Autonomic regulation of the airways Flashcards
How do airways regulate diameter?
The airway has smooth muscle which can contract and relax to regulate the diameter
- This is specifically important when considering asthma and COPD
Give three phenotypes of asthma
- usually <50
- Infrequent sputum production
- No clear aetiology with smoking
Give three phenotypes of COPD
- Usually >35
- Usually >10 pack-years
- Sputum is produced and is common in chronic bronchitis
How are the smooth muscles in the airways regulated?
- By autonomic nervous system
- Contractile signals cause an increase in intracellular calcium in smooth muscle, which activates actin-myosin contraction - Regulated by inflammation particularly with asthma
How is the nervous system split?
Broadly into the Central and Peripheral
What is the central Nervous system further split into?
Spinal cord and brain
What is the peripheral nervous system further split into?
1.Efferent and afferent
2. Efferent - Autonomic (smooth muscle) + Somatic (skeletal muscle)
3. Autonomic - Sympathetic + Enteric + Parasympathetic
What outputs does the autonomic nervous system convey?
Coveys all outputs from the CNS to the body, except for skeletal muscular control
- Two nerves in the series known as pre and post ganglionic fibres
Give three examples of parasympathetic responses
- Constrict Bronchi
- Slows heart rate
- Constricts pupils
Give three examples of sympathetic responses
- Dilates bronchi
- Accelerates heart hate and constricts arterioles
- Dilates pupils
What does the somatic nervous system release?
- At the terminal ganglion acetyl-choline is released which has its effects on nicotine 1 receptors on the effector organ
- Only one singular ganglion
How does the parasympathetic nervous system convey signals?
- It has two ganglions, that lie very close to the effector organ
- Releases acetyl choline which has an effect on nicotine 2 receptors
- At site of effector, acetyl choline released and has an effect on muscarinic receptors
How does the parasympathetic nervous system convey signals?
- The first ganglion lies in the spinal cord
- Releases acetyl choline which has an effect on nicotine 2 receptors
- Neuro-adrenaline released from the sympathetic nervous system and has it’s effect on alpha and beta receptors in the target organ
How is the parasympathetic nervous system in the lungs responsible for bronchoconstriction?
- Vagus nerve neurons terminate in the parasympathetic ganglia in the airway wall
- Short post-synaptic fibres reach the muscle and release acetyl-choline, which acts of muscarinic receptors of the M3 subtype (receptors) on the muscle cells
- This then stimulates airway smooth muscle constriction
How can inhibiting the parasympathetic nervous system be beneficial?
- For conditions such as asthma and COPD which is already narrowing the airway
- Drugs that can do this block the M3 receptor, and are called anti-cholinergics or anti-muscarinics. This will induce broncho-dilation so opening up the airways
What are some examples of antimuscarinics?
- Ipatropium bromide is an inhaled treatment to relax airways in asthma and COPD, but it is short acting antimuscarinic (SAMA)
- SAMA are less widely used since LAMA (long acting) were developed
- Ipatropium still used in high dose in nebulisers as part of acute management of severe asthma and COPD
Why are LAMAs better?
- Long duration of action, often only given once daily
- Increase bronchodilation and relieve breathlessness in asthma and COPD
- Reduce acute attacks
What are some examples of inhaled antimuscarinics?
- Titropium
- Glycopyronium
- Alcidinium
- Umecilidinium
What does sympathetic nervous system regulate?
Fight or flight
How are the effects of the sympathetic nervous system activated?
- Nerve fibres release noradrenaline which activates adrenergic receptors (alpha/beta)
- Activation of beta2 receptors on the airway smooth muscle causes muscle relaxation (by activating adenylate cyclase, raising cyclic AMP)
What are some examples of SABA (short-acting beta2 agonists)
- Salbutamol
What are some examples of LABA (long-acting beta2 agonists)
- Formoterol
- Salmeterol
When are SABAs and LABAs given?
- With steroids in asthma, often without steroids in COPD
- Given with LAMA in COPD
- Used for an acute rescue of bronchoconstriction
- Prevention of bronchoconstriction
- Reduction in rates of exacerbations
What are the adverse effects of B2-agonists?
- Raising cAMP may activate Na/K exchange pump driving a cellular influx of potassium
- Tachycardia (cardiac side effects)
- Hyperglycaemia: loss of insulin sensitivity, increased liver glucose release
What is drug deposition and how is it governed?
- Making sure you are getting the right amount of drugs to the right place
- Particle size is main factor that governs this deposition
- 1-10um size generally in the range of respiration
- Other factors: type of device, flow rate, underlying disease
What does asthma need for immediate management?
- Oxygen to maintain 94-98% saturation
- Salbutamol nebuliser 5mg
- Ipratropium nebuliser 0.5mg
