Anti Tuberculosis

Question 1

First line tb

Answer 1

Isoniazid 
Ethambutol 
Pyrazinamide
Rifampicin
Streptomycin

Question 2

Second line Tb

Answer 2

Amikacin

Levofloxacin

Question 3

3rd like TB

Answer 3

Cycloserine

Question 4

Moa isoniazid

Answer 4

Inhibit mycolic acid synthesis

Question 5

MOA ethambutol

Answer 5

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

Question 6

Pyrazinamide MOA

Answer 6

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.

Question 7

Rifamycin MOA

Answer 7

Inhibits RNA synthesis by targeting DNA-dependent RNA polymerase

Question 8

Cidal static

Isoniazid
Ethambutol
Pyrazinamide
Rifampicin

Answer 8

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)

Question 9

First line TB drug target

Answer 9

Inhibit actively dividing bacteria

Question 10

Ethambutol distribution

Answer 10

Enters erythrocytes

And is slowly released from there

Question 11

Rifampicin distribution

Answer 11

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

Question 12

Precaution for isoniazid

Answer 12

Give Pyridoxine (vit B6) to prevent neuropathy and pellagra

Question 13

ADR isoniazid

Answer 13

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.

Question 14

Isoniazid absorption

Answer 14

Readily absorb

Question 15

Distribution isoniazid

Answer 15

Breast milk

CNS (same concentration as plasma)

Question 16

Ethambutol ADR

Answer 16

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

Question 17

Ethambutol absorption

Answer 17

Well absorb in gut

Question 18

Pyrazinamide is inactive at ________ but active at _________

Answer 18

Inactive at neutral pH

Active at pH 5.5

Question 19

Pyrazinamide ADR

Answer 19

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

Question 20

Pyrazinamide is a strong _______

Answer 20

Urate retention agent.

Question 21

_________ oxidize pyrazinoic acid

Answer 21

Xanthine oxidase

Question 22

Absorption of pyrazinamide

Answer 22

Well absorption

Question 23

Distribution of pyrazinamide

Answer 23

Widely distributed including inflamed meninges

Question 24

Rifampin absorption

Answer 24

Well absorption

Question 25

ADR rifampicin

Answer 25

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.

Question 26

Y thrombocytopenia occur w rifampicin

Answer 26

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

Question 27

Isoniazid DDI

Answer 27

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)

Question 28

Ethambutol DDI

Answer 28

Aluminum salts (reduced absorption )

Question 29

Pyrazinamide DDI

Answer 29

Rifampicin Isoniazid Increase hepatotoxicity

Question 30

Rifampicin DDI

Answer 30

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