Beta-2-agonists - Indications
- Asthma = short acting (SABAs) are used to relieve breathlessness. Long acting (LABAs) are used mainly in stage 3 of Tx in chronic asthma but must be given alongside ICS
- COPD = SABA are used to relieve breathlessness whilst LABAs are used as an alternative option/second line therapy of COPD.
- Hyperkalaemia = nebulised Salbutamol (SABA) can be used as an additional Tx for urgent treatment of high serum K+ concentration.
Where are B2 receptors found
B2 receptors are found within smooth muscle on airways/bronchi, GI tract, uterus and blood vessels.
What is the MOA of B2-agonists in asthma and COPD?
The B2-receptors are G-coupled protein receptors and so once activated by ligand binding they trigger a cascade which leads to smooth muscle relaxation.
This will relieve any constiction in the airways which then improves airflow through them relieving any breathlessness.
What is the MOA of B2-agonists in Hyperkalaemia?
B2-agonists stimulate Na+/K+ ATPase pumps on the cell surface membrane and this causes more K+ to move out from the extracellular surface and into the intracellular compartment hence making it useful in the treatment of hyperkalaemia but they shouldn’t be used on their own for this.
What are the side effects of B2-agonists?
- common flight or fight effects such as tachycardia, palpitations anxiety and tremor.
- Increased serum glucose through the promotion of glycogenesis
- can increases lactate levels at high doses
- LABAs can cause muscle cramps.
What are contraindications for B2-agonists?
- CVD as side effect of tachycardia may provoke angine or arrhythmias.
- LABA cannot be used if the patient is not on ICS
What are important interactions of B2-agonists that you should be aware of?
- Beta-blockers reduce the effect of B2-agonists.
- High dose nebulised B2-agonists with theophylline and corticosteroids can lead to hypokalaemia (serum K+ should be monitored)
Give examples of SABAs and LABAs?
SABAs = salbutamol and terbutaline LABAs = salmeterol and formoterol
What are indications for anti-muscarinics?
- COPD = SAMAs/short acting are used to relieve breathlessness due to things like exertion or acute exacerbation. LAMAs used to prevent breathlessness and exacerbations.
- Asthma: SAMAs are used as adjuvant therapy to relieve breathlessness during acute exacerbations alongside SABAs. LAMAs are added to high-dose ICS and usually step 4 of asthma management
What is the MOA for bronchodilator anti-muscarinics?
They bind to the muscarinic receptors and act like a competitive inhibitor of acetylcholine.
Stimulation of the muscarinic receptor usually stimulates parasympathetic ‘rest & digest’ effects.
Therefore, blocking the receptor, anti-muscarinics have the opposing effects - reducing smooth muscle tone (relaxing the airways)
What are examples of these bronchodilator anti-muscarinics?
SAMA = ipratropium, LAMA = tiotropium, glycopyrronium, aclidinium
How are antimuscarinics used in CVS and GI?
link to the indications?
As blockade of muscarinic receptors leads more flight and fight effects - it increased heart rate and conduction
It reduces smooth muscle tone and peristaltic contractions.
It reduces secretions from glands in the respiratory tract and the gut.
Therefore they can be used in severe/symptomatic bradycardia to increase HR, used in IBS for their antispasmatic effect.
Give examples of anti-muscarinics used for CVS/GI purposes
- Atropine (first line bradycardia)
- Hyoscine butylbromide (first-line in IBS)
- Glycoppyronium
What are the side effects of bronchodilator anti-muscarinics?
Adverse effects are uncommon in inhaled antimuscarinics because they are metabolised rapidly.
- dry mouth
- irritation of respiratory tract with nasopharyngitis, sinusitis and cough
- GI disturbance such as constipation
- urinary retention
- blurred vision & headaches
What are contraindications for antimuscarinic bronchodilators?
- Angle-closure glaucoma - has to be used very cautiously as it can lead to a dangerous rise in intraocular pressure.
- Arrhythmias
- urinary retention.
What interactions do anti-muscarinic bronchodilators have?
Very low systemic absorption = no significant interactions.
What are the indications for Inhaled Corticosteroids/Glucocorticoids?
- Asthma = treat airway inflammation and control symptoms when they are not being well controlled by SABAs
- COPD = control symptoms and prevent exacerbations in patients with severe airflow obstruction on spirometry and/or recurrent exacerbations - ICS usually are prescribed in combination of LABAs or LABA bronchodilators.
What is the MOA of ICS?
The corticosteroid passes through the plasma membrane and act as a ligand, binding to cytoplasmic receptors,
This forms a corticosteroid-receptor complex which translocates to the nucleus to modify the transcription of large numbers of genes.
This modification of gene expression = Pro-inflammatory interleukins, cytokines and chemokines are downregulated whilst anti-inflammatory proteins are upregulated. Therefore, reducing mucosal inflammation, widen airways and reduced mucus secretion thus improving the symptoms and reduced exacerbations in asthma and COPD.
What are the side effects of ICS?
- Oral candidiasis/thrush = due to the immunosuppressive effect
- Hoarse voice
- may increase the risk of pneumonia in COPD
- less common due minimal amount getting absorbed in the blood but rarely can lead to systemic side effects if given at a high dose - includes adrenal suppression, growth retardation (in children) and osteoporosis.
What are the contraindications for ICS?
- COPD patients with a Hx of pneumonia - cautious if given at high doses
- Children who are more susceptible to growth suppression
What are examples of ICS?
- beclomethasone
- budenoside
- fluticasone
What are the indications for Oxygen?
- Hypoxaemia = to increase oxygen delivery to tissues
- Pneumothorax = to accelerate reabsoprtion of pleural gas
- Carbon monoxide (CO) poisoning = reduce the half life of carboxyhaemoglobin.
What is the MOA of Oxygen for each of these indications?
In Hypoxaemia, supplemental oxygen will increase the partial pressure of oxygen in alverolar gas and this increases the amount and rate of diffusion into the blood. This results in an increased delivery of oxygen to tissue hence resolving the hypoxia.
In Pneumothorax, oxygen has additional effect of reducing the fraction of nitrogen in the alveolar air. Due to pleural air mainly consisting of nitrogen it increases the rate of reabsorption of pleural air.
In Carbon monoxide poisoning, the Oxygen competes for binding sites on haemoglobin and thereby shortens the half life of carboxyhaemoglobin allowing haemoglobin to carry more oxygen to tissues.
What are the side effects of giving supplemental oxygen?
- most commonly side effects are related more to the delivery device e.g. discomfort of a facemask
- lack of water vapour leads to dry throat - improved by humidification.
- hyperoxaemia may be harmful
