Asthma & COPD Flashcards
Define Asthma
Reversible increases in airway resistance involving bronchoconstriction and inflammation
What is the effect of Asthma on measures of lung function?
Reversible decreases in FEV1:FVC (<70-80%)
Variations in PEF, improving w/ B2 agonist (morning dipping)
Describe the parasympathetic control of bronchial calibre
ACh - muscarinic M3 receptors
Bronchoconstriction AND increased mucus
Describe the sympathetic control of bronchial calibre
Circulating adrenaline - B2 adrenoceptors
Relaxation of bronchial SM
Sympathetic fibres release NA - B2 adrenoceptors
Inhibit mucus secretion
Decrease PNS activity
What factors lead to an asthmatic attack?
Genetic predisposition, provoked by:
- Allergens
- Cold air
- Viral infections
- Smoking
- Exercise
What are the two phases of an asthmatic attack?
Early (immediate)
Late
Sometimes just one or the other
What are the clinical features of Asthma?
Wheezing Breathlessness Tight chest Cough Decreases in FEV1, reversed by B2 agonist
What are Spasmogens?
Factors released from mast cells Stimulate bronchospasm (early)
What are Chemotaxins?
Factors released from mast cells Stimulate inflammation (late)
What type of cell releases Spasmogens/Chemotaxins?
Mast cells (mononuclear)
Describe the time course of an asthmatic attack?
Early phase - 1 hour after stimulus, large drop in PEF followed by quick improvement
Late phase - 3-8 hours, gradual drop in PEF
What are the five Spasmogens involved in an asthmatic attack?
Histamine
Prostaglandin D2
Leukotrienes C4 & D4
Platelet Activating Factor (PAF)
How are Spasmogens produced?
Arachidonic acid separated from membrane by PLA2
Leukotrienes produced by LOX
Prostaglandins by COX
What are the two Chemotaxins involved in an asthmatic attack?
Leukotriene B4
Platelet Activating Factor (PAF)
How do Chemotaxins lead to the late phase of an asthmatic attack?
Attract leukocytes (esoinophils + mononuclear cells) Leads to inflammation + airway hyper-reactivity
What are the two types of therapy for Asthma?
Bronchodilators
Preventative
What is the purpose of Bronchodilators?
Reverse bronchospasm (early phase) RAPID RELIEF
What is the 1st choice Bronchodilator?
Salbutamol
What is Salbutamol?
B2 adrenoceptor agonist
Increases FEV1
How does Salbutamol work?
Acts on B2 adrenoceptors to increase cAMP`
How are B2 agonists given?
Inhalation
What is the problem with long term use of B2 agonists?
Prolonged use leads to receptor down-regulation
What are LABAs?
Long acting beta agonists (SALMETEROL)
What are LABAs used for?
Long term prevention/control (ie. overnight)
What are the 2nd choice Bronchodilators?
Xanthines (THEOPHYLLINE)
How do Xanthines work?
Phosphodiesterase inhibitors - elevate cAMP
How are Xanthines given?
Oral/i.v.
What are the problems with Xanthines?
Narrow therapeutic index
Large range of interactions
Removed by hepatic metabolism
Hypokalaemia (esp. w/ B2 agonists)
What are the 3rd line Bronchodilators?
Muscarinic receptor antagonists
What are the two common Muscarinic receptor antagonists?
Ipratropium (short acting, t.d.s.)
Tiotropium (long acting, o.d.)
How do Muscarinic receptor antagonists work?
Block parasympathetic bronchoconstriction
How are Muscarinic receptor antagonists given?
Inhalation - prevents antimuscarinic side effects
How are Muscarinic receptor antagonists mainly used?
Little value in asthma
Widely used in COPD
What are the four types of preventative medication?
Corticosteroids
Steroids
Cromones
Leukotriene Receptor Antagonists (LTRAs)
How do Corticosteroids work?
Anti-inflammatory
Activation of intracellular receptors - altered gene transcription (decreased cytokines) - production of lipocortin
What are the two main Corticosteroids?
Beclometasone (inhalation)
Prednisolone (oral)
How does Lipocortin have it’s positive effect?
Inhibits PLA2
Decreased production of Leukotrienes/Prostaglandins
How do steroids work?
Given w/ B2 agonists
Reduce receptor down regulation
What are the side effects of steroids?
Inhalation - Throat infections, hoarseness
Oral administration - Adrenal suppression, diabetes, osteoporosis, immunosuppression
How should patients be counselled to take inhaled steroids?
Rinse out mouth after inhalation
Use spacer
How do Cromones work?
Poorly
Uncertain MoA
-reduce reflexes of sensory nerves?
-reduce PAF/cytokine release?
What is the main Cromone used clinically?
Sodium Cromoglicate
How do LTRAs work?
Antagonise actions of LTs
What is the main LTRA used clinically?
Montelukast
What is the first stage of treating asthma?
Occasional bronchodilator (SABA)
What is the second stage of treating asthma?
SABA + regular inhaled steroid
What is the third stage of treating asthma?
Step 2 + LABA (or LTRA/Xanthine)
What is the fourth stage of treating asthma?
Step 3 + Increase dose of inhaled steroid
What is the fifth stage of treating asthma?
Step 4 + Add oral steroid
What is the management of acute asthma?
Oxygen (40-60%)
Nebulised SABA (salbutamol/terbutaline)
Oral prednisolone/i.v. hydrocortisone
What steps should be added to normal management when treating an acute, life-threatening attack?
Nebulised ipratropium
s. c. SABA
i. v. aminophylline (if patient not on Xanthine)
i. v. magnesium sulphate
Define COPD
Chronic Obstructive Pulmonary Disease
Combination of Chronic Bronchitis + Emphysema
Describe Chronic Bronchitis
Increased mucus
Airway obstruction
Intercurrent infections
Describe Emphysema
Destruction of alveoli
What is the effect of COPD on measures of lung function?
FEV1 reduced
Little variation in PEF
Describe Mild COPD
FEV1 60-80% of predicted, smoker’s cough, little/no breathlessness
Describe Moderate COPD
FEV1 59-40% of predicted, breathless on mild exertion, possibly wheezing + cough
Describe Severe COPD
FEV1 <40% of predicted, breathless on mild exertion/rest, wheeze +cough
What is the main structure of treatment in COPD?
Smoking cessation
Regular bronchodilators
What is the baseline treatment for COPD?
SABA or Short acting antimuscarinic
If the FEV1 is >50% in a COPD patient how should treatment be modified?
Add LABA or Long acting antimuscarinic (in place of SA)
If the FEV1 is <50% in a COPD patient how should treatment be modified?
Add LABA + inhaled steroid
Replace SA antiM with LA antiM
What is the final stage of treatment for severe COPD?
LA antiM + LABA + inhaled steroid
What role do antibiotics play in treating COPD?
Antibiotics for intercurrent infections
Patients given antibiotics to have for start of exacerbation
What are the clinical signs of an exacerbated chest infection?
2 of:
Purulent sputum, increased sputum, breathlessness
What role does oxygen therapy play in treating COPD?
Severe disease
24-28% Ox for 15hrs/day
How should NSAIDs be used in asthma?
AVOIDED
Provoke asthma, increase LT production
How should B-blockers be used in asthma/COPD?
AVOIDED
ccause bronchospasm