Anti Tuberculosis Flashcards
First line tb
Isoniazid Ethambutol Pyrazinamide Rifampicin Streptomycin
Second line Tb
Amikacin
Levofloxacin
3rd like TB
Cycloserine
Moa isoniazid
Inhibit mycolic acid synthesis
MOA ethambutol
Inhibits cell Wall Synthesis by inhibiting mycobacterial arabinosyl transferases, which are encoded by the embCAB operon
Pyrazinamide MOA
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.
Rifamycin MOA
Inhibits RNA synthesis by targeting DNA-dependent RNA polymerase
Cidal static
Isoniazid
Ethambutol
Pyrazinamide
Rifampicin
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)
First line TB drug target
Inhibit actively dividing bacteria
Ethambutol distribution
Enters erythrocytes
And is slowly released from there
Rifampicin distribution
Well distributed throughout the tissues, including phagocytes and meninges in meningitis
Precaution for isoniazid
Give Pyridoxine (vit B6) to prevent neuropathy and pellagra
ADR isoniazid
- Allergic skin reaction
- Neurotoxicity (peripheral neuropathy, optic neuritis, CNS effect-mental abnormalities, seizure - in susceptible patients )
- Pathological hepatitis - due to metabolite monoacetylhydrazine
- Pellagra (vegans and breastfeed take note )
- Hemolysis and lupus like syndrome in G6PD patients.
Isoniazid absorption
Readily absorb
Distribution isoniazid
Breast milk
CNS (same concentration as plasma)
Ethambutol ADR
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
Ethambutol absorption
Well absorb in gut
Pyrazinamide is inactive at ________ but active at _________
Inactive at neutral pH
Active at pH 5.5
Pyrazinamide ADR
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
Pyrazinamide is a strong _______
Urate retention agent.
_________ oxidize pyrazinoic acid
Xanthine oxidase
Absorption of pyrazinamide
Well absorption
Distribution of pyrazinamide
Widely distributed including inflamed meninges
Rifampin absorption
Well absorption
ADR rifampicin
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.
Y thrombocytopenia occur w rifampicin
Associated complement fixing ab (igg, igm) against platelets (rifampicin dependent ab)
Isoniazid DDI
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)
Ethambutol DDI
Aluminum salts (reduced absorption )
Pyrazinamide DDI
Rifampicin
Isoniazid
Increase hepatotoxicity
Rifampicin DDI
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
