Singer: Bronchodilator Therapy Flashcards
What is the cellular mechanism of asthma?
allergen –> activates mast cells, dendritic cells, TH2 cells –> inflammation
vagal stimulation from sensory nerves causes vasoconstriction
epithelial shedding
mucous hypersecretion
The vagal nerve is involved in (blank)
bronchoconstriction
Why might you have an increased FEV1 in mild asthma?
you actually get hypertrophy and hyperplasia, which gives you more muscle to exhale forcefully
What then happens to FEV1 in moderate and severe asthma?
it decreases
Asthma is an inflammatory disease coupled with changes in (blank)
airway smooth muscle
**hypertrophy, hyperplasia
There is very little inflammation involved in COPD. Really what is happening is bronchioles are losing their shape and becoming clogged with mucous. So are anti-inflammatory therapies useful?
no - patients are largely resistant to corticosteroids
3 reactions in COPD
fibrosis of small airways
alveolar wall destruction
mucus hypersecretion
There is some evidence that (blank) may play a role in the development of asthma
epigenetics (allergens, antibiotics, pollution, diet)
Routes of drug delivery to the lungs
inhaled - direct effect on lungs
swallowed - thru GI tract, liver, can get into systemic circulation and cause side effects
3 bronchodilators used to treat asthma
Beta2 adrenergic agonists
theophylline
anti-cholinergics
List some beta 2 agonists
NE epi isoproterenol albuterolol salmeterol formoterol
How do beta agonists work?
bind to Beta-2 receptors –> activate Gs –> increase in cAMP –> increase protein kinase A –> LOWER INTRACELLULAR Ca+ –> less constriction
Beta-2 agonists have other effects, too. Name a few.
Prevent mediator release from mast cells
Prevent microvascular leakage and edema
Increase mucous secretion from submucosal glands and ion transport across airway epithelium
Reduction in neurotransmission in human airway cholinergic nerves by an action at presynaptic b2 receptors to inhibit acetylcholine release.
Short acting beta agonist
Drug of choice of acute attacks
albuterol
Long acting beta agonists
Always used in combo with corticosteroids in asthma
Salmeterol
Formoterol
Negative side effects of Beta 2 agonists
Muscle tremor
Tachycardia
Hypokalemia
Restlessness
Hypoxemia
**Increased mortality with LABA
Seizures with theophyilline
How do methylxanthines work?
inhibit phosphodiesterases and adenosine
What methylxanthine should we remember?
theophylline
**like caffeine in structure
What is one thing we should remember about theophylline?
it causes seizures
What effects do methylxanthines (theophylline) have on the lung?
decreases inflammatory cells
causes bronchodilation
decreased leak
Other effects of methylxanthines?
CNS – increased alertness, reduced fatigue, tremor, insomnia, anxiety
Cardiovascular – increased cardiac contractility, reduced peripheral vascular resistance
Metabolic –diuresis, increased basal metabolic rate
**think of the effects of coffee
How is theophylline administered?
orally or IV
Why is theophylline not used often?
increased clearance in children and marijuana smokers **induces CYP12
reduced clearance in liver disease, heart failure, pneumonia
reduced clearance w co-administration of anti-heart burn meds
Side effects of theophylline?
nausea vomiting gastric discomfort diuresis behavioral disturbances cardiac arrhythmias epileptic seizures
What muscarinic receptors are involved in the airway?
M1, M2, M3
prototypical nonselective inhibitor of cholinergic transmission
tertiary ammonium derivative that has system effects
atropine
nonselective inhibitor of cholinergic receptors
quaternary ammonium derivative
can be combined with albuterol (Combivent)
Ipratropium (Atrovent)
Inhibits M1, M2, M3 receptors but dissociates quickly from M2
Also quaternary ammonium derivative
Tiotropium (Spiriva)
What do muscarinic receptor antagonists do for pts with COPD?
contol vagal tone –> decrease constriction of airways
What are some side effects of anti-cholinergics?
Ipratropium –> bitter taste, can precipitate glaucoma
Triotropium –> dry mouth
Inhaled corticosteroids we should know
Beclomethasone
Budesonide
Fluticasone
How do corticosteroids work?
repress gene transcription –> via deacetylation –> less inflammatory response
Corticosteroids not only decrease inflammatory immune cells, what else do they do?
act on epithelial cells to decrease cytokines and mediators
decrease leak
increase Beta receptors
decrease mucous secretion
Formulated as a pro-drug, which is activated once it’s inhaled
beclomethasone
These corticosteroids have greater first pass metabolism
They have less systemic effects and less adverse effects
Fluticasone
Budesonide
Local side effects of inhaled corticosteroids?
oropharyngeal candidiasis
cough & dysphonia
Systemic side effects of inhaled corticosteroids?
Adrenal suppression and insufficiency Growth suppression Bruising Osteoporosis **esp w long term treatment Cataracts Glaucoma Metabolic abnormalities (glucose, insulin, triglycerides) Psychiatric disturbances (euphoria, depression) Pneumonia
Which leukotriene antagonist should we be aware of?
Montelukast
How to leukotriene antagonists work?
block leukotriene receptors –> prevent bronchoconstriction, eos recruitment, mucus secretion, plasma leakiness
How is Montelukast administered? Who is it commonly used in?
orally;
widely used to treat children
good for mild/moderate asthma and aspirin-sensitive asthma
The newest therapy for asthma?
anti-IgE
What anti-IgE drug should we be aware of?
Omalizumab
When should Omalizumab (anti-IgE antibody) be used for asthma?
severe asthma that doesn’t respond to inhaled corticosteroids or long-acting beta agonist
**expensive, and must be injected every 2-4 weeks
For a pt with mild, well controlled asthma, what should you prescribe?
albuterol
If the asthma is a little worse than mild, what should you prescribe?
low dose ICS
leukotriene antagonist
If asthma is really severe, what should you use?
Omalizumab
or
long-term oral corticosteroid
Newer option for asthma, which burns open airways essentially
bronchial thermolplasty
