Lecture 5- anti-tb agents

Question 1

clinical diagnosis of active tb based on

Answer 1

• history
• risk factors
• clinical presentation
• physical exam findings
• chest xray findings

Question 2

when is tx initiated?

Answer 2

when sputum obtained by ziehl neelsen stain PoS

Question 3

what is the MOH clinical guieline for active tb tx

Answer 3

• 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

Question 4

what are the first line anti TB drugs (5)

Answer 4

R ifampacin
Isoniazid
pyrazinamide
Ethambutol
Strptomycin

Question 5

first line anti TB drugs adverse

Answer 5

cutaneous- pruritis, rash

Question 6

RIP adverse

Answer 6

GI- anorexia, nausea

admin after light meal or before bedtime

Question 7

rifampacin spectrum

Answer 7

bactericidal

kills growing and active baciili and stationary phase bacilli

Question 8

rifampacin MOA

Answer 8

inhibits gene transcription of mycobacteria by blocking dna-dep RNA polymerase–> cannot synthesize mRNA and protein-die

Question 9

rifam resistance

Answer 9

occurs due to mutation in gene that encodes for RNA poly beta chain

Question 10

rifampacin ROA

Answer 10

oral

well absorbed on empty stomach

Question 11

rifampacin metabolidm

Answer 11

hepatic, elim in bile

Question 12

rifampacin preg

Answer 12

cat C

give mother and baby vit K shot to avoid postpartum haemorrhage (thrombocytonpenia SE)

Question 13

rifamapcin DDI

Answer 13

induce cyp450 enzymes

Question 14

rifam adverse

Answer 14

• cutaneous eg. flushing, rash
• fever, chillds
• orange discolouration of bodily fluids eg. tears, sweat
• resp SOB

Question 15

isoniazid spectrum

Answer 15

bactericidal effect on rapidly growing active bacilli

Question 16

isoniazid MOA

Answer 16

activated by catalse peroxidase enzyme

inhibit formation of mycolic acids of bac cell wall–> dna damage

Question 17

isoniazid resistance

Answer 17

mutation to cat-per enzyme and reg genes in mycolic synthesis

Question 18

isoniazid roa

Answer 18

oral
met in liver through acetylation by n-acetyltransferase
acetylation rate has 2 phenotypes

Question 19

isoniazid in preg

Answer 19

cat c

rec to also take pyridoxine simul (given to prevent b6 def)

Question 20

does RI need dose adjustment with renal impair’/

Answer 20

no

Question 21

what is pyridoxine? and func?

Answer 21

naturally occuring form of vit B6
prevent peripehral neuropathy
give to mother and child

Question 22

isoniazid DDi

Answer 22

inihibtor of cytochrome P450

affects drugs like phenytoin

Question 23

pyrazinamide moa

Answer 23

prodrug- needs to be converted into active form pyrazinoic acid by pyrazinamidase
active form accums in bac cytoplasm–> decrease intracellular pH–> inactivate critical pathways

Question 24

pyrazinamide resistance?

Answer 24

mutation to pyrazinamidase enzymes

Question 25

pyrazinamide indication

Answer 25

ACTIVE tb

Question 26

pyrazinamide ROA and absorption

Answer 26

oral admin

well absorbed, can cross BBB

Question 27

pyrazinamide preg

Answer 27

cat c

Question 28

pyrazinamide renal and hepa

Answer 28

avoid in liver disease, hepatoxic

dose adjsutment for renal impari

Question 29

pyrazinamides adverse

Answer 29

GI, photosen, hepatotoxicity, hyperurecemia/ gout

Question 30

ethambutol spectrum

Answer 30

rapidly growing bacilli

Question 31

ethambutol moa

Answer 31

inhibit arabinosyltransferase enzyme (encoded by embB gene)–> affect cell wall

Question 32

ethambutol resistance

Answer 32

mutation of embB gene

Question 33

ethambutol roa and absorption

Answer 33

oral
80% absorbed
met by liver

Question 34

ethambutol elim

Answer 34

in urine

Question 35

ethambutol adverse effects

Answer 35

visual toxicity
- greater risk in kidney failure and elderly
hyperurecemia/gout

Question 36

ethambutol preg

Answer 36

cat c

safe to use

Question 37

ethambutol DDI

Answer 37

antacids reduce max conc of E

Question 38

which drugs are prodrugs?

Answer 38

isoniazid

pyrazinamide

Question 39

which drug has hepatotoxicity adverse effect

Answer 39

rifampacin
isoniazid
pyrazinamide

Question 40

which drug will casue visual tox

Answer 40

ethambutol

Question 41

which drug req dose adjustment with renal failure?

Answer 41

pyrazinamide

ethambutol

Question 42

what class does streptomycin belogn to

Answer 42

aminoglycoside

Question 43

ROA of stryptomycin?

Answer 43

IM

Question 44

streptomycin moa

Answer 44

disotry structure of ribosomes by binding and blocking ofrmation of initiation complex or inhibit translocation

Question 45

streptomycin elim

Answer 45

in urine

Question 46

streptomycin adverse

Answer 46

ototoxicity- vertigo, hearing loss
neurotoxicity
nephrotox

Question 47

should have higher suspicion of drug resistant tb in what population? (4)

Answer 47

who were previously treated,

2. who fail treatment,
3. who are known contacts of patients with multi drug resistant tuberculosis (MDR-TB), or
4. who come from countries with high prevalence of drug resistant tuberculosis

Question 48

what is multidrug resistance

Answer 48

tb resistant to rifampicin and isoniazid

Question 49

how to treat multidrud resistance?

Answer 49

multiple second line drugs that are less potent, more toxi, more costly
need give for longer time

Question 50

what is extensively drug resistant tb

Answer 50

additional resistance to fluoroquinolones and second line agents

Question 51

what is considered a cure

Answer 51

2 consecutive negative sputum smear

- Nonconversion of sputum cultures at two months is a good surrogate marker for risk of relapse.