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MBBS IV - Supplementary Courses > Tuberculosis - Treatment (III) > Flashcards

Tuberculosis - Treatment (III) Flashcards

1
Q

4 first line drugs for TB

Standard Regimen

A

Isoniazid (H) -300mg
Rifampicin (R) - 600mg
Ethambutol (E) - 900mg
Pyrazinamide (Z) - 1.5g

for 60kg patient

Standard Rx: 2HREZ/ 4HR
2 months 4 drugs + 4 months 2 drugs

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2
Q

Location for TB drug admin?

A

Supervised daily treatment at chest clinics under DoH

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3
Q

4 common, mild adverse reactions to standard TB regimen

A

GI: discomfort, low appetite (Pyrazinamide)

Skin reaction/ allergy

Vestibular (Streptomycin)

Liver derangement

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4
Q

Serious adverse reaction special for ethambutol?
- 3 symptoms

  • Management?
A

ETHAMBUTOL OPTIC NEUROPATHY (metal chelating effect)
Bilateral progressive painless visual blurring
Changed color vision
impair central vision

  • Stop ethambutol
  • Optic neuropathy generally reversible and low dose is advised
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5
Q

Serious Hepatitis symptoms caused by which TB drug?

Symptoms?

A

Rifampicin

Abdominal pain
Brown urine **
Fever, fatigue, flu-like symptoms
Nausea and vomiting

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6
Q

2 Serious adverse reactions specific for isoniazid?

A

Nervous system damage: Dizziness, tingling/ numbness at mouth

Peripheral pneuropathy

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7
Q

2 Serious adverse reactions specific for pyrazinamide

A

Stomach upset

Gout*: abonormal uric levels, joint aches

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8
Q

3 Serious adverse reactions specific for rifampicin

A

Bleeding problems: easy bruising, slow clot

Discoloration of body fluids: orange urine, sweat or tears

Drug interactions: many drugs

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9
Q

Management of GI upset from TB drugs?

A
  1. Exclude hepatitis by blood test
  2. Take drugs with food, take at bedtime
  3. No split doses, use single daily dose regimen
  4. Antiemetics (but not antacids)
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10
Q

2 forms of fixed dose combination of TB drugs?

Drawback?

A

Rifater: H, R, Z

Rifinah: H, R

  • Cannot modify dose e.g. for patient with renal impairment, cannot modify dose
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11
Q

Management of non-petechial rash from TB drugs

mild rash? severe rash?

A
  1. Exclude other causes (e.g. viral infections)
  2. Mild rash = antihistamine or topical steroid
  3. Moderate to severe rash = stop TB drugs, give anti-histamine, systemic steroid
  4. Watch for progression and mucosal involvement, consult dermatologist
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12
Q

List 5 emergency complications of TB drugs

A

Hepatitis (HRZ)

Retrobulbar neuritis (E)

Thrombocytopenia (R)

Acute renal failure (R)

SJS

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13
Q

Hepatotoxicity from TB drugs.

  • Host risk factors?
  • When to stop TB drugs?
  • Management
A

Risk factors: alcoholics, Chronic viral hepatitis

Threshold: ALT 3x OR Bilirubin 2x upper limit of normal

Stop treatment, reintroduce regimen with less hepatotoxicity (e.g. streptomycin, amikacin, ethambutol …etc)

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14
Q

ALT levels continue to rise after stopping TB drugs after clinical signs of hepatitis.
Normal or Abnormal?

A

Normal

ALT takes 1-2 weeks to reach peak levels then return to normal in drug-induced hepatitis

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15
Q

4 risk factors for hepatotoxicity from TB drugs?

A

Old
Low BMI
Malnutrition
Pre-existing liver diseases: alcoholic liver disease, chronic viral hepatitis

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16
Q

ALT and ALP levels fluctuates around normal levels after starting TB drugs.
Should TB drugs be stopped?

A

No

ALT and ALP fluctuation is normal

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17
Q

Severe end-stage drug-induced hepatotoxicity.

  • How to assess?
  • Treatment?
  • Prevention?
A

Serum bilirubin 2X + Transaminase increase

Both increase at the same time = severe hepatotoxicity.
(Hepatotoxicity = only transaminase rise)

End- stage liver transplant

Stopping TB drugs earlier = better prognosis

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18
Q

Recommended dosage for ethambutol?

A
  • 15mg/kg/day (normal kidney)

- 7.5mg/kg/day (impaired kidney, GFR <30mL/min)

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19
Q

Management of ethambutol optic toxicity

A
  1. Maintain low dose at 15mg/kg/day
  2. Drug-susceptibility test for ethambutol > stop if positive
  3. Lower dose for renal impairment
  4. Warn all patients to report change in vision ASAP
  5. Check vision of at-risk patients monthly
20
Q

Which TB drug causes acute kidney injury?

  • Mechanism?
  • Pathologies?
A

Rifampicin

Type II or III hypersensitivity reaction: rifampicin antigens + anti-rifampicin antibody complexes deposit in renal vessels, glomerular, interstitial space

Acute interstitial nephritis
Acute tubular necrosis

21
Q

Which TB drug causes thrombocytopenia?

A

Rifampicin

Antiplatelet antibodies generated&raquo_space; low platelet

22
Q

Which TB drug causes peripheral neuropathy?

  • Host risk factors?
  • Prophylaxis?
A

Isoniazid

Risk factors: elderly, DM, alcoholism, slow acetylator phenotype, HIV, renal failure

Prophylaxis: Pyridoxine 10-20mg/day up to high dose 50-100mg/day

23
Q

Which TB drug causes the most drug interactions?

- Mechanism? ***

A

Rifampicin

Powerful inducer of CYP450 enzyme system > increase metabolism/ catabolism of many drugs > decrease drug effectiveness

24
Q

Give examples of drugs that interact with rifampicin (6 main classes)

A 
Anticoagulants: Warfarin 
HIV: PI and NNRTI 
Oral hypoglycemic drugs (sulphonylureas)
Anticonvulsants: phenytoin 
Contraceptives
Immunosuppressants
25
Q

Special management for young, female patients taking rifampicin in TB regimen?

A

Stop oral contraceptives, change to other contraceptive methods

26
Q

Effect of rifampicin on warfarin and corticosteroids?

A

Need much higher dose of warfarin and corticosteroids (e.g. for Addison disease) than normal

27
Q

Treatment for HIV patients with TB infection?
Which drugs should not be used?
Which HIV drugs to use?

A

Normal HIV patient: TB treatment first + ART treatment within 8 weeks

Severely immunocompromised HIV patient: TB treatment first + ART treatment within 2 weeks

Do not use protease inhibitor (PI) or NNRTI

Use Efavirenz-based or Raltegravir-based regimen + 2 NRTIs

28
Q

If a patient is on long-term therapy with drugs that interact with Rifampicin, should rifampicin be substituted in treating TB infection?

A

No

Rifampicin should be kept. Should not be substituted because of drug interactions.

29
Q

Isoniazid drug interaction:

  • Mechanism?
  • Drugs interacted?
  • Effect with Rifampicin?
A

Isoniazid = potent inhibitor of CYP isozymes&raquo_space; Increase concentration of some drugs to toxic levels

Examples: Increase benzodiazepine levels (metabolized by oxidation)

Rifampicin induce CYP, Isoniazid inhibit CYP&raquo_space; overall effect balances each other

30
Q

Fluoroquinolone drug interaction:

  • Mechanism?
  • Drugs interacted?
  • Management if taking interactive drugs and fluoroquinolone?
A

Interfere GI absorption of antacids, sucralfate, metal cations&raquo_space; Low systemic levels

Take interacting drugs at least 2 hours before fluoroquinolone

31
Q

Most effective method in control of TB?

A

Direct Observed Therapy

Take every dose under supervision = complete whole course, lower treatment failure, drug resistance, disease spread

32
Q

Risk factors for TB therapy default

A 
Smoking 
History of default 
Poor initial adherence pattern 
Strong side effects from treatment 
Hospitalization
33
Q

3 factors that determine probability of TB transmission

A
  1. Infectiousness of person with TB (e.g. Positive culture, sputum smear, CXR, symptoms…etc)
  2. Duration and frequency of exposure (e.g. close contacts)
  3. Environment of exposure (e.g. crowded, poorly ventilated)
34
Q

5 aims of TB contact tracing.

A
  1. Find source of infection
  2. Find contacts with active TB, isolate
  3. Find uninfected close contacts for BCG vaccine
  4. Educate contacts about TB, seek medical advice early with symptom
  5. Find Latent TB for preventative regimen
35
Q

WHO recommendation for close contact TB inestigation?

A

If contact has:

  • sputum smear-positive pulmonary TB
  • PLHIV
  • is a Child under 5
36
Q

Define Mono- , Rifampicin- , and Polyresistance TB

A

Mono-resistant: 1 first line drug only

Rifampicin resistant

Polyresistance: More than 1 first line drug other than Isoniazid and rifampicin

(Isoniazid and rifampicin = MDR-TB, not polyresistant)

37
Q

Define MDR-TB and XDR -TB

A

MDR-TB = Resisatnt to at least both Isoniazid and Rifampicin

XDR - TB = Resistant to any fluoroquinolone + At least one of 3 injectables (Capreomycin, Kanamycin, Amikacin) + MDR

38
Q

Drawback to conventional TB drug susceptibility testing?

A

Slow: microscopy, culture from isolated clinical specimen for susceptibility testing

  • Time for resistance amplification
  • Wrong treatment for patient
  • Resistant strains keep spreading
39
Q

Name 2 fast TB drug susceptibility test?

A

Xpert MTB/ RIF Ultra

Line Probe Assays - 1st line = rifampicin and isoniazid resistance; 2nd line = fluoroquinolone and injectable resistance

40
Q

Treatment of MDR-TB (5 drugs)

A

At least:

  • Pyrazinamide
  • Fluoroquinolone
  • Parenteral agent (injectables)
  • Ethionamide
  • Cycloserine or PAS
41
Q

Treatment of XDR-TB

A

MDR regimen + FQ + bedaquiline or linezolid

42
Q

List 2 new Add-on agents/ Group D TB drugs

Are these commonly used?

A

Bedaquiline (diarylquinoline) = not really used (long QT interval)

Delamanid (nitromidazopyran, inhibit mycolic acid biosynthesis) = not used

43
Q

Adverse effects of Bedaquiline

A

QT prolong

Hepatotoxicity

CYP3A4 drug interaction

Long half life

44
Q

Linezolid.
Used or not in MDR-TB?
Adverse effects?

A

No
Peripheral neuropathy
Bone marrow suppression

45
Q

Current recommendation of MDR-TB: Class A and Class B?

A

Class A: (use 3)

  • Levofloxacin
  • Bedaquiline
  • Linezolid

Class B: (choose 1)

  • Clofazimine
  • Cycloserine or terizodone
46
Q

Isoniazid resistant TB treatment

A

Rifampicin + ethambutol + Pyrazinamide + Levofloxacin

6 months

47
Q

Effects of BCG vaccine?
Efficacy globally?
Effects on primary infections or latent TB?

A

Protective against meningitis and disseminated TB in children

Slow decline globally

Does not prevent primary infection, prevent reactivation of latent pulmonary infection

MBBS IV - Supplementary Courses (54 decks)

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