Anti Tuberculosis Flashcards

1
Q

First line tb

A
Isoniazid 
Ethambutol 
Pyrazinamide
Rifampicin
Streptomycin
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2
Q

Second line Tb

A

Amikacin

Levofloxacin

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3
Q

3rd like TB

A

Cycloserine

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4
Q

Moa isoniazid

A

Inhibit mycolic acid synthesis

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5
Q

MOA ethambutol

A

Inhibits cell Wall Synthesis by inhibiting mycobacterial arabinosyl transferases, which are encoded by the embCAB operon

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6
Q

Pyrazinamide MOA

A

Inhibits cell membrane synthesis

Pyrazinamide is converted to active form pyrazinoic acid under acidic conditions in macrophage lysosomes.
Which disrupts mycobacterial cell membrane metabolism and transport functions.

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7
Q

Rifamycin MOA

A

Inhibits RNA synthesis by targeting DNA-dependent RNA polymerase

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8
Q

Cidal static

Isoniazid
Ethambutol
Pyrazinamide
Rifampicin

A

Cidal (mainly intra cellular) in rapid multiplying bacteria. Static in dormant bacteria.

Most active against isoniazid and rifampicin resistant MTB

Static (intracell)

Cidal (intra and extra)

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9
Q

First line TB drug target

A

Inhibit actively dividing bacteria

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10
Q

Ethambutol distribution

A

Enters erythrocytes

And is slowly released from there

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11
Q

Rifampicin distribution

A

Well distributed throughout the tissues, including phagocytes and meninges in meningitis

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12
Q

Precaution for isoniazid

A

Give Pyridoxine (vit B6) to prevent neuropathy and pellagra

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13
Q

ADR isoniazid

A
  1. Allergic skin reaction
  2. Neurotoxicity (peripheral neuropathy, optic neuritis, CNS effect-mental abnormalities, seizure - in susceptible patients )
  3. Pathological hepatitis - due to metabolite monoacetylhydrazine
  4. Pellagra (vegans and breastfeed take note )
  5. Hemolysis and lupus like syndrome in G6PD patients.
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14
Q

Isoniazid absorption

A

Readily absorb

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15
Q

Distribution isoniazid

A

Breast milk

CNS (same concentration as plasma)

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16
Q

Ethambutol ADR

A

1) GIT - diarrhea
2) allergic rash
3) hyperuricaemia (asymptotic), occasional gouty arthritis (due to inhibition of uric acid secretion)

4) optic neutitis with visual abnormality. (Most significant)
- reduced visual acuity, red/green color blindness; loss of peripheral vision with central scotomata

Best avoided in children under 8yo

17
Q

Ethambutol absorption

A

Well absorb in gut

18
Q

Pyrazinamide is inactive at ________ but active at _________

A

Inactive at neutral pH

Active at pH 5.5

19
Q

Pyrazinamide ADR

A

1) hepatotoxicity (dose related)
2) GIT - nausea, vomiting
3) rashes , photosensitivity
4) arthralgia (Joint stiffness)
5) hyperuricaemia (mostly asymptomatic)
- it’s metabolites pyrazinoic acid interfere with tubular secretion of UA. Rarely cause acute gouty arthritis

20
Q

Pyrazinamide is a strong _______

A

Urate retention agent.

21
Q

_________ oxidize pyrazinoic acid

A

Xanthine oxidase

22
Q

Absorption of pyrazinamide

A

Well absorption

23
Q

Distribution of pyrazinamide

A

Widely distributed including inflamed meninges

24
Q

Rifampin absorption

A

Well absorption

25
Q

ADR rifampicin

A

1) harmless orange colour to urine, sweat, and tears (soft contact lenses may be permanently stained)
2) skin eruption, fever and GIT disturbance are the most common side effects.

3) hepatitis (occasional)
4) hyperbilirubinaemia
5) transaminasaemia
6) immunologically mediated reactions
- thrombocytopenia
- flu-like syndrome. Usually with low doses of intermittent rifampicin. There maybe accompanying acute tubular necrosis.

26
Q

Y thrombocytopenia occur w rifampicin

A

Associated complement fixing ab (igg, igm) against platelets (rifampicin dependent ab)

27
Q

Isoniazid DDI

A

1) phenytoin
2) carbamazepine

(Isoniazid is liver microsomal enzyme inhibitor and reduces the metabolism of these drugs)

3) rifampicin
4) pyrazinamide
5) alcohol intake
( increase risk of hepatotoxicity)

6) aluminum salts (reduce absorption)

28
Q

Ethambutol DDI

A

Aluminum salts (reduced absorption )

29
Q

Pyrazinamide DDI

A

Rifampicin
Isoniazid

Increase hepatotoxicity

30
Q

Rifampicin DDI

A

1) warfarin
2) HIV protease inhibitors
3) most non-nucleoside reverse transcriptase inhibitors (nNRTIs)
4) oral contraceptives
5) isoniazid (hepatotoxicity)
6) pyrazinamide (hepatotoxicity)

Rifampicin is a liver enzyme inducer, induces its own metabolism and that of other drugs.

7) methadone
Increases the urinary excretion of methadone “methadone withdrawal” signs