TB Flashcards
What is the WHO Rx success target for TB
85%
Two Phases of TB treatment
Intensive phase
Continuation phase
Objectives of each phase of TB RX
Intensive - Clinical improvement and negative sputum
Continuation - Prevent relapse and sterilisation
Name 3 metabolic populations of TB
Rapid multipliers
Slow multipliers
Sporadic multipliers
Which TB drugs target each metabolic population of bacilli
Rapid - INH>RIF>EMB
Slow - PZA>RIF>INH
Sporadic - RIF>INH
Difference between TB and gram + cell wall
TB has Capsule + Mycolic acid + Arabinogalactan layers. Over and above the Peptidoglycan and Cell membrane layers of gram +
MOA of INH
Inhibits mycolic acid synthesis
AEs of INH
Peripheral neuropathy (vit B6) Hepatitis
PK of INH
Prodrug (activated by cKatG and mycobacterial catalase peroxidase)
How is INH metabolised
Acetylation (genetically determined)
MOA of Rif
Inhibits RNA synthesis
Bind subunit of bacterial DNA-dependent RNA polymerase
Most common AEs of Rif
Rash
Fever
Nausea
Vomiting
Less common AEs of Rif
Hepatitis
Hypersensitivty
PK of Rif
Absorption decreased with food.
Autoinduction.
Excreted into bile.
Main challenges of dual HIV/TB therapy
- Interactions
- Toxicity
- IRIS
- Pill burden
Options for lop/rit dose when given with rif
Double dose.
or
Add 300mg rit to the 400mg lop dose.
MOA of pyrazinamide
- Inhibit fatty acid synthase (inhib mycolic acid synthesis)
- Reduces intracellular pH
- Disrupt membrane transport.
AEs of pyrazinamide
Hepatiis
Gout
Hypersensitivity
PK of pyrazinamide
Good tissue penetration
Active at low pH
MOA of ethambutol
Inhibits arabinogalactan synthesis
AEs of ethambutol
Retrobulbar neuritis (dose dependent) Hyperuricaemia (gout)
PK of ethambutol
Poor CNS penetration Renal elimination (adjust in KD)
3 hepatotoxic TB drugs
PZA, INH, RIF
Risk factors for TB dili
- Age
- Female
- Malnutrition
- HIV
- Chronic Hep B/C
When TB dili usually occur?
Definition of TB dili
ALT >120 and symptomatic or ALT>200 and assymptomatic or Total bilirubin >40umol/l
What can TB dili be confused with
/.Asymptomatic transaminitis (ALT
Define MDR TB
Resistance to Rif and INH
Define XDR TB
Resistance to INH, Rif and NB second line drugs (Quinolones and injectables)
Treatment of MDR TB intensive phase
[6months - or until culture conversion] Kanamycin Moxifloxacin Ethionamide Terizidone Pyrazinamide
Treatment of MDR TB continuation phase
[18 months] Moxifloxacin Ethionamide Terizidone Pyrazinamide
If hearing loss, renal insufficiency or peripheral neuropathy in MDR Rx, which drug should you consider
Capreomycin
egs of Flouroqinolones
Ofloxacin
Levofloxacin
Moxifloxacin
egs of Aminoglycasides
Streptamycin
Amikacin
Kanamicin