Airway Pharmacology Flashcards
How do beta-2-adrenergic receptor agonists cause airway smooth muscle relaxation?
Salbutamol activates beta 2 receptors
How do Phosphodiesterase inhibitors cause ASMC to relax?
Theophyline reduces cAMP breakdown
How do long acting muscarinic receptor antagonists cause relaxation of airway smooth muscle cells?
Tiotropium blocks Ach induced contraction
What intracellular effects are associated with ASMC relaxation?
- PKA activation
- Increased Ca2+ mobilisation
- Inhibition of cAMP breakdown
- Increasing cAMP production
Outline how corticosteroids produce anti-inflammatory effects
- Diffuses through cell membrane
- Binds glucocorticoid receptor
- Translocates to nucleus
- Complex binds DNA and affects transcription
- Reduced pro-inflammatory protein expression
- Reduced proliferation, activation and trafficking of
leukocytes
Which pro-inflammatory mediator is blocked by Montelukast and why?
Leukotrienes are blocked by Montelukast to reduce inflammation
How effective are anti histamine drugs in allergic asthma therapy?
Not at all - do not aid allergic asthma therapy
What adverse effects does Salbutamol cause?
- tachycardia
- tremor
- palpitations
- anxiety
What adverse effects are caused by the use of Corticosteroids?
- Hypercortisolism
- Osteoporosis
- Depression
- Candidiasis
How often should inhaled Corticosteroids (e.g. beclometasone) be administered?
Inhaled Corticosteroids must be administered on a continual (bi-daily) basis to achieve maximum efficacy
Why are Inhaled Corticosteroids administered twice a day?
They are preventer drugs which work on a gradual basis, by preventing symptoms, rather than reversing them once they’ve occurred
When is an inhaled Corticosteroid administered?
When asthma symptoms aren’t adequately controlled by single short-acting beta-2 agonist (Salbutamol) therapy, an inhaled Corticosteroid should be added
If a patient presents with:
Ongoing breathing difficulties and regular periods of wheezing, whilst taking Salbutamol and avoiding allergen exposure,
What medication should be administered?
Continue with Salbutamol alone
How effective are drugs at treating respiratory disease?
Drugs are effective at treating some aspects of respiratory disease but not all
What are the advantages of respiratory drugs usage?
Good at reducing / treating symptoms:
- reverse airway smooth muscle contraction
- reduce mucus secretion
- reduce allergic inflammation of airways
- reduce sensitivity to irritating stimuli
What areas are respiratory drugs not so good at??
Drugs aren’t good at healing the underlying cause of pathology e.g:
- Resolving causes of inflammation
- Reverse airway / lung remodelling
- Repair damage to tissues
What pathological changes are induced by inflammatory mediators, during an asthma attack?
Airway smooth muscle contraction
Increased mucus secretion + microvascular leak
Airway oedema + swelling
What is the effect of the pathological changes caused by inflammatory mediators?
The changes combine to substantially decrease airway lumen size, increase airway resistance, limiting airflow
How is airway smooth muscle contraction prevented?
Bronchodilators e.g.
Beta-2 adrenergic receptor agonists
- SABA e.g. Salbutamol
- LABA e.g. salmeterol
Long acting muscarinic receptor antagonists
- triptropium
Phosphodiesterase inhibitors
- theophyline
How do bronchodilators relieve asthmatic symptoms?
Work by relaxing airway smooth muscles
What are the contractile mediators involved in Airway smooth muscle contraction?
Ach, Prostaglandins, CYsLTs bind to GPCRs (M3) activating Gq/11 pathway :
- activates phospholipase C
- Ca2+ stores in SR mobilised
- Interacts with calmodulin => contraction
What mechanism causes the relaxation of airway smooth muscle?
Beta-2 adrenergic receptor activation of Gs pathway, induces ASMC relaxation via adenylate cyclase and PKA
Outline how salbutamol (beta-2 adrenergic receptor agonist) causes ASMC relaxation
Salbutamol binds to beta-2 adrenergic receptor activating Gs pathway
- increased AC -> cAMP
- Activates PKA
- Decreases Ca2+ mobilisation causing relaxation
How do muscarinic receptor antagonists (e,g, tiotropium) cause ASMC relaxation?
Muscarinic receptor antagonists relax ASMC by inhibitng the contractile mechanism of Ach at the M3 receptor
Which Leukotriene functions are targeted when treating airway inflammation ?
- proliferation
- Ab production; crosslinking + degranulation
- Inflammatory mediator receptor binding
- Tissue infiltration from blood stream (adhesion molecule
expression) - Chemotaxis
- Cytokine receptor binding
- Cytokine production and release
- Apoptosis
What is the use of corticosteroids?
Used as preventor drug to reduce airway inflammation
Give examples of inhaled corticosteroids
Fluticasone
Budesonide
Beclometasone
Name oral systemic steroids used to reduce airway inflammation
predenisone
dexamethasone
How do corticosteroids reduce inflammation?
affect function of various immune and structural cells
either increase:
- proinflammatory cytokines
- or inflammatory proteins
Outline the mechanism of action of corticosteroids
- Corticosteroid (CS) administered
- CS diffuses through membrane + binds to intracellular
glucocorticoid receptor - Drug-Receptor complex translocates to nucleus
- Drug-receptor complex binds DNA
- > altered gene transcription
- CS increase/decrease expression depending on gene/
protein - Gene translated to protein
What are the advantages of drug treatments ?
drug efficacy
- increased quality of life
- less symptoms + disease severity - disease resolution
- increased life expectancy
What are the disadvantages of drug treatments?
Costs
- decreased quality of life
- increased risk of other disease developments
- economic costs - not everyone can afford
What are metered dose inhalers?
device delivering medication to the lungs, in the form of a short burst of aerosolized medicine; usually self-administered by patient via inhalation
What is the benefit of using metered dose inhalers?
Maximises therapeutic : adverse effect ratio by administering drugs directly to desired tissue
Less drug reaches systemic circulation where it’s distributed to other tissues which cause side effects
Quicker rescue/reliever dose
How do beta 2 agonists (salbutamol) cause side effects?
Beta-2 agonists (salbutamol) induce side effects by activating receptors in extra-respiratory tissues if long term / high doses administered
Explain the effects of salbutamol on the heart?
Higher concentrations affect Beta-1 receptors on SAN/myocardium
cause tachycardia and palpitations
What effects does salbutamol (beta-2 agonist) produce on airway smooth muscle?
cause bronchodilation via Beta-2 receptors
What is the effect of salbutamol (beta 2 agonist) on skeletal muscle in other tissues?
Causes tremor and muscle growth
What are the side effects caused by (salbutamol) beta 2 agonists when administered long term / in high doses?
- growth retardation
- osteoporosis
- skin ulcerations
- hypercortisolism
- candidasis
- depressions
How is pharmacotherapy used to treat asthma?
Asthma Pharmacotherapy is administered in a step-wise manner:
- SABA as required
- add ICS
- Add LABA, ↑ ICS, add LTRA, PDEi
- max ICS dose and 4th drug
- Add oral CS refer to specialist care, anti-IgE
How is COPD therapy carried out?
In a progressive one direction stepwise manner
