Lecture 10 - Bronchodilators Flashcards
1
Q
Side effects of corticosteroids
A
- not common when using less than 1000 ug/day
- oropharyngeal thrush
- dysphonia
- immunosuppression, adrenal suppression in response to stress, osteroporosis, muscle wasting, hyperglycemia, cataracts, brusing, moon face, hyperextension, buffalo hump
2
Q
Corticosteroids improve lung function: study
A
- it takes several weeks for the treatment to start having an effect
- the key is to combine a short acting with a long acting reliever
- comes back at normal after 8 weeks - but patients have to keep going
- low values are generally in the morning, low values in the evening
3
Q
Corticosteroids MOA
A
- Nuclear receptors have to cross into cells or ligand activated transcription factors
- not found in membranes
- regulate gene transcription - steroid and thyroid hormones
- can both increase and decrease gene transcription
- increase: Annexin-1, b adrenergic receptor
- decreases- cytokines (inflammtation(
4
Q
Low dose corticosteroid MOA
A
- repress gene transcription by trans-repression.
- binds the glucocorticoid receptor then binds to CBP and then interact with HDAC2 -> winds up the genes and shuts down transcription of inflammatory genes
5
Q
High dose corticosteroid MOA
A
- cis repression: negative GRE
- trans activation: GRE, anti-inflammatory
- forms homodimer which migrates to nucleus
6
Q
Corticosteroid resistance
A
- asthmatic people are more likely to smoke
- non-smokers: improvement with use of glucocorticosteroids
- in smokers: increase free radicalproduction and inflammation leads to no benefits from glucocorticosteroids
7
Q
Mechanism of smoking and decrease effectiveness of glucocorticosteroids
A
- cigarette smoke and inflammation leads to increase free radical and NO which combine to form Peroxynitrite, which activates PI3Kdelta
- this phosphorylates and inactivates HDAC2 -> winds up and represses transcription of inflammatory genes
- low dose might be a powerful antioxydant
8
Q
Diagnosis of asthma
A
- history
- physical examination
- Consider other diagnoses
- documenting variable airflow limitation
9
Q
Drug target ASM and/or inflammation
A
- Smooth muscle has a b2 adrenoceptor on it - for people with asthma, number of most cells in smooth muscle - increases contraction via histamine
- epithelium - other target for b2 receptors - mucocilliary transport very weak - more obstruction
10
Q
ANS control
A
- sympathetic NS: open up airway via activation of adrenal glands and release of adrenaline - acts on b2
- Parasympathetic NS: via vagus nerve
- short post ganglionic nerve fiber in airway - releases Ach which binds M3AChR - release of calcium in cells in smooth muscle - contraction
- IgE in mast cel when cross link cause increase calcium in mast cells - release of Histamine - bing H1R on smooth muscle cell - contraction
11
Q
SNS - special ganglia in the adrenal medulla
A
- sympathetic activation leads to Ach release from presynaptic nerve which act on nicotinic ACh receptors of chromaffin cells in medulla to cause release of noradrenaline and adrenaline
12
Q
B adrenoceptor agonist
A
- SABA: adrenaline, salbutamol, albuerol, fenoterol, terbutaline sulphate
- LABA: salmeterol, formoterol
- UltraLABA: indacaterol, vilanterol
13
Q
Anti-cholinergic drigs
A
- SAMA: ipratropium bromide
- LAMA: tiotropium bromide
14
Q
Antileukotrienes
A
- act on cysLT1 antagonists - promote contraction nearly equally effective as corticosteroids
15
Q
Phosphodiesterase inhibitors
A
- increase cAMP t1/2
- intracellular mediator that helps reduce calcium
- selctive PDE4: roflumilast: COPD
