asthma Flashcards
What causes an asthma in general
bronchoconstriction and inflammatory cells and debris filling the airways
what are the characteristic of asthma
- recurrent reversible airway obstruction
- hyperresponsiveness of airway
- chronic airway inflammation
What are the types of inflammation for asthma
type 1 inflammation: allergic asthma
type 2 inflammation: eosinophilic asthma
what is type 1 inflammation mediated by
IgE
What happens during a type 1 inflammation reaction
antigen bounded to IgE crosslinks on the Fc3RI receptor on mast cell
mast cell degranulates, releasing histamines, leukotrienes and other inflammatory mediators
what interleukins promote mast cell activity
IL4 and IL13 plays a role in IgE production
WHat happens in a type 2 inflammation reaction
IL5 causes eosinophils to have a late reaction, releasing other inflammatory mediators
How does B2 agonist help with asthma
bronchodilation
What are some examples of fast acting B2 agonists and long acting B2 agonist
fast acting: salbutamol, formoterol(fast acting and long acting)
long acting: salmeterol
what is long acting B2 agonist contraindicated for
for patients of all ages without concomitant use of asthma preventer medication like inhaled corticosteroids
How long does formoterol act, what is its onset of action timing, how is it taken
12 hr, fast acting 2-3 minutes, via inhalation/ oral
what is the duration of action for salbutamol, what is the method of administration
3-6 hrs, via IV in emergency
What are the adverse effects of B2 agonist
too high a dose can escape into systemic absorption causing
- tremors, muscle cramp, peripheral vasodilation, hypokalemia, hyperglycemia, tachycardia palpitation, B2 adrenoceptor tolerance
How does B2 agonist regulate bronchial tone
It increases adenylyl cyclase, converts Ac to phosphodiesterases, increase cAMP which promotes bronchodilation
What are examples of muscarinic receptor antagonist
ipratropium bromide(short acting), and tiotropium bromide(long acting)
What are some adverse effect of muscarinic receptor antagonist
- parasympatholytic effects like dry mouth, urinary retention especially in elderly
How does muscarinic receptor antagonist regulate bronchial tone
blocking ach which causes bronchoconstriction through parasympathetic effects
What molecules causes bronchoconstriction
leukotriene, adenosine, acetylcholine
what is the mechanism of action for methylxanthines
inhibits phosphodiesterases , blocks adeosine receptors, increase adrenaline release from adrenal medulla, CNS stimulant action on respiration
has some anti-inflammatory effect on mast cell and T cell, and also decrease microvascular leakiness
What are some examples of methylxanthine
theophylline and aminophylline
What are the adverse effect of methylxanthine
narrow therapeutic window
many drug drug interactions
GI effect: nausea, vomitting, abdominal discomfort, anorexia
CNS effect: tremor, nervousness, anxiety, insomnia, seizure
CVS: arrythmia
What are some ways in general that are used for anti inflammatory
- inhaled corticosteroids
- leukotriene pathway inhibitors
- mast cell stabilisers
- anti IgE monoclonal antibody
- anti IL4, IL5 signallng monoclonal antibodies
why is inhaled corticosteroids good
- high receptor binding affinity ( so low dose required)
- extensive first pass metabolism ( lesser systemic side effects)
- highly lipophillic ( can be absorbed by tissues much easier)
What are some examples of inhaled corticosteroid
- budesonide
- fluticasone
- ciclesonide
what is the adverse effect of fluticasone
greater risk of adrenal suppression, affect adrenal gland secretion
Ciclesonide is a prodrug, what is it activated by
esterase, which is found in the lungs
What are the effects of glucocorticoid receptor
- reduce pro inflammatory mediators, T cell, mast cell, decrease pro inflammatory cytokines, decrease mucus, decrease shedding of epithelial cells, decrease 5-LOX, reduce production of leukotrienes, decrease inducible nitric oxide synthase, which decrease nitric oxide production
- increase anti inflammatory mediators like annexin A1 and B2 adrenoceptors
what is inhaled corticosteroids used for
- first line prophylactic for asthma treatment
- nocturnal asthma due to delayed eosinophilic reaction
what are some adverse effect of inhaled corticosteroid
- oropharyngeal candidiasis
- dysphonia
- cough/ throat irritation
- adrenal suppression
- easy bruising
- posterior subcapsular cataract
- osteoporosis
What are some example of leukotriene pathway inhibitors
- 5LOX inhibitor like zileuton
- cysLT receptor antagonist like montelukast
What are leukotriene pathway inhibitors good for
treating aspirin induced/ nsaid exacerbated asthma
treat exercise induced asthma
What are some side effect of leukotriene pathway inhibitors
few and mild, gi disturbances, headache
suicide thinking and neurophychiatric adverse effect in some patients
What is an example of a mast cell stabiliser
cromoglicic acid
What does cromoglicic acid do
decrease mast cell degranulation induced by IgE mediated Fc3ri crosslinking
decrease secretion of inflammatory mediators from eosinophils, neutrophils and macrophages
control chloride channels to inhibit cellular activation
increase secretion of annexin A1, inhibits prostaglandin and leukotriene
What is cromoglicic acid used for
prophylactic control of asthma by inhalation only.
prophylactic control of allergic rhinitis, allergic conjunctivities, vernal keratoconjunctivitis
what is an example of anti ig-E monoclonal antibody
omalizumab
What does omalizumab do
depletes level of free IgE in serum, so reduced binding to antigen, decreases Fc3RI expression on mast cell, reduce the trigger of allergic asthma
What are the cons of anti-IgE monoclonal antibody
-expensive
- associated with small increase in risk of heart attack, transient ischemic attacks and blood clot
- potential for anaphylaxis
What are examples of anti IL4 and IL5 signalling monoclonal antibodies
Reslizumab (IL5)
Dupilumab(IL4)
What is reslizumab and dupilumab indicated for
patients with severe persistent eosinophilic asthma older than 18
