W21 - Tuberculosis Flashcards
what is tuberculosis
contagious and airborne infectious disease caused by bacteria
is tb curable
yes
is tb preventable
yes
what are the majority of causes
reactivation of latent infection and delayed diagnosis for lack of awareness
What is TB caused by
bacteria belonging to the mycobacterium tuberculosis complex
what are mycobacterium
different from gram +ve and gram -ve bacteria, they are obligate aerobes that synthesise mycolic acids. They are slow growing between 2 - 10 weeks. Life cycle have different microenvironments that can affect drug susceptibility
describe the mycobacterium life cycle
initial infection: a carrier exposes MTB to the air via coughing
host macrophages in the lung phagocytize the pathogen inflammatory response triggered
bacterial burden is contained inside foamy macrophages
macrophages form the encapsulated vascularised granuloma
other immune cells are present
granuloma matures
cells die and caesum develops at the core of the necrotic granuloma
extracellular baccilli enter their dormant state
Grulomas can fuse to the airways of the lungs and burst, releasing the pathogen to spread to new tissue and new hosts
how is tb transmitted
respiratory route
what is the signs and symptoms of tb
cough for > 3 weeks purulent sputum hameoptysis weight loss malaise fever night sweats
What does isoniazid do
inhibition of biosynthesis of mycolic acids, synthesis of cell wall
what does rifampicin do
inhibition of RNA polymerase
what do pyrazinamide do
intracellular acidification
what do pyrazinamide do
plasma membrane disruption
what does ethambutol do
inhibition of arabinoyl transferase involved with syntesis of cell wall
what should the initial phase of TB be treated with (2 months)
isoniazid
rifampicin
pyrazinamide
ethambutol
what should the continuation phase of Tb be treated with
Rifampicin
Isoniazid
what is the mechanism of action of isoniazid
inhibits biosynthesis of mycolic acids constituents of mycobacterial cell wall
what prodrug activated
bacterial catalase
what effects does isoniazid
bacteriostatic for resting bacilli
bactericidal for extracellular dividing microorganisms
what pharmacokinetic of isoniazid
orally active
metabolism by acetylation
Mechanism of action of rifampicin
inhibits DNA dependent RNA polymerase of mycobacteria.
What are the effects of rifampicin
bactericidal effect on the three MTB population
what are the three MTB population
Open pulmonary cavities: plenty of oygen, rapid growth, drug resistance develops
Closed lesions in the lung oxygen starved slow growing dormant bacilli, poor blood supply limited penetration of drug
Intracellular low pH drugs may be inactive, lack of oxygen, slow intermittent growing bacilli.
what are the side effects of rifampicin
causes orange red coloration of urine and other body fluids.
what are some rare but serious adverse effect
hepatotoxicity
toxic syndrome
what is the mechanism of action ethambutol
uncertain
impairs biosynthesis of bacterial cell wall
orally active
what is a pharmacokinetic property of ethambutol
orally active
what effect does ethambutol have
bacteriostatic
what are the adverse effect ethambutol
uncomon - optic neuritis
what is the mechanism of action of pyrazinamide
May involve metabolism of drug within bacteria
Pro drug converted to tis active form
what are the effect of pyrazinamide
bacteriostatic at acidic pH
interferes with the bacteriums ability to synthesize new fatty acids
what are the adverse effects
Hepatoxicity
Increased plasma urate
Tuberculin skin testing results
0 - 5 mm negative
6 - 144 mm positive infection
> 15 mm strongly positive
what is active TB
in any site other than the lungs or tracheobronchial tree
