Asthma pharmacology Flashcards
Describe an asthmatic airway
- Wall inflammed and thickened
- Relaxed smooth muscles when not exacerbated/during an attack
Describe an asthmatic airway during an attack
- Wall inflammed& thickened
- Tightened smooth muscles
- Air trapped in alveoli
What kind of asthmatics should (SABA) short acting beta 2 agonist( as- needed reliever inhaler) be reserved for
-Patients with infrequent symptoms( less than twice a month) of short duration, with no night waking due to asthma & no risk factors for exacerbations
Outline the different bronchodilators
- ) Selective Beta-2 aderenoceptor agonists
- Inhaled( can also be given IV in intensive care)
- Short acting: salbutamol
- Long-acting: Formoterol, salmeterol, Vilanterol - ) Anticholinergic/muscarinic receptor antagonists:
- inhaled
- Short acting
Describe the mechanism of salbutamol
- Stimulates the beta 2 adrenergic receptors-the predominant receptors in bronchial smooth muscle
- Stimulation of the beta 2 adrenergic receptors leads to activation of adenyl cyclase enzyme leading to cAMP formation from ATP
- high levels of cAMP relaxes bronchial smooth muscle and inhibits the release of bronchoconstrictor mediators such as histamine & leukotrienes from mast cells in the airways
- After inhalation,salbutamol reaches the lungs directly and acts within 3-5mins with a peak at 15-20mins
- after oral administration about 50% of salbutamol absorbed from GIT with a slower onset of action,reaching a peak at about two hours after intake
- Overall duration of action of salbutamol is 4-6 hours
outline the mechanism of anticholinergic/muscarinic receptor antagonists
- Block effects of ach released from cholinergic parasympathetic nerve fibres to smooth muscle&mucus glands…
1. )prevents smooth muscle constriction
2. )prevents mucus hypersecretion - less effective than b2 adrenoceptor agonists
- side effects=unusual,include dry mouth,palpitations,headache,dizziness,blurred vision
what is the major difference between the mechanism of action of the b2 agonists & the anticholinergics ?
- the b2 agonists PROMOTE bronchodilation
- the anticholinergics RESTRICT bronchoconstriction
outline the benefits of inhaled corticosteroids
- reduce asthma symptoms
- increase lung function
- improves QOL
- reduces the risk of exacerbations,hospitalisations &death
- corticosteroids suppress Th2/type 2 airways inflammation
- Reduce the infiltration and activation of eosinophils,Th2 cells &other inflammatory cells
outline the characteristics of fluticasone furoate(FF)/vilanterol
- an ICS with enhanced affinity for the glucocorticoid receptor (fast association &slow dissociation)
- Results in a longer duration of action and prolonged retention in the lung; enables its use as a once-daily ICS
- Longer duration of action enables once-daily dosing: potential to improve patient convenience& enhance adherence to treatment
- FF/vilanterol is the only currently available once daily ‘ICS/LABA combination inhaler’ licensed in asthma
What is the complication association with asthmatic patients that have elevated blood eosinophilic levels?
-Experience a higher rate of exacerbations and lower asthma control
Outline the characteristics of the leukotriene receptor antagonist: Montelukast
- Leukotrienes are a group of potent arachidonic acid-derived inflammatory mediators
- The CysLT1 receptor mediates the bronchoconstrictive and proinflammatory effects of cysteinyl-leukotrienes (LTC4, LTDV & LTE4)
- Montelukast is a competitive antagonist of the CysLT1 receptor
- once daily oral administration
- Likely to work best in a subgroup of asthma patients with ‘aspirin exacerbated respiratory disease’ (AERD) as they have increased production of cysteinyl-leukotrienes
- side effects are GI disturbances and headaches
What are the cons of taking oral corticosteroids(prednisolone)
can cause: -Obesity -Diabetes -Cataracts -Reflux -Glaucoma -Osteoporosis -Skin disease -Psychiatric issues We therefore limit its chronic use due to its association with multiple side effects
Explain the use of Mepolizumab & Benralizumab in asthma.
- Can be used in the treatment of severe eosinophillic asthma
- Eosinophils are the central effector cell in asthma
- IL-5 is critically involved in the synthesis, maturation, homing & activation of eosinophils
- Mepolizumab( serum neutralising antibody) targets serum IL-5
- Benralizumab (non-serum neutralising ab) targets IL-5 receptor
- Both significantly reduce number of esoniophils, asthma exacerbations & systemic steroid exposure
Explain the use of Omalizumab in asthma
- Depletes IgE, ‘disarms’ mast cells: reduces allergen-induced mast cell activation and decreases expression of IgE high affinity receptors on mast cells, blocks effects of IgE on dendritic cells
- Decreases exacerbation rates
- Omalizumab is given by subcutaneous injection every 2-4 weeks, at a dose and frequency determined by body weight & serum IgE levels
- Anti IgE (omalizumab) eliminates the seasonal peaks in asthma exacerbations
How can we classify asthma treatments
- Those that relieve (bronchodilators)
- Those tjhat control ( anti-inflammatory) disease
