Airway pharmacology Flashcards
Bronchodilator drugs
- Used to reverse inflammation of airways
- Bronchodilator drugs act by binding to a specific receptor or enzyme expressed by the ASM cell and inducing an intracellular change which interrupts the contractile process (thereby causing relaxation).
β2 agonists mechanism of action
- Activation of β2 adrenergic receptors present in membrane of ASM cells
- Includes a signalling cascade that increase production of cAMP and activation of PKA which reduces Ca2+ mobilisation, inducing relaxation
Examples of Short acting β 2 agonists
SALBUTAMOL
Examples of long acting β 2 agonists
SALMETEROL
FORMOTEROL
When is short acting β2 agonists used for
Administered when required as reliever therapy
Metered dose inhaler
What are long acting β2 agonists used for
Used as an add on preventer treatment, in combination with inhaled CORTICOSTEROIDS
In metered dose inhalers, with twice daily, continual dosing
Long acting muscarinic receptor antagonists
A second class of bronchodilator drug e.g. TIOTROPIUM
Mechanism of action for long acting muscarinic receptor antagonists
- Blocking acetylcholine receptors present on ASM cells
- Reduces the level of contraction in situations where ACh plays a role in inducing ASM contraction
When are long acting muscarinic receptor antagonists used
- Used to treat chronic bronchitis in COPD patients, and as an add on, preventer therapy in asthma
- Dosed on a dailym continual basis via metered dose inhalers
- may also provide benefit in patients with obstructive airway diseases by reducing mucus secretion and inhibiting cough
Corticosteroids
most effective and widely used drug for reducing allergic inflammation in asthma
Examples of corticosteroids
fluticasone
beclometasone
budesonide
Mechanism of action for corticosteroids
- Achieve their anti-inflammatory effect by binding to glucocorticoid receptors present within the cytosol of immune and structural cells
- The bound drug receptor complex migrates to nucleus of the cell where it binds to DNA. Modulating transcription, translation and protein expression
What are leukotrienes
Are a group of pro-inflammatory lipid mediators that are implicated in the asthmatic immune response
What releases leukotrienes
Mast cells and eosinophils
What do leukotrienes do
Induce further inflammation and airway pathology via receptor mediated actions
Mechanism of action for leukotriene receptor antagonists
When blocking leukotriene receptors it reduces the level of inflammation.
Example of leukotriene receptor antagonists
Montelukast - administered orally and used as an add-on preventer therapy with continual dosing
Biologics
refer to drugs consisting of complex biomolecules
Mechanism of action for biologics
Used in asthma therapy to block or inhibit specific pro-inflammatory protein involved in the inflammatory cascade
All drugs are capable of inducing adverse effects due to either
- Interacting excessively with their primary target
- Interacting with targets expressed in other tissues
Several other drugs used in respiratory disease are delivered by other routes of administration. Used when:
- Drug intended to have a systemic effect
- The drug has a narrow therapeutic window, and so a consistent dose must reach the systemic circulation
- It is not possible to formulate the drug as an inhaler due to the physical/chemical properties of the drug
Reasons for adverse effects β2 agonist
- Although majority of β receptors present within the heart of β1 sub-type there is still a significant number of β2 receptors
- At high doses β2 agonist will interact with β1 receptors
- β2 receptors are found on skeletal muscle, posing risk of tremor. And hypertrophy and muscle growth
Adverse effects associated with corticosteroids
Growth retardation
Skin ulcers
Osteoporosis - effects of glucocorticoids on bone metabolism
Hypercortisolism - increased expoure to glucocorticoids
Candidiasis
Adverse effects of β2 adrenergic receptor agonists
Tremor - β2 receptors expressed on skeletal muscle
Tachycardia - β1 receptors expressed by cells of SA node in heart
Palpitations - β1 receptors expressed by myocardium
