2. Drugs used in respiratory disorders Flashcards
1
Q
Pharmacotherapeutics for asthma
A
- Bronchodilators to reverse bronchoconstriction
2. Anti-inflammatory
2
Q
Types of bronchodilators for asthma
A
- SABA (relievers) (first-line)
- LABA (controllers) (first-line)
- Muscarinic receptor antagonists (second-line)
- Theophylline (second-line)
- Leukotriene receptor antagonists (weak) (second-line)
3
Q
Types of anti-inflammatory for asthma
A
- Glucocorticoids (corticosteroids/steroids) (first-line)
- Mast cell stabilisers - Cromoglicic acid
- Leukotriene pathway inhibitors / receptor antagonists
- Anti-IgE antibody
- Anti-interleukin 5 / interleukin-4 signalling antibodies
4
Q
MOA of beta2-adrenoceptor agonists
A
- Airway smooth muscle relaxation → bronchodilation
- Mast cell stabilisation
- Decrease microvascular leakiness
- Increase mucociliary clearance
5
Q
Examples of beta2-adrenoceptor agonists
A
- Epinephrine (IV/SC in emergency)
- Salbutamol (3-6h SABA, fast acting) → IV in emergency
- Fomoterol (12h LABA, fast acting 2-3 mins)
- Salmeterol (12h LABA, slow-acting)
6
Q
Adverse effects of beta2-adrenoceptor agonists
A
beta2-adrenoceptor-mediated sympathomimetic effects:
- Tremor and muscle cramps
- Peripheral vasodilation (e.g. flushing)
- Palpitations & tachycardia (nonselective beta-agonism leading to beta1-adrenoceptor effects)
- Hypokalemia / Hyperglycaemia
- Beta2-adrenoceptor tolerance → increased risk of asthma-related death
7
Q
What must be given together with LABAs
A
Glucocorticoids → upregulate beta2-adrenoceptor expression
8
Q
Example of muscarinic receptor antagonists
A
Ipratropium bromide → SAMA
Tiotropium bromide → LAMA
9
Q
MOA of mscarinic receptor antagonists
A
- Inhibit M3 receptor-mediated bronchoconstrictions
2. Reverse vagal-nerve mediated bronchospasm & mucus secretion
10
Q
Uses and efficacy of muscarinic receptor antagonists
A
- Adjunct to inhaled beta2 agonists and inhaled glucocorticoids
- Patients intolerant to beta2 agonists
11
Q
Adverse effects of muscarinic receptor antagonists
A
- Limited systemic side effects as not well absorbed into systemic circulation when taken by inhalation
- Unpleasant taste
- Typical parasympatholytic effects
- Dry mouth
- Urinary retention (in elderly)
12
Q
Examples of methylxanthines
A
- Theophylline
2. Aminophylline
13
Q
MOA of methylxanthines
A
- Inhibits phosphodiesterases
- Blocks adenosine receptors
- Increase adrenaline release from adrenal medulla
- CNS stimulant action on respiration
- Not used as an anti-inflammatory but has some anti-inflammatory effects
- Effects on mast cells and T-cells
- Decrease microvascular leakiness
14
Q
Uses and efficacy of methylxanthines
A
- Can be administered IV in acute severe asthma
2. Less effective bronchodilators than beta2 agonists
15
Q
Adverse effects of methylxanthines
A
- Narrow therapeutic window
- Many drug-drug interactions → caution for potential drug interactions
- GI: nausea, vomiting, abdominal discomfort, anorexia
- CNS: nervousness, tremor, anxiety, insomnia, seizures
- CVS: arrhythmias
16
Q
Example of cysteinyl-leukotriene receptor antagonists
A
Montelukast
17
Q
Uses of CysLT receptor antagonists
A
- Adjunct therapy for mild to moderate asthma
2. Not used alone as reliever to rescue asthma attack
18
Q
Efficacy of CysLT receptor antagonist
A
- Relaxes airways in mild asthma (about 1/3 as effective as salbutamol, additive effects with beta2-adrenoceptor agonist)
- Effective in aspirin-sensitive asthma
- Effective in exercise-induced asthma
19
Q
Uses of MgSO4
A
- Adjunct treatment of severe acute asthma
- Intravenous or nebulized
- Mechanisms incompletely understood
- Relaxes airway smooth muscle
- Modulates release of acetylcholine and histamine
- Anti-inflammatory effect - Adverse effects rarely reported
20
Q
Examples of inhaled corticosteroids
A
Budesonide, Fluticasone, Cicleosonide
21
Q
Characteristics of inhaled corticosteroids
A
- High receptor binding affinity → very low dose required
- Extensive first pass metabolism → less systemic side effects
- High lipophilicity
22
Q
What is an example of “soft steroid”
A
Ciclesonide → prodrug that requires esterase activation in the lung thus avoiding systemic side effects
23
Q
Adverse effects of inhaled corticosteroids
A
Side effects rare due to limited systemic absorption
24
Q
Can inhaled corticosteroids be administered IV as well?
A
Yes, it can be administered IV in acute asthma attack but must be administered early as onset of action is slow
25
MOA of inhaled corticosteroids
1. Reduce pro-inflammatory mediators
- decrease T cells, mast cells, eosinophils
- decrease shedding of epithelial cells
- decrease mucus secretion
- decrease pro-inflammatory cytokines
- decrease phospholipase A2
- decrease COX2
- decrease 5-LOX
- decrease inducible nitric oxide synthase
2. Increase anti-inflammatory mediators
- increase annexin A1
- increase beta2-adrenoceptors
i. Do not relax airway smooth muscles directly
ii. Decrease airway hyper-responsiveness in 4-6 weeks
iii. Decrease frequency of acute asthma exacerbation
iv. Possibly prevent airway wall remodelling
v. Decrease the need for beta2 agonist
vi. Decrease risk of death from asthma
26
Uses of inhaled corticosteroids
1. First line prophylactic for asthma treatment
| 2. For nocturnal asthma
27
Adverse effects of inhaled corticosteroids
Largely limited by route of administration
- Oropharyngeal candidiasis
- Dysphonia
- Cough / throat irritation
- Adrenal suppression (e.g fluticasone)
- Easy bruising (especially in elderly)
- Posterior subcapsular cataracts
- Osteoporosis
28
Examples of leukotriene pathway inhibitors
1. Montelukast - CysLT receptor antagonist
| 2. Zileuton - 5-LOX inhibitor
29
Uses for leukotriene pathway inhibitors
1. Prophylaxis & chronic treatment of asthma
2. Aspirin-induced / NSAID exacerbated asthma
3. Exercise-induced asthma
30
Efficacy of leukotriene pathway inhibitors
1. Less effective than glucocorticoids
2. Decrease frequency of asthma attacks
3. Decrease use of inhaled steroids
4. Decrease use of beta2 agonist
5. Decrease peripheral blood eosinophil levels
31
Side effects of leukotriene pathway inhibitors
Few and mild, headache and GI disturbances
Caution: suicidal thinking and neuropsychiatric adverse effects in some patients
Associated with Churg-Straus syndrome → likely due to concomitant glucocorticoid withdrawal when prescribing leukotriene pathway inhibitors
32
Example of mast cell stabiliser
cromoglicic acid
33
MOA of cromoglicic acid
1. Mast cell stabiliser
2. Decrease mast cell degranulation induced by IgE-mediated FcεRI cross-linking
3. Decrease secretion of inflammatory mediators from eosinophils, neutrophils and macrophages
4. Controls chloride channels to inhibit cellular activation
5. Increase secretion of annexin A1
- Annexin A1 inhibits prostaglandin and leukotriene production
34
Uses for cromoglicic acid
1. Prophylactic control of asthma (by inhalation only)
| 2. Prophylactic control of allergic rhinitis, allergic conjunctivitis, and vernal keratoconjunctivitis
35
Efficacy of cromoglicic acid
1. Prevents antigen, cold, dry air and exercise-induced bronchospasm
2. Single-dose before antigen-challenge or exercise prevents bronchospasm
3. ↓ bronchial hyper-reactivity in 4 weeks
4. ↓ need for bronchodilator therapy
5. But less effective than inhaled glucocorticoids
6. Inter-individual variability in response → not possible to predict which patients will respond
36
Side effects of cromoglicic acid
1. Throat and nasal irritation, mouth dryness, cough
| 2. Unpleasant/Bitter taste
37
An example of anti-IgE monoclonal antibody
Omalizumab
38
Uses and MOA of Omalizumab
1. Used for severe asthmatics with allergies and an elevated IgE level
2. Depletes levels of free IgE in serum
3. Decreases FcεRI expression on mast cells (basophils)
39
Limitations of omalizumab
1. Expensive
2. Associated with small increase in risk of heart attack, transient ischaemic attacks (TIA) and blood clots
3. Potential for anaphylaxis
40
Example of Anti-IL-5/IL-4 signalling monoclonal antibodies
Reslizumab (IL-5)
41
Limitation of reslizumab
1. Expensive
2. Oropharyngeal pain
3. Potential for anaphylaxis
42
Drugs used in the management of COPD
1. Bronchodilators: SAMAs, SABAs, LAMAs and LABAs
2. Anti-inflammatories: Inhaled corticosteroids
3. Theophylline
4. Phosphodiesterase-4 (PDE-4) inhibitors: roflumilast
5. Azithromycin
6. Mucolytics: erdosteine
7. Antibiotics
8. Vaccinations against respiratory infections
9. Smoking cessation
43
What is the ABCD of COPD?
Exacerbations per year: ≤ 1 (with no hospital admission) → Group A and B
Exacerbations per year: ≥ 2, ≥ 1 leading to hospital admission → Group C and D
44
Treatment for Group A COPD
Any bronchodilator (SABA or LABA)
45
Treatment for Group B COPD
A long acting bronchodilator (LABA or LAMA)
46
Treatment for Group C COPD
LAMA
47
Treatment for Group D COPD
LAMA or LAMA + LABA or ICS + LABA
48
Example of phosphodiesterase-4 (PDE-4) inhibitors
roflumilast
49
MOA of roflumilast
Inhibition of PDE-4 prevents breakdown of cAMP resulting in
1. Reduced inflammatory cell activity
2. Inhibition of fibrosis
3. Relaxation of smooth muscle
50
Uses and efficacy of roflumilast
1. Reduces episodes of exacerbation
| 2. Slows progress of fibrosis
51
Adverse effects of roflumilast
1. Headaches, dizziness, insomnia
2. Weight loss, diarrhoea, nausea, decreased appetite
3. Rarely: anxiety, depression, and suicidal ideation
4. Caution in patients with hepatic impairment
52
MOA of azithromycin
1. Macrolide antibiotic prevents bacteria from growing by interfering with their protein synthesis
2. Additionally, anti-fibrotic and airway smooth muscle relaxant through mechanisms that are not completely understood
53
Uses and efficacy of azithromycin
1. Anti-fibrotic and airway smooth muscle effects reduces risk of exacerbations
2. Prevention and treatment of exacerbations due to bacterial infection
54
Adverse effects of azithromycin
Many adverse effects including:
• Common: Diarrhoea, nausea, vomiting
• Severe: Cardiac arrythmia
• Contraindicated history of cholestatic jaundice or hepatic dysfunction
55
Vaccination for stable COPD
PPSV23 and PCV13 recommended for all patients ≥ 65 years old
PPSV23 recommend for younger COPD patients with significant comorbid conditions including chronic heart or lung disease
56
Pharmacotherapy for smoking cessation
1. Nicotinic
- Nicotine replacement
- Vareniciline (partial agonist)
2. Antidepressant (NET/DAT inhibitors)
- Bupropion
- Nortryptiline
