Respiratory Pharmacology Flashcards
1
Q
What is asthma?
A
- Reversible airflow obstruction (expiratory wheeze)
- Airway inflammation
- Bronchial hyper responsiveness (BHR, airways are irritable)
- Narrowing of lumen
- Airway produces mucous- builds up inside airway passage
2
Q
Describe extrinsic asthma
A
- Identifiable external trigger
- Allergy to common environmental agent (developed allergy)
- Typically develops in childhood (atopic march)
- Young children get eczema which resolves with age- may then develop asthma symptoms
3
Q
Describe intrinsic asthma
A
- No obvious external trigger
- Often develops in adults after a viral infection
- Smoking might play a role
- Tends to be more severe and difficult to control
4
Q
What triggers asthma?
A
- Allergy- household-pets, dust
- Inflammation- worsened by respiratory infection
- Work place- exposed to chemicals- inflammatory response
- Exercise
- Constriction- exercise, temp changes, strong odours, emotion, cold air
- Other: tobacco, medications, food additives, air pollution, reflux diseases
5
Q
Describe FEV1 in asthma
A
- Normal in between attacks
- Allergen exposure- less rapid FEV1, below 50% in minutes
- Wheezing
6
Q
Describe the early phase response in asthma
A
- Early phase response driven by mast cells-degranulated
- -> Histamine, leukotriene C4 and prostaglandin D2
- Lung function recovers (60-90 mins)
7
Q
Describe the late phase response in asthma
A
- Driven by eosinophils- recruited airways following early phase
- Leukotriene C4 (lipid mediator)
- Eosinophil granule proteins- basic proteins that damage
- Cytokines (inflammatory and newly synthesised 4-8 ours)
8
Q
Describe the pharmacological approach of relievers in asthma
A
- Block or reverse bronchial smooth muscle contraction
- No effect on underlying inflammation- symptomatic relief
- Given by inhaler for ‘rescue’ in acute attacks
- Long-acting drugs for chronic bronchodilation
9
Q
Describe the pharmacological approach of preventers in asthma
A
- Taken every day for prophylaxis
- Reduces airway inflammation or BHR
10
Q
Describe the autonomic control of airways
A
- Parasympathetic input- McT3 receptors
- Bronchoconstriction + mucus hyper secretion
- Anti-musc block ACh and reduce symptoms
- Adr interact B1 receptors on heart
- B2 agonists activate B2 receptors which leads to Bronchodilation and decreased mucus secretion (sympathetic)
- Adr is only used in extreme cases- not day-to-day
11
Q
Describe β-2 adrenoceptor agonists as relievers
A
- Stimulate β-2 receptors
- ATP–> cAMP (leads to bronchodilation and maybe inhibit mast cell activation)
- E.g. Rimiterol (short- 2hrs), salbutamol (medium- 5 hrs) and Salmeterol (long- 24 hrs)
12
Q
Describe short-acting β-2 agonists
A
- E.g. salbutamol
- Dosage- inhaler as needed, nebuliser and IV- status asthmaticus
- Often + steroid for moderate asthma
- Side effects: skeletal muscle tremor, hypokalaemia, receptor dawn regulation
13
Q
Describe long-acting β-2 agonists
A
- Salmeterol- binds to an eco-site via flexible tail and repeatedly stimulates receptor
- Formoterol- dissolves in plasma membrane and diffuses out to stimulate receptor
14
Q
What are the effects of long and short acting β-2 agonists?
A
- Salbutamol must be taken every 4-6 hrs to maintain bronchodilation
- Salmeterol 1/2x a day and is useful in nocturnal asthma
- Overuse- receptor down-regulation
- If patient is using β-2 agonist inhaler regularly- add steroid to treat underlying inflammation
15
Q
Describe methylxanthines as relievers
A
- Target phosphodiesterases
- Same effect
- E.g. theophylline- slow release oral preparation
- E.g. aminophylline- more soluble- IV use
- Increases cAMP by stopping its breakdown into AMP
- inhibition of PDE
16
Q
Describe the use of theophylline as a methylxanthine reliever
A
- Not front-line drug in UK
- Oral administration only
- Variable gut absorption and hepatic metabolism
- Plasma conc increased by heart failure, liver disease and some drugs
- Plasma conc decreased by smoking, alcohol and other drugs
- Side effects: nausea, insomnia, dysrhythmia) can be severe due to narrow TI
17
Q
Describe how anti-muscarinics can be used as relievers
A
- Parasympathetic
- Mc 1 and 3 receptors
- Blocks Ach interaction and reduces bronchoconstriction and hyper secretion
- Inhaled
- Low efficacy- added for moderate-severe asthma
- Side effects- poorly absorbed in lung so classic anti-musc side effects rare
- E.g. ipratrpoium, oxitropium and tiotrpium (all atropine-like)
18
Q
What are preventers?
A
- Target inflammation
- Main group- corticosteroids
19
Q
What is the mechanism of action of corticosteroids?
A
- Diffuse across membrane and bind to intracellular glucocorticoid receptors
- GRE inhibition
- inhibit inflammatory genes cytokine, COX2, adhesion molecules and IGs
- GRE induction
- anti-inflam genes- IL10, annexin 1, β-2-adrenoceptor, ribonucleases
20
Q
What are the actions of corticosteroids in inflammatory cells?
A
- T lymphocytes
- -> reduction in numbers of eosinophils by apoptosis, cytokines and number of mast cells
- Reduction in cytokines- macrophages
- Reduction in numbers od dendritic cells
21
Q
What are the actions of corticosteroids in structural cells?
A
- Epithelial cells
- Endothelial cells- reduced leakage
- Airway smooth muscle- increased β-2 receptors and decreased cytokines
- Mucus glands- decreased mucus secretions
22
Q
Describe the administration of corticosteroids
A
- Beclomethasone/ Budesonide- daily inhalers
- Fluticasone- daily inhaler, most potent, first-pass hepatic metabolism reduces systemic side effects
- Oral prednisolone- severe asthma
- IV hydrocortisone- status asthmaticus
- Compliance with steroid inhalers is often poor because results not often shown physically
23
Q
What are effects of chronic oral steroids?
A
- Abnormalities in fat, protein and carboydrate metabolism
- Rare with inhaled steroids used properly
- Long-term use leads to Cushingoid features
24
Q
Describe the use of steroids in children
A
- Recommended inhaled steroids for chldren
- Risk reduced with lowest possible dose, limiting systemic side effects with effective inhaler technique and using drugs such as fluticasone (inactive by 1st pass metabolism)
- No evidence for growth restriction with inhaled steroids
