PHARM: Asthma and COPD Flashcards
asthma Sx
- chest tightness
- night-time or early morning coughing
- SOB
- wheezing
- chest tightness
changes in lung histology due to asthma
- inflammatory cells (depends on type of asthma)
- excessive mucus - obstruction and barrier to inhaler therapy
- thickening of basement membrane = fibrosis
- increased smooth muscle = increased contraction
what is airway hyperresponsiveness and why does it occur?
- amplified response to bronchoconstrictors (e.g. smoke, cold air, exercise) = airways contract too easily and too much
- due to inflammation and airway remodelling in asthma
difference between healthy airways and allergic asthmatic airways re: immune response to aeroallergens
- normal: TH1 response
- allergic: TH2 response
two types of Tx TARGETS for asthma
- inflammation: ICS or biologics (b/c we know it’s eosinophilic inflammation) - preventer
- immediate bronchoconstriction: B2-agonists (SABA/LABA) - b/c we know the chemical mediators e.g. histamine - reliever
- can’t really target induction phase or airway remodelling yet due to lack of knowledge
limitations of salbutamol
- underlying inflammation left untreated - THEREFORE mostly used with ICS
- potential loss of efficacy due to tolerance
- can cause tachycardia and fine tremor
varying levels of asthma Tx based on severity
- 1) SABA only
- 2) low-dose ICS daily AND SABA PRN (low compliance due to 2 puffers) OR combined low-dose ICS-LABA PRN
- 3) low-dose ICS-LABA daily AND low-dose ICS-LABA or SABA PRN
- 4) medium-high ICS-LABA daily AND low-dose ICS-LABA or SABA PRN
- 5) add-ons e.g. additional dilator, biologics, surgical Tx
what drives contraction and relaxation of the bronchi
CONTRACTION
- allergic mediators e.g. histamine
- parasympathetic (vagus): Ach > M3 receptors
RELAXATION
- sympathetic: circulating adrenaline
- B2 agonists: salbutamol (SA) and formoterol (LA)
SABA - salbutamol (ventolin)
- onset and duration
- MOA
- can it be used on its own?
- what does it protect against?
- AEs
- fast onset (5-15 mins) and short duration (3-6 hrs)
- MOA: B2 agonist = increased cAMP = decreased Ca2+ release = less muscle contraction
- can be used on its own
- can protect against immediate bronchoconstriction but not underlying inflammation
- acute systemic AEs at high doses - tachycardia (B1) and muscle tremor (B2)
- if frequently overused, receptors are desensitised
LABA - formoterol
- onset and duration
- what can it protect against
- AEs
- can it be used on its own?
- rapid onset but long duration (12 hrs) = can protect against exercise-induced asthma and nocturnal asthma
- AEs: increased mortality b/c long-acting nature masks Sx of underlying inflammation (e.g. cough) = must combine with ICS
other bronchodilators that can be used for asthma
- irpatroprium (SAMA)
- tiotropium (LAMA)
- theophylline
- montelukast
ipratropium (SAMA) + tiotropium (LAMA):
- MOA
- AEs
- MOA: inhaled LA/SA M3 antagonists = bronchodilation and decreased mucus but no effect on allergic mediators of contraction
- AEs: blurred vision, dry mouth, urinary retention
theophylline
- MOA
- AEs
- oral phosphodiesterase inhibitor = inhibits cAMP breakdown = decreased Ca2+ = bronchodilation
- low potency on its own, but increases effectiveness of B2 agonists
- AEs: narrow therapeutic index and many side effects due to actions at other phosphodiesterase
montelukast MOA + AEs
- oral leukotriene receptor antagonist - PROPHYLACTIC ONLY
- doesn’t affect other mediators of contraction
- AEs: neuropsychiatric effects
inhaled corticosteroids (ICS)
- MOA
- when should it be used
- AEs
- MOA: reduce inflammation and prevents airway spasm via inhibiting phospholipase A2, COX-2 and IgE
- minimises airway remodelling and hyperresponsiveness
- should be used at all stages of asthma or if eosinophils are elevated in COPD
- AEs: dysphonia (voice disorder due to layngeal muscle atrophy), oral candidiasis due to immunosuppression (use mouthwash to reduce local absorption)
oral corticosteroids
- uses
- AEs
- short term use for severe asthma/COPD or exacerbations (eosinophilic)
- dose-limiting adverse effects with chronic use (increased use = increased effects)
- AEs: HTN, cataracts, moon face, abdominal fat, immunosuppressive effects
when are injected biologics used for asthma?
- only for uncontrollable asthma
- must be combination therapy b/c only addresses inflammation, not bronchoconstriction
corticosteroids MOA
- transrepression = inhibits transcription factors that increase pro-inflammatory proteins
- transactivation = increases expression of anti-inflammatory proteins
omalizumab
- mode of administration
- what is it
- use
- subcutaneous (every 2-4 wks)
- monoclonal antibody against IgE = reduced mast cell mediators e.g. histamine
- for severe, persistent, ALLERGIC asthma
- low potential for anaphylaxis
mepolizumab
- mode of administration
- what is it
- use
- contraindications
- subcutaneous (every 4 wks)
- monoclonal antibody against IL-5 = inhibits eosinophilic inflammation
- for severe, persistent asthma with elevated eosinophils
- contraindications: <6 yo, with other asthma biologics
very last resort for asthma Tx
- bronchial thermoplasty
- essentially cooking the airways with an endoscope to reduce the smooth muscle
difference in Sx between mild, moderate and severe COPD
- mild: few Sx, SOB on moderate exertion, little to no effect on daily activities
- moderate: SOB when walking, limitation of daily actives, cough and sputum
- severe: SOB on minimal exertion, severe limitation of daily activities, chronic cough, frequent exacerbations
lung changes in COPD
- mucus in airway due to goblet cell hyperplasia - chronic bronchitis
- inflammatory cells in airways
- scarring of airways
- larger, fewer alveoli = less SA:V ratio = decreased gas exchange = emphysema
chronic bronchitis Sx (‘blue bloater’)
- overweight, cyanotic
- elevated haemoglobin
- peripheral oedema
- wheezing + productive cough
emphysema symptoms (‘pink puffer’)
- older and thin - cachexia and muscle wasting
- severe SOB
- pink skin
- lung hyperinflation
Tx for acute Sx of COPD
- SABA e.g. salbutamol to mimic sympathetic imput - bronchodilation
- SAMA e.g. ipratroprium to block parasympathetic input
- LABA e.g. formoterol plus LAMA e.g. tiotropium for longer term relief if SA drugs are effective
- triple inhaler for moderate to severe COPD (LABA, LAMA, ICS)
genetic cause of COPD
- alpha-1-antitrypsin deficiency
- neutrophil elastase = produced by WBCs to break down bacteria, but damaging to lungs
- alpha-1 antitrypsin coats lungs, protecting them from this enzyme
- in deficiency, alpha-1 antitrypsin is trapped in liver = liver damage, and lungs will be damaged due to neutrophil elastase
- can lead to early onset emphysema if there are high neutrophils due to smoking or infection etc.
Tx for a1-antitrypsin deficiency
- prolastin made from human plasma, given IV weekly
comparison of immune response in asthma vs COPD
- asthma = eosinophilic inflammation
- COPD = neutrophilic inflammation
