Treatment of Asthma and COPD Flashcards
(35 cards)
What are the primary routes of administration of drugs in asthma ? What are the pros or cons of these methods ?
♦ Primarily inhalation of aerosol or dry powder: rapid + reduced systemic side effects (Particle size important)
♦ Oral/injectable
What are the major groups of drugs in asthma ?
Bronchodilators (relievers)
Anti-inflammatory drugs (preventers)
What are the main inhaler devices used in asthma ?
♦ MDI (metered dose inhaler)
♦ Breath-actuated (e.g. autoinhaler, easibreathe), especially for patients who cannot manage MDI
♦ Accuhaler - dry powder
♦ Via spacer/aerochamber (for patients with coordination problems)
What is a common side effect of inhalers ? How can we prevent this ?
- Systemic side effects, because 90% usually swallowed and absorbed form gut.
- Using a spacer or rinsing one’s mouth helps with this
How do spacer inhalers work ?
- Large particles of aerosol are deposited in the chamber before the patient inhales. Inhaled aerosol is enriched
- Inhaled aerosol is enriched with small particles that more readily travel to the small airways
How do nebulisers work ? When are they used
- Drug (usually reliever, may be antibiotic) broken down into fine mist using oxygen or air
- Used in acute asthma attacks
Identify the main drugs to treat and prevent asthma.
1) B2 receptor agonists
• SABA- salbutamol
• LABA- salmeterol
2) Glucocorticoids
• beclometasone, budesonide
3) Cysteinyl leukotriene antagonist (LTRA)
• montelukast
4) Methylxanthines
• theophylline and derivatives
5) Monoclonal antibodies (anti-IgE treatment)
• Omalizumab
6) Muscarinic receptor antagonists (seldom used)
• Ipratropium
Describe stepwise pharmacological treatment of asthma.
Anytime need to use SABA three times a week or more, consider moving up.
→ FIRST LINE (intermittent asthma): Short acting beta agonists (stimulate B2, bronchodilate)
→ Step 2: If patient needs to use inhaler frequently: ICS (inhaled corticosteroids) + SABA for exacerbations
→ Step 3: Initial add-on therapy:
inhaled LABA + low dose ICS + SABA for exacerbations
→ No response to LABA:
Higher dose ICS + SABA for exacerbations
Yes response to LABA but still inadequate control:
inhaled LABA + medium dose ICS + SABA for exacerbations
→ Step 4: Still inadequate control:
Higher dose ICS + inhaled LABA + SABA for exacerbations + methylxanthine/LTRA
→ Step 5: Still inadequate control:
Daily steroid tablets + high dose ICS + other treatment to minimise use of steroid tablets+ refer to specialist care
Move down steps if possible to find and maintain lowest controlling step.
What is the mechanism of action of beta 2 receptor agonists ? What are their side effects ?
MECHANISM OF ACTION
- Stimulate bronchial smooth muscle beta 2 receptors, relax muscles, dilates airways, reducing breathlessness
- Inhibits mediator release from mast cells and infiltrating leucocytes (i.e. anti-inflammatory?)
- Increases ciliary action of airways epithelial cells - aid mucus clearance
SIDE EFFECTS (if given orally, IV, or high dose inhaled)
- Sympathomimetic effects (e.g. hypertension, excessive cardiac stimulation and cardiac arrhythmias)
- Electrolyte disturbances (e.g. Potassium reduction)
- Hyperglycaemia
- Paradoxical bronchospasm
When muscarinic receptor antagonists are used in the treatment of asthma (which is seldom), what is their mechanism of action ?
Inhibit muscarinic receptors in the lungs
Bronchodilators
What is the mechanism of action of glucocorticoids ? What are the main side effects of glucocorticoids ?
MECHANISM OF ACTION (anti-inflammatory, i.e. preventers)
- Inhibit formation of cytokines (by Th2 cells)
- Inhibit activation and recruitment to airways of other inflammatory cells (e.g. eosinophils, mast cells)
- Inhibit generation of inflammatory prostaglandins and leukotrienes, thereby reducing mucosal oedema
SIDE EFFECTS
- Systemic effects, especially if chronic high dose inhalation, or IV or oral (osteoporosis, growth retardation, adrenal insufficiency)
- Dysphonia (hoarseness)
- Oropharyngeal candidiasis
- High doses may increase risk of pneumonia
Describe the onset and timeline of the effects of inhaled corticosteroids, and explain the effect of this on adherence.
ICSs have slow onset and longer term effects (i.e. months) which include reduction in airway responsiveness to allergens and irritants including exercise.
-This often means adherence to ICSs can be poor as no effects can be seen in the short term.
How are glucocorticoids administered ? Give examples of glucocorticoids for the different routes.
Usual route:
-INHALED (e.g. beclomethasone, budesonide)
In acute severe attacks:
-ORAL (e.g. prednisolone)
or
-IV (e.g. hydrocortisone)
Describe the mechanism of action of leukotriene receptor antagonists (i.e. LTRA i.e. Lukasts). Also describe their main side effects.
MECHANISM OF ACTION (asthma prophylaxis)
-Block effects of bronchoconstrricting cysteinyl leukotrienes (specifically CysLT1) in the airways, resulting in bronchodilation
-Reduce eosinophil recruitment to the airways, thereby reducing inflammation, epithelial damage, and airway hyper-reactivity
♣ This results in ↓ exercise-induced asthma (and atopic asthma), ↓ both early and late phase bronchoconstrictor responses to allergens
SIDE EFFECTS
- Abdominal pain
- Headache
- Hyperkinesia in children (i.e. increase in muscular activity that can result in excessive movements)
Which step in the stepwise treatment of asthma should LTRAs be incorporated in ?
Step 3 or 4
How are LTRAs administered ? Give examples of 2 LTRAs.
Oral administration for LTRAs
e.g. Montelukast tablets
Describe the mechanism of action of methylxanthines. Describe their side effects.
MECHANISM OF ACTION
♫ Inhibits (non-specifically) phosphodiesterase (PDE)
-Results in increased intracellular cAMP in bronchial smooth result resulting in relaxation (i.e. bronchodilation)
-Anti-inflammatory actions (since PDE also involved with inflammatory cells)
♫ Inhibits adenosine receptor
-Results in bronchodilation
SIDE EFFECTS (dose-related!) -GI upset -Arrhythmias -CNS stimulation -Hypotension Narrow therapeutic index!
Give 2 examples of methylxanthines.
Theophylline, Aminophylline
When are monoclonal antibodies used in the treatment of asthma ?
Monoclonal antibodies are used in the treatment of severe persistent allergic asthma
Give an example of monoclonal antibody and state its mechanism of action.
Omalizumab- antibody to IgE, inhibits mediator release from basophils and mast cells (i.e. preventer)
Identify the administration route, and onset of effects of monoclonal antibodies in asthma. Name any major cons to using monoclonal antibodies.
- Monoclonal antibodies (i.e. MABS) are injected
- Onset is slow (peaks at 3 to 4 months)
- EXPENSIVE
Describe the NICE guidelines for stepwise asthma treatment.
Step 1: SABA Step 2: SABA + low dose ICS Step 3: SABA + low dose ICS + LTRA Step 4: SABA + ICS + LABA +/- LTRA Step 5: Trial of additional drugs
How is asthma evolution monitored during long term treatment ?
Using peak expiratory flow rate:
- In untreated asthma, low peak flow rate (if <50% predicted, severe asthma) + large nocturnal dip present (i.e. reading lower in the morning)
- In treated asthma, diurnal variation is reduced and peak flow rate increases
Describe management of acute severe asthma.
1) Immediate treatment (adults):
- Oxygen (to maintain spO2 at 94-98% range)
- Salbutamol or terbutaline + ipratropium via nebuliser
- IV steroids (hydrocortisone) then eventually oral steroids (prednisolone)
- + or - antibiotics
2) If patient still not improving, consider (in high dependency unit):
- IV magnesium sulphate
- switch from nebulised to IV salbutamol or aminophylline
Acronym SOS I AM.
→ In the meantime, monitor blood gases and patient exhaustion/alertness
