Airway pharmacology

Question 1

Bronchodilator drugs

Answer 1

• 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).

Question 2

β2 agonists mechanism of action

Answer 2

• 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

Question 3

Examples of Short acting β 2 agonists

Answer 3

SALBUTAMOL

Question 4

Examples of long acting β 2 agonists

Answer 4

SALMETEROL

FORMOTEROL

Question 5

When is short acting β2 agonists used for

Answer 5

Administered when required as reliever therapy

Metered dose inhaler

Question 6

What are long acting β2 agonists used for

Answer 6

Used as an add on preventer treatment, in combination with inhaled CORTICOSTEROIDS
In metered dose inhalers, with twice daily, continual dosing

Question 7

Long acting muscarinic receptor antagonists

Answer 7

A second class of bronchodilator drug e.g. TIOTROPIUM

Question 8

Mechanism of action for long acting muscarinic receptor antagonists

Answer 8

• Blocking acetylcholine receptors present on ASM cells

- Reduces the level of contraction in situations where ACh plays a role in inducing ASM contraction

Question 9

When are long acting muscarinic receptor antagonists used

Answer 9

• 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

Question 10

Corticosteroids

Answer 10

most effective and widely used drug for reducing allergic inflammation in asthma

Question 11

Examples of corticosteroids

Answer 11

fluticasone
beclometasone
budesonide

Question 12

Mechanism of action for corticosteroids

Answer 12

• 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

Question 13

What are leukotrienes

Answer 13

Are a group of pro-inflammatory lipid mediators that are implicated in the asthmatic immune response

Question 14

What releases leukotrienes

Answer 14

Mast cells and eosinophils

Question 15

What do leukotrienes do

Answer 15

Induce further inflammation and airway pathology via receptor mediated actions

Question 16

Mechanism of action for leukotriene receptor antagonists

Answer 16

When blocking leukotriene receptors it reduces the level of inflammation.

Question 17

Example of leukotriene receptor antagonists

Answer 17

Montelukast - administered orally and used as an add-on preventer therapy with continual dosing

Question 18

Biologics

Answer 18

refer to drugs consisting of complex biomolecules

Question 19

Mechanism of action for biologics

Answer 19

Used in asthma therapy to block or inhibit specific pro-inflammatory protein involved in the inflammatory cascade

Question 20

All drugs are capable of inducing adverse effects due to either

Answer 20

• Interacting excessively with their primary target

- Interacting with targets expressed in other tissues

Question 21

Several other drugs used in respiratory disease are delivered by other routes of administration. Used when:

Answer 21

• 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

Question 22

Reasons for adverse effects β2 agonist

Answer 22

• 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

Question 23

Adverse effects associated with corticosteroids

Answer 23

Growth retardation
Skin ulcers
Osteoporosis - effects of glucocorticoids on bone metabolism
Hypercortisolism - increased expoure to glucocorticoids
Candidiasis

Question 24

Adverse effects of β2 adrenergic receptor agonists

Answer 24

Tremor - β2 receptors expressed on skeletal muscle
Tachycardia - β1 receptors expressed by cells of SA node in heart
Palpitations - β1 receptors expressed by myocardium