Beta2 Receptor Agonists
Examples
Short acting β2 receptor agonists:
- Salbutamol
- Terbutaline
- Salmeterol
- Formoterol
- Vilanterol
Indications
Short acting β2 agonists
- Relief of symptoms in acute and chronic asthma, used on an ‘as required’ basis
- Prophylaxis of allergen or exercise induced bronchospasm
- Relief of symptoms in COPD (only in patients who demonstrate reversibility, note the reversibly in this disease is often small and therefore β2 agonists have a limited role).
- A tocolytic agent, used to halt premature labour. Specialist use only.
- Rarely, treatment of hyperkalemia (nebulised).(unlicensed)
- Treatment of chronic bronchospasm. Long acting β2 agonists are used as an adjuvant therapy in asthmatic patients who are inadequately controlled with inhaled steroids alone. They are given as regular therapy.
- Relief of symptoms in COPD (only in patients who demonstrate reversibility, note the reversibly in this disease is often small and therefore β2 agonists have a limited role).
Contraindications
Caution
- In cardiovascular disease high doses of β2 receptor agonists may cause tachy-arrhythmias.
- Avoid in Pregnancy, because of the tocolytic actions (unless under specialist care).
Mechanism
β agonists act by stimulating the sympathetic nervous system. One of the actions of the sympathetic system is bronchodilation.
When pre-ganglionic sympathetic nerves are stimulated they release acetylcholine which acts on nicotinic receptors to release norepinephrine from the post ganglionic sympathetic nerve. Norepinephrine then acts on α and β adrenoceptor sub types (α 1, 2 and β 1, 2, 3) to produce sympathetic effects on various tissues around the body (see figure 1). β2 agonists work by mimicking the effect of norepinephrine on β2 receptors. This produces sympathetic effects on tissues containing β2 receptors.
See Autonomic and Neuromuscular physiology 1 - 2 Dr Davies and Autonomic and Neuromuscular pharmacology Dr Rod Scott, science for medicine.
β2 adrenoceptors are also found on skeletal muscle, nerve terminals, mast cells and other smooth muscle including (figure 2):
- Blood vessels
- GI tract
- Uterus
- Bladder detrusor (muscle)
- Seminal tract
- Cillary muscle
Administration
Inhalation
- Aerosol: Taken as required, via an MDI (metered dose inhaler) or a dry powder device +/- a spacer device. Note: there are a number of dry powder formulations available.
- Nebulised solutions: Used in acute severe asthma, repeated as required to control symptoms. Review the treatment and clinical response regularly.
- Nebulised solutions are also used in chronic COPD unresponsive to inhaled therapy.
Adverse Reactions
The dose delivered by inhalation rarely causes adverse effects.
β2 agonists are delivered to the airways direly via inhaler device or nebuliser. This produces the desired effect of bronchial smooth muscle dilation and at the same time minimises the effects on other tissues containing β2 adrenoreceptors.
Short and long acting β2 adrenergic agonist are selective and therefore act principally on the β2 adrenoceptor subtype. Therefore β1 effects (cardiac stimulation and amylase secretion) and β3 effects (thermogenesis of skeletal muscle and lipolysis of fat tissue) are not usually seen at doses which produce broncho-dilatation. However in high concentrations β2 agonist may cause β1 and β3 activation, leading to adverse effects such as tachyarrythmias and hyperglycaemia (only an issue in diabetic patients).
In high doses β2 agonists stimulate skeletal muscle adrenoceptor causing a fine tremor.
Hypokalaemia. β2 agonists decrease the plasma potassium concentration by causing a shift of ions into the cell. This may be important when high doses are used.
Rarely, paradoxical bronchospasm can occur.
β2 agonists are delivered to the airways direly via inhaler device or nebuliser. This produces the desired effect of bronchial smooth muscle dilation and at the same time minimises the effects on other tissues containing β2 adrenoreceptors.
Short and long acting β2 adrenergic agonist are selective and therefore act principally on the β2 adrenoceptor subtype. Therefore β1 effects (cardiac stimulation and amylase secretion) and β3 effects (thermogenesis of skeletal muscle and lipolysis of fat tissue) are not usually seen at doses which produce broncho-dilatation. However in high concentrations β2 agonist may cause β1 and β3 activation, leading to adverse effects such as tachyarrythmias and hyperglycaemia (only an issue in diabetic patients).
In high doses β2 agonists stimulate skeletal muscle adrenoceptor causing a fine tremor.
Hypokalaemia. β2 agonists decrease the plasma potassium concentration by causing a shift of ions into the cell. This may be important when high doses are used.
Rarely, paradoxical bronchospasm can occur.
Interactions
It is strongly advised to avoid prescribing beta-blockers for patients who require beta-2 agonists as these completely contradict one another and can precipitate an asthma attack.
Common
Theophyllines, diuretics and corticosteroids increase the risk of developing hypokalaemia.
Rare
Other sympathomimetic drugs may lead to cardiovascular side effects, some are available over the counter (ephedrine), or may be a component of herbal medications.
Atomoxetine (used for ADHD); if given with parenteral salbutamol, increases the risk of cardiovascular side effects.
Common
Theophyllines, diuretics and corticosteroids increase the risk of developing hypokalaemia.
Rare
Other sympathomimetic drugs may lead to cardiovascular side effects, some are available over the counter (ephedrine), or may be a component of herbal medications.
Atomoxetine (used for ADHD); if given with parenteral salbutamol, increases the risk of cardiovascular side effects.
Education
Most asthmatic patents receive dual therapy with corticosteroids and β2 agonists. Ensure the patient understands that short acting β2 agonists only relieve the symptoms of asthma, patients often referred to this as a ‘reliever’ (or the ‘BLUE’ one). In comparison corticosteroids are referred to as a ‘preventer’ (or the BROWN one). To achieve maximum efficacy, it is important to stress the different roles these drugs play in the treatment of asthma.
Ensure that the patent knows how to use an inhaler device (+/- spacer) correctly. Ask them to demonstrate how to use it. It is generally now recommended that most patients with asthma would benefit from use of a spacer as this increases distribution of the drug into the correct location rather than the back of the throat.
Warn patients to seek medical help if they require increasing doses of inhaled short acting β2 agonists to relieve symptoms.
All patents with asthma require an annual asthma review, with either a doctor or asthma nurse specialist.
Ensure that the patent knows how to use an inhaler device (+/- spacer) correctly. Ask them to demonstrate how to use it. It is generally now recommended that most patients with asthma would benefit from use of a spacer as this increases distribution of the drug into the correct location rather than the back of the throat.
Warn patients to seek medical help if they require increasing doses of inhaled short acting β2 agonists to relieve symptoms.
All patents with asthma require an annual asthma review, with either a doctor or asthma nurse specialist.
Pharmacokinetics
Metabolism
Salbutamol has significant first pass metabolism in the liver. This is not important in with normal inhaled therapy.
There is no dosage adjustment required in hepatic or renal insufficiency.
Salbutamol has significant first pass metabolism in the liver. This is not important in with normal inhaled therapy.
There is no dosage adjustment required in hepatic or renal insufficiency.
