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CHLORAMPHENICOL (CMC)-block protein production (therapeutic use (JANGAN…
CHLORAMPHENICOL (CMC)-block protein production
activity spectrum
broad (G+ve & G-ve)
low income countries
therapeutic use
secondary (due to) atypical organism
typhoid fever (Salmonella typhi-G-ve)
rickettsial infection (atypical)
meningitis (if pen. & cepha x effective)
anthrax (Bacillus anthracis-G+ve)
JANGAN
trivial infection (sikit2)
prophylactic agent (langkah berjaga2)
'common cold, influenza, throat infections'
dose
<2 week; 25mg/kg/d
infant, adult: 50mg/kg/d
pharmacokinetic
oral
C base (capsule)
C palmitate (susp)
extent of absorption/ bioavailability (F)=80%
hydrolysis in GIT by pancreatic lipase
IV
F=70%
C Na succinate
hydrolysis in liver, lungs, kidney (into active drug) by esterase
TDM
therapeutic range: 10-25ug/ml
C max (capsule): 1hr
C max (susp): 1.5-3 hr
C max (IV):0.5-1.5hr
trough (at end of dosage interval)
no study shows relationship between trough conc. & efficacy/ adverse effect
Side effects: 2 types
dose dependent
sore throat, fever, pallor (pale), fatigue, bleeding
bone marrow suppression- reticulocytopenia (reticulocyte: immature RBC)
leucopenia (sikit WBC)
anemia
thrombocytopenia (low platelet)
Gray Baby Syndrome
fatal
2-9 days after start
1st h4 hrs
blue lips
vomit
refusal to suck
irregular & rapid resp.
abdominal distention
period of cyanosis (jari/kaki biru2)
passage of loose
green stool
ashen-gray color
hypothermic (abnormal low B.T)
how?
drug fail conjugate with glucuronic acid
inadequate acitivity glucuronyl transferase in liver (1st 3-4 weeks)
x excreted in renal
acidosis (badan terlebih acid)
dose independent (idiosyncratic) any dose., 1:40,000
aplastic anemia
treatment
exchange transfusion
charcoal
hemoperfusion
drug2 interaction
inhibit metabolism of
tolbutamide
chlorpropamide
warfarin (anticoagulant)
oral contraceptic pills
potent hepatic enzyme inhibitor
stimulate metabolism
phenytoin (seizure)
rifampin (TB)