Asthma Flashcards
What are the common effects of asthma?
Muscle oedema - excess mucous production + thickening of sub mucosal layer leading to substantial narrowing of airways.
Smooth muscle hypertrophy and overactive, increasing sensitivity to stimuli (exercise, temperature, allergen)
What is asthma?
Chronic inflammatory disorder of the airways leading to variable airflow obstruction.
This is a reversible condition (often spontaneous reversibility, or reversible with treatment)
What are the two main types of asthma?
Extrinsic: common in children
Intrinsic: usually develops in adulthood
How does asthma differ from other respiratory diseases like COPD?
In the reversibility nature. COPD is not reversible
What can reduce incidence of exercise induced asthma?
Proper warm up and cool down
What is extrinsic asthma..
A type of asthma, common in children and is associated with a genetic disposition.
This is precipitated by a known allergen like mould or pollen.
What is intrinsic asthma?
Usually develops in adulthood.
This is triggered by non-allergenic factors like viral infections/irritants, exercise, or emotional upset.
What is the pathophysiology of acute inflammation asthma?
Acute inflammation is caused by an inhaled allergen in allergic patients leading to an early phase allergic reaction which may be followed by a late phase reaction.
What happens in the early phase of acute asthma inflammation?
There is an activation of cells bearing IgE antibodies in response to an allergen.
This causes rapid activation of airway mast cells + macrophages.
These release pro inflammatory mediators (histamines + eicosanoids), inducing contraction of airway smooth muscle.
Mast cells also secrete mediators (PAF + LTB4) leading to narrowing of airways,
There is also plasma protein leakage which induces a thickened airway wall and narrowing of airway lumen with reduced mucous clearance.
This results in narrowing of lumen of the airways and airflow obstruction
What happens in the late phase of acute asthma inflammation?
This late phase usually occurs 6-9 hours post allergen aggravation. Antigen presenting cells (macrophages) engulf the antigen and present it to CD4+ T lymphocytes, thus activating them.
The CD4+ T lymphocytes in turn activate monocytes, eosinophils, basophils, neutrophils which secrete various chemicals to stimulate submucosal oedema leading to airway narrowing
What is the pathophysiology of chronic asthma inflammation?
Lymphocytes secrete mediators which initiate eosinophilopoesis.
Lymphocytes also secrete chemicals which damage epithelial cells
Eosinophils secrete cytokines and various mediators thus also damaging epithelial cell wall, resulting in damaged epithelium, mucous overproduction, and hyper responsiveness
What is PAF and LTB4?
Platelet activating factor and Leukotriene B4
These mediators are secreted by mast cells in the early phase of acute asthma inflammation and result in narrowing of the airways
What are IgE antibodies?
Allergen specific immunoglobulin E antibody
What is eosinophilopoesis?
An increase in eosinophil production in bone marrow
This is initiated by mediators secreted by lymphocytes in chronic asthma inflammation
What do eosinophils do?
In asthma they migrate to the airways to release inflammatory mediators (LTs, granule proteins) cytotoxic mediators and cytokines
What do T lymphocytes do?
In asthma, these are activated by antigen presenting cells.
Their activation leads to the release of cytokines
What happens in mast cell degranulation?
This results in the release of mediators (histamine, eosinophil and neutrophil chemotactic factors) in response to allergens
What do alveolar macrophages do in asthma?
Release inflammatory mediators (platelet deriving factor and leukotrienes)
What do neutrophils do in asthma?
They are a source of mediators (including thromboxanes, leukotrienes, and platelet activating factors)
What are common triggers of asthma?
Respiratory infection: cold, flu
Allergens: airborne pollens, dust mites, animal dander, fungal spores, moulds,
Environment: cold air, fog, tobacco smoke
Emotions: anxiety, stress, laughing, pre-menstrual changes
Medications: NSAIDs, β-blockers, aspirin (if patient allergic, do not give nurofen as they are from same family.)
Food additives: food colouring, preservatives, strong smells
Occupational stimuli: fumes, chemicals, dust
How is asthma typically presented clinically?
Wheezing, breathlessness, chest tightness, increased night time cough
Tiredness with activities you would normally complete easily
Decrease in PEFR (<350-400 )
Worsening allergy symptoms (persistent runny nose, dark circles under eyes, itchy inflammed skin)
Ronchi
What is ronchi?
The coarse rattling sound somewhat like snoring
This is usually caused by secretion in bronchial airways
What happens in exercise induced bronchospasm?
During exercise, pulmonary functions FEV1 and PEFR increase during the first few minutes, but begin to decrease after 7 mins
There is a refractory period lasting up to 3 hours after exercise (which will fail to produce EIB or will produce a lesser reaction)
Patients will respond to histamine hence acute hypo responsiveness of airway smooth muscle does not appear to be a factor
How is EIB defined?
Exercise induced bronchospasm:
A drop in FEV1 greater than 15% of baseline
What factors should be considered in the differential diagnosis of asthma?
Chest X-rays can be used to exclude other things (infections like pneumonia)
Airway obstruction showing reversibility requires administration of treatment if FEV1 improves by 15% or PEFR increases by 200mL. This confirms asthma
If person is smoker and does not show reversible airway obstruction, assess them for COPD
What are the drug classes involved in the treatment of asthma?
β adrenergic bronchodilators Antimuscarinics bronchodilators Inhaled corticosteroids Oral corticosteroids Leukotriene receptor antagonists Sodium cromoglycate
What is the mechanism of action of β2 agonists?
Dilate bronchi by direction action on β2 adrenoreceptors of smooth muscle.
Stimulation activates cytoplasmic G proteins, -> production of cAMP
This decreases unbound intracellular Ca producing smooth muscle relaxation, mast cell membrane stabilisation and skeletal muscle stimulation
There is a need to monitor serum potassium due to hyperkalaemia
This class of drugs is further divided into short acting and long acting
What is a short acting β2 agonist?
E.g. Salbutamol, terbutaline.
Acts within 15-30 minutes and relief in 4-6 hours
Used for mild - mod symptoms and EIB
Adverse effects: tremor and hyperkalaemia
What are long acting β2 agonists?
E.g, salmeterol, formoterol
These act within 1-2 hours and provide relief for up to 12 hours
Used for patients who regularly use ICS
Should not be used for relief in attack
Should only be used if standard ICS dose fails to control asthma
Should not be initiated in patients with rapidly deteriorating asthma
Should not be used in EIB unless CS are also used
Adverse effects: tremor, hyperkalaemia, nausea, dizziness, cardiac dysrrhthmias. High doses of β2 agonists assoc. with hypokalaemia
What are antimuscarinic bronchodilators?
These are competitive inhibitors of muscarinic receptors e.g. Ipratropium, tirotropium
Not routinely used in asthma
Adverse effects: dry mouth, cough, constipation
What is the mechanism of action of antimuscarinic bronchodilators?
Relax bronchial constriction by blocking action of ACh (neurotransmitter of PNS) not as effective as β2 agonists.
Reduces force of asthma attack,
Tend to be used more in COPD
What is ipratropium?
Marketed as Atrovent.
Non selective muscarinic receptor blocker
Relaxes smooth muscles without influencing secretions
Has slow onset of action (30-60min) but acts for up to 6 hours
20-40μg 3-4x daily
What is tirotropium?
Marketed as Spiriva.
Is given as inhalation in powder form from a handihaler
Has prolonged action (72 hours after single dose)
18μg once daily
What are inhaled corticosteroids?
E.g. Fluticasone,
These are used for mild-mod asthma
Not for patients who don’t completely respond to initial inhaled β2 agonist
Relieves bronchial obstruction by improving the responsiveness of β2 receptors.
Alleviates symptoms 3-7 days after initiation
Adverse effects: dose and duration dependent, includes growth retardation in children, adrenal suppression, decreased bone mineral density, hoarseness.
When should inhaled corticosteroids be used?
Use when β2 agonists are required more than 2x a week
if asthma disturbs sleep more than once a week
if patient has suffered exacerbations in last 2 hours
What is the mechanism of action of inhaled corticosteroids?
Relieves bronchial obstruction by inhibiting numerous phases of inflammatory response:
Readily crosses membrane be combines with glucocorticoid receptor activated complex to enter the nucleus,
Acts as a transcription factor leading to gene activation
Resulting in specific mRNA production resulting in increased production of anti inflammatory mediators.
Reduces inflammatory cell activation, recruitment and infiltration.
Decreases vascular permeability required for regular prophylaxis of asthma but needs to b e used regulatory for max benefit
What are oral corticosteroids?
E.g. Prednisolone, prednisone
Used in treatment of acute asthma attacks
Works slowly over several hours to reverse swelling of airways
Needs to be continued for several days after asthma symptoms settle to ensure swelling does not return
What are Leukotriene receptor antagonists?
E.g. Montelukast, zarfirkulast These are less effective and cause more adverse effects than a low dose ICS
However are effective for night time asthma, so decreases nocturnal awakenings
Adverse effects: abdominal pain, thirst, headache, charg Strauss syndrome (rare) diarrhoea, dyspepsia, nausea, vomiting
What is the mechanism of action of Leukotriene receptor antagonists?
Reduce pro inflammatory and bronchoconstriction effects of Leukotriene C4, D4, E4
What is Zileutin?
Inhibitor of Leukotriene synthesis
Decreases nocturnal awakenings?
What is sodium cromoglycate?
E.g. Sodium cromoglycate (10mg, 2puff qid can increase to 6-8 x daily)
Nedocromil sodium (4mg, 2 puffs qid, can be deceased to bd)
These are Mast cell stabilisers.
Indicated for prophylaxis of mild persistent asthma in children and adults
Can be used for patients not responding completely to inhaled β agonists
Least toxic anti asthma drug. Sometimes successful in 60-70% of children
Most patients improve within 1-2 weeks but may take longer to achieve max benefit.
Adverse effects: coughing and wheezing, bad taste, headache
What is the mechanism of mast cell stabilisers like sodium cromoglycate?
These prevent the release of mediators that would normally attract inflammatory cells, and inhibits the response to allergen challenge (prevent, not treat)
Do not cause bronchodilation
What are the asthma combination therapies?
These are therapies which a combined to provide better patient outcomes and compliance
E.g. SMART, Symbicort, Serotide,
What is SMART?
Single inhaler maintenance and reliever therapy
This combines a deterrent and reliever in one inhaler
What is Symbicort?
Combination inhaler which contains budesonide (ICS) and eformoterol (LABA)
What is Serotide?
Combination therapy containing fluticasone (ICS) and salmeterol (LABA)
This halves the dose of the corticosteroid used, thus decreasing the side effects assoc.
LABA on its own can cause exacerbation. This is decreased when combined with ICS
Why is fluticasone not used with a SABA in Serotide
The differing half life of SABA would mean it needs to be taken more frequently.
What are the 4 different severities of asthma?
Mild
Mild-mod
Moderate
Severe
What is used to treat mild asthma?
Inhaled short acting β2 agonists when required
What is used to treat mild-mod asthma?
Low dose of ICS (400μg/day, titrate up to 800μg/day if necessary) and SABA
What is used to treat moderate asthma?
Add LABA to ICS and SABA
Can Increase ICS to 1600μg/day consider adding oral theophyline or anti leukotrienes
What is used to treat severe asthma ?
Oral steroids (prednisolone) for at least 2 weeks, then check.
How is chronic asthma treated?
Review asthma treatment for 3 months (type of treatment depends on the severity)
If asthma control has been achieved, a stepwise reduction may be possible in which case you would need to reduce the dose of ICS slowly (minimises side effects)
What is GINA?
Global initiative for asthma.
Where health care workers aim to
Prevent chronic and troublesome symptoms
Maintain normal pulmonary function
Prevent recurrent exacerbations,
Minimise need for A&E visits and hospitalisations
Achieve optimal pharmacotherapy with minimal adverse effects
Achieve a Minimal need for β2 agonist therapy
What needs to be done when monitoring and counselling an asthma patient?
Health care workers should develop a partnership in care through patient education.
Identify treatment goals with patient.
Check Patients understanding (including experience of asthma, misunderstandings, fears, bad experiences.)
Continue communicating between the doctor, nurse and patient.
Select the best inhaler device AND review regularly to check competency and ensure effective delivery
Select the best medicine regime for the patient to achieve good control.
Make sure patient knows which medications to take and how to take them
Monitor severity using symptoms, patients opinion and PEF metre.
Why is a self management plan needed?
It enables the patient to take control of their condition,
Thus can improve compliance
What does a self management plan include?
Symptom monitoring (assessing symptoms of a patient) Triggers (avoid possible triggers) Measuring PEFR (assess improvement or deterioration) Drug usage and how to deal with fluctuations (educates patient) When to seek medical help & what to do in an emergency (better response in case of attack)
What are some non pharmacological therapies for the treatment of asthma?
Barrier methods to control exposure to allergen (if allergic asthma)
Avoid/minimise exposure too triggers if possible
Environmental approaches (air filtration devicesm steam cleaning carpets, furnishings, domestic mechanical ventilation)
Insulation (stabilises temperature)
Decrease/cessation of tobacco smoking
Fish-oil tablets may be beneficial via provision of mega 3 which tends to be low in western diet.
What happens if you have homozygous Arg-16 ?
You are predisposed to asthma even with β2 agonist treatment.
Inhaled ipratropium bromide is only indicated as adjunctive therapy in severe acute asthma, and is not completely responsive to β2 agonists alone as it does not improve outcomes in chronic asthma
What are the different kinds of inhalation devices available for asthma patients
Metered dose inhaler
Spacer
Dry powdered inhaler
Nebuliser
What is a metered dose inhaler?
The most commonly used inhalation device.
Lung deposition of the medication is often improved with a spacer.
What are the advantages of a metered dose inhaler?
Multi dose Small More socially acceptable Wide range of drugs available Can fit into spacers and be used adjunctively
What are some disadvantages of metered dose inhalers?
There is a need for good technique. Patients with poor hand breath coordination and limited dexterity find it hard to use.
Even with good technique, only 10% of the drug is delivered to the airways.
Medication can irritate throat
If medication is inhaled, can cause oral candidiasis
What is a spacer?
Compartment which works by reducing the velocity of the aerosol and subsequent impaction on oropharynx.
What are the advantages of a spacer?
Designed to make it easier for patient to get required dose.
When used adjunctively with MDI, removes need to coordinate actuation with inhalation
Useful if high dose of salbutamol needs to be given.
Reduces velocity of aerosol and its impaction on the oropharynx
Allows time for evaporation of propellant so larger proportion of particles can be inhaled and deposited into lungs
Good for patients prone to candidiasis with inhaled corticosteroids
What are the disadvantages of using a spacer?
Bulky
Not as socially acceptable to patients as MDI
What is a dry powdered inhaler?
The medicine is given as tiny granules which is inhaled.
This required breath activation, hence only useful device to contain preventor
What are the advantages of a dry powder inhaler?
There is no propellant, so onto coordination is required
What are the disadvantages of a dry powder inhaler?
There is some manipulation required with its use.
It is difficult if the patient has a poor grip (e.g. Elderly patient, patient with Rheumatoid arthritis)
There is also no sensation of having received a dose on inhalation
