Pharmacology of Asthma Flashcards
How is asthma generally diagnosed? When can this be a problem?
Via spirometry, can’t be done in children
What are the 2 components of an asthma attack?
Acute phase (bronchoconstriction and breathlessness) Late phase (inflammation exacerbates asthma)
What are some advantages of using nebulisers?
You can completely control the dose and concentration of the drugs you are giving
You can give multiple medications at a time
You can control what they breath and guarantee its all being delivered to them
What is the target of beta 2 agonists?
Beta 2 receptor
What is the location where beta 2 agonists work?
Bronchus
What is the effect of beta 2 agonists?
They decrease calcium entry and cause relaxation of smooth muscle
What hormone do beta 2 agonists mimic?
Adrenaline
What are the 2 main ways drugs for asthma can be administered?
Inhaled
Orally ingested
Out of inhaled and oral medicine, which is more effective?
Inhaled as it directly reaches the lung and doesn’t have to go into the blood and then the lungs
Why is local management always better?
The drug goes directly to the target so you have to give less and there is less chance of side effects
How much inhaled salbutamol actually reached the lungs and why?
20%
Most is swallowed
Some is exhaled
Some is absorbed into the blood
Why do spacers increase the amount of salbutamol that reaches the lungs?
By stopping loss of drug by exhalation
What is the target of flucatisone?
Glucocorticoid receptor
What is the location where flucatisone works?
Eosinophils mainly and other inflammatory cells like mast cells, dendritic cells, macrophages
What is the effect of flucatisone?
It reduces interleukin 5 production causing eosinophil apoptosis so eosinophilic inflammation is reduced.
Generally reduces no of inflammatory cells and the no of cytokines they produce
Why is it unideal to give children glucocorticoids chronically? How is it recommended to give them instead?
They are steroids so are really powerful and can stump growth. Try to only give them when needed in exacerbations
Why is bioavailability of orally ingested drugs usually very low?
They are metabolised by the liver before they enter systemic circulation
What is the target of montelukast?
Leukotriene receptors, its an antagonist of CysT1 on eosinophils
Where is the location where montelukast works?
Bronchus
What is the effect of montelukast?
Inhibition of leukotriene receptors C4, D4 and E4. This results in bronchodilation as they are powerful brochoconstriction
Also decreases the migration of eosinophils
Why are oral pills useful for children in asthma management?
They have higher adherence- the parents can easily monitor and make sure the child takes them
What is the target of NSAIDs?
Cyclooxygenase
Why may NSAIDs be harmful for asthmatics?
The blockage of cyclooxygenase means arachidonic acid is forced down the other path to form leukotrienes which cause bronchoconstriction
What is the oral bioavailability of fluticasone?
1 %
What are systemic side effects of fluticasone?
Growth retardation Hyperglycaemia Decreased bone mineral density Immunosuppression Effects on mood
What are the local side effects of fluticasone?
Sore throat
Hoarse voice
Opportunistic oral infections
Out of fluticasone and cortisol, which has the higher affinity for glucocorticoid receptors?
Fluticasone
What is important to remember about the administration of montelukast?
It should be administered at least 2 hours before exercise
How does salbutamol work?
It is an agonist of the beta 2 adrenergic receptor, upon binding it reduces calcium influx so the muscle cant constrict and causes bronchodilation
What are the main side effects of salbutamol?
Palpitations Agitation Tachycardia Arrhythmia Hypokalaemia (at higher doses)
How long acting is salbutamol? What is its half life?
Its short acting, has a half life of 2.5-5hrs
What is the selectivity of salbutamol like?
Not highly selective so cardiac side effects can be seen
How does salbutamol cause hypokalemia?
Via affecting sodium potassium ATPase
What drugs exacerbate side effects of salbutamol? Which side effect specifically do they exacerbate?
Corticosteroids, they increase the hypokaelmic effects of salbutamol
Describe the pharmacology of mometasone
Same as fluticasone
Describe the pharmacology of budesonide
Same as fluticasone, its oral bioavailability is higher (>10%) but it is less potent
