Drug for Asthma and COPD Flashcards
What is the class of first-line bronchodilator drugs for asthma?
Beta-2 adrenoceptor agonists
What is the class of first-line anti-inflammatory drugs for asthma?
Corticosteroids
What is the class of first-line anti-inflammatory drugs for COPD?
Corticosteroids
What is the class of first-line and second line bronchodilator drugs for patients with stable COPD who show increasing frequency of acute exacerbations (more than two serious exacerbations in the last year or one leading to hospitalisation)?
Long-acting muscarinic antagonist (LAMA) for first line; LABA (second line)
LAMA: tiotropium bromide
LABA: indacaterol
Name an example of a short-acting inhaled bronchodilator drug.
Salbutamol (5-15 min onset, 4-6 hours duration, SABA)
Name an example of a long-acting inhaled bronchodilator drug that is also fast-acting used as both a controller and reliever for asthma?
Formoterol (2-3 min onset, 12 hours duration, LABA)
Name an example of an ultra-long-acting bronchodilator drug that is also fast-acting used for COPD.
Indacaterol (5 min onset, 24 hrs duration LABA)
Name an example of a long-acting inhaled bronchodilator drug that is slow-acting used for asthma.
Salmeterol (12 h LABA)
Slow-acting so used only as controller NOT reliever
What is the MOST dangerous adverse effect of beta-2 agonists in asthma?
Downregulation of beta-2 receptors results in reduced efficacy of beta-2 agonist-induced bronchodilation when required to relieve acute asthma attack.
The risk of receptor downregulation is greatest with LABAs. LABAs used alone increase the risk of death from asthma.
What must be co-prescribed with LABAs to reduce the risk of downregulation of beta-2 agonists?
A corticosteroid must always be co-prescribed with LABAs for asthma.
The LABAs are formulated in combined inhalers together with corticosteroids to ensure that the two drugs are taken together.
The concern even extends to SABAs if they are over-used. Increasingly for patients ≥12 years-old, salbutamol is being replaced with formoterol+ budesonide inhaler.
Name a SAMA that can be combined as an adjunct with beta-2 agonist to produce greater bronchodilation in asthma?
Ipratropium bromide (SAMA)
List common adverse effects of inhaled muscarinic receptor antagonists.
Limited systemic side effects as not well absorbed into systemic circulation when taken by inhalation
Unpleasant taste
Typical parasympatholytic effects:
Dry mouth
Urinary retention (especially in the elderly)
Briefly explain the mechanisms of action of methylxanthines such as theophylline.
Inhibits phosphodiesterases (PDEs)
Blocks adenosine receptors
↑ Epinephrine release from adrenal medulla
CNS stimulant action on respiration
NOT used clinically as an anti-inflammatory but it has some weak anti-inflammatory effects
Effects on mast cells and T-cells
↓ Microvascular leakiness
List adverse effects of methylxanthines such as theophylline.
Narrow therapeutic window (therapeutic range for theophylline: 5-20 mg/L)
Many drug-drug interactions: Caution for potential drug interactions
Gastrointestinal: Nausea, vomiting, abdominal discomfort, anorexia
CNS: Nervousness, tremor, anxiety, insomnia, seizures
Cardiovascular: Arrhythmias
Name an example of a soft steroid
Ciclesonide
What is a soft steroid?
An inhaled prodrug that is converted by esterases in the lungs into the active steroid (e.g., ciclesonide).
As the drug is only active in cells expressing esterases adverse effects are minimised even if the drug escapes into the systemic circulation.
List SEVEN more common adverse effects of inhaled corticosteroids.
Oropharyngeal candidiasis (opportunistic infection due to localised immunosuppression)
Dysphonia (enfeebled voice due to localised muscle wasting)
Cough / throat irritation
Adrenal suppression (e.g. fluticasone)
Easy bruising (especially in elderly)
Posterior subcapsular cataracts (especially in elderly)
Osteoporosis (especially in elderly)
Name an example of a 5-lipoxygenase inhibitor
Zileuton
Name an example of a CysLT receptor antagonist
Montelukast
What class of drugs is particularly useful as an adjunct anti-inflammatory in NSAID-exacerbated respiratory disease or aspirin-sensitive asthma?
Leukotriene pathway inhibitors (e.g., zileuton)
Q
What class of drugs is both anti-inflammatory and weakly bronchodilator?
CysLT receptor antagonists (e.g., montelukast)
What types of asthma respond well to cromoglicic acid?
Cromoglicic acid is a mast cell stabiliser. Allergic (antigen), cold, dry air and exercise challenge-induced asthma often responds well to a dose of cromoglicic acid before the challenge.
Name a monoclonal antibody drug for allergic asthma
Omalizumab (anti-IgE monoclonal antibody)
What are the common limitations or adverse effects when using omalizumab?
Expensive. Associated with a small increase in the risk of heart attack, transient ischaemic attacks (TIA) and blood clots. Potential for anaphylaxis.
Name ONE anti-IL5 signalling monoclonal antibody for severe, persistent eosinophilic asthma
Reslizumab (anti-IL-5, IV)
Mepolizumab (anti-IL-5, SC)
Benralizumab (anti-IL-5 receptor)
List adverse effects or limitations when using reslizumab to treat asthma
Only approved for severe, persistent eosinophilic asthma in patients ≥18 years old
Expensive
Oropharyngeal pain
As for all monoclonal antibodies, potential for anaphylaxis
Name a PDE-4 inhibitor used in the treatment of COPD
Roflumilast
Briefly explain the mechanisms of action of roflumilast.
Inhibition of PDE-4 prevents breakdown of cAMP resulting in:
- Reduced inflammatory cell activity
- Inhibition of fibrosis
- Relaxation of smooth muscle
List adverse effects of roflumilast
Headaches, dizziness, insomnia
Weight loss, diarrhoea, nausea, decreased appetite
Rarely: anxiety, depression, and suicidal ideation
Caution in patients with hepatic impairment
List advantages of azithromycin in treatment of COPD
Macrolide antibiotic prevents bacteria from growing by interfering with their protein synthesis - prevention and treatment of acute exacerbations due to bacterial infection
Additionally, anti-fibrotic and airway smooth muscle relaxant through mechanisms that are not completely understood
List adverse effects of azithromycin
- Common: Diarrhoea, nausea, vomiting
- Severe: Cardiac arrhythmia
- Contraindicatedhistory of cholestatic jaundice or hepatic dysfunction
Name a thiol mucolytic used in COPD
Erdosteine
What are the adverse effects of beta-2 agonist bronchodilators? (3)
- Tremour (most common) and muscle cramps
- Peripheral vasodilation –> flushing
- Palpitation and tachycardia (beta-1 adrenoceptor effects)
What are the first line drugs for asthma (bronchodilators and anti-inflammatory drugs)?
Bronchodilation
* Fast-acting β2 agonists [SABA] (relievers)
* Long-Acting β2 agonists [LABA] (controllers)
Anti inflammatory
* Glucocorticoids (Corticosteroids / Steroids)
What are the second line drugs for asthma (brochodilators and anti-inflammatory drugs)?
Bronchodilation
* Muscarinic receptor antagonists
* Theophylline (methylxanthines)
* Leukotriene receptor antagonists (weak)
Anti-inflammatory
* Mast cell stabilisers – Cromoglicic acid
* Leukotriene pathway inhibitors/receptor antagonists
* Anti-IgE antibody
* Anti-Interleukin-5/Interleukin-4 signalling antibodies
Name 3 inhaled corticosteriods. (first line anti inflammatory drug for asthma)
- Budesonide
- Fluticasone
- Ciclesonide
What are the classes of drug (and theri examples) used in COPD management?
- Bronchodilators SAMA, SABA, LAMA (1st) and LABA (2nd)
- Anti-inflammatories: inhaledcorticosteriods
- Theophylline (bronchodilator)(class: methylxanthines)
- Phosphodiesterase-4 inhibitors (roflumilast)
- Azithromycin
- Mucolytics (erdostein)
