Respiratory Pharmacology Flashcards
What is asthma?
Chronic inflammatory airway disease intermittent airway obstruction and hyper-reactivity small airways - reversible spontaneously/ with drugs heterogenous
More eosinophils (COPD more neutrophils), mucosal oedema and plugging, bronchospasms, wheezing, coughing
Asthma management in adults BTS/ SIGN
Suspected:
Consider monitored initiation of low dose ICS
Diagnosed - move up and down:
Use SABA as required - move up if >_3 doses/ week
- regular preventer low dose ICS
- initial add on + inhaled LABA
- additional controller increase ICS medium dose OR + LTRA (leukotriene R anatagonist)(consider stopping LABA if not effective)
- specialist therapies
*LTRA cheaper but LABA effective in more ppl
How do inhaled corticosteroids work for asthma, give 3 examples, dangers of the medication?
Regular preventer when receiver not sufficient -
pass through plasma membrane -> activate cytoplasmic receptors -> passes in to nucleus -> modifies transcription -> upregulates genes for B2 receptors/ anti-inflammatory mediators Or represses genes for inflammatory mediators (interleukins, chemokines, cytokines)
✅reduced mucosal inflammation/ mucus, widens airways
Beclometasone, budesonide, fluticasone
❌ can cause local immunosuppressive action - candidiasis, horse voice, pneumonia risk possible severe COPD
How do inhaled corticosteroids get absorbed?
Poor oral bioavailability - almost complete first pass metabolism
Lipophilic side chain added - slow dissolution in aq bronchial fluid - high affinity for glucocorticoid receptor
Act locally BUT High doses all have potential systemic side effects
What are the two broad categories of beta 2 agonists, give examples of each?
SABA (short acting) - symptom relief through reversal of bronchoconstriction only used P.r.n e.g. fast salbutamol/ terbutaline
LABA (long acting) - add on therapy to ICS and p.r.n SABA (_>3/ week) e.g. fast - formoterol (12hrs) more potent and efficacious or slow - salmeterol (12h)/ vilanterol (24hrs)
How do beta agonists work? What’s a problem if used too often?
Major action airway SM, increased mucus clearance by action cilia
Prevent bronchoconstriction prior to exercise
Can develop a tolerance if SABA used too often especially in young adults often a quick fix
Adverse effects of beta agonists
Adrenergic - flight or fight effects (tachycardia, palpitations, anxiety and tremor)
SVT esp COPD patients (increases SAn-> increased HR, decreased refractory period at AVn)
Increased glycogenolysis (liver) Increased renin (kidney)
Muscle cramps (LABA)
LABA should only be prescribed alongside ICS - increased risk of death alone
May be reduced by beta blockers
Why should LABA only be added alongside ICS?
Alon can mask airway inflammation and near-fatal and fatal attacks
Combined Inhaler - adherence
How do leukotriene receptor antagonists work, give an example? Side effects
LTC4 released by mast cells/ eosinophils-> increased bronchoconstriction/ mucus/ oedema through CysT1 - GPCR
LTRA blocks CysLT1
Useful in 15% asthmatics - most end up taking LABA but cheaper so tried first
E.g. montelukast
❌headaches, GI, dry mouth, hyperactivity
How do long acting muscarinic anatagonists work? When are they used? Give an example, side effects
LAMA
Severe asthma and COPD
Relative selectivity M3 - anticholinergic effects inhibition muscarinic receptors
❌ typical anticholinergic: dry mouth, urinary retention, dry eyes
E.g. tiotropium
Ipratropium bromide - SAMA (less selective for M3 R)
What is theophylline? How is it administered? Why is it dangerous?
A methylxanthine (caffeine) Adenosine receptor anatagonist (aminophylline soluble form- iv in some acute asthma patients - Interaction with CYP450 enzymes so increases concentrations of current theophylline therapy)
Narrow therapeutic index - life threatening complications e.g. arrhythmia
When are oral steroids used for asthma? Give an example
Severe uncontrolled asthma - need a steroid card
Post acute exacerbation _>5 days
Post acute COPD 5-7days
E.g. prednisolone
What’s the criteria for acute severe and life- threatening asthma?
Acute severe: Unable complete sentences Peak flow >33-50% best/ predicted RR _> 25/ min HR _> 110/ min
Life threatening:
Above + one:
Arterial O2 sats: <92%
Partial arterial pressure O2 <8kPa
Normal partial arterial pressure CO2 (4.6-6kPa)
Silent chest, cyanosis, poor respiratory effort, arrhythmia, exhaustion, altered conscious level, hypotension
Treatment of acute severe and life threatening asthma
SPO2 level 94-98%
High dose nebulised beta2 agonist - continuous if necessary
Oral steroids should be prescribed 7-14 days continuous ICS alongside
Nebulised ipratropium bromide - short acting muscarinic anatagonist alongside beta 2 agonist if poor response
Consider IV aminophylline if life threatening - caution if taking p.o theophylline
5 tasks in management of COPD
1 - confirm diagnosis
2 - stop smoking
3 - record respiratory function
4 - offer vaccinations e.g. flu/ pneumococcal
5 - consider medication
