Lecture 18- Respiratory pharmacology Flashcards
Asthma pathophysiology
- Chronic inflammatory airway disease often caused by exposure to allergens or other environment exposure
- Causes intermittent airway obstruction and hyper-reactivity in small airways
- Non allergic around 30-40%
- Reversible
- A heterogeneous disease (don’t know everything about asthma)
What does good Asthma control look like:
- Minimal symptoms during the day and night
- Minimal need for reliever medication
- No exacerbations
- No limitation of physical activity
- Normal lung function (FEV1 and/or PEF >80% predicted or best)
- Aim is for early control with stepping up OR down as required
what does uncontrolled asthma look like
Before stepping up or down asthma treatment check…
- Adherence
- Inhaler technique
- Eliminate/reduce trigger factors
Chronic asthma management 2 slightly different guidelines
BTS vs NICE
BTS
- low dose ICS (preventrer) + SABA prn
- add on LABA
- then consider increasing ICS and adding LTRA
NICE
- low dose ICS + SABA prn
- option 1: add on ICS/LABA
- or option 2: add on LTRA
Can step up and step down therapy
- LTRA cheaper than LABA
- Most end up on LABA anyway
name some Steroids- inhaled corticosteroids (ICS) used to treat athma (as preventer)
- Beclomethasone
- Budesonide
- Fluticasone
uses of ICS in asthma
- First line treatment
- Regular preventer when reliver alone not sufficient
Pharmacokinetics steroids
- Poor bioavailability
- Due to lipophilic side chain added
- Slow dissolution in aqueous bronchial fluid
- High affinity for glucocorticoid receptor
- Local effect
- Most IC are substrate of CYP450 3A4
- If steroids absorbed po transported from stomach to liver via hepatic portal system (almost complete first pass metabolism)
- But at high doses all ICS potential to produce systemic side effects
- If steroids absorbed po transported from stomach to liver via hepatic portal system (almost complete first pass metabolism)
MOA of ICS
- Pass through plasma membrane, activate cytoplasmic receptors, activated receptor then passes in to nucleus to modify transcription
- Reduces mucosal inflammation, widens airways, reduces mucus
- Reduces symptoms, exacerbations and prevents death
Adverse drug response ICS
- If taken correctly very few significant ADRS
- Local immunosuppressive action e.g. candidiasis, horse voice (in pharynx)
- Wash mouth out after
- Pneumonia risk at high doses
Drug-drug interactions ICS
CYP450 3A4 inhibitors e.g. budesonide
name some drugs under B agonists
SABA and LABAs
SABA uses
*
- ‘reliever’
- Symptom relief through reversal of bronchoconstriction
- Only to be use prn (when required)
- May be used prior to exercise to prevent bronchoconstriction
- When used regularly can reduce asthma control – tolerance?
- Seen as a quick fix esp in young adults
uses of LABA taken with ICS
Add on therapy to ICS and prn SABA
Mode of action B agonists
- Bind to B2 receptors (GPCR)
- Increase cAMP
- Increase PKA
- Cause airway smooth muscle to relax
- Also increase mucus clearance by action of cilia
Adverse drug response B agonists
*
- Adrenergic- fight or flight effects
- Tachycardia
- Palpitations
- Anxiety
- Tremor
- Increase glycogenolyis (liver)
- Increased renin (kidney
- Supraventricular tachycardia
Contraindication B agonist
- Should only be prescribed alongside ICS
- Alone can mask airways inflammation in near fatal and fatal attacks (LABA now always prescribed mixed with ICS)
- CVD- tachycardia may provide angina
Drug-drug interactions B agonist
B-blockers may reduce effects of B2 agonists
Additional asthma controller therapies:
- leukotriene receptor antagonist (LTRA) e.g. Montelukast (PO)
- Long acting muscarinic antaognist (LAMA) e.g. tiotropium
- theophylline
Uses of LTRA
- Alternative to LABA in NICE guidelines
- Only useful in 15% of asthmatics- most end up moving up to LABA
MOA of LTRA
- Inhibit leukotrienes released by mast cells/eosinophils by blocking CysLT1 receptor
- Reducing bronchoconstriction
- Reducing mucus
- Reducing oedema
Adverse drug response LTRA
- Headache
- GI disturbance
- Dry mouth
- hyperactivity
uses of LAMA e.g. tiotropium
- Severe asthma and COPD
Mode of action LAMA
- Relatively antagonistic for M3 receptor (SAMA much less selective)
- Block vagally mediated contraction of airway smooth muscle
Adverse drug response LAMA
- Infrequent
- Anticholingeric effects
- Dry mouth
- Urinary retention
- Dry eyes
uses of theophylline
- Chronic poorly controlled asthma
MOA theophylline
- Adenosine receptor antagonist
- Reduce bronchoconstriction
Adverse drug response theophylline
- Narrow therapeutic index
- Life threatening complications inc arrhythmia – must measure [plasma]
Drug-drug interactions theophylline
CYP450 inhibitors- will increase theophylline
Self management plans
- Important for all asthmatics
- Written instruction on when and how to step up AND step down treatment
- Better day to day management and reduced exacerbations
- Think about who is involved
- Adult
- Child
- Cognitively impaired
- Carer
- Should be reviewed following treatment for exacerbation and on discharge from hospital following acute attack
define features of acute severe asthma
- Unable to complete sentences
- Peak flow 33-50% best or predicted
- Respiratory rate ≥ 25/min
- Heart rate ≥ 110/min
Plus any of the following considered life-threatening:
- Peak flow < 33% best or predicted (if recordable)
- Arterial oxygen saturation (SpO2) < 92%
- Partial arterial pressure of oxygen (PaO2) < 8 kPa
- Normal partial arterial pressure of carbon dioxide (PaCO2) (4.6–6.0 kPa)
- Silent chest, Cyanosis, Poor respiratory effort, Arrhythmia, Exhaustion, Altered conscious level, Hypotension
treatment of acute severe and life threatening asthma
- Oxygen!!
- Increase to 94-98%
- High dose (nebulised) B2 agonist- continuous if necessary
- Driven in with oxygen
- Oral steroid (prednisolone) should be prescribed for minimum 5 days (IV if not oral- preferably oral)
- Continuous IC alongside
- Nebulised ipratropium bromide (ipratropium) – short acting muscarinic antagonist (SAMA) alongside b2 agonist if poor response alone
- Ipratropium less selective for M3 receptors compared to tiotropium, M2 activity too
- Consider IV aminophylline if life threatening/near fatal and no success with above
- Caution with taking PO theophylline
name a SAMA (short acting muscarinic antagonist
ipratropium bromide
Ipratropium is in a class of medications called bronchodilators. It works by relaxing and opening the air passages to the lungs to make breathing easier
COPD management
management of acute COPD exacerbations
In acute exacerbations – requiring hospitalisation
- nebulised salbutamol and/or ipratropium should be prescribed
- *If patient is hypercapnic or acidotic nebuliser should be driven by air and not oxygen**
- Oral steroids
- they can be less effective than in eosinophilic asthma due to reduced action on neutrophils
- Antibiotics (narrow spectrum – less severe, broad spectrum – greater severity)
- Review of chronic treatment and action plan
inhaler selection and prescribing
Inhaler options
- Pressurised metered dose inhalers (pMDI)
- Breath-actuated pMDI
- Dry powder inhalers (DPI)
Pressurised metered dose inhalers (pMDI)
- Inhalation and actuation of device
- Slow breath in and hold
- Can be used with a spacer to improve delivery
- Breath-actuated pMDI
- Newer
- Automatic actuation upon inspiration
- Dry powder inhalers (DPI)
- Micro ionised drug plus carrier powder
- Own inspiratory flow- fast deep inhalation (vs pressure metered dose inhalers)
