Tuberculosis: Treatment and prevention 3

Question 1

MoA for clofazimine

Answer 1

Membrane destabilisation
Reactive species

Question 2

MoA for PAS

Answer 2

Mycobactin (decreased iron uptake)
Inhibition of folic acid synthesis

Question 3

MoA of Bedaquiline

Answer 3

ATP synthase

Question 4

MoA of ethambutol

Answer 4

Cell wall sythesis

Question 5

MoA of meropenem imipenem amoxicillin, clauvulanic acid and cycloserine terizidone

Answer 5

Inhibition of peptidoglycan synthesis

Question 6

MoA of isoniazid
Protiomide
Ethionamide

Answer 6

Mycolic acid biosynthesis

Question 7

MoA of PA-824 Delamanid

Answer 7

Reactive species a
Mycolic acid biosynthesis

Question 8

MoA of moxifloxacin
Gatilofloxacin
Ofloxacin

Answer 8

DNA gyrase

Question 9

MoA of rifampicine and rifabutin

Answer 9

Inhibition of RNA synthesis

Question 10

MoA of linezolid, sutezolid AZD5847, Amikacin, kanamycin, capreomycin, clarithromycin

Answer 10

Ribosome-inhibit protein synthesis

Question 11

Bedaquiline increases risk of what?

Answer 11

Increased risk of mortality

Question 12

MoA of bedaquiline

Answer 12

Ihibits mycobacterial ATP synthase

Question 13

Pks of bedaquiline: metabolism

Answer 13

PKs: metabolised by CYP3A4 need LFT monitoring (ALT, AST, bili)

Question 14

DI for dedaquiline

Answer 14

DI: CYP3A4 inhibitors / inducers, hepatotoxic drugs.
DI: fluoroquinolones, macrolides, clofazimine, diseases

Question 15

Major adverse effects of bedaquiline

Answer 15

Major adverse effects: QT prolongation (ECG monitoring – stop if
>500ms)

Question 16

MoA od terizidone

Answer 16

MOA: Inhibits peptidoglycan synthesis

Question 17

Distribution of Terizidone

Answer 17

• Widely distributed including CSF

Question 18

The major effects and DI for Terizidone

Answer 18

Major adverse effects:
* Peripheral neuropathy (treat with pyridoxine or amitriptyline)
* DI: isoniazid
* Seizures, anxiety, depression, psychosis
* CI: psychiatric disorders / symptoms

Question 19

Pks of clofazimine

Answer 19

• Pharmacokinetics:
• Accumulate in tissues: fat, skin, liver, kidneys and reticulo-endothelial cells – cause
  red-brown pigmentation of conjunctiva and skin; may impart red colour to urine,
  sweat, tears, sputum
• Eliminated in bile and faeces

Question 20

Adverse effects of Clofazimine and DI

Answer 20

Adverse effects: common - red/brown pigmentation of conjunctiva and skin
and body fluids
* QT prolongation
* DI: fluoroquinolones, macrolides, bedaquiline

Question 21

what to monitor when using clofazimine

Answer 21

Monitor hepatic function

Question 22

counselling for clofazimine

Answer 22

• Counselling: take with food to diminish GI upset

Question 23

Delamanid is used for which age group and monitor what?

Answer 23

Children 3-6 years (monitor for neuropsychiatric adverse effects:
insomnia, hallucinations, night terrors)

Question 24

Major advese effects of Delamanid and DI and counselling

Answer 24

Major adverse effects:
* Common, nausea, vomiting and dizziness
* QT prolongation (discontinue if QTcF is >500ms or ventricular
arrhythmia)
* DI: fluoroquinolones, macrolides, bedaquiline, clofazimine
* DI – hepatotoxic drugs & CYP3A4 inhibitors
* Counselling: take with food to diminish GI upset

Question 25

MoA of pretomanid

Answer 25

MOA: inhibit bacterial cell wall mycolic acid biosynthesis

Question 26

List drugs to treat resistant forms of pulmonary TB

Answer 26

Pretomanid Bedaquiline Linezolid

Question 27

Major adverse effects of pretomanid

Answer 27

Major adverse effects: Peripheral neuropathy, acne, anaemia,

Question 28

DI for pretomanid

Answer 28

DI: Avoid alcohol and hepatotoxic agents, strong or moderate CYP3A4 inducers, including herbal supplements

Question 29

Explain the TB chemoprophylaxis

Answer 29

TB test and treat approach: offering either TPT or active TB treatment to achieve TB elimination, it is imperative to implement TPT more comprehensively for everyone with significant TB exposure and all other individuals at high risk of TB. In most instances, people who should be offered TPT will share a household with at least one person who is concurrently on TB treatment. Therefore, where possible, a 'family-centred' approach to TPT initiation and adherence support should be adopted

Question 30

TPT and IPT stands for what

Answer 30

Abbreviations * Tuberculosis preventive therapy (TPT) * Isoniazid preventive therapy (IPT)

Question 31

It is important to rule out TB disease before initiating which TB chemoprophylaxis

Answer 31

TPT

Question 32

All people considered for TPT should undergo what?

Answer 32

All people considered for TPT should undergo clinical evaluation (symptom check and physical examination - CXR) and be tested with GeneXpert (Xpert), even if asymptomatic.

Question 33

List peole who acquire TPT

Answer 33

TB contacts: All adults, adolescents and children (including newborns or infants) exposed to TB require TPT ,once T.B disease has been excluded through evaluation - irrespective of HIV status, pregnancy, or previous TB disease or treatment status. Significant TB exposure can occur in any setting, e.g. in the household, workplace, place of learning or care, or other. * People living with HIV: All adults, adolescents and children including infants living with HIV (irrespective of a known significant TB exposure) should receive a course of TPT once TB disease has been excluded through testing. People newly diagnosed with HIV should always be tested for TB prior to initiating antiretroviral treatment (ART). * Inmates in correctional facilities after ‘significant TB exposure’ * Healthcare workers * People who previously had TB after ‘significant TB exposure’