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Toronto Notes 2019 Autonomic Pharmacology Sympathetic Nervous System
• sympatheticpre-ganglionicfibresoriginateinthespinalcordatspinallevelsT1-L2/L3
• pre-ganglionicfibresconnectwithpost-ganglionicfibresvianicotinicreceptorslocatedinoneoftwo
groups of ganglia:
1. paravertebral ganglia (i.e. the sympathetic trunk) that lie in a chain close to the vertebral column 2. pre-vertebral ganglia (i.e. celiac and mesenteric ganglia) that lie within the abdomen
• post-ganglionicfibresconnectwitheffectortissuesvia:
Clinical Pharmacology CP11
Sympathetic
ACh
NE
αβ
Adrenergic receptors
Parasympathetic
Preganglionic neuron
■ β1 receptors in cardiac tissue
■ β2 receptors in smooth muscle of bronchi and GI tract ■ α1 receptors in vascular smooth muscle
■ α2 receptors in vascular smooth muscle
■ M3 muscarinic receptors located in sweat glands
Table 3. Direct Effects of Autonomic Innervation on the Cardiorespiratory System
Ganglion
Nicotinic receptors
Postganglionic neuron
Organ
Heart
1. Sinoatrial
2. Atrioventricular node 3. Atria
4. Ventricles
Blood Vessels
1. Skin, splanchnic 2. Skeletal muscle 3. Coronary
Lungs
1. Bronchiolar smooth muscle 2. Bronchiolar glands
Sympathetic NS
Action
Increased HR Increased conduction Increased contractility Increased contractility
Constriction Constriction Dilatation Constriction Dilatation
Relaxation Increased secretion
Parasympathetic NS
Action
Decreased conduction Decreased conduction Decreased conduction Decreased HR
Dilatation Dilatation Dilatation Dilatation Dilatation
Constriction Stimulation
ACh
ACh
Muscarinic receptors
©Wendy Gu 2016
Receptor
β1 β1 β1 β1
α1, β2
α
β2 (large muscles) α1, β2
β2
β2 α1, β2
Receptor
M M M M
M M M M M
M M
Figure 11. Autonomic nervous system efferent tracts
Opioid Therapy and Chronic Non-Cancer Pain
General Management Principles
• whenfirstconsideringtherapyforpatientswithchronicnon-cancerpain,optimizenon- opioid pharmacotherapy and non-pharmacologic therapy, rather than a trial of opioids (strong recommendation)
• Generalapproachestoopioiduseshouldincludeavoidinginitiativehighdoseswhenpossibleanda slow, collaborative approach when tapering
• forpatientswithchronicnon-cancerpainbeginningopioidtherapy,restricttheprescribeddosetoless than 90 mg morphine equivalents daily, rather than having no upper limit or a higher limit on dosing (strong recommendation)
■ for patients with chronic non-cancer pain who are currently using 90 mg morphine equivalents of opioids per day or more, taper opioids to the lowest effective dose, potentially including discontinuation, rather than making no change in opioid therapy (weak recommendation)
• forpatientswithchronicnon-cancerpainwhoareusingopioidsandexperiencingseriouschallengesin tapering, formal multidisciplinary program is suggested (strong recommendation)
• formoreinformation,pleaserefertonationalopioidguidelinesforacomprehensiveapproachtoopioid use