2 years or until skin smears are negative
Annual exams for at least 2 years
Annual exams for at 14 least 5 years
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 regimen I. 2 HRZE (2 RIPE) / 4HR (4 RI) I. New pulmonary smear (+) cases II. New seriously ill pulmonary smear negative cases with parenchymal involvement III. New seriously ill extrapulmonary TB cases
II. I.
2 HRZES (2 RIPES) / 1 HREZ (1 RIPE) / 5 HRE (5 RIE) Failure cases
III.
Relapse cases X-ray smear (+)
2 HRZ (2 RIP) / 4 HR (4 RI) New cases, smear (--) but with minimal pulmonary TB on x-ray confirmed by medical officer II. New extrapulmonary TB (Not serious) I.
• • • •
H = Isoniazid H R = Rifampicin Z = Pyrazinamide E = Ethambutol
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INH & rifampicin- hepatotoxic Streptomycin & ethambutol- parenteral route Rifampicin- nephrotoxic Pyrazinamide- increase uric acid- gout Ethambutol- cause optic neuritis in chidren