Paul (Pharmacology of asthma drugs) Flashcards
5 distinguishing features of asthma
Chronic
Inflammation
Airways hyper-responsiveness and bronchiconstriction
Reversibility
Trigger factors
Classification of asthma
Extrinsic (atopic)
- Early onset
- Episodic
- Most common
Intrinsic (non-atopic)
- Late onset
- Chronic
Aetiology of asthma
Genetic predispodition
Atopy
Airway hyper-responsiveness
Gender
Ethnicity
Environmental factors
Indoor and outdoor allergens
Occupational sensitisers
Tobacco smoke
Air pollution
Diet and drugs
Obesity
Early response- type 1 allergic response
Bronchoconstriction
Mucosal oedema
- vascular vasodilation/permeability
Hyper-secretion of mucus
Immediate onset
Lasts about 1 hour
How FEV1 varies with time when an allergen is inhaled.
FEV1 is at 100% before inhalation. At hour 1 there is an acute asthmatic response (AAR) which drops FEV1 to 75%. Increases back up to 100% at hour 2 and stays high til hour 4 where it starts to decrease. Late asthmatic response (LAR) reached at hour 6 where. the FEV1 is at its minimum value of 25% and slowly increases over the next 6+ hours back to 100%.
Late response (allergic and non-allergic asthma)
2-4 hours after exposure
Maximum after 6-8- hours
Attracts inflammatory cells
Infiltration of local area with eosinophils
Mediator release- Th2 lymphocytes and neutrophils
- inflammatory mediators e.g. cytokines
- tissue destruction
- tissue remodelling
- reflex neural bronchoconstriction
- via vagus
Pathophysiology
Asthma = Inflammation + Bronchoconstriction
Inflammation
- mucosal infiltration with inflammatory cells
- oedema of the bronchioles
- hypertrophy of the glands and of smooth muscle
- damaged epithelium
Bronchoconstriction
- mast cell mediator release
- vagal stimulation
Asthma triggers
Alcohol
Animals and pets
Colds and flu
Emotions
Exercise
Food
Hormones (females)
House dust mites
Moulds and fungi
Pollen
Pollution
Recreational drugs
Sex
Smoking
Stress
Weather
Pharmacological management
Bronchodilators (“relievers”)
- beta-agonists (short acting and long acting)
- Xanthines
- Anti-cholinergics
Anti-inflammatory drugs (“preventers”)
- corticosteroids
- leukotriene modifiers
- anti IgE antibody
- sodium chromoglycate
Non-pharmacological methods
Avoidance of allergens
Stop smoking
Lose weight
Homeopathy
Breathing and relaxation
Acupuncture
Food avoidance
Herbal medicines
Ephedra Sinica (Ma Huang)
Chinese herbal remedy for asthma
Used 5000 years ago
Ephedrine- acts as an alpha and beta agonist
Banned in some states and Canada
28 deaths in the last 6 years
Adrenergic agonist- stimulates ALL alpha and beta receptors in the body which causes side effects e.g. palpitations
The ‘Royal College of Physicians 3 questions’
Answering ‘no’ to all 3 questions is consistent with controlled asthma.
1- Have you had difficulty sleeping because of your asthma symptoms (including cough)?
2- Have you had your usual asthma symptoms during the day (e.g. cough, wheeze, chest tightness, or breathlessness)?
3- Has your asthma interfered with your usual activities (e.g. housework, work, school)?
Not yet been validated in children
Beta-2 adrenoceptors in the lung
Sparsely innervated (supplied with nerves) by ANS
High concentrations in the lung
Density is constant
70% b2
- airway and vascular smooth muscle (uterus is also a smooth muscle. Salbutamol can be used to treat premature childbirth as uterus also has beta receptors)
- epithelium and sub-mucosal glands
- mast cells
- pre-junctional on cholinergic nerves
- inflammatory cells
30% b1
- localised to sub-mucosal glands
Effects of b2 adrenoceptos stimulation
Functional antagonism of bronchoconstrictors.
- bronchodilator of ALL airways
Inhibition of release of histamine and leukotrienes.
Inhibit plasma exudation.
Inhibit cholinergic transmission.
Inhibit mediator release from inflammatory cells (short term effect).
Increase mucus clearance.
SABAs vs LABAs
SABA
- faster onset
- duration of 4 hours
- e.g. salbutamol, terbutaline
- used for rescue
LABA
- slower onset
- duration of 12 hours
- e.g. formoterol, salmeterol
- used for maintenance
Salmeterol and formoterol should be prescribed in conjunction with inhaled corticosteroids- results in improved pulmonary function than just increasing the dose. Data suggests that up to 30% of patients prescribed these were not taking inhaled corticosteroids.
