Pharmacology of Asthma Flashcards
What are the 5 main asthma drugs?
- Salbutamol
- Fluticasone
- Mometasone
- Budesonide
- Montelukast
What is the primary mechanism of action of salbutamol?
Agonist at the β2 receptor on airway smooth muscle cells
Activation reduces Ca2+ entry and this prevents smooth muscle contraction
What is the drug target site for salbutamol?
Beta 2 (β2) adrenergic receptor
What are the main side effects of salbutamol?
Palpitations/ agitation
Tachycardia/ Arrythmias
Hypokalaemia (at higher doses)
What is the primary mechanism of action of fluticasone?
Very powerful drugs - multiple actions on many different cell types
Fluticasone directly reduces the number of inflammatory cells such as eosinophils, monocytes, mast cells, macrophages, and dendritic cells = reduces the number of cytokines they produce
What is the drug target site for fluticasone?
Glucocorticoid receptor
What are the main side effects of fluticasone?
Local side effects:
Sore throat, hoarse voice, opportunistic oral infections
Systemic side effects:
Growth retardation in children Hyperglycaemia Decreased bone mineral density Immunosuppression Effects on mood
What is the primary mechanism of action of mometasone?
Very powerful drugs - multiple actions on many different cell types
Mometasone directly reduces the number of inflammatory cells such as eosinophils, monocytes, mast cells, macrophages, and dendritic cells = reduces the number of cytokines they produce
What is the drug target site for mometasone?
Glucocorticoid receptor
What are the main side effects of mometasone?
Local side effects:
Sore throat, hoarse voice, opportunistic oral infections
Systemic side effects:
Growth retardation in children Hyperglycaemia Decreased bone mineral density Immunosuppression Effects on mood
What is the primary mechanism of action of budesonide?
Very powerful drugs - multiple actions on many different cell types
Budesonide directly reduces the number of inflammatory cells such as eosinophils, monocytes, mast cells, macrophages, and dendritic cells = reduces the number of cytokines they produce
What is the drug target site for budesonide?
Glucocorticoid receptor
What are the main side effects of budesonide?
Local side effects:
Hoarse voice, opportunistic oral infections
Systemic side effects:
Growth retardation in children Hyperglycaemia Decreased bone mineral density Immunosuppression Effects on mood
What is the drug target site for montelukast?
CysLT1 leukotriene receptor
What are the main side effects of montelukast?
Mild side effects:
Diarrhoea
Fever
Headaches
Nausea or vomiting
Serious side effects:
Mood changes
Anaphylaxis
What are asthma differentials?
Differentials:
Infection induced asthma
Exercise induced asthma
Atopic (allergen-induced) asthma
NSAID induced asthma
What are the 2 stages of an asthma attack?
Early: Brochospasm
Late: Inflammation
Consider the NICE guidelines for the treatment of asthma in the under 5’s
What drug would you choose as your first treatment for an under 5yr old and what is the mechanism of action for this medication?
SABA - short acting beta agonist e.g. Salbutamol
Targets beta-2 adrenergic receptors
Located on the bronchiole smooth muscle cells
Acts as an agonist
Reduces Ca2+ entry and prevents smooth muscle contraction
Prevents bronchoconstriction = opens up the airways to reduce bronchospasm
SABA vs LAMA?
SABA = short acting beta agonist
LAMA = long acting muscarinic antagonist = causes bronchodilation
What is a nebuliser?
What is an inhaler?
And what is a spacer?
Nebuliser = transforms liquid medication into a mist, that is inhaled and allows the drug to directly hit the target site, automatic medication release
Inhaler = dried powder format rather than mist
Spacer = holds the medicine in place so you can breathe it in easier, allows for medicine delivery to be more effective. Lower percentage of the drug entering the mouth at once, so less medication is lost through exhalation
What are the 2 methods of administration of Salbutamol, and why do you think the inhalation route is preferred over the oral route?
Topical (inhalation) = via mouth into the lungs
Oral = ingestion, via mouth into the stomach
Inhalation = preferred due to direct delivery to the lungs and faster action, rather than oral, which takes a long time to travel through the system and may be broken down by the liver
Why is a nebuliser the best method for delivering Salbutamol in an emergency situation?
Nebuliser - delivers medication as a mist, automatically
Requires less co-ordination than inhalers
Therefore a patient who may not be able to use an inhaler, the nebuliser = delivered to patients of all ages, and only requires normal breathing pattern
What are the advantages of a nebuliser?
Many drug solutions
Can deliver combinations
Minimal patient cooperation required
Can deliver to patient of all ages
Evidence suggests that only 20% of the inhaled dose of salbutamol (or any inhaled drug) penetrates deep enough into the lungs to be able to influence lung function (e.g. reduce breathlessness)
What do you think happens to the other 80% of inhaled salbutamol?
Some of the salbutamol goes down the oesophagus instead of the trachea
Poor inhaler technique / use
Some of the salbutamol absorbed by the mucus membranes in the oral cavity into systemic circulation
Exhalation of some of the salbutamol
Muco-ciliary clearance = salbutamol that enters the lungs is removed
Salbutamol absorbed within the systemic circulation of the lungs
What do NSAIDs do in asthma?
What can be used as treatment for NSAID induced asthma?
NSAID induced asthma = overactivation of leukotrienes
NSAIDs block cyclooxygenase activity, leads to build up of arachidonic acid, which increases leukotriene production, which causes increased bronchoconstriction
Treatment- Montelukast:
Targets and blocks the leukotrienes, C4, D4, E4
On phospholipid membranes
Causes reduced bronchoconstriction
What is the half life of salbutamol?
It’s half life is 2.5 - 5hrs
Describe the selectivity of beta-2 agonists
Beta 2 selectivity is not absolute – as a result, cardiac (beta 1) effects can be seen
What is something we need to be aware of on administration of salbutamol?
Hypokalaemia can be caused via an effect on sodium/ potassium ATPase. This effect can be exacerbated by coadministration with corticosteroids
How do Fluticasone and Mometasone compare to cortisol?
Greater affinity for the glucocorticoid receptor compared to cortisol.
What is the bioavailability of fluticasone and Mometasone?
Oral bioavailability <1%. Therefore, any systemic delivery via the inhaled route is predominantly through the pulmonary vasculature.
What is the bioavailability of budesonide?
Oral bioavailability >10%. Therefore, inhaled budesonide will still result in some systemic absorption through the gastro-intestinal tract.
How does budesonide compare to fluticasone and mometasone?
Less potent than fluticasone and mometasone
How should montelukast be taken for prophylaxis of exercise?
For induced bronchoconstriction (caused by exercise), montelukast should be administered at least 2 hours before initiating exercise.
