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meds:1-autonomic-pharmacology:home [2019/12/13 15:38]
psychdb [Table]
meds:1-autonomic-pharmacology:home [2020/09/14 23:11] (current)
psychdb [Summary]
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 ====== Introduction to the Autonomic Nervous System ====== ====== Introduction to the Autonomic Nervous System ======
 +{{INLINETOC}}
 ===== Primer ===== ===== Primer =====
 The **Autonomic Nervous System (ANS)** plays a significant role in unconscious and automatic processes in the human body. As prescribers of medications,​ what you prescribe can have profound impacts on the ANS, and it is important to be aware of how and //why// medications affect the ANS. The **Autonomic Nervous System (ANS)** plays a significant role in unconscious and automatic processes in the human body. As prescribers of medications,​ what you prescribe can have profound impacts on the ANS, and it is important to be aware of how and //why// medications affect the ANS.
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 <WRAP half column> <WRAP half column>
  
-== Central and Peripheral Nervous System == +==== Central and Peripheral Nervous System ====
-Before we talk about the effects of anticholinergics/​cholinergics,​ we need to review briefly the anatomical structures that these drugs affect. They primarily (but not exclusively) affect the nervous system.  +
 The nervous system can be broken down into: The nervous system can be broken down into:
   - **Central Nervous System** (CNS), your brain and spinal cord   - **Central Nervous System** (CNS), your brain and spinal cord
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 <WRAP half column> <WRAP half column>
  
-== Autonomic Nervous System (ANS) ==+==== Autonomic Nervous System (ANS) ====
 The **Autonomic Nervous System (ANS)** operates independently of the CNS (e.g. - you do not need to consciously tell your heart to beat faster when you run). However, the ANS can be influenced by the brain (e.g. - salivating at the smell of food). The **Autonomic Nervous System (ANS)** operates independently of the CNS (e.g. - you do not need to consciously tell your heart to beat faster when you run). However, the ANS can be influenced by the brain (e.g. - salivating at the smell of food).
  
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 </​WRAP>​ </​WRAP>​
  
 +<​imgcaption image1|>​{{:​meds:​1-autonomic-pharmacology:​nervous_system.png?​direct&​700|The Nervous System}}</​imgcaption>​
 ===== Anatomy 101 ===== ===== Anatomy 101 =====
-<​imgcaption ​image1|>{{ :​meds:​side-effects:​pns_and_cns.png?​direct&​450|The Innervation of the Sympathetic and Parasympathetic Nervous Systems}}</​imgcaption>​+<​imgcaption ​image2|>​{{:​meds:​side-effects:​pns_and_cns.png?​direct&​450|The Innervation of the Sympathetic and Parasympathetic Nervous Systems}}</​imgcaption>​
  
 The Sympathetic and Parasympathetic Nervous Systems exit the brain and spinal cord and enter "relay stations” known as a ganglion. The parasympathetic ganglia are located close to the organs they innervate. Sympathetic ganglia, on the other hand, are in the sympathetic chain (which runs along the spinal column) and are far away from the organs (see <imgref image1>​). Messages from the brain pass from the //​pre//​ganglionic neuron, through the ganglion, to the //​post//​ganglionic neuron, and finally to the target organ. The Sympathetic and Parasympathetic Nervous Systems exit the brain and spinal cord and enter "relay stations” known as a ganglion. The parasympathetic ganglia are located close to the organs they innervate. Sympathetic ganglia, on the other hand, are in the sympathetic chain (which runs along the spinal column) and are far away from the organs (see <imgref image1>​). Messages from the brain pass from the //​pre//​ganglionic neuron, through the ganglion, to the //​post//​ganglionic neuron, and finally to the target organ.
  
-== Acetylcholine (Ach) ==+==== Acetylcholine (Ach) ==== 
 +<alert icon="​fa fa-arrow-circle-right fa-lg fa-fw" type="​success">​See main article: **[[meds:​2-neurotransmitters-and-receptors:​home|]]**</​alert>​
 Acetylcholine (Ach) is the “preganglionic nerve to ganglion to postganglionic nerve” neurotransmitter for both the sympathetic and parasympathetic systems. Acetylcholine is also the “postganglionic nerve to organ” neurotransmitter for the parasympathetic system (PNS) Acetylcholine (Ach) is the “preganglionic nerve to ganglion to postganglionic nerve” neurotransmitter for both the sympathetic and parasympathetic systems. Acetylcholine is also the “postganglionic nerve to organ” neurotransmitter for the parasympathetic system (PNS)
  
-== Norepinephrine (NE) ==+==== Norepinephrine (NE) ====
 Norepinephrine (NE) is the “postganglionic nerve to organ” neurotransmitter for the sympathetic system (SNS) Norepinephrine (NE) is the “postganglionic nerve to organ” neurotransmitter for the sympathetic system (SNS)
  
-== Summary ==+==== Summary ​====
 So which neurotransmitter binds onto which receptor on the autonomic pathway? So which neurotransmitter binds onto which receptor on the autonomic pathway?
 <WRAP group> <WRAP group>
 <WRAP half column> <WRAP half column>
-<panel title="​Neurotransmitters and Receptors"​ no-body="​true">​+<panel title="​Neurotransmitters and Receptors"​ no-body="​true"​><​mobiletable 1>
 ^ Neurotransmitter ​                    ^ Acetylcholine (ACh)                         ^ Norepinephrine (NE), Epinephrine (E)  ^ ^ Neurotransmitter ​                    ^ Acetylcholine (ACh)                         ^ Norepinephrine (NE), Epinephrine (E)  ^
 ^ Preganglionic neuron (SNS/​PNS) ​      | {{fa>​check}} ​                               | -                                     | ^ Preganglionic neuron (SNS/​PNS) ​      | {{fa>​check}} ​                               | -                                     |
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 ^ Receptor ​                            | Muscarinic (M) and nicotinic (N) receptors ​ | Alpha (α) and beta (β) receptors ​     | ^ Receptor ​                            | Muscarinic (M) and nicotinic (N) receptors ​ | Alpha (α) and beta (β) receptors ​     |
 ^ Receptor Subtype Examples ​           | M1, M2, M3                                  | α1, α2, β1, β2                        | ^ Receptor Subtype Examples ​           | M1, M2, M3                                  | α1, α2, β1, β2                        |
-</​panel>​+</​mobiletable>​</​panel>​
 </​WRAP>​ </​WRAP>​
 <WRAP half column> <WRAP half column>
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 ==== Alpha (α) and Beta (β) ==== ==== Alpha (α) and Beta (β) ====
 The following table details the function and location of sympathetic receptors, as well as example agonists and antagonists. The following table details the function and location of sympathetic receptors, as well as example agonists and antagonists.
-<callout type="​success"​ title="​Learn this table and you will learn to better care for your patients!"​ icon="​true"></​callout>​ 
 <panel title="​Alpha (α) and Beta (β) Receptor Function and Location"​ no-body="​true">​ <panel title="​Alpha (α) and Beta (β) Receptor Function and Location"​ no-body="​true">​
 +<​mobiletable 1>
 ^ Receptor ​     ^ Function ​                                                                       ^ Location ​                                                                                                                                                                                                                                                          ^ Agonist ​                                                                                                                                     ^ Antagonist ​                                                                                                                                                                                                           ^ ^ Receptor ​     ^ Function ​                                                                       ^ Location ​                                                                                                                                                                                                                                                          ^ Agonist ​                                                                                                                                     ^ Antagonist ​                                                                                                                                                                                                           ^
 ^ Alpha-1 (α1)  | Constriction of smooth muscles ​                                                 | <​HTML><​ul><​li>​Blood vessels and skin piloerectors (vasoconstriction and goosebumps)</​li><​li>​Sphincters (bladder, GI)</​li><​li>​Uterus (contraction)</​li><​li>​Eye (constriction of radial muscle, leading to pupillary <​b>​d</​b>​ilation (my<​b>​d</​b>​riasis)</​ul></​HTML> ​ | <​HTML><​ul><​li>​Epinephrine</​li><​li>​Phenylephrine</​li></​ul></​HTML> ​                                                                            | <​HTML><​ul><​li>​Prazosin (selective α1 antagonist)</​li><​li>​Tamsulosin (selective α1 antagonist)</​li><​li>​Terazosin (selective α1 antagonist)</​li><​li>​Trazodone</​li></​ul></​HTML> ​                                         | ^ Alpha-1 (α1)  | Constriction of smooth muscles ​                                                 | <​HTML><​ul><​li>​Blood vessels and skin piloerectors (vasoconstriction and goosebumps)</​li><​li>​Sphincters (bladder, GI)</​li><​li>​Uterus (contraction)</​li><​li>​Eye (constriction of radial muscle, leading to pupillary <​b>​d</​b>​ilation (my<​b>​d</​b>​riasis)</​ul></​HTML> ​ | <​HTML><​ul><​li>​Epinephrine</​li><​li>​Phenylephrine</​li></​ul></​HTML> ​                                                                            | <​HTML><​ul><​li>​Prazosin (selective α1 antagonist)</​li><​li>​Tamsulosin (selective α1 antagonist)</​li><​li>​Terazosin (selective α1 antagonist)</​li><​li>​Trazodone</​li></​ul></​HTML> ​                                         |
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 ^ Beta-1 (β1)   | Increases cardiac performance,​ liberation of energy, and conservation of water  | <​HTML><​ul><​li>​Heart</​li><​li>​Fat cells (lipolysis)</​li><​li>​Kidneys (releases renin to conserve water)</​li></​ul></​HTML> ​                                                                                                                                             | <​HTML><​ul><​li>​Dobutamine (used as a positive inotrope for heart failure and cardiogenic shock)</​li></​ul></​HTML> ​                             | <​HTML><​ul><​li>​Atenolol</​li><​li>​Bisporolol (selective β1 receptor antagonist)</​li><​li>​Metoporolol (selective β1 receptor antagonist)</​li><​li>​Propranolol (β1- and β2-adrenergic receptor antagonist)</​li></​ul></​HTML> ​ | ^ Beta-1 (β1)   | Increases cardiac performance,​ liberation of energy, and conservation of water  | <​HTML><​ul><​li>​Heart</​li><​li>​Fat cells (lipolysis)</​li><​li>​Kidneys (releases renin to conserve water)</​li></​ul></​HTML> ​                                                                                                                                             | <​HTML><​ul><​li>​Dobutamine (used as a positive inotrope for heart failure and cardiogenic shock)</​li></​ul></​HTML> ​                             | <​HTML><​ul><​li>​Atenolol</​li><​li>​Bisporolol (selective β1 receptor antagonist)</​li><​li>​Metoporolol (selective β1 receptor antagonist)</​li><​li>​Propranolol (β1- and β2-adrenergic receptor antagonist)</​li></​ul></​HTML> ​ |
 ^ Beta-2 (β2)   | Relaxation of smooth muscles (e.g. in the lungs), and liberation of energy ​     | <​HTML><​ul><​li>​Lungs (bronchodilation)</​li><​li>​Blood vessels in muscles (vasodilation)</​li>​uterus (uterine relaxation)<​li>​GI (intestinal relaxation)</​li><​li>​Bladder (relaxation)</​li><​li>​Liver (liberate glucose via glycogenolysis)</​li></​ul></​HTML> ​             | <​HTML><​ul><​li>​Salbutamol [AKA Albuterol] (Short-acting β2 agonist, SABA)</​li><​li>​Formoterol (Long-acting β2 agonist (LABA)</​li></​ul></​HTML> ​ | <​HTML><​ul><​li>​Propranolol (β1- and β2-adrenergic receptor antagonist)</​li></​ul></​HTML> ​                                                                                                                               | ^ Beta-2 (β2)   | Relaxation of smooth muscles (e.g. in the lungs), and liberation of energy ​     | <​HTML><​ul><​li>​Lungs (bronchodilation)</​li><​li>​Blood vessels in muscles (vasodilation)</​li>​uterus (uterine relaxation)<​li>​GI (intestinal relaxation)</​li><​li>​Bladder (relaxation)</​li><​li>​Liver (liberate glucose via glycogenolysis)</​li></​ul></​HTML> ​             | <​HTML><​ul><​li>​Salbutamol [AKA Albuterol] (Short-acting β2 agonist, SABA)</​li><​li>​Formoterol (Long-acting β2 agonist (LABA)</​li></​ul></​HTML> ​ | <​HTML><​ul><​li>​Propranolol (β1- and β2-adrenergic receptor antagonist)</​li></​ul></​HTML> ​                                                                                                                               |
-</​panel>​+</​mobiletable>​</​panel>​
  
 ==== Modulating Sympathetic Activity ==== ==== Modulating Sympathetic Activity ====
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 ===== Parasympathetic Receptors ===== ===== Parasympathetic Receptors =====
-<callout type="success">​{{fa>arrow-circle-right?color=green}} ​See main article: **[[meds:​toxidromes:​anticholinergic-cholinergic]]**</​callout>+<alert icon="​fa ​fa-arrow-circle-right ​fa-lg fa-fw" type="​success">​See main article: **[[meds:​toxidromes:​anticholinergic-cholinergic]]**</​alert>
 The following table details the function and location of parasympathetic receptors, as well as example agonists and antagonists. The following table details the function and location of parasympathetic receptors, as well as example agonists and antagonists.
 ==== Muscarinic (M) and Nicotinic (N) ==== ==== Muscarinic (M) and Nicotinic (N) ====
 <panel title="​Muscarinic (M) and Nicotinic (N) Receptor Function and Location"​ no-body="​true">​ <panel title="​Muscarinic (M) and Nicotinic (N) Receptor Function and Location"​ no-body="​true">​
 +<​mobiletable 1>
 ^ Receptor ​       ^ Function ​                                                        ^ Location ​                                                                                                                                                                                                                                                                                                                                                                                                                                                                    ^ Agonist ​                                                                                                                                                              ^ Antagonist ​                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   ^ ^ Receptor ​       ^ Function ​                                                        ^ Location ​                                                                                                                                                                                                                                                                                                                                                                                                                                                                    ^ Agonist ​                                                                                                                                                              ^ Antagonist ​                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   ^
 ^ Nicotinic (N)   | "Nerve to nerve" and "nerve to muscle"​ communication ​            | <​HTML><​ul><​li>​Sympathetic and parasympathetic ganglia</​li><​li>​Neuromuscular junction (NMJ)</​li></​ul></​HTML> ​                                                                                                                                                                                                                                                                                                                                                                     | <​HTML><​ul><​li>​Nicotine</​li><​li>​Varenicline</​li><​li>​Succinylcholine (indirect anticholinergic)*</​li></​ul></​HTML> ​                                                      | <​HTML><​ul><​li>​Pancuronium</​li><​li>​Vecuronium</​li></​ul></​HTML> ​                                                                                                                                                                                                                                                                                                                                                                                                                                                                                | ^ Nicotinic (N)   | "Nerve to nerve" and "nerve to muscle"​ communication ​            | <​HTML><​ul><​li>​Sympathetic and parasympathetic ganglia</​li><​li>​Neuromuscular junction (NMJ)</​li></​ul></​HTML> ​                                                                                                                                                                                                                                                                                                                                                                     | <​HTML><​ul><​li>​Nicotine</​li><​li>​Varenicline</​li><​li>​Succinylcholine (indirect anticholinergic)*</​li></​ul></​HTML> ​                                                      | <​HTML><​ul><​li>​Pancuronium</​li><​li>​Vecuronium</​li></​ul></​HTML> ​                                                                                                                                                                                                                                                                                                                                                                                                                                                                                |
 ^ Muscarinic (M)  | Opposes //most// sympathetic actions at the level of the organs ​ | <​HTML><​ul><​li>​Lungs (bronchoconstriction)</​li><​li>​Heart (bradycardia,​ decreased conduction, decreased contractility)</​li><​li>​Sphincters of GI and bladder (relaxes)</​li><​li>​Bladder wall (constriction)</​li><​li>​GI (intestinal contraction)</​li><​li>​Eye (contraction of the circular muscle = pupilary constriction/​miosis)</​li><​li>​Eye (contraction of the ciliary muscle = focus for near vision)</​li><​li>​Glands:​ lacrimal, salivary, bronchial (secretions)</​li></​ul></​HTML> ​ | <​HTML><​ul><​li>​Pilocarpine (stimulates secretion of large amounts of saliva and sweat, and increases aqueous humour turnover in open angle glaucoma)</​li><​li>​Methacholine</​li></​ul></​HTML> ​ | <​HTML><​ul><​li>​Atropine (non-selective antagonism),​ causes tachycardia</​li><​li>​Benztropine (selective M1 muscarinic receptor antagonist)</​li><​li>​Ipratropium (non-selective antagonism),​ bronchodilation</​li><​li>​Tiotropium (non-selective antagonism),​ bronchodilation</​li><​li>​Scopolamine</​li><​li>​Hydroxyzine</​li><​li>​Diphenhydramine "​Benadryl"​ (non-selective antagonism)</​li><​li>​Dimenhydrinate "​Gravol"</​li><​li>​Oxybutynin</​li><​li>​Procyclidine (non-selective antagonism),​ for idiopathic or drug-induced Parkinson'​s</​li></​ul></​HTML> ​ | ^ Muscarinic (M)  | Opposes //most// sympathetic actions at the level of the organs ​ | <​HTML><​ul><​li>​Lungs (bronchoconstriction)</​li><​li>​Heart (bradycardia,​ decreased conduction, decreased contractility)</​li><​li>​Sphincters of GI and bladder (relaxes)</​li><​li>​Bladder wall (constriction)</​li><​li>​GI (intestinal contraction)</​li><​li>​Eye (contraction of the circular muscle = pupilary constriction/​miosis)</​li><​li>​Eye (contraction of the ciliary muscle = focus for near vision)</​li><​li>​Glands:​ lacrimal, salivary, bronchial (secretions)</​li></​ul></​HTML> ​ | <​HTML><​ul><​li>​Pilocarpine (stimulates secretion of large amounts of saliva and sweat, and increases aqueous humour turnover in open angle glaucoma)</​li><​li>​Methacholine</​li></​ul></​HTML> ​ | <​HTML><​ul><​li>​Atropine (non-selective antagonism),​ causes tachycardia</​li><​li>​Benztropine (selective M1 muscarinic receptor antagonist)</​li><​li>​Ipratropium (non-selective antagonism),​ bronchodilation</​li><​li>​Tiotropium (non-selective antagonism),​ bronchodilation</​li><​li>​Scopolamine</​li><​li>​Hydroxyzine</​li><​li>​Diphenhydramine "​Benadryl"​ (non-selective antagonism)</​li><​li>​Dimenhydrinate "​Gravol"</​li><​li>​Oxybutynin</​li><​li>​Procyclidine (non-selective antagonism),​ for idiopathic or drug-induced Parkinson'​s</​li></​ul></​HTML> ​ |
-</​panel>​+</​mobiletable>​</​panel>​
  
 <callout type="​question"​ title="​How Does Succinylcholine Work?" icon="​true">​Succinylcholine is a direct nicotinic receptor **agonist** but is used clinically as an indirect **anticholinergic**. It is a direct cholinergic agonist because it binds to the same binding site as acetylcholine and activates the receptor in the same manner. However, unlike endogenous acetylcholine, ​ succinylcholine activates the nicotinic receptors so intensely that a depolarizing block occurs immediately followed by a desensitizing block (think of the phases of the action potential). This is what gives succinylcholine its paralyzing effects in anesthesia. In contrast, non-depolarising neuromuscular blocking agents (NMBAs), such as pancuronium,​ are direct cholinergic antagonists.</​callout>​ <callout type="​question"​ title="​How Does Succinylcholine Work?" icon="​true">​Succinylcholine is a direct nicotinic receptor **agonist** but is used clinically as an indirect **anticholinergic**. It is a direct cholinergic agonist because it binds to the same binding site as acetylcholine and activates the receptor in the same manner. However, unlike endogenous acetylcholine, ​ succinylcholine activates the nicotinic receptors so intensely that a depolarizing block occurs immediately followed by a desensitizing block (think of the phases of the action potential). This is what gives succinylcholine its paralyzing effects in anesthesia. In contrast, non-depolarising neuromuscular blocking agents (NMBAs), such as pancuronium,​ are direct cholinergic antagonists.</​callout>​
  
 +==== Muscarinic Subtypes ====
 +<panel title="​Muscarinic Subtypes"​ subtitle=""​ no-body="​true"​ footer="">​
 +<​mobiletable 1>
 +^ Muscarinic Receptor Subtype ​ ^ Location ​                        ^ Description ​                                                                                                                                   ^
 +^ M1                           | Central nervous system ​          | Involved in perception, attention, and cognition. Delirium is also associated with the antagonism of post-synaptic M1 receptors. ​              |
 +^ M2                           | Brain, heart                     | Decreases heart rate below baseline normal sinus rhythm by slowing the speed of depolarization. ​                                               |
 +^ M3                           | Smooth muscles, salivary glands ​ | Causes contraction of smooth muscle, including bronchoconstriction and bladder voiding. ​                                                       |
 +^ M4                           | Brain, lungs, salivary glands ​   | There is a possible role for M4 receptors in regulating salivary protein secretion. Thought to be involved in [[meds:​antipsychotics:​second-gen-atypical:​7-clozapine#​sialorrhea|clozapine-induced sialorrhea]]. ​ |
 +</​mobiletable></​panel>​
 ==== Modulating Parasympathetic Activity ==== ==== Modulating Parasympathetic Activity ====
 Most of the time, the SNS and PNS are opposing each other. Therefore, to change this balance, one system can be strengthened,​ or the other weakened. Most of the time, the SNS and PNS are opposing each other. Therefore, to change this balance, one system can be strengthened,​ or the other weakened.