pharmacological treatment of asthma and COPD Flashcards
what are the features of asthma?
- airway narrowing (reversible)
- airway hyper responsiveness
- airway inflammation
what is the pathogenesis of asthma?
acute and chronic inflammatory responses in airway
what are the goals of treatment for asthma?
- no daytime systoms
- no time time waking
- no need for rescue medication
- no asthma attacks
- no limitations on activity
- normal lung function FEV1>1%)
- minimal side effects from medication
what are the routes of administration for treating asthma?
primarily inhaled
- directly delivered to the site of action
- rapid response
- allows smaller doses than systemic route
- reduces side effects
- efficacy. of route depends on type and severity of asthma
- oral and injectable treatment aswel.
what are the different types of inhaler device?
- MDI= metered dose inhaler
- breathe - acuated
- accuhaler = dry powder
- spacer/ aero chamber
what is the purpose of ‘spacers’?
- large particles of aerosol are deposited in the chamber before the patient inhales
what is good about ‘spacers’/ nebulisers?
people who take inhalers are more prone to getting a hoarse voice or oral thrush, so by taking their medication through a spacer they are less likely to develop these symptoms.
what are the downsides to nebulisers?
- they are not used as much because they need yearly maintenance
- people who have them in their house are less likely to call an ambulance when they are having an asthma attack which is bad.
- higher risk of side effects
describe nebuliser route?
- use O2, ultrasonic power or compressed air to break up the drug in solution into fine mist.
- uses a face mask/mouth piece
- gives a high dose of reliever quickly in acute severe asthma.
what are the 5 steps up and down of pharmacological treatment of asthma?
1) intermittent receiver therapy
2) regular preventer therapy
3) initial add on therapy
4) additional controller therapy
5) specialist therapies
what are the 5 main drugs used to treat and prevent asthma? (receivers and preventers)
1) beta-2 agonist = salbutamol (short acting)
2) glucocorticoids = beclometasone, budesonide
3) beta- 2 agonist = salmeterol (long acting)
4) cysteine leukotriene antagonist (LRTA) = montelukast
5) a) methylxanthines = theophylline
b) monoclonal antibodies = anti-IgE treatment = omalizumab
describe the mechanism of action of B2 agonist
(LABA and SABA)
what steps do these cover?
THESE WILL COVER STEPS 1 AND 2!!!!
- they stimulate bronchial smooth muscle B2 receptors, relax smooth muscle, dilate airways and reduce breathlessness (basically reduce symptoms)
- inhibit mediator release from mast cells and infiltrating leukocytes
- increase ciliary action of away epithelial cells, aiding in mucus clearance.
describe the difference ion duration of LABA and SABA?
SABA= fast acting last up to 5 hrs, used as required
LABA= given regularly (with inhaled steroid), lasts longer (up to 12 hrs, given to prevent bronchospasm in patients requiring long term therapy
what are the side effects of B2 agonists?
(you tend to only get side effects if its a high dose that is given orally or through IV)
- sympathomimetic effects (increase in heart rate, tremor etc)
- muscle pain/cramps
- electrolyte disturbances
- hyperglycaemia
- paradoxical bronchospasm
describe step 2?
what drug is given?
give INHALED CORTICOSTEROIDS
- this is regular preventer therapy
- acts as an anti-inflammatory and immunosuppressive
- slow onset of action
- longer term it will effect the airways responsiveness to allergens and irritants
when will you add an inhaled corticosteroid?
- add if has symptoms of or using SABA more than 3 times a week
- if waking up in the middle of the night with wheeze
- ## is they have had an asthma attack in the last 2 years
describe the mechanism of action of inhaled corticosteroids?
- bind to glucocorticoid receptor, modify immune response
- inhibit formation of cytokines
- inhibit activation and recruitment to airways of inflammatory cells
- inhibits generation of inflammatory prostaglandins and leukotrienes, reducing coal oedema.
- DECREASE MUCOSAL INFLAMMATION, WIDENS AIRWAY AND REDUCES MUCUS SECRETION.
WHAT ARE THE SIDE EFFECTS OF CIRTICOSTEROID USE?
- oropharyngeal cadidiasis (oral thrush)
- dysphonia (hoarseness)
- systemic effects
- osteoporosis
- adrenal insufficiency
- growth retardation
what drugs are given at step 4?
LRTA’s (leukotriene receptor antagonist)
BUT
first try increasing dose if the inhaled corticosteroids.
LRTA’s = montelukast
- for prophylaxis treatment (not for an acute attack) therefore it must be taken daily orally
mechanism of action of step 4 drugs (LRTA’s)?
- blocks leukotrienes
- blocks the effect of bronchocontstricitng cysteinyl leukotrienes (specifically CysLT1) in the airways, resulting in bronchodilator.
- reduces eosinophil recruitment to always, reducing inflammation, epithelial damage and airway hyper- reactivity
when are LRTA’s good?
- exercise induced asthma
- reduce both early and late phase bronchocontriction reposes to allergies
what are the side effects to LRTA’s
- abdominal pain
- headache
- hyperkinesia in children
what is step 5? “specialist therapies”
what drug is given?
EXAMPLE A
- immunomodulatory and anti-inflammatory action at lower doses
- bronchodilator (at higher dose)
EXAMPLE A (theophylline) = methylxanthines which are used in the chronic chronic persistent asthma
describe the mechanism of action of methylxanthines?
- phosphodiesterase inhibitors (PDE)
- PDE implicate in inflammatory cells (therefore inhibition reduces inflammation)
- PDE inhibition increases intracellular cAMP in bronchial smooth muscle, causing relaxation
- blocks adenosine receptor, resulting in bronchodilator
- activates histone deacetylase (immunomodulatory)
what are the side effects of methylxanthine?
narrow therapeutic index drug group, measuring serum drug concentrations, be aware of potential for drug interactions.
dose or rate related:
- gi upset
- arrhythmias
- CNS stimulation
- hypotension
example B of specialist therapies drug?
when are they used?
monoclonal antibodies (the mass) eg- Omalizumab
‘preventer’
- used is severe persistent allergic asthma
describe the mechanism of action of monoclonal antibodies (MABS)
- antibody to IgE, inhibits mediate release from basophils and mast cells
-injectible - slow to work (peaks at 3 to 4 months)
- reduces excererbations and is steroid sparing
down sides to MABS?
- can cause anaphylaxis and increase the risk of strokes and heart disease
- expensive
describe a monitoring plan?
- peak Flow meter, 3 times, twice a day.
- should see a nocturnal dip
<50% then severe asthma
manaamnet of acute severe asthma?
SOS
- SABA via a nebuliser
- Oxygen (94-98%)
- steroid h(hydrocortisone or prednisolone)
give an antibiotic if triggered by an infection
how should the short acting b2- agonist be given?
give 2-10 puffs, each to be inhaled separately through a spacer
what do you give the patient is still not improving?
IV magnesium sulphate (bronchodilators, anti-inflammatory)
switch from neublised to IV salbutamol or IV methylxanthine
What is the recommendation for all COPD patients?
- Smoking cessation,
- Early use of bronchodilators,
- Inhaled corticosteroids,
- Immunise against pneumovax and flu
- Pulmonary rehab
- Self management,
- Optimise treatment for co-morbidities
What are the features of muscarinic receptor antagonists?
They cause bronchodilation, decrease mucus secretion and may increase mucociliary clearance. Long acting muscarinic antagonists can improve outcomes, has a slower onset of action, not effective against allergen challenge.
Describe the overview of the NICE COPD guidelines if there is suggestion of asthma/steroid responsiveness
Step one - If required SABA or SAMA.
Step two - LABA and ICS combination.
Step three - LAMA and LABA and ICS
Describe the overview of the NICE COPD guidelines if there is no suggestion of asthma/steroid responsiveness
Step one - If required then SABA or SAMA.
Step two - LABA and LAMA.
Step three - LABA, LAMA and ICS trial
what are the different types of Long acting muscarinic antagonist (LAMA)
and SAMA?
SAMA = short acting
Ipratropium - non selective, nebulised route
LAMA= long acting
tittropium = more selective for M3 receptor
what are the side effects to muscarinic antagonists
uncommon
- constipation
- dry mouth
- naesuae
- headache
- cough
describe the use of inhaled corticosteroid in COPD?
what may a high dose increase the risk of?
- they have limited benefit
- inflammatory cells are responsible for COPD (neutrophils and macrophages) , so they are less responsive than lymphocytes and eosinophils to the action of corticosteroids.
- only use of FEV1<50% and you have 2 or more exacerbations in a year which have required steroids or antibiotics
- a high dose may increase the risk of pneumnia and osteoporosis
What are some other treatments for COPD?
- Methylxanthines,
- Mucolytics - If chronic productive cough, reduced sputum viscosity.
- Phosphodiesterase Type-4 inhibitors,
- Long term antibiotics,
- Anti-IgE monoclonal antibody.
- Long term oxygen
Describe the assessment of COPD
- Primarily based on patient symptoms,
- Changes in lung function (spirometry)
- Risk of exacerbation
Describe the treatment of acute severe COPD exacerbations
- Nebulise SABA/SAMA,
- Add oral prednisolone,
- Antibiotics if infected
- Physio
- 24-28% O2,
- If extreme then NIV or intubation
Describe features of asthma-COPD overlap syndrome
- Higher eosinophil count
- FEV1 swings,
- Diurnal variation in PEFR
- Respond better to steroids
- More reversible to Beta 2 agonists.
