Asthma (theraputics) Flashcards
What is asthma
Asthma is a chronic inflammatory disease of the airways based upon an allergic disorder mediated by IgE
What are the common symptoms of asthma
Wheezing
Shortness Of Breath (dyspnoea)
Coughing - particularly at night and on waking
Severe – cyanosis, difficulty speaking full sentences, drowsiness
Triggers from allergens
What are the key facts surrounding children and asthma
Commonly presents in children and will typically co-present with atopic disorders such as eczema
A night time cough is a key symptom
What is the main difference between asthma and COPD
Reversibility! If we give certain agents (salbutamol, short acting beta agonist) the hyper-reactivity in the airway is reversible
What is the aim for the tratment of patients with asthma
To control symptoms, including nocturnal & exercise-induced exacerbations, prevent patients’ having exacerbations. Reduce reliance on rescue therapy – indeed most effective control would be a patient that has no need for rescue medication (salbutamol inhalers).
Achieve best possible lung function (FEV1 &/or PEF > 80% predicted or best), minimising side effects of medication.
How do we define controlled asthma
Control is defined as:
• No daytime symptoms
• No night-time symptoms
• No need for rescue medication
• No limitations on activity, including exercise
• No exacerbations
• Normal lung function (in practical terms FEV1 and/or PEF >80% predicted or best) with minimal side effects from treatment
What types of drug treatments are used for asthmatic patients
we use inhaled and oral routes of administration
What are the different types of inhalers
Reliever - Short-acting b-agonists (SABA) i.e. salbutamol
Produces quick symptom relief, normally prn (well controlled asthmatics shouldn’t need to use these)
Preventer - Inhaled corticosteroids i.e. beclomethasone
Act on underlying inflammation
Usually bd regardless of symptoms
Controller - Long-acting b-agonists (LABA) i.e. salmeterol
Slow onset, long acting
Usually bd
What is a nebuliser and when are they used
Nebulisers vaporise aqueous solution of drug (namely salbutamol and ipratropium) to a mist for inhalation through a mask or mouthpiece. They offer high dose delivery and are particularly useful in acute or chronic/ severe asthma since co-ordination is not needed. You will see these used a lot in the hospital setting. Used for ‘brittle asthma’
How do β-2 Agonists work
Relax airway smooth muscle by stimulating beta2- adrenergic receptors, which increases cyclic AMP and produces functional antagonism to bronchoconstriction.
Cause bronchial smooth muscle relaxation and enhance mucociliary clearance
What are the two types of β-2 Agonists (give examples of the drugs)
- Short-acting (SABA):
Salbutamol and terbutaline
Onset 1-5 mins, duration 4-6 hours
1st line relievers offer quick symptomatic relief - Long-acting (LABA):
Salmeterol: Onset 10-20mins, duration 12 h
Formoterol: Onset 1-3 mins, duration 12 h (can be used in a MART reigime)
What are the ADRs of β-2 Agonists
– fine tremor in the extremities – nervous tension – headache – peripheral vasodilatation – tachycardia – hypokalaemia - low potassium
What are corticosteroids and how are they administered
Anti-inflammatory reducing bronchial hyper-response to triggers.
Can be administered:
• Inhaled (ICS) for maintenance: e.g. beclomethasone, budesonide, ciclesonide
– Available in combination with LABA
- classed as either low, medium or high doses
• Oral: prednisolone (usually 40-50mg of 5/7 for acute attack) minimum effective dose in Step 5
• IV: hydrocortisone (in acute severe situations)
• Suppress inflammatory process
When are corticosteroids indicated (stepping up therapy)
• Indicated if:
– Exacerbation of asthma in last 2 years
– Using inhaled ß2-agonist >3 times per week
– Symptomatic >3 times per week
– Waking 1 night per week with symptoms
What are the ADRs of corticosteroids (oral and inhaled
Inhaled:
Hoarseness or dysphonia - use spacer/dry powder
Oral candidiasis - Rinse mouth after use/spacer
Adrenal suppression – only in sustained doses >1500mcg beclomethasone daily
Oral
Hypertension, adrenal suppression, osteoporosis, skin thinning, hyperglycaemia, moon face, Acne
We must use the lowest dose that will control symptoms for shortest time possible
What are leukotrine antagonists and how do they work
Antagonise bronchoconstriction, airway oedema and mucous production.
Examples = Oral montelukast and zafirlukast
What are the typical ADRs of leukotrine antagonists
Abdominal pain, Headache, Thirst (can lead to bedwetting in children), Rash, Sleep disturbance/CNS effects
How do methylxanthines work
They are phosphodiesterase inhibitors that inhibit leukotriene synthesis and thus inflammation and bronchodilation
Examples: Oral: theophylline
IV/oral: aminophylline (salt of theophylline)
What are the issues surrounding methylxanthines
Narrow Therapeutic Index
– SR preparations used to give more predictable effect
– brand must remain constant
Give the effects of overdosing on methylxanthines
- Therapeutic range: 10-20mg/L
- <20mg/L: nausea, diarrhoea, nervousness, headache
- > 20mg/L: vomiting, insomnia, arrhythmias
- > 35mg/L: hyperglycaemia, arrhythmias, convulsions, death
Clearance of methylxanthines (and therefore ADRs) is affected by CYP450 metabolism (hence they interact with many other drugs). Detail the effects of increased and decreased clearance and what causes it
• decreased clearance (increased plasma levels)
CCF, liver disease, obesity (dose by IBW)
- enzyme inhibition e.g. cimetidine, erythromycin, allopurinol, ciprofloxacin (interactions can lead to toxicity)
• increased clearance (decreased plasma levels)
Smoking, alcohol
- enzyme induction e.g. carbamazepine, rifampicin, phenytoin, smoking (interactions can lead to sub therapeutic doses)
What are cromones and when are they used
Mast cell stabilisers. Inhibits mediator (histamine) release from mast cells
An example is Nedocromil: Preventer in 5-12 year olds
What are the ADRs of cromones
N&V, bitter taste, dyspepsia
What would we use to treat very brittle, uncontrolled asthma
Immunosuppressants such as methotrexate, ciclosporin, gold (amino-modulating drugs)
These are steroid-sparing agents - reduce the need for steroids
Specialist use - rarely used
What are Anti IgE monoclonal antibodies used for. Give an example
Licensed as add-on therapy in adults and children > 12 for severe persistent allergic asthma
• S/C injection every 2 to 4 wks.
• Only initiated by specialist centres
• Patients must fulfil specific criteria (NICE)
• Discontinue after 16 wks. if inadequate response
An example is Omalizumab
Inhibits binding of IgE to mast cell receptors therefore preventing inflammatory response to trigger
Give an example of a long acting antimuscarinic (LAMA)
Titotropium - licenced for asthma as an additional drug for patients with persistant poor control.
Also seen in the treatment of COPD
How do we manage chronic adult asthma and which guidelines do we follow to do this
All patients should be offered inhaled short acting beta-2 agonist as required
Patients with infrequent, short-lived wheeze:
Regular preventer therapy
Add low dose inhaled steroid
We use BTS/SIGN guideline 2016. NICE guidelines are also used however the have differences. Which is used is based on local policy.
What are the add on therapies we can offer to adults with cronic asthma when the condition isn’t improved by the initial interventions
Initial add-on therapy:
Add LABA to low dose ICS
Assess control & continue if good
Additional add-on therapies for persistent poor control
No response to LABA - stop & increase inhaled steroid dose
If benefit but inadequate response, continue LABA & increase inhaled steroid to medium dose
If control still inadequate, consider trials of:
- leukotriene antagonist
- SR theophylline
- LAMA
If contol is still not gained after the introduction of inhaled corticosteroids, a laba, leukotriene antagonists etc. what is the next step
We move them onto High dose therapies: Increase ICS to high dose Add a fourth drug: LTRA (leukotrine antagonist) SR theophylline Beta-agonist tablet LAMA REFER TO SPECIALIST
We could also move to continuous or frequent use of oral steroids:
Daily oral steroid at the lowest dose to provide control
Maintain high dose ICS
REFER TO SPECIALIST
What is the key concept used in the management of asthma
Management is step-wise in both directions and stepping down treatment is important.
Treatment is reviewed every 3-6 months with a view to stepping up/down
What is PEF
Peak Expiratory Flow rate(L/min) Gives us an idea of lung function Is effort dependent Is a best of 3, patient records PEF “diary”. We can use this to monitor trends (if they're declining) Is dependent on sex, age, height
Allows patient/HCP to monitor contro
What is the aim for a PEF reading
Measured depending on the patients % predicted normal or best
Aim >70% or 0.7 (if FEV1/FEV)
“Normal” > 80% of their predicted best
<50% acute severe asthma (need care asap)
What indicators do we use to tell if a patient has severe or life threatening severe acute asthma
Severe determined by four features:
PEF<50% normal/best, inability ability to talk full sentences, Respiratory Rate >25, HR>110
Life-threatening if:
the above PLUS: silent chest, cyanosis, bradycardia, confusion, exhaustion, coma, difficulty speaking full sentences. PEF<33% normal/best
Both cases require hospitalisation (life threatening needs icu)
What drugs do we give if a patient is having a life threatening asthma attack
Immediate Rx
-oxygen: highest possible conc. 40-60%, aim for arterial oxygen saturation 94-98%
-beta-agonist: neb or multiple doses (10-20 puffs) via spacer
-Corticosteroid: prednisolone 40-50mg po or 100mg iv hydrocortisone (hold ICS)
Consider
-Ipratropium (short acting muscarinic) nebs
Single dose IV -magnesium sulphate (stabilises T-cells and mast cells)
-iv aminophylline/iv salbutamol
How do we manage acute asthma
During hospitalisation
- Stepdown treatment - iv => neb => inhaler
- oral steroid at least 5/7
- re-start steroid inhaler
- discharge criteria (inc. reiterating asthma diary and recording PEF daily)
- action plan
- check inhaler technique
Transfer to ITU if
- Deteriorating PEF
- Persistent hypoxia
- Hypercapnia (retaining CO2)– acidotic (blood pH rises ~ 7.4)
- exhaustion, drowsiness
- coma, resp. arrest
What vitals do we monitor in acute asthma (9)
- PEF
- O2 saturation (Aim 94-98%)
- arterial blood gases – inc. pH for acidosis
- HR/RR (tachy-cardia/ponea)
- theophylline levels if they’re on it (if cont >24h)
- serum K+ as salbutamol causes hypokalemia (nebulised SABA)/glucose
- Hydration
- White cell count (asthma attack may have been caused by a chest infection)
- C Reactive Protein (inflammatory marker)
