Automatic Regulation Of The Airways Flashcards
Regulation of airways tone
Airway smooth muscle is regulated, and can thus contract and relax to regulate airway diameter
Clearly important in obstructive lung diseases, e.g. asthma and COPD
Breathing is
Regulated by the autonomic nervous system
-Contractile signals cause increase in intracellular calcium in smooth muscle, which activates actin-myosin contraction
Regulated by inflammation
Nervous system
Slide 12
Automatic Nervous System
The peripheral autonomic nervous system divides into sympathetic and parasympathetic branches, which typically have opposing effects
The autonomic nervous system conveys all outputs from the CNS to the body, except for skeletal muscular control
Two nerves in series, the pre- and post-ganglionic fibres
Image
Our working model
Unlike the somatic system, the ANS has two neurons separated by the autonomic ganglion
In the sympathetic system, the ganglion is within a chain adjacent to the spinal cord
In the parasympathetic system, the ganglion is within or very close to the effector organ
The sympathetic and parasympathetic systems are also different in their use and release of neurotransmitters
Parasympathetic bronchoconstrcition
Vagus nerve neurons terminate in the parasympathetic ganglia in the airway wall
Short post-synaptic nerve fibres reach the muscle and release acetylcholine (ACh), which acts on muscarinic receptors of the M3 subtype on the muscle cells
This stimulates airway smooth muscle constriction
Narrows the airway in asthma and in COPD
Inhibition of the parasympathetic nervous system will be beneficial
Drugs that do this in the airway block the M3 receptor, and are called anti-cholinergics or anti-muscarinics
Antimuscarinics
Ipratropium bromide (Atrovent) can be used as inhaled treatment to relax airways in asthma and COPD, but is a short acting antimuscarinic (SAMA)
SAMA less widely used since long acting muscarinic antagonists (LAMAs) were developed
Ipratropium is still used in high dose in nebulisers as part of acute management of severe asthma and COPD
LAMAs
Have long duration of action (many hours), often given once daily (tiotropium)
Increase bronchodilatation and relieve breathlessness in asthma and COPD
Seem to reduce acute attacks (exacerbations) as well
Have other benefits, e.g. on parasympathetic regulation of mucus production
Sympathetic regulation
Sympathetic NS Regulates the fight-and-flight response
Nerve fibres release noradrenaline which activates adrenergic receptors, of which there are two main types (alpha/beta)
Nerve fibres in humans mainly innervate the blood vessels, but airway smooth muscle cells have adrenergic receptors (beta)
Activation of beta2 receptors on the airway smooth muscle causes muscle relaxation (by activating adenylate cyclase, raising cyclic AMP)
SABAs and LABAs
Short-acting (salbutamol) and long-acting (formoterol, salmeterol) beta2 agonists are valuable drugs
Given with steroids in asthma, often without steroids in COPD
Often given with LAMA in COPD
Acute rescue of bronchoconstriction
Prevention of bronchoconstriction
Reduction in rates of exacerbations
Adverse effects of B2-agonists
Raising cAMP may activate Na/K exchange pump driving cellular influx of potassium
Tachycardia (cardiac side effects)
Hyperglycaemia: loss of insulin sensitivity, increased liver glucose release
Drug deposition
Particle size is main factor that governs deposition
1-10 µm size generally in the range of respiration
Other factors:
-device (e.g. MDI, DPI)
-flow rate
-underlying disease
-regional differences in lung ventilation
Fundamentals of treatment
Concordance with therapy is poor
Inhaler education is key
Device selection is vital
Goals of treatment
Most patients have poor control
Aim to improve control
Address important issues for patient (exercise, for example)
Maximum relief of symptoms for minimum side effects
Immediate management
Oxygen if needed to maintain oxygen saturations 94 – 98%
Salbutamol nebuliser 5 mg
Ipratropium nebuliser 0.5mg
Prednisolone 30-60 mg (±hydrocortisone 200mg iv)
Magnesium or aminophylline i.v. (bolus/load)
