Respiratory medicines Flashcards
Describe the broad mechanism of action of beta agonists, adverse effects
Mechanism of action
Beta agonists relax bronchial smooth muscle by stimulating beta-1 adrenoceptors.
Beta agonists are indicated for asthma and COPD.
Adverse effects
Many of the adverse effects are related to activity on beta-1 adrenoceptors in addition to beta-2 adrenoceptors. Examples include:
- hypokalaemia (note: salbutamol is used to treat hyperkalaemia)
- insomnia
- tremor
- palpitations
- tachycardia
- headaches
- muscle cramps
- lactic acidosis (rarely)
Describe short acting beta agonists
Examples: salbutamol and terbutaline
Onset of action: 5-15 minutes
Duration of action: 3-6 hours
Indications
- first line in managing acute asthma
- symptom relief in asthma and COPD
- prevention of exercise-induced asthma
- previously considered step 1 SABA PRN (as a single agent) only. New guidelines instead recommend LABA (formeterol) with ICS PRN (budesonide) in adult patients
Extra information: high or increasing use indicates poor asthma control
Most salbutamol is available as MDI. Ventolin can be either MDI or DPI.
Describe long-acting beta agonists
Examples: salmeterol, formoterol, olodaterol
Onset of action: 5-30 minutes
Duration of action: 12-24 hours
Indications:
- maintenance treatment of asthma with ICS (Not for mono therapy)
- maintenance treatment in COPD with or without ICS
- note: formeterol with ICS can be used for acute asthma symptoms and is now recommended as step 1 vs. SABA alone, for adult patients
Extra information:
- Used as combination inhaler with ICS in asthma (and COPD where the 2 drugs classes are indicated)
- Olodaterol only comes in combination with antimuscarinic
- Vilanterol comes in combo with ICS OR antimuscarinic and a combination of all 3 classes
Describe general mechanism of action and adverse effects of muscarinic antagonists
Mechanism of action
Muscarinic antagonists promote bronchodilation by inhibiting cholinergic bronchomotor tone. They act on muscarinic receptors (M1-3) with varying degrees of specificity.
Muscarinic agents are used in both asthma and COPD.
Adverse effects
- dry mouth
- throat irritation
- blurred vision
- urinary retention
- constipation
- palpitations/tachycardia
- glaucoma
Describe SAMAs
SAMAs
or short acting muscarinic antagonists
Examples: ipratropium
Onset of action: <15 min
Duration of action: 3-6 hours
Indications: symptom relief in asthma and COPD
Extra information:
- an alternative to SABA in acute breathlessness in COPD
- addition to SABA in acute asthma
Describe LAMAs
LAMAs
or long-acting muscarinic antagonists.
Examples: aclidinium, glycopyrronium, tiotropium, umeclidinium
Onset of action: 30 mins
Duration of action: 12-24 hours
Indications:
- maintenance treatment in COPD with or without LABA, with or without ICS
Extra information:
- preferred to LAMA for stable COPD
- individual or combination inhalers (usu. with LABA)
Describe the mechanism of action and adverse effects of inhaled corticosteroids
Mechanism of action
is complex, and includes although not limited to:
- Reduced airway inflammation and bronchial hyper-reactivity.
- Reducedclonal proliferation of T-helper cells by reducing IL-2 and reduction in cytokines
- Inhibit allergen-induced influx of eosinophils
- Up regulation of beta receptors.
Adverse effects
can be divided into local and systemic effects:
- Local effects (can be minimised by rinsing mouth with water and spit immediately after using. The use of a spacer may also limit local side effects)
- Local infections eg oral candidiasis
- Pneumonia in COPD patients
- dysphonia
- Systemic effects (less common with inhaled compared with systemic, but still occur in some patients particularly at high dose for long periods)
- impaired glucose control
- fractures
- adrenal suppression
- psychosis
- glaucoma
- bruising
Describe the mechanism of action and adverse effects of methylxanthines
Methylxanthines
e.g. theophylline and aminophylline
Mechanism of action
Not fully understood:
- Non-selective phophodiesterase inhibitor
- Smooth muscle relaxation, anti-inflammatoryand increased diaphragm contractility
Adverse effects
- GIT - including GORD, vomiting, diarrhoea
- Insomnia, irritability, anxiety
- tremor, palpitations (arrhythmias at high doses)
- Rarely seizures
Other information
- Narrow therapeutic window requiring therapeutic drug monitoring (TDM)
- Drug interactions including tobacco smoking (CYP 450interactions)
- IV aminophylline used rarely in acute asthma
- Methylxanthines not routinely recommended for bronchodilation in asthma or COPD due to beta agonists and antimuscarinic agents and the high risk of toxicities with methylxanthines
- Theophylline is orally administered. Aminophilline is intravenous
Describe mechanism of action and adverse effects of leukotriene receptor antagonists
Leukotriene receptor antagonists (montelukast)
Mechanism of action
- Inhibit leukotriene release from mast cells by eosinophils or by blocking the specific leukotriene receptors on bronchial tissues preventing bronchoconstriction, mucous secretion and oedema
- Orally administered selective antagonist of leukotrienes
- Indicated for maintenance treatment of asthma
### Adverse effects
- generally well tolerated
- headache, abdominal pain and diarrhoea
- neuropsychiatric effects: nightmares, hallucinations, mood, behavioural changes
Describe the mechanism of action and indications of benralizumab
Mechanism of action:
Humanised monoclonal antibody that binds to and blocks the interleukin‑5 receptor (expressed on eosinophils and basophils), reducing the production and survival of eosinophils. Benralizumab also induces eosinophil (and basophil) apoptosis.
Indications
Maintenance treatment for severe refractory eosinophilic asthma (add-on to optimised standard therapy)
Describe mechanism of action and indications of mepolizumab
Mechanism of action
Humanised monoclonal antibody that binds to interleukin‑5 (IL‑5), reducing the production and survival of eosinophils.
Indications
Maintenance treatment for severe refractory eosinophilic asthma (add-on to optimised standard therapy)
Add-on treatment for relapsed or refractory eosinophilic granulomatosis with polyangiitis (EGPA; also known as Churg-Strauss syndrome)
Describe mechanism of action and indications of omalizumab
Mechanism of action
Recombinant humanised monoclonal antibody directed against immunoglobulinE (IgE); reduces the immune system’s response to allergen exposure.
Indications
Maintenance treatment of moderate-to-severe allergic asthma in patients treated with inhaled corticosteroids and with raised serum IgE levels
Chronic spontaneous urticaria inadequately controlled with antihistamines
Describe the mechanism of action and indications of dupilumab
Mechanism of action
Monoclonal antibody directed against the IL-4 receptor and IL-13 signal transduction
Indications
Moderate to severe asthma
Reduced exacerbations, better lung function and control compared with placebo especially in high eosinophil levels.
