Drugs for Asthma Flashcards
What are the 2 major forms of asthma?
1) Allergic asthma (Type 1 HS/IgE-mediated)
2) Eosinophilic asthma (Type 2 HS/Cell-mediated)
Why does the use of LABAs alone make asthma outcomes worse and how is it prevented?
ß2-adrenoceptor tolerance
Must take with ICS to upregulate ß2-adrenoceptor expression
What are the 1st line drugs in for asthma?
1) SABA (salbutamol)
2) LABA (formoterol, salmeterol)
3) ICS (eg. budesonide, fluticasone)
What is used as a “reliever” in an acute asthma attack?
Fast-acting SABAs (Salbutamol)
What is the given as a “controller” in chronic asthma or to prevent progression from early to late?
LABA (Formoterol/Salmeterol) + ICS (Budesonide, Fluticasone)
What is the moa of ß2-adrenoceptor agonists used in asthma?
1) Airway smooth muscle relaxation → bronchodilation
2) Mast cell stabilization
3) ↓Microvascular leakiness
4) ↑ Mucociliary clearance
What do you give to a px having an anaphylactic rxn?
IM Adrenaline (IV/SC if possible)
How are SABAs and LABAs usually administered?
Inhalation
(but also oral if cannot use inhaler)
- and IV in emergency
What are 3 AEs of ß2-agonists used in asthma?
Sympathomimetic:
1) Tremor (commonest side effect) and muscle cramps
2) Peripheral vasodilatation (e.g. flushing)
3) Palpitations & tachycardia (ß1-adrenoceptor effects)
4)HypoK+/Hypergly
– Usually transient and/or insignificant but beware of DDIs with other drugs causing hypoK+/hypergly
5) ***ß2-adrenoceptor tolerance
ß-agonists are (1st/2nd) line in asthma but usually (1st/2nd) line in COPD.
1st line in asthma
2nd line in COPD (group A but LABAs first line with LAMAs in B and E)
What are 2 bronchodilators used in 2nd line for asthma?
SAMA: Ipratropium bromide
LAMA: Tiotropium bromide
What are 2 methylxanthines used in asthma treatment for bronchodilation?
1) Theophylline (Oral-ER and IV)
2) Aminophylline (Oral-ER, IV and rectal)
When are methylxanthines used to treat asthma?
IV in acute severe asthma
What are 2 AES of methylxanthines used in asthma?
1) Narrow therapeutic window (therapeutic range: 5-20 mg/L)
2) Many DDIs
3) GI: Nausea, vomiting, abdominal discomfort, anorexia
4) CNS: Nervousness, tremor, anxiety, insomnia, seizures (in children)
5) CVS: Arrhythmias
What is the use of magnesium sulphate in asthma treatment?
Adjunct treatment of severe acute asthma
What is the moa of Magnesium sulphate in asthma?
1) Relaxes airway smooth muscle
2) ↓ release of acetylcholine and histamine
3) Anti-inflammatory effect
What are 3 factors that make budesonide, fluticasone and ciclesonide good choices as ICS in asthma treatment?
1) High receptor binding affinity (very low dose required)
2) Extensive first pass metabolism (less systemic side effects)
3) Highly lipophilicity
What is the moa of ICS in asthma?
1) ↑anti-inflammatory mediators:
- ↑ Annexin A1
- ↑ ß2 adrenoceptors
2) ↓Pro-inflammatory mediators
- ↓ T cell, mast cell, eosinophils
- ↓shedding of epithelial cells
- ↓ mucus secretion
- ↓ inflammatory cytokines
- ↓ phospholipase A2
- ↓ COX2 → prostaglandins
- ↓ 5-LOX → leukotrienes
- ↓ NO synthase
What are 2 uses of ICS for asthma?
1) 1st line prophylactic for asthma treatment
2) Nocturnal asthma
What are 4 AEs of ICS used in asthma?
1) Oropharyngeal candidiasis (due to localised immunosuppression)
2) Dysphonia (enfeebled voice due to localised muscle wasting)
3) Cough / throat irritation
4) Adrenal suppression (e.g., fluticasone)
5) Easy bruising (especially in elderly)
6) Posterior subcapsular cataracts
7) Osteoporosis
How are leukotriene pathway inhibitors administered?
Oral
What are 2 leukotriene pathway inhibitors?
1) Montelukast - Cysteinyl-Leukotriene (CysLT) receptor antagonist
2) Zileuton - 5-lipoxygenase (5-LOX) inhibitor
What are 2 uses of leukotriene pathway inhibitors (eg. Montelukast, Zileuton) used in asthma?
1) Prophylaxis & chronic treatment of asthma
2) Aspirin-induced/NSAID exacerbated asthma
3) Exercise-induced asthma
What are 2 AEs of leukotriene pathway inhibitors (eg. Montelukast, Zileuton) used in asthma?
Few and mild
1) Headache
2) GI disturbance
a/w Churg-Straus syndrome
3) Suicidal thinking and neuropsychiatric adverse effects in some patients
Leukotriene pathway inhibitors (eg. Montelukast, Zileuton) used in asthma are (weak/strong) bronchodilators?
Weak
What are the moas of Cromoglicic acid used in asthma?
Mast cell stabiliser:
1) Controls Cl- channels to inhibit cellular activation
2) mast cell degranulation induced by IgE-mediated FcεRI crosslinking
3) ↓secretion of inflammatory mediators from eosinophils, neutrophils and macrophages
4) ↑ annexin A1 secretion
– Annexin A1 inhibits prostaglandin and leukotriene production
What are 2 uses of cromoglicic acid in asthma?
1) Prophylactic control of asthma (by inhalation route only)
2) Prophylactic control of allergic rhinitis, allergic conjunctivitis, and vernal keratoconjunctivitis
What are 2 mAbs used in asthma treatment?
1) Omalizumab (Anti-IgE)
2) Reslizumab (Anti-IL-5)
What is the moa of Omalizumab used in asthma?
Anti-IgE
Used for severe asthmatics with allergies and an elevated IgE level
Subcutaneous injection every 2 to 4 weeks
Depletes levels of free IgE in serum
Decreases FcεRI/ expression on mast cells (basophils)
What are 2 drawbacks of using omalizumab for asthma treatment?
1) Expensive
2) a/w small increase in risk of heart attack, transient ischaemic attacks (TIA) and blood clots.
3) Potential for anaphylaxis
When is reslizumab indicated?
severe, persistent eosinophilic asthma in px ≥18 y/o
What are 2 drawbacks of using reslizumab for asthma treatment?
1) Expensive
2) Oropharyngeal pain
3) Potential for anaphylaxis
