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Anti- tuberculosis (Second line (Aminoglycoside : streptomycin :…
Anti- tuberculosis
Risk factor
For infection
Time dependent
Family member
Co-worker
Co-infection
For disease
Age <2y , >65y
Immunocompromise
HIV
First line
Rifamycin
Rifampin
จับกับ rpoB
Drug resistance
PK
Absorbtion
Food decrease rifampin Cmax by 1/3
จึงต้องให้ 1-2 ชม. ก่อนทานอาหาร
Metabolite by liver
Excrete in bile 2/3 urine 1/3
ADR
High dose : flu -like symptoms
Overdose : red man syndrome
Inhibit RNA polymerase
Isoniazid
Inhibit mycolic acid synthesis
Inhibit cell wall synthesis
PK
Well absorb from GI
Metabolite by NAT2
Excrete in urine
Enzyme inducer of CYP2E1
Hepatotoxic
Increase AST,ALT
หลังจากให้ยา 1-2 เดือน
Peripheral neuropathy
จึงต้องให้ pyridoxine(B6)ทุกครั้งที่รับยา
Convulsion inpatient with seizure
Overdose
1.5g
Ataxia
Peripheral neuropathy
Dizziness
Slurred speech
30mg/kg
Seizue
Treatment : IV B6 gramต่อgram
Pyrazinamide
Inhibit mycolic acid synthesis
Inhibit cell membranes synthesis
pncA mutation
Resistance
PK
Well absorb in GI
Metabolite by microsomal deamidase
Excrete by Kidney
ADR
Liver toxicity ให้มากกว่าสองเดือน
Inhibit urate excretion
Hyperuricemia
Acute gout
Machanism of TB
Cell wall
High efflux pump
Low pH
DNA mutation
Alteration of enzyme
Transmission
Airborne
Second line
ตรวจ drug susceptibility
Aminoglycoside
: streptomycin
: Amikacin
:kanamycin
: capremycin
Inhibit 30s ribosome
Ototoxicity&nephrotoxicity
Ethionamide
Block mycolic acid synthe sis
Gastric irritation
Para-aminosalicylic acid (PAS)
First TB drug
Cycloserine
ให้วันละ 2 ครั้ง ร่วมกับ B6
Fluroquinolone:
Ciprofloxacin
levofloxacin
moxifloxacin
Principle of anti-TB treatment
Firstline:HRZE
Combination drug
Initial phase
ให้ HRZE สองเดือน
Continuation phase
HR สี่เดือน
Precaution
Taking at bed
B6 with isonazid
Renal failure ไม่ให้ isonazid , rifampin
Resistance
Multidrug resistance (MDRTB)
Isoniazid
Rifampin
Extensively drug resistant
(XDRTB)
Isoniazid
Rifampin
Any fluoroquinolone
1 of 3 injection of second line drug
Ethambutol
PK
80% bioavailability
Bioexponential decline
12 ชม.แรก half-life 3hr
12 ชม.หลัง half-life 9hr
embAB mutation
Resistance
ADR
Decrease renal excretion of urate
Increase serum urate
Inhibit cell wall synthesis