Lecture 13- Treatment of Asthma Flashcards
Goals of Asthma treatment
- Control chronic symptoms
- Maintain normal activity levels and exercise
- Maintain near-normal pulmonary function
- prevent exacerbation of asthma
- Minimise ED/hospital visits
- Avoid adverse medication effects
Types of Asthma treatment
1) Relievers: short term, rapid onset, for acute attack. Relaxes smooth muscle in airway
2) Preventer: No relief, just long-term control. Take daily
3) Others
Bronchodilators/reliever types
1) Inhaled beta-adrenergic agonist
2) Anticholinergic agents
3) Xanthine drugs
Inhaled beta-adrenergic agonist
Used 3000 years ago from plants.
- > Relieves bronchiconstriction by relaxing SM
- > Protects from cold/exercise constrictor stimuli
- > Increases mucociliary clearance due to increased ciliary beat frequency
- > may reduce inflammation due to inhibition of mediator release from inflamm cells
How does B-adrenergic agonist relax SM
B2 agonist diffuses then bonds with a transmembrane receptor, which activates Gs protein, which activates AC (adenylate cyclase) which enhances ATP and converts it to cAMP. Then as cAMP increases, PKA activity/concentration increases also. This has lots of consequences
-Ca2+ & K+ channel activated, lots of K+ outside the cell.
- Inc. Na/K ATPASE
- Decr. PI hydrolysis
- Inc. Na/Ca exchange
-Decr. MLCK
This ALL cause SM relaxation and inhibits mediator release.
Theophylline
SImilar function to B-adrenergic agonist.
Because it inhibits transformation from cAMP to AMP, therefore retaining the cAMP concentration.
Is the B-agonist selective or non-selective
non-selective. Lots of receptors at other areas,
LUNGS: Mainly B2 eg) SM, epithelium, submucosal, club cell etc
When the B2 is activated, it causes SM relaxation, reduces edema and inhibits mediator release
OTHER: in places like Heart(inc HR), arterioles, skeletal muscle(tremor) ((think of hospital)))
..and fat cells (lipolysis- weight control?)
Therefore receptors in other tissues are activated = ADVERSE EFFECTS
Route of Administration
- Inhalation: Very high concentration, fast onset and less systematic (adverse) effects
- Oral: inc adverse effects. BUT helpful if patient can’t breath or is clogged with spetum.
- Direct endotracheal instillation
Types of inhalers
- Metered dose inhalers (aerosol spray): we can deliver 15-20% of drug to the lung. DOn’t need to force to inhale in, just a little training.
- Dry powder device: 25-30% drug to lung, no training required. Not suitable for kids if they can’t breathe or if particles are too large.
Issues with inhalers
- Small airways & tidal volume
- Rapid respiration
- nose breathing
- aversion to masks
- cognitive ability
- Fussiness & crying
Spacer largely improves this by increasing the % of medicine reaching the lungs. Reduces systematic/adverse effects from swallowing meds
Nebulizers
Machine that generates hot warm steam mixed with meds. Comforts airways
easier for patient to cough sputum
allows for mixing of meds
What do we use to decide which B-agonist to use? Commonly used drugs are?
Onset of Action : rapid or slow
Duration of Action: short-acting or long-acting
As an acute attack can occur within 5-10 mins, and we need quick relief, we need a “ rapid-onset long-action drug”
—–> ‘formoterol’
Short-Acting B2-adrenoreceptor Agonists
Rapid onset but short-duration
max effect: with 30min
duration: 4-6hrs
Effective in preventing cold/exercise/allergin triggered asthma
also used for acute severe asthma- use ‘as needed’
Done inhaled or orally
ADVERSE EFFECTS:
- Tremor (due to B2 receptor in skeletal muscle)
- Tolerance/tachyphlaxis (down-reg of B2 receptors) don’t confuse with sputum clogging
- Hypokalemia
- Tachycardia
Long-Acting B2-adrenoreceptor Agonists
Long duration: ~24hr
Use on regular basis
Prevent bronchospasm in patients requiring bronchodilator therapy
Inhaled corticosteroid (ICS) and LABA used as combined therapy»_space; thought to be better asthma control… but turned out to make asthma episodes MORE SEVERE when they did occur.
FDA LABA view
LABAs shouldn’t be used as 1st line to treat asthma.
Only used if other meds don’t control asthma
Don’t relieve sudden wheezing (use bronchodilator)
