CAM201 Respiratory Drugs Flashcards
Indications for use of inhaled glucocorticoids and oral glucocorticoids in asthma?
Inhaled Glucocorticoids = preventers. Daily use of inhaled glucocorticoids is recommended for treatment of asthma. They have been shown to reduce incidence of acute exacerbations, and manage late-phase inflammation.
Oral glucocorticoids are not used in every-day treatment. 7 days of 60mh d is often used after an acute exacerbation to manage inflammation.
How to steroids work?
Anti-inflammatory Action. Similar process in oral and inhaled steroids.
Suppress genes and transcription factors involved in inflammation
Decrease leukocyte adhesion and activation (decrease immune cell activity)
Decrease vascular permeability (reducing oedematous swelling)
Decrease production of inflammatory mediators
Major Adverse effect of steroids?
Steroids are classed as ‘adrenals’. They can suppress adrenal activity such that the body is unable to adequately respond to stressors, such as infection.
What are SABA and LABA? When are they indicated?
Mainly used in general for asthma. Also used in COPD.
Inhaled Short acting beta agonists = symptom relievers. Rapid onset, short acting.
Long Acting Beta Agonists = symptom preventers. Slower onset, longer acting.
LABA indicated when patient is using symptom reliver more than twice weekly.
LABA must NEVER be used in isolation, must always have an ICS preventer as well. Is asthma bad enough to require LABA, then also must need an ICS
Both: Antagonise B2 receptors on bronchial smooth muscle and mucous glands. Cause bronchodilation and decreased mucous secretion.
Note that evidence suggests that COPD is more responsive to M3 antagonists (muscarinc antagonists: Isopropium Bromide, Triopropium Bromide)
Cellular mechanisms of inhaled beta agonists:
LABA/SABA. Bind to B2 receptors on bronchial SMC and mucous glands. They induce a SNS action.
Activate Adenylate cyclase, which converts ATP to cAMP, which up-regulates PKA, which inhibits MLCK, which prevents myosin head phosphorylation, preventing cross-bridge cycling.
= RELAXATION / decreased mucous secretion
Muscarinic Agents: Indications? What do they do?
There is evidence to suggest that muscarinics are more effective at decreasing bronchodilation in COPD than beta agonists. This is because they affect M3 receptors, which are more prominent in larger airways.
Not really indicated in asthma, as asthma mainly involves smaller airways.
Muscarinics are competitive inhibitors of ACh at M3 receptors. They antagonise vagal tone, leading to bronchodilation and decreased mucous production.
Short acting: Isotropium Bromide
Long acting: Triotropium Bromide
When are combination preventer/symptoms controllers indicated?
E.g. seretide, symbicort.
Often used in asthma.
Less commonly used in COPD - only if the patient responds to ICS
Ideal Asthma management involves:
Depends on severity. Not all patients require a long-acting symptom controller and a preventer.
The need for symptom controllers depends on the frequency of exacerbations (i.e.how frequently the patient requires their reliever).
If patient is using reliever more than twice weekly, they require a symptom controller and a preventer.
Symptom controllers must NEVER be used alone. They must always be used with a preventer. This is because patients in need of symptom controllers also require management of long-term inflammation. Symptom controllers can mask the worsening inflammation until it reaches a critical point, resulting in severe bronchospasm.
ICS preventers have been shown to decrease number of acute exacerbations, and also reduce late phase inflammation (reducing long-term inflammatory complications - minimalising airway remodelling, etc)
Drawing up asthma management plans with patients also increases compliance and can help to educate patients and alert them to signs that their condition is worsening, and when to see their GP about making alterations to treatment.
What are Inhaled Cl- channel blockers?
How do they work?
When are they indicated?
They are both preventers and relievers. I.e. have both bronchodilatory and anti-inflammatory actions.
Indicated in allergic, exercise-induced and irritant-induced asthma.
By blocking Cl- channels, they inhibit Ca+ influx, and cause bronchidilation.
Also stabilise mast cell activity (prominent cell in asthms pathogenesis) by decreasing cytokine release.
How do Inhaled leukotriene antagonists work?
What are they?
When are they implicated?
Inhaled leukotriene antagonists are both symptom controllers and preventers. Have anti-inflammatory properties and bronchdilatory properties.
Leukotrienes hae been found superior to LABAs in exercise-induced asthma, however they are VERY expensive.
Limited evidence for efficacy in COPD.
What are Xanthines? When are they indicated?
Both preventers and relievers. Cause bronchodilation and anti-inflammatory effect.
Useful in persistent asthma, require 4d dosage, so not exactly convenient…
Muscarinics: Intracellular pathway
Muscarinics are non-specific competitive (with ACh) binders of M3 receptors in bronchial smooth muscle.
Also act on mucosal glands to decrease mucous secretion
Bind to M3 receptor
Results in decrease degradation of intracellular cGMP, thus raising intracellular levels of cGMP
cGMP affects Ca++ behaviour, resulting in decreased Ca++ intake
Resulting in smooth muscle relaxation (bronchodilation)
Ideal COPD Management
STOP SMOKING
For mild COPD: short acting bronchodilators/gland affectors are sufficient to relieve intermitted acute exacerbations (symptom reliever). Can use SABAs or muscarinics.
In more moderate-severe COPD, it is recommended that they also use a long acting bronchodilator/gland affecter (symptom controller). Then they can use their symptom reliever for acute exacerbations.
The use of inhaled corticosteroids in COPD patients is controversial. There appears to be concerns that there is not sufficient evidence to suggest that COPD patients gain long term benefits from use of ICS. Also, the risk vs benefit ratio is controversial.
Annual influenza vaccinations are recommended for all COPD patients as they help to reduce worsening of condition and incidence of exacerbations by preventing infection.
Annual Pneumococcal vaccinations are recommended in COPD patients >65yo.
‘Goals of COPD Management’ - not specifics, just the dot points
1) Prevention of disease Progression
(stop smoking)
2) Relief of symptoms - Pharmacological treatment
(short acting bronchodilators/decrease mucous)
3) Prevention of complications
(e.g. vaccinations to prevent infection)
4) Prevention of Exacerbations in more moderate and severe COPD
(introduction of long acting bronchodilators/mucous controllers)
*Surgery - can improve lung function and quality of life, but higher short-term mortality
*Lung transplants are reserved for very severe cases with no co-morbidities
