TB Flashcards
1st line TB treatment
Intenstive 2 months
- Rif, INH, PZA, etham
Continuation phase 4 months
- RIf, INH
When do patients become sputum negative?
After 2 months
Role of INH
- NB in early therapy
- bactericidal
- rapidly reduces bacterial count
- active mainly against aerobic organisms in cavities
Role of Rif
- killing slow metabolisers
- sterilizing patient’s sputum
Role of PZA
- active at low pH
- ideal for killing organisms inside causeous necrotic foci
MOA of INH and Etham
Inhibits cell wall synthesis
MOA of Rif
Inhibits RNA synthesis
- binds to the subunit of bacterial DNA-dependent RNA polymerase
MOA of PZA
- disrupts plasma membrane
- disrupts energy metabolism
Adverse effects of INH
- dose and duration related
- peripheral neuropathy
- hepatitis
Pharmacokinetics
Produg - activated by cKatG,
Penetrates tissues well
Genetically determined acetylation
Toxicity effects of rifampicin
- rash, fever, nausea, vomiting
- hepatitis
- hypersensitivity
Pharmacokinetics of RIF
- variable absorption (food decreases)
- excreted into bile
- autoinduction
- strong CYP inducer
Challenges of dual HIV/TB therapy
- Drug-drug interactions
- overlapping toxicity
- pill burden
- IRIS
Toxicity effects of PZA
- hepatitis
- gout
- hypersensitivity
Pharmacokinetics of PZA
- penetrates tissues well
- active at low pH
Toxicity effects of ehtambutol
- retrobulbar neuritis
- hyperuricaemia and gout
Pharmacokinetics of ethambutol
- poor CNS penetration
- renal elimination (adjust in renal disease)
3 potentially hepatotoxic 1st line drugs
- PZA
- INH
- Rif
Risk factors for hepatotoxicity with TB meds
- age
- female
- malnutrition
- HIV
- Chronic Hep B/C
When does DILI usually occur?
- within the first 3 months
Definition of DILI
- ALT >120 and symptomatic
- ALT >200 and asymptomatic
- Total BR <40
MDR definiton
Resistance to INH and RIF
XDR definition
Resistance to INH, RIF and important 2nd line drugs (quinolones, injectables)
MDR treatement regimen
5 drugs for 6 months
4 drugs for 18 months
MDR intensive phase drugs
- kanamycin
- moxifloxacin
- ethionamide
- terizidone
- pyrazinamide
MDR continuation phase drugs
- moxiflox
- ethionamide
- terizidone
- pyrazinamide
2nd vs 1st line TB drugs
- more toxic
- more expensive
- longer duration
- less successful
