Tuberculosis Flashcards
What is tuberculosis?
Caused by mycobacterium tuberculosis which is a slow growing acid fast bacterium.
What is the structure of mycobacterium tuberculosis?
Acid fast:
Cell wall rich in lipids, v. hydrophobic, resistant to drying and weak disinfectants.
What is the first stage in the primary progression of TB?
Bacili inhaled in droplets, phagocytosed by macrophages.
The macrophages do not destroy the bacili.
What is the second stage in the progression of TB?
The M.TB now in the macrophages multiplies for 7-21 days before the macrophage burts open. The incoming macrophages then phagocytose the released M.TB.
What is the third stage in the progression of TB?
Cell mediated immune response is initiated and tubercules are formed.
What is the fourth stage of the progression of TB?
Multiplication of M.TB inside macrophages continues until uncontrolled lysis occurs.
Enzymes are thus released that destroy local tissue causing the formation of lesions.
What are the signs and symptoms indicative of TB infection?
Cough, afternoon fever, weight loss, blood stained sputum, night sweats.
How is active TB diagnosed?
Chest X ray: white lesions replace alveoli with scar tissue.
Sputum test: smears and/or cultures: visualise TB in sputum via microscopy and staining.
How is latent TB diagnosed?
Tuberculin skin test, if lesion forms > 10mm diameter after 48-72hr.
Molecular assay:
- Xpert MTB/RIF assay
- IFNgamma tests
How can TB be prevented?
Immunisation: BCG vaccine given to high risk groups.
New vaccines in clinical trials.
What are the main criteria for anti-TB drugs?
- Active intracellular, as TB infects cells.
- Combination therapy conducive: interaction with other anti-TB drugs must be at a minimum
- Ability to treat distinct TB populations.
What are the 4 first line drugs used as anti-TB drugs?
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
What are the effects of Rifampicin use?
Inhibits RNA synthase.
Decreased absorption via food, can cause liver damage, hypersensitivity, decreased actions of other drugs and red coloured bodily fluids.
Bactericidal
How does Isoniazid work?
Decreases the synthesis of mycolic acids.
Decreases efficacy of hormonal birth control.
Prodrug
bactericidal or static
How does pyrazinamide function as an anti-TB drug?
Bactericidal pro-drug that deceases the synthesis of mycolic acid and damages the TB bacterial membrane.
Bactericidal
Ethambutol
First line anti-TB alongside: Rifampicin, isoniazid and pyrazinamide.
How does ethambutol function against TB?
Increases the permeability of the cell wall.
Bacteriostatic
Optic neuritis which is reversible.
Which anti-TB drug decreases efficacy of hormonal contraceptive?
Isoniazid
Decreases the synthesis of mycolic acids.
Decreases efficacy of hormonal birth control.
Prodrug
Rifampicin
First line anti-TB alongside: Ethambutol, isoniazid and pyrazinamide.
Which of the 4 first line anti-TB drugs are bactericidal only?
Rifampicin.
Isoniazid (can be both)
Pyrazinamide.
Ethambutol is only bacteriostatic.
What are the second-line anti-TB drugs?
Streptomycin: aminoglycoside Capreomycin: aminoglycoside Cycloserine: neurological side effects Ciprofloxacin: Quinolone drug Azithromycin: newer macrolide.
Which anti-TB drug colours bodily fluids red?
rifampicin:
Inhibits RNA synthase.
Decreased absorption via food, can cause liver damage, hypersensitivity, decreased actions of other drugs and red coloured bodily fluids.
Cycloserine
2nd line antiTB
Can cause neurological side effects,
What is the treatment for standard TB? (Short-course)
Isoniazid + Rifampicin + Pyrazinamide + ethambutol for two months.
THEN: Isoniazid and Rifampicin alone for a further 4 months.
Streptomycin
2nd line anti-TB.
Aminoglycoside.
Why would pyridoxal phosphate be included in TB therapy?
To obviate peripheral neuropathy caused by isoniazid)
Azithromycin
2nd line antiTB
Never macrolide
50s subunit
For latent TB, what is the treatment?
6-9 months of daily Isoniazid alone
OR
three months of weekly (12 doses total) of Isoniazid/rifapentine combination.
How does TB resistance develop and what strains are resistant?
Poorly managed TB care.
MDR-TB: strains resistant to >2 first line drugs
XDR-TB: strains resistant to >2 first line drugs and >3 of 6 second line drugs.
XXDR-TB and DR-TB not recognised by WHO but believed to exist.
What is MDR-TB?
Strains resistant to >2 first line drugs.
What is XDR-TB?
Strains resistant to >2 first line drugs AND >3 of 6 second line drugs.
