Pharmacology of Asthma Flashcards
What is the primary mechanism of action of Salbutamol?
Agonist at the Beta 2 receptor on airway smooth muscle cells. Activation reduces Ca2+ entry, preventing smooth muscle contraction.
What is the drug target of Salbutamol?
Beta 2 adrenergic receptor
What are the main side effects of Salbutamol?
- palpitations
- agitation
- tachycardia
- arrhythmias
- hypokalaemia (at higher doses)
What is the main classification of salbutamol?
- SABA (short acting beta agonist)
- half life of 2.5-5 hours
How selective is salbutamol?
- not absolute
- cardiac (beta 1) effects can be seen
- hypokalaemia caused by an effect on. Na/KATPase
(effect worsened with corticosteroids)
What is the primary mechanism of action of Fluticasone?
- powerful
- multiple actions, on different cell types
- directly decreases inflammatory cells (eosinophils, monocytes, mast cells, macrophages and dendritic cells) and the cytokines that they produce.
(inhibits IL5)
What is the primary drug target of Fluticasone?
Glucocorticoid receptor (in eosinophils)
What are the local side effects of Fluticasone?
- sore throat
- hoarse voice
- opportunistic oral infections
What are the systemic side effects of Fluticasone?
- growth retardation in children
- hyperglycaemia
- decreased bone mineral density
- Immunosuppression
- effect on mood
Why is Fluticasone effective?
Has a higher affinity for the glucocorticoid receptor in comparison to cortisol
What is the mode of delivery of Fluticasone?
oral bioavailability <1%
systemic delivery via the inhaled route is through pulmonary vasculature
What is the primary mechanism of Mometasone?
- powerful
- multiple actions on different cell types
- directly decreases inflammatory cells (eosinophils, monocytes, mast cells, macrophages, and dendritic cells) and the cytokines they produce.
What is the primary target of Mometasone?
Glucocorticoid receptor
What are the local side effects of Mometasone?
- sore throat
- hoarse voice
- opportunistic oral infections
What are the systemic side effects of Mometasone?
- growth retardation in children
- hyperglycaemia
- decreased bone mineral density
- immunosuppression
- effects on mood
Why is Mometasone effective?
greater affinity for the glucocorticoid receptor in comparison of cortisol.
What is the mode of delivery of Mometasone?
oral bioavailability of <1%, due to excretion be the liver (therefore not a LT option, and WILL cause liver damage)
systemic delivery via inhalation is through pulmonary vasculature
What is the primary mechanism of action of Budesonide?
- powerful
- multiple actions on different cell types
- directly decreases inflammatory cells
(eosinophils, monocytes, macrophages and dendritic cells) and the cytokines they produce.
What is the primary drug target of Budesonide?
Glucocorticoid receptor
What are the local side effects of Budesonide?
- hoarse voice
- opportunistic oral infections
What are the systemic side effects of Budesonide?
- growth retardation in children
- hyperglycaemia
- decreased bone mineral density
- immunosuppression
- effects on mood
How effective is Budesonide?
less potent than Fluticasone and Mometasone
What is the mode of delivery of Budesonide?
oral bioavailability <10%
inhaled Budesonide results in systemic absorption through the GI tract
What is the primary mechanism of action of Montelukast?
Antagonism of CysLT1 leukotriene receptor on eosinophils, mast cells and airway smooth muscle cells decreases eosinophil migration, broncho-constriction, and inflammation induced oedema
What is the primary drug target of Montelukast?
CysLT1 leukotriene receptor
What are the mild side effects of Montelukast?
- diarrhoea
- fever
- headaches
- nausea
- vomiting
What are the serious side effects of Montelukast?
- mood changes
- anaphylaxis
When should Montelukast be administered to prevent exercise-induced bronchoconstriction?
at least 2 hours before initiating exercise
When is an asthma case NOT considered urgent?
- no previous history of hospitalisation
- normal physical examinations
- not unconscious or drowsy
- able to speak
What is the short term therapeutic objective when treating an asthma?
Relief
- reduce symptoms of breathlessness and expiratory wheeze during an acute attack
What is the long term therapeutic objective when treating an asthma?
Prevention
- dampen/prevent the late phase of an attack
- reduce the risk of further attacks
- attempt to improve asthma attacks
What is the first line treatment for children <5 with suspected asthma?
offer SABA, reliever therapy
- symptom relief and all maintenance therapy
Why is inhalation the preferred administration route of Salbutamol?
- lower inhaled dose
- direct delivery to tissues (instead of systemic)
- fewer side effects
What is the advantages of using inhalation to administrate drugs?
- minimal patient co-operation required
- all ages
- normal breathing pattern
- concentration and dose can be modified
- can deliver combinations of different drugs
Why is only 20% of inhaled salbutamol actually impacting the lungs?
- poor inhalation technique
- absorbed in the oesophagus, can cause a yeast infection due to inhaled steroids
- absorbed in the blood and straight to the heart (quick access to the bloodstream)
How do NSAIDs induce asthma?
prevents the conversion of arachidonic acid to prostaglandins (via cyclooxygenase) by inhibition cycloosygenase. Therefore increased luekotrines are produced leading to more inflammation and more bronchospasms.
