Drug control in asthma Flashcards
What is asthma?
Recurrent reversible obstruction of airflow in airways in response to non-noxious stimuli
Difficulty in breathing; wheezing; cough
What are reasons in having asthma?
Genetically susceptibility Trigger also required Allergic in >30% Post-viral (after infection) Psychogenic (e.g. stress can be an asthma trigger)
How many people are being treated for asthma in Scotland?
390,00
How many deaths a day are caused by asthma in the UK?
5 deaths/day (2000/yr)
What is extrinsic asthma?
Atopic, allergic
What is intrinsic asthma?
Non-atopic, non-allergic
What are triggers of asthma?
Pollen Dust Animal hair Sting Aspirin Cold air Irritant chemicals Pollutants
What is the immune system?
Guards against bacteria, viruses, cancer and parasites. Normally a protective mechanisms
What is an antigen?
Protein or modified protein
How is antibody synthesis induced?
By monocytes (blood) macrophages, lymphocytes, mast cells- IgE
What is the equation for the immune reaction?
A/g + A/b –> immune reaction
What does cell-fixed a/b provide?
Recognition
Anchor
Trigger
What chemical mediators (cytokines) are released by the cell?
Interleukins Prostaglandins (PG) --> recruit other cells to the site of infection Leukotrienes (LT) Thromboxanes (Tx) Histamine Platelet activating factor )PAF)
What are the effects of cytokine mediators?
Vasodilation
Pain/itch
Oedema- fluid leaks out of tissue, causes congestion
Smooth muscle contraction- contraction of bronchioles
What is an allergy?
An inappropriate immune response
Form of reaction, mediators involved, vary in different tissues
What are some effects of an allergic reaction?
Skin- rash, itch
Gut- vomitting
Eyes, nose- hypersecretion
What are the stages of asthma?
Intermediate
Late
What is the intermediate stage of asthma?
Bronchoconstriction (airways constrict), may or may not be vasodilation
Anaphylaxis leads to death
What are the late stages of asthma?
Oedema–> congestion
Hyper secretion –> mucus
Inflammatory cells
Bronchoconstriction and hyperreactivity
What does is mean if there is an increase in FEV1 in lungs?
Treatment is working, lungs are getting better
What is innervation of the lungs?
Parasympathetic
Sympathetic
Non-adrenergic non-cholinergic (NANC)
Sensory- irritation–> reflex constriction via parasympathetic
What are upper airways constricted by?
Ach via M3 receptors
What are M3 receptors?
Parasympathetic nerves
What constricts the lower airways?
NANC transmitters
What relaxes the lower airways?
NANC transmitters (e.g. NO) and circulating adrenaline (beta 2)
What is not in the airway muscle?
Sympathetic nerve supply
What constricts blood vessel smooth muscle?
NA from sympathetic nerves (alpha 1)
What relaxes blood vessel smooth muscle?
Circulating adrenaline (beta 2)
What system does mucus secretion decrease?
Sympathetic system
What system does mucus secretion increase?
Parasymathetic system, inflammatory mediators and chemical/physical stimuli
What is the immediate phase of drug therapy?
Smooth muscle relaxants (treat bronchospasm)
What is the late phase of drug therapy?
Steroids (treat inflammation)
What drugs are used to treat asthma?
Beta-adrenoreceptors agonists Muscarinic antagonists Theophylline Antihistamines LT antagonists Glucocorticoids (anti-inflammatory steroids)
What are beta-adrenoceptor agonists?
Adrenaline
Alpha + beta agonist
What do B1 adrenoreceptors agonists affect?
Heart
What do B2 adrenoreceptor agonists affect?
Bronchi
What is salbutamol?
Beta 2 only
Inhaled aerosol or powder
What does saltbutamol do?
Relaxes bronchioles
Decreases secretion
Increases FEV1
What is the mechanism of saltbutamol?
Increases adenylate cyclase
Increases cAMP
Decreases Ca2+ entry
What are examples of drugs for muscarinic antagonists?
Ipratropium
Tiotropium
What does Ipratropium do?
N+ poor absorber
Blocks bronchoconstriction due to parasympathetic reflex
More useful in bronchitis
What does Tiotropium do?
Prolonged (24hr) M3 selective muscarinic antagonist
Better than the older ipratropium
What is theophylline?
Bronchodilator
How does theophylline relax smooth muscle?
Inhibition of phosphodiesterase
Increases cAMP
Increases cGMP
Increases release of NA and Adr
What are some possible serious side effects of theophylline?
Arrythmia, convulsions, low TI
What benefits are antihistamines?
Little benefit in asthma (much more in hayfever etc)
What do antagonists of leukotrienes (LTs) do?
Drugs to block either the LT receptor or the synthesis of LTs
E.g. montelukast
What is an example of a useful glucocorticoid (anti-inflammatory steroids)?
Beclomethasone- very important as prohphylactic
How do glucocorticoides suppress immune system?
Decreases lymphocyte and mass cell number
Decreases reactivity
Decreases mediator synthesis and release
Decreases b.v. permeability
What is the glucocorticoid mechanism?
Cytoplasmic receptor Nuclear binding RNA fro lipocortin (Annexin-1) Block PLA2 Block COX-2
What are the advantages of inhalation?
Rapid response Targetted at bronchi Need less drug Less side effects Avoid liver metabolism
