Lecture 5- anti-tb agents Flashcards
clinical diagnosis of active tb based on
- history
- risk factors
- clinical presentation
- physical exam findings
- chest xray findings
when is tx initiated?
when sputum obtained by ziehl neelsen stain PoS
what is the MOH clinical guieline for active tb tx
- assess baseline level for liver enzymes
- adults- test visual activity and coloru vision
standard 6 months regimen
- 2month intensive (RIPES)
- 4 month continuation phase of daily rifam and isoniazid
what are the first line anti TB drugs (5)
R ifampacin Isoniazid pyrazinamide Ethambutol Strptomycin
first line anti TB drugs adverse
cutaneous- pruritis, rash
RIP adverse
GI- anorexia, nausea
admin after light meal or before bedtime
rifampacin spectrum
bactericidal
kills growing and active baciili and stationary phase bacilli
rifampacin MOA
inhibits gene transcription of mycobacteria by blocking dna-dep RNA polymerase–> cannot synthesize mRNA and protein-die
rifam resistance
occurs due to mutation in gene that encodes for RNA poly beta chain
rifampacin ROA
oral
well absorbed on empty stomach
rifampacin metabolidm
hepatic, elim in bile
rifampacin preg
cat C
give mother and baby vit K shot to avoid postpartum haemorrhage (thrombocytonpenia SE)
rifamapcin DDI
induce cyp450 enzymes
rifam adverse
- cutaneous eg. flushing, rash
- fever, chillds
- orange discolouration of bodily fluids eg. tears, sweat
- resp SOB
isoniazid spectrum
bactericidal effect on rapidly growing active bacilli
isoniazid MOA
activated by catalse peroxidase enzyme
inhibit formation of mycolic acids of bac cell wall–> dna damage
isoniazid resistance
mutation to cat-per enzyme and reg genes in mycolic synthesis
isoniazid roa
oral
met in liver through acetylation by n-acetyltransferase
acetylation rate has 2 phenotypes
isoniazid in preg
cat c
rec to also take pyridoxine simul (given to prevent b6 def)
does RI need dose adjustment with renal impair’/
no
what is pyridoxine? and func?
naturally occuring form of vit B6
prevent peripehral neuropathy
give to mother and child
isoniazid DDi
inihibtor of cytochrome P450
affects drugs like phenytoin
pyrazinamide moa
prodrug- needs to be converted into active form pyrazinoic acid by pyrazinamidase
active form accums in bac cytoplasm–> decrease intracellular pH–> inactivate critical pathways
pyrazinamide resistance?
mutation to pyrazinamidase enzymes
pyrazinamide indication
ACTIVE tb
pyrazinamide ROA and absorption
oral admin
well absorbed, can cross BBB
pyrazinamide preg
cat c
pyrazinamide renal and hepa
avoid in liver disease, hepatoxic
dose adjsutment for renal impari
pyrazinamides adverse
GI, photosen, hepatotoxicity, hyperurecemia/ gout
ethambutol spectrum
rapidly growing bacilli
ethambutol moa
inhibit arabinosyltransferase enzyme (encoded by embB gene)–> affect cell wall
ethambutol resistance
mutation of embB gene
ethambutol roa and absorption
oral
80% absorbed
met by liver
ethambutol elim
in urine
ethambutol adverse effects
visual toxicity
- greater risk in kidney failure and elderly
hyperurecemia/gout
ethambutol preg
cat c
safe to use
ethambutol DDI
antacids reduce max conc of E
which drugs are prodrugs?
isoniazid
pyrazinamide
which drug has hepatotoxicity adverse effect
rifampacin
isoniazid
pyrazinamide
which drug will casue visual tox
ethambutol
which drug req dose adjustment with renal failure?
pyrazinamide
ethambutol
what class does streptomycin belogn to
aminoglycoside
ROA of stryptomycin?
IM
streptomycin moa
disotry structure of ribosomes by binding and blocking ofrmation of initiation complex or inhibit translocation
streptomycin elim
in urine
streptomycin adverse
ototoxicity- vertigo, hearing loss
neurotoxicity
nephrotox
should have higher suspicion of drug resistant tb in what population? (4)
who were previously treated,
- who fail treatment,
- who are known contacts of patients with multi drug resistant tuberculosis (MDR-TB), or
- who come from countries with high prevalence of drug resistant tuberculosis
what is multidrug resistance
tb resistant to rifampicin and isoniazid
how to treat multidrud resistance?
multiple second line drugs that are less potent, more toxi, more costly
need give for longer time
what is extensively drug resistant tb
additional resistance to fluoroquinolones and second line agents
what is considered a cure
2 consecutive negative sputum smear
- Nonconversion of sputum cultures at two months is a good surrogate marker for risk of relapse.
