Distribution: wide not in CSF Metabolism in the liver up to 15% Mainly unchanged in the urine

Tuberculosis: treatment and prevention Flashcards by luyanda mtshali

what are the goals of Goals of TB treatment

Cure the patient of TB
* Prevent transmission of TB to
others
* Prevent the development of
acquired resistance
* Prevent relapse
* Prevent death from TB or its
complications

How well did you know this?

Not at all

Perfectly

Principles of TB treatment

Combination Therapy
* Usually, combination tablet
* Intensive and continuation
phase

Period
* Period varies until TB
bacteria are eradicated in
different places

Adherence
* Counselling sessions

How well did you know this?

Not at all

Perfectly

Drugs used as treatment for TB

isoniazid
ethambutol
pyrazinamide
Rifampicin

How well did you know this?

Not at all

Perfectly

First line TB treatment: mechanisms of action of the drugs

Isoniazid (INH /H)
Inhibits synthesis of the mycolic acid layer of the mycobacterial cell wall

Ethambutol (E)
Inhibits synthesis of the arabinogalactan
layer of the mycobacterial cell wall

Pyrazinamide (PZA / Z)
Converted to an acid in the cytoplasm of the mycobacterium, acidify the intracellular environment and
compromise the integrity of the cell
membrane (only effective in dormant mycobacteria)

Rifampicin (Rif / R)
Inhibits mycobacterial RNA synthesis by binding to and inhibiting the

How well did you know this?

Not at all

Perfectly

site and stage of infection: Rifampicin

Bactericidal for intra and extracellular bacteria.
Sterilising activity

How well did you know this?

Not at all

Perfectly

Drug used foe excellent early bactericidal activity

Isoniazid

How well did you know this?

Not at all

Perfectly

site and stage of infection: pyrazinamide

Mycobactericidal for intracellular mycobacteria in an acidic
medium.
Most useful during intensive phase

How well did you know this?

Not at all

Perfectly

Ethambutol

Bacteriostatic (bactericidal at hight doses)

How well did you know this?

Not at all

Perfectly

: monitoring safety of TB treatment

Hepatotoxicity monitoring (rifampicin, isoniazid, pyrazinamide).
Monitor liver function: DILI (drug-induced liver injury) * High risk patients: chronic infectious hepatitis, pre-existing liver disease, MDR
TB patients, high levels of alcohol consumption, other hepatotoxic drugs,
HIV+, females and elderly
* Screening for hepatotoxicity: new onset abdominal pain, nausea & vomiting,
jaundice / dark urine
* Check bilirubin and transaminases (5x the upper limit / 3x the upper limit
with jaundice

How well did you know this?

Not at all

Perfectly

Management of adverse effect of Rifampicin

Side-effect
CI: oral contraceptives
Nausea, GI disturbances
Discoloration of body fluids
(tears, saliva, urine, faeces) orange
/ red
Enzyme induction

take with FOOD

How well did you know this?

Not at all

Perfectly

management of adverse effect of Isoniazid

Adverse: Peripheral neuropathy (burning /
pins & needles in feet & legs)

supple with pyridoxine

How well did you know this?

Not at all

Perfectly

management of adverse effect of Ethambutol

Optic neuritis

Vision check-ups

How well did you know this?

Not at all

Perfectly

management of adverse effect of Pyrazinamide

joint pain (gout), hepatotoxic.

How well did you know this?

Not at all

Perfectly

Pharmacokinetics: Rifampicin

Metabolism in the liver – cause
autoinduction and potent
enzyme inducer * Elimination: primarily biliaryfaecal route
Hepatotoxic
Drug-interactions with drugs
metabolised in the liver * Oral contraceptives & progestin
implants (replace with injectable
contraceptives) * Orange/red/brown pigmentation
of body fluid

How well did you know this?

Not at all

Perfectly

Pharmacokinetics Isoniazid

Distribution: wide including the
CSF
Metabolism in the liver via
acetylation (slow acetylators at
greater risk of neurotoxicity) * Inactive metabolites excreted in
the urine
Hepatotoxic
Neurotoxic (peripheral
neuropathy, seizures, psychosis,
ataxia & optic neuritis) reversed
by pyridoxine (B6) * Drug-interactions with drugs
metabolised in the liver (weak
enzyme inhibitor) * Caution in patients with ep

How well did you know this?

Not at all

Perfectly

Ethambutol

Distribution: wide not in CSF
Metabolism in the liver up to
15%
Mainly unchanged in the urine

How well did you know this?

Not at all

Perfectly

cautions of Ethambutol

Cautions: renal failure, in
children under 8 years (visual
symptoms difficult to assess),
hyperuricaemia
* Ocular toxicity – patient selfmonitoring (reading fine print),
monitor: colour discrimination
and visual field

How well did you know this?

Not at all

Perfectly

Pharmacokinetics: Pyrazinamide

Distribution: wide including the
CSF
Dose-related hepatotoxicity
Hyperuricaemia (caused by
decreased uric acid clearance)
associated with arthralgia (may
precipitate gout

How well did you know this?

Not at all

Perfectly

The wanted. outcomes of TB

Prevent TB transmission
Cure with minimal problems
Cure with chronic lung disease

How well did you know this?

Not at all

Perfectly

The unwanted outcomes of Tb

Transmission of TB
* MDR / XDR
* Death

How well did you know this?

Not at all

Perfectly

MDR-TB

is a form of tuberculosis that is resistant to at least two of the most potent first-line anti-TB drugs, isoniazid and rifampicin. It poses a significant challenge to tuberculosis control efforts worldwide due to its complexity, prolonged treatment duration, increased costs, and higher rates of treatment failure and mortality compared to drug-susceptible TB.

Drug-resistant TB: categories

Mono-resistant TB
* Poly-resistant TB
* MDR-TB
* Rifampicin resistant-TB (RR-TB)
* Resistance to at least rifampicin
* Extensively drug-resistant TB (XDR-TB)
* Pre-XDR-T

Multidrug resistant

MDR In vitro resistance to:
* Rifampicin
* Isoniazid
* With or without resistance to other
anti-TB drugs.

XDR (extensively DR)

MDR TB
+
In vitro resistance to: * Any fluoroquinolone * AND
Any injectable drug
Extremely difficult and expensive to treat with a high mortality (90%) in HIV co-infected

Isoniazid resistance is caused by

* inhA mutation and * katG mutation

Drug-resistant TB treatment regimens

Short regimen Pre -2024 – old regimen being phased out: Short course: * At least 6 drugs used for 9 months. for adults, pregnant and kids> than 6 yrs 2024 – new regimen being phased in: * BPaL-L: * At least 3 drugs used for 6 month. for 6 months

Long regimen

Long regimen * 18 months * Complicated EPTB / extensive disease on CXR * Children < 6 years * Hx of previous treatment with 2nd line drugs for more than 1 month * Contact with XDR / Pre-XDR * Both INH mutations

The 6-month BPaL-L regimen;

short course Bedaquiline, * Pretomanid, * Linezolid (600 mg) * With or without levofloxacin (if sensitive)

core drugs for long regime

* Bedaquiline, * Linezolid * Levofloxacin (substitute if fluoroquinolone resistance) * Clofazimine * Terizidone

Co-administer pyridoxine to prevent peripheral neuropathy due to terizidone: dose for adult and children

50 mg for adults 25 mg for children

Bedaquilline

do not use for kids for less than 6 yrs

since Bedaquiline is used in kids greater than 6 yrs it is substituted by what drugs

* Delamanid (3 to 6 years) * Para-aminosalicylic acid (less than (<)3 years)

The mechanism of action of bedaquiline

inhibit mycobacterium ATP synthase metabolised by CYP3A4 need LFT monitoring (ALT, AST, bili) * DI: CYP3A4 inhibitors / inducers, hepatotoxic drugs * Major adverse effects: QT prolongation (ECG monitoring – stop if >500ms) * DI: fluoroquinolones, macrolides, clofazimine, disease

The drug that inhibits peptidoglycan synthesis and is widely distributed including CSF

Terizidone

Major adverse effects of Terizidone

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

a weak enzyme inducer drug

isoniazid

which drug causes renal failure and hyperuricemia in children less than 8 years ?

Ethambutol remember it is not given to kids < 8 for TB treatment, affects the optic nerve, not metabolized by the liver that much. and it is bacteriostatic but can kill at high doses. excreted in urine inhibit synthesis of arabinogalactan

drug that is dose-related hepatotoxicity and widely distributed in the CFS.

Pyrazinamide

drug that is bactericidal in an acidic medium.

Pyrazinamide.

extremely difficult and expensive to treat and has a high motility rate in HIV infected patients.

extra Drug-resistant.

individualized long regimen designed according to who grouping?

if Rifampicin-resistant meningitis if resistant to Bedaquiline, linezolid, pretomanid and cfs

Bedaquiline is safe to use in ?

above 6 years

inhibit peptidoglycan synthesis and is widely distributed including CFS

Terizidone

Major adverse effects: Terizidone

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

adverse effect of clofazimine

Adverse effects: common - red/brown pigmentation of conjunctiva and skin and body fluids * QT prolongation * DI: fluoroquinolones, macrolides, bedaquiline * Monitor hepatic function * Counselling: take with food to diminish GI upset

* 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

clofazimine

used in children between 3-6 years. substutite of bedaquiline. and has adverse effect of insomia, hallucination, night terrors.

delamanid

Pretomanid

MOA: inhibit bacterial cell wall mycolic acid biosynthesis * Administered with bedaquiline and linezolid to treat resistant forms of pulmonary TB * Major adverse effects: Peripheral neuropathy, acne, anaemia,

SYMPTOMS FOR SCREEN

Cough (any duration) * Fever * Unexplained weight loss * Night sweats * History of previous TB * Adherence to ART