Pharmacological Treatment of Asthma and COPD Flashcards
What are the goals of treatment of asthma?
- no day-time symptoms
- no night-time waking due to asthma
- no need for rescue medication
- no asthma attacks
- no limitations on activity including exercise
- normal lung function (FEV1 and/or PEF >80%)
- minimal side-effects from medication
What is the approach to treatment of asthma?
- start at appropriate level
- achieve early control
- maintain control by stepping up/down when needed
- checking concordance/compliance/adherence at every change
What are the advantages of inhaled administration of asthma medicine?
- direct delivery to site of action
- rapid response with rescue medication
- allows smaller doses than systemic route
- reduces side-effects
What determines the efficiency of the route of administration?
- type and severity of asthma
- particle size of medicine
- inhaler technique
What are the different inhaler devices?
- MDI: metered dose inhaler (press down and breathe in- only 10% delivered to lungs)
- accuhaler: dry powder (fast inhalation, over 5 seconds, patient has to hold breath for 10 seconds after)
- via spacer/aerochamber
What are the advantages of spacers and how does it work?
- gives patients another 10 seconds roughly to breathe in medicine
- improves lung deposition of the medicine
- breaks down the particle size of the drug
- larger particles sit at the bottom of the spacer so smaller particles can enter the smaller airways
Describe how the nebulised route works and the advantages and disadvantages of it
- uses O2, compressed air or ultrasound to break up drug solutions into fine mist
- inhaled in a facemask/mouthpiece
- advantage: gives high doses quickly to give a fast response
- disadvantage: increased risk of side-effects
What are the 5 pharmacological treatment steps for asthma?
- intermittent reliever therapy
- regular preventer therapy
- initial add-on therapy
- additional controller
- specialist therapies
What are the 5 classes of ‘relievers and preventers’ of asthma?
- beta2-adrenoreceptor agonists
- glucocorticoids
- cysteinyl leukotriene antagonist
- methylxanthines
- monoclonal antibodies
Describe the mechanism of action of Beta2-agonists
- step 1 and 3
- short and long acting
- stimulate bronchial smooth muscle receptors, relaxes muscles, dilates airways reducing breathlnessness
- inhibit mediator release from mast cells and infiltrating leukocytes (short-acting)
- increase ciliary action of airway epithelial cells (aids mucus clearance)
Beta2-agonist for step 1
- intermittent reliever
- short acting (SABA) lasts 5 hours
- eg. salbutamol, terbutaline
- reliever
Beta2-agonist for step 3
- initial add on therapy (given combined with inhaled steroid)
- long acting (LABA) up to 12 hours
- eg. salmeterol, formoterol
- given to prevent bronchospasm (at night/exercise) in patients that need long term therapy
What are the side effects of Beta2-agonists?
- sympathomimetic effects (tachycardia/tremor/headache)
- muscle pain/cramps
- electrolyte disturbances (hypokalaemia)
- hyperglycaemia
- paradoxical bronchospasm (very rare)
What drugs are used for step 2, when would you give them and what are the outcomes of it compared to other treatment?
- inhaled corticosteroids
- given if person has symptoms or is using SABA more than 3 times a week
- if waking up at night with wheeze
- if had an asthma attack in last 2 years
- slower onset of action
- longer term effects over months (reduction in airways responsiveness to allergens and irritants)
What is the mechanism of action of inhaled corticosteroids?
- bind to glucocorticoid receptor modifying immune response
- inhibits formation of cytokines (including IL)
- inhibits activation and recruitment of inflammatory cells to airways
- inhibits generation of inflammatory prostaglandins and leukotrienes (reduces mucosal oedema)
- decreases mucosal inflammation, widens airways and reduces mucus secretion)
What are some examples of corticosteroids used in asthma?
- inhaled: beclomethasone, budesonide, fluticasone
- oral: prednisolone
- IV: hydrocortisone
What are the side effects of corticosterids?
- oropharyngeal candidiasis (oral thrush infection)
- dysphonia (hoarseness)
- systemic side effects (if chronic high dose):
- osteoporosis
- adrenal insufficiency
- growth retardation
What treatments are given for step 4 and examples?
- additional controller therapy
- increasing dose of ICS
- or add a leukotriene receptor antagonist LTRA
- eg. montelukast, zafirlukast
What are LTRAs taken for and their mechanism of action?
- for prophylaxis and taken daily by oral route
- not good in acute attacks
- blocks the effects of bronchoconstricting leukotrienes (specifically CysLT1) in airways resulting in bronchodilatory effect
- reduces eosinophil recruitment to airways reducing inflammation, epithelial damage and airway hyper-reactivity
What are the side effects of LTRAs and what are they good for?
- good for exercise induced asthma
- good for children who cannot take inhalers
- abdo pain
- headache
- hyperkinesia in children
What drugs are used for step 5 and examples?
- specialist therapies
- chronic persistent asthma
- methylxanthines eg. theophylline, aminophylline
- monoclonal antibodies eg. omalizunab
Describe the action of methylxanthines
- immunomodulatory and anti-inflammaotry action bronchodilator
- phosphodiesterase inhibitors (PDE)
- PDE implicated in inflammatory cells so reduces inflammation
- PDE inhibition increases intracellular cAMP in bronchial smooth muscle causing bronchodilation
- activates histone deacetylase
What are the side effects of methylxanthine?
- narrow therapeutic index
- GI upset
- arrythmias
- CNS stimulation
- hypotension
Describe the action of monoclonal antibodies, how they are administered and the disadvantages
- antibody to IgE, inhibits mediator release from basophils and mast cells
- preventer
- injected (fortnightly/monthly)
- slow working (peaks at 3/4 months)
- reduces exacerbations and is steroid sparing
- can cause anaphylaxis and increases risk of strokes/heart disease
- expensive
What are the first 3 treatments for exacerbations of asthma?
- SOS
- SABA
- oxygen
- steroids
What are the recommendations for COPD patients?
- smoking cessation
- early use of long acting bronchodilator
- ICS
- immunise
- pulmonary rehab
- self-management plan
- optimise co-morbidities
Muscarinic receptor antagonist for COPD
- short acting and long acting
- cause bronchodilation, decreases mucus secretion, can increase mucociliary clearance
- slower onset of action
- not effective against allergens
Name some examples of muscarinic receptor antagonists used for COPD and their side effects
- SAMA: ipratropium (acute - nebulised route, non-selective)
- LAMA: tiotropium, aclidinium (selective for M3 receptor)
- side effects:
- constipation
- dry mouth
- nausea
- headache
- cough
- urinary retention (men)
Describe the step-wise process of treating an exacerbation in COPD
- give SABA or SAMA
- if no asthmatic features: LABA + LAMA
- still no improvement add ICS
- if asthmatic features: LABA +ICS
- if still no improvement add LAMA
When would you use inhaled corticosteroids in a COPD patient and what are the limitations of it?
- if FEV1 <50% predicted
- 2 or more exacerbations in a year that requried antibiotics/steroids
- limited benefit
- high doses can risk pneumonia and osteoporosis
What effect does ICS have on COPD?
inflammatory cells responsible for COPD (neutrophils and macrophages) become less responsive than lymphocytes and eosinophils to corticosteroids
What are the other treatment options for COPD?
- methylxanthines (theophylline, aminophylline)
- mucolytics (if chronic productive cough to reduce mucus viscosity - carbocysteine)
- phosphodiesterase type-4 inhibitor (roflumilast)
- long term antibiotics (azithromycin)
- IgE monoclonal antibody
- long term oxygen
How would you assess COPD?
- based on symptoms, activities of daily living (ADL), exercise capacity, speed of symptom relief with SABA
- changes in lung function (spirometry)
- risk of exacerbation
What makes a COPD patient high risk?
- if 2 or more exacerbation in last year
- or FEV1 <50% predicted
Describe what measurements would be seen in a patient with Asthma COPD overlap syndrome (ACOS)
- higher eosinophil count
- FEV1 numbers all over the place
- diurnal variation in PEFR
- respond better to steroids
- more reversible to B2 agonists
How would you treat acute, severe exacerbations in COPD?
- nebulise SABA/SAMA (on air)
- oral prednisolone
- antibiotics if infectied
- physio
- 24/28% oxygen
- if extreme: NIV/intubation
