Module 10: The Autonomic Nervous System

Lesson 4: Drugs that Affect the Autonomic System

Thuốc Ảnh Hưởng Đến Hệ Thần Kinh Tự Chủ

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Mỗi bài học (lesson) bao gồm 4 phần chính: Thuật ngữ, Luyện Đọc, Luyện Nghe, và Bàn Luận.
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Dưới đây là danh sách những thuật ngữ Y khoa của module The Autonomic Nervous System.
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Medical Terminology: The Autonomic Nervous System

acetylcholine (ACh)
neurotransmitter that binds at a motor end-plate to trigger depolarization
adrenal medulla
interior portion of the adrenal (or suprarenal) gland that releases epinephrine and norepinephrine into the bloodstream as hormones
adrenergic
synapse where norepinephrine is released, which binds to α- or β-adrenergic receptors
afferent branch
component of a reflex arc that represents the input from a sensory neuron, for either a special or general sense
agonist
any exogenous substance that binds to a receptor and produces a similar effect to the endogenous ligand
alpha (α)-adrenergic receptor
one of the receptors to which epinephrine and norepinephrine bind, which comes in two subtypes: α1 and α2
antagonist
any exogenous substance that binds to a receptor and produces an opposing effect to the endogenous ligand
anticholinergic drugs
drugs that interrupt or reduce the function of the parasympathetic system
autonomic tone
tendency of an organ system to be governed by one division of the autonomic nervous system over the other, such as heart rate being lowered by parasympathetic input at rest
baroreceptor
mechanoreceptor that senses the stretch of blood vessels to indicate changes in blood pressure
beta (β)-adrenergic receptor
one of the receptors to which epinephrine and norepinephrine bind, which comes in three subtypes: β1, β2, and β3
cardiac accelerator nerves
preganglionic sympathetic fibers that cause the heart rate to increase when the cardiovascular center in the medulla initiates a signal
cardiovascular center
region in the medulla that controls the cardiovascular system through cardiac accelerator nerves and vasomotor nerves, which are components of the sympathetic division of the autonomic nervous system
celiac ganglion
one of the collateral ganglia of the sympathetic system that projects to the digestive system
central neuron
specifically referring to the cell body of a neuron in the autonomic system that is located in the central nervous system, specifically the lateral horn of the spinal cord or a brain stem nucleus
cholinergic
synapse at which acetylcholine is released and binds to the nicotinic or muscarinic receptor
chromaffin cells
neuroendocrine cells of the adrenal medulla that release epinephrine and norepinephrine into the bloodstream as part of sympathetic system activity
ciliary ganglion
one of the terminal ganglia of the parasympathetic system, located in the posterior orbit, axons from which project to the iris
collateral ganglia
ganglia outside of the sympathetic chain that are targets of sympathetic preganglionic fibers, which are the celiac, inferior mesenteric, and superior mesenteric ganglia
craniosacral system
alternate name for the parasympathetic division of the autonomic nervous system that is based on the anatomical location of central neurons in brain-stem nuclei and the lateral horn of the sacral spinal cord; also referred to as craniosacral outflow
dorsal longitudinal fasciculus
major output pathway of the hypothalamus that descends through the gray matter of the brain stem and into the spinal cord
dorsal nucleus of the vagus nerve
location of parasympathetic neurons that project through the vagus nerve to terminal ganglia in the thoracic and abdominal cavities
Edinger–Westphal nucleus
location of parasympathetic neurons that project to the ciliary ganglion
efferent branch
component of a reflex arc that represents the output, with the target being an effector, such as muscle or glandular tissue
endogenous
describes substance made in the human body
endogenous chemical
substance produced and released within the body to interact with a receptor protein
epinephrine
signaling molecule released from the adrenal medulla into the bloodstream as part of the sympathetic response
exogenous
describes substance made outside of the human body
exogenous chemical
substance from a source outside the body, whether it be another organism such as a plant or from the synthetic processes of a laboratory, that binds to a transmembrane receptor protein
fight-or-flight response
set of responses induced by sympathetic activity that lead to either fleeing a threat or standing up to it, which in the modern world is often associated with anxious feelings
G protein–coupled receptor
membrane protein complex that consists of a receptor protein that binds to a signaling molecule—a G protein—that is activated by that binding and in turn activates an effector protein (enzyme) that creates a second-messenger molecule in the cytoplasm of the target cell
ganglionic neuron
specifically refers to the cell body of a neuron in the autonomic system that is located in a ganglion
gray rami communicantes
(singular = ramus communicans) unmyelinated structures that provide a short connection from a sympathetic chain ganglion to the spinal nerve that contains the postganglionic sympathetic fiber
greater splanchnic nerve
nerve that contains fibers of the central sympathetic neurons that do not synapse in the chain ganglia but project onto the celiac ganglion
inferior mesenteric ganglion
one of the collateral ganglia of the sympathetic system that projects to the digestive system
intramural ganglia
terminal ganglia of the parasympathetic system that are found within the walls of the target effector
lesser splanchnic nerve
nerve that contains fibers of the central sympathetic neurons that do not synapse in the chain ganglia but project onto the inferior mesenteric ganglion
ligand-gated cation channel
ion channel, such as the nicotinic receptor, that is specific to positively charged ions and opens when a molecule such as a neurotransmitter binds to it
limbic lobe
structures arranged around the edges of the cerebrum that are involved in memory and emotion
long reflex
reflex arc that includes the central nervous system
medial forebrain bundle
fiber pathway that extends anteriorly into the basal forebrain, passes through the hypothalamus, and extends into the brain stem and spinal cord
mesenteric plexus
nervous tissue within the wall of the digestive tract that contains neurons that are the targets of autonomic preganglionic fibers and that project to the smooth muscle and glandular tissues in the digestive organ
muscarinic receptor
type of acetylcholine receptor protein that is characterized by also binding to muscarine and is a metabotropic receptor
mydriasis
dilation of the pupil; typically the result of disease, trauma, or drugs
nicotinic receptor
type of acetylcholine receptor protein that is characterized by also binding to nicotine and is an ionotropic receptor
norepinephrine
signaling molecule released as a neurotransmitter by most postganglionic sympathetic fibers as part of the sympathetic response, or as a hormone into the bloodstream from the adrenal medulla
nucleus ambiguus
brain-stem nucleus that contains neurons that project through the vagus nerve to terminal ganglia in the thoracic cavity; specifically associated with the heart
parasympathetic division
division of the autonomic nervous system responsible for restful and digestive functions
parasympathomimetic drugs
drugs that enhance or mimic the function of the parasympathetic system
paravertebral ganglia
autonomic ganglia superior to the sympathetic chain ganglia
postganglionic fiber
axon from a ganglionic neuron in the autonomic nervous system that projects to and synapses with the target effector; sometimes referred to as a postganglionic neuron
preganglionic fiber
axon from a central neuron in the autonomic nervous system that projects to and synapses with a ganglionic neuron; sometimes referred to as a preganglionic neuron
prevertebral ganglia
autonomic ganglia that are anterior to the vertebral column and functionally related to the sympathetic chain ganglia
referred pain
the conscious perception of visceral sensation projected to a different region of the body, such as the left shoulder and arm pain as a sign for a heart attack
reflex arc
circuit of a reflex that involves a sensory input and motor output, or an afferent branch and an efferent branch, and an integrating center to connect the two branches
rest and digest
set of functions associated with the parasympathetic system that lead to restful actions and digestion
short reflex
reflex arc that does not include any components of the central nervous system
somatic reflex
reflex involving skeletal muscle as the effector, under the control of the somatic nervous system
superior cervical ganglion
one of the paravertebral ganglia of the sympathetic system that projects to the head
superior mesenteric ganglion
one of the collateral ganglia of the sympathetic system that projects to the digestive system
sympathetic chain ganglia
series of ganglia adjacent to the vertebral column that receive input from central sympathetic neurons
sympathetic division
division of the autonomic nervous system associated with the fight-or-flight response
sympatholytic drug
drug that interrupts, or “lyses,” the function of the sympathetic system
sympathomimetic drug
drug that enhances or mimics the function of the sympathetic system
target effector
organ, tissue, or gland that will respond to the control of an autonomic or somatic or endocrine signal
terminal ganglia
ganglia of the parasympathetic division of the autonomic system, which are located near or within the target effector, the latter also known as intramural ganglia
thoracolumbar system
alternate name for the sympathetic division of the autonomic nervous system that is based on the anatomical location of central neurons in the lateral horn of the thoracic and upper lumbar spinal cord
varicosity
structure of some autonomic connections that is not a typical synaptic end bulb, but a string of swellings along the length of a fiber that makes a network of connections with the target effector
vasomotor nerves
preganglionic sympathetic fibers that cause the constriction of blood vessels in response to signals from the cardiovascular center
visceral reflex
reflex involving an internal organ as the effector, under the control of the autonomic nervous system
white rami communicantes
(singular = ramus communicans) myelinated structures that provide a short connection from a sympathetic chain ganglion to the spinal nerve that contains the preganglionic sympathetic fiber
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Dưới đây là các bài văn nằm ở bên trái. Ở bên phải là các bài luyện tập (practice) để đánh giá khả năng đọc hiểu của bạn. Sẽ khó khăn trong thời gian đầu nếu vốn từ vựng của bạn còn hạn chế, đặc biệt là từ vựng Y khoa. Hãy kiên nhẫn và đọc nhiều nhất có kể, lượng kiến thức tích tụ dần sẽ giúp bạn đọc thoải mái hơn.
An important way to understand the effects of native neurochemicals in the autonomic system is in considering the effects of pharmaceutical drugs. This can be considered in terms of how drugs change autonomic function. These effects will primarily be based on how drugs act at the receptors of the autonomic system neurochemistry. The signaling molecules of the nervous system interact with proteins in the cell membranes of various target cells. In fact, no effect can be attributed to just the signaling molecules themselves without considering the receptors. A chemical that the body produces to interact with those receptors is called an endogenous chemical, whereas a chemical introduced to the system from outside is an exogenous chemical. Exogenous chemicals may be of a natural origin, such as a plant extract, or they may be synthetically produced in a pharmaceutical laboratory.

Table 1 summarizes the sympathetic and parasympathetic effects of different drug types.
One important drug that affects the autonomic system broadly is not a pharmaceutical therapeutic agent associated with the system. This drug is nicotine. The effects of nicotine on the autonomic nervous system are important in considering the role smoking can play in health.

All ganglionic neurons of the autonomic system, in both sympathetic and parasympathetic ganglia, are activated by ACh released from preganglionic fibers. The ACh receptors on these neurons are of the nicotinic type, meaning that they are ligand-gated ion channels. When the neurotransmitter released from the preganglionic fiber binds to the receptor protein, a channel opens to allow positive ions to cross the cell membrane. The result is depolarization of the ganglia. Nicotine acts as an ACh analog at these synapses, so when someone takes in the drug, it binds to these ACh receptors and activates the ganglionic neurons, causing them to depolarize.

Ganglia of both divisions are activated equally by the drug. For many target organs in the body, this results in no net change. The competing inputs to the system cancel each other out and nothing significant happens. For example, the sympathetic system will cause sphincters in the digestive tract to contract, limiting digestive propulsion, but the parasympathetic system will cause the contraction of other muscles in the digestive tract, which will try to push the contents of the digestive system along. The end result is that the food does not really move along and the digestive system has not appreciably changed.

The system in which this can be problematic is in the cardiovascular system, which is why smoking is a risk factor for cardiovascular disease. First, there is no significant parasympathetic regulation of blood pressure. Only a limited number of blood vessels are affected by parasympathetic input, so nicotine will preferentially cause the vascular tone to become more sympathetic, which means blood pressure will be increased. Second, the autonomic control of the heart is special. Unlike skeletal or smooth muscles, cardiac muscle is intrinsically active, meaning that it generates its own action potentials. The autonomic system does not cause the heart to beat, it just speeds it up (sympathetic) or slows it down (parasympathetic). The mechanisms for this are not mutually exclusive, so the heart receives conflicting signals, and the rhythm of the heart can be affected (Figure 1).
The neurochemistry of the sympathetic system is based on the adrenergic system. Norepinephrine and epinephrine influence target effectors by binding to the α-adrenergic or β-adrenergic receptors. Drugs that affect the sympathetic system affect these chemical systems. The drugs can be classified by whether they enhance the functions of the sympathetic system or interrupt those functions. A drug that enhances adrenergic function is known as a sympathomimetic drug, whereas a drug that interrupts adrenergic function is a sympatholytic drug.

A. Sympathomimetic Drugs

When the sympathetic system is not functioning correctly or the body is in a state of homeostatic imbalance, these drugs act at postganglionic terminals and synapses in the sympathetic efferent pathway. These drugs either bind to particular adrenergic receptors and mimic norepinephrine at the synapses between sympathetic postganglionic fibers and their targets, or they increase the production and release of norepinephrine from postganglionic fibers. Also, to increase the effectiveness of adrenergic chemicals released from the fibers, some of these drugs may block the removal or reuptake of the neurotransmitter from the synapse.

A common sympathomimetic drug is phenylephrine, which is a common component of decongestants. It can also be used to dilate the pupil and to raise blood pressure. Phenylephrine is known as an α1-adrenergic agonist, meaning that it binds to a specific adrenergic receptor, stimulating a response. In this role, phenylephrine will bind to the adrenergic receptors in bronchioles of the lungs and cause them to dilate. By opening these structures, accumulated mucus can be cleared out of the lower respiratory tract. Phenylephrine is often paired with other pharmaceuticals, such as analgesics, as in the “sinus” version of many over-the-counter drugs, such as Tylenol Sinus® or Excedrin Sinus®, or in expectorants for chest congestion such as in Robitussin CF®.

A related molecule, called pseudoephedrine, was much more commonly used in these applications than was phenylephrine, until the molecule became useful in the illicit production of amphetamines. Phenylephrine is not as effective as a drug because it can be partially broken down in the digestive tract before it is ever absorbed. Like the adrenergic agents, phenylephrine is effective in dilating the pupil, known as mydriasis (Figure 2). Phenylephrine is used during an eye exam in an ophthalmologist’s or optometrist’s office for this purpose. It can also be used to increase blood pressure in situations in which cardiac function is compromised, such as under anesthesia or during septic shock.

Other drugs that enhance adrenergic function are not associated with therapeutic uses, but affect the functions of the sympathetic system in a similar fashion. Cocaine primarily interferes with the uptake of dopamine at the synapse and can also increase adrenergic function. Caffeine is an antagonist to a different neurotransmitter receptor, called the adenosine receptor. Adenosine will suppress adrenergic activity, specifically the release of norepinephrine at synapses, so caffeine indirectly increases adrenergic activity. There is some evidence that caffeine can aid in the therapeutic use of drugs, perhaps by potentiating (increasing) sympathetic function, as is suggested by the inclusion of caffeine in over-the-counter analgesics such as Excedrin®.

B. Sympatholytic Drugs

Drugs that interfere with sympathetic function are referred to as sympatholytic, or sympathoplegic, drugs. They primarily work as an antagonist to the adrenergic receptors. They block the ability of norepinephrine or epinephrine to bind to the receptors so that the effect is “cut” or “takes a blow,” to refer to the endings “-lytic” and “-plegic,” respectively. The various drugs of this class will be specific to α-adrenergic or β-adrenergic receptors, or to their receptor subtypes.

Possibly the most familiar type of sympatholytic drug are the β-blockers. These drugs are often used to treat cardiovascular disease because they block the β-receptors associated with vasoconstriction and cardioacceleration. By allowing blood vessels to dilate, or keeping heart rate from increasing, these drugs can improve cardiac function in a compromised system, such as for a person with congestive heart failure or who has previously suffered a heart attack. A couple of common versions of β-blockers are metoprolol, which specifically blocks the β1-receptor, and propanolol, which nonspecifically blocks β-receptors. There are other drugs that are α-blockers and can affect the sympathetic system in a similar way.

Other uses for sympatholytic drugs are as antianxiety medications. A common example of this is clonidine, which is an α-agonist. The sympathetic system is tied to anxiety to the point that the sympathetic response can be referred to as “fight, flight, or fright.” Clonidine is used for other treatments aside from hypertension and anxiety, including pain conditions and attention deficit hyperactivity disorder.
Drugs affecting parasympathetic functions can be classified into those that increase or decrease activity at postganglionic terminals. Parasympathetic postganglionic fibers release ACh, and the receptors on the targets are muscarinic receptors. There are several types of muscarinic receptors, M1–M5, but the drugs are not usually specific to the specific types. Parasympathetic drugs can be either muscarinic agonists or antagonists, or have indirect effects on the cholinergic system. Drugs that enhance cholinergic effects are called parasympathomimetic drugs, whereas those that inhibit cholinergic effects are referred to as anticholinergic drugs.

Pilocarpine is a nonspecific muscarinic agonist commonly used to treat disorders of the eye. It reverses mydriasis, such as is caused by phenylephrine, and can be administered after an eye exam. Along with constricting the pupil through the smooth muscle of the iris, pilocarpine will also cause the ciliary muscle to contract. This will open perforations at the base of the cornea, allowing for the drainage of aqueous humor from the anterior compartment of the eye and, therefore, reducing intraocular pressure related to glaucoma.

Atropine and scopolamine are part of a class of muscarinic antagonists that come from the Atropa genus of plants that include belladonna or deadly nightshade (Figure 3). The name of one of these plants, belladonna, refers to the fact that extracts from this plant were used cosmetically for dilating the pupil. The active chemicals from this plant block the muscarinic receptors in the iris and allow the pupil to dilate, which is considered attractive because it makes the eyes appear larger. Humans are instinctively attracted to anything with larger eyes, which comes from the fact that the ratio of eye-to-head size is different in infants (or baby animals) and can elicit an emotional response. The cosmetic use of belladonna extract was essentially acting on this response. Atropine is no longer used in this cosmetic capacity for reasons related to the other name for the plant, which is deadly nightshade. Suppression of parasympathetic function, especially when it becomes systemic, can be fatal. Autonomic regulation is disrupted and anticholinergic symptoms develop. The berries of this plant are highly toxic, but can be mistaken for other berries. The antidote for atropine or scopolamine poisoning is pilocarpine.

OpenStax. (2022). Anatomy and Physiology 2e. Rice University. Retrieved June 15, 2023. ISBN-13: 978-1-711494-06-7 (Hardcover) ISBN-13: 978-1-711494-05-0 (Paperback) ISBN-13: 978-1-951693-42-8 (Digital). License: Attribution 4.0 International (CC BY 4.0). Access for free at openstax.org.

Drug typeExample(s)Sympathetic effectParasympathetic effectOverall result
Nicotinic agonistsNicotineMimic ACh at preganglionic synapses, causing activation of postganglionic fibers and the release of norepinephrine onto the target organMimic ACh at preganglionic synapses, causing activation of postganglionic fibers and the release of ACh onto the target organMost conflicting signals cancel each other out, but cardiovascular system is susceptible to hypertension and arrhythmias
Sympatho-mimetic drugsPhenylephrineBind to adrenergic receptors or mimics sympathetic action in some other wayNo effectIncrease sympathetic tone
Sympatholytic drugsβ-blockers such as propanolol or metoprolol; α-agonists such as clonidineBlock binding to adrenergic drug or decrease adrenergic signalsNo effectIncrease parasympathetic tone
Parasymphatho-mimetics or muscarinic agonistsPilocarpineNo effect, except on sweat glandsBind to muscarinic receptor, similar to AChIncrease parasympathetic tone
Anticholinergics or muscarinic antagonistsAtropine, scopolamine, dimenhydrinateNo effectBlock muscarinic receptors and parasympathetic functionIncrease sympathetic tone

The nicotinic receptor is found on all autonomic ganglia, but the cardiovascular connections are particular, and do not conform to the usual competitive projections that would just cancel each other out when stimulated by nicotine. The opposing signals to the heart would both depolarize and hyperpolarize the heart cells that establish the rhythm of the heartbeat, likely causing arrhythmia. Only the sympathetic system governs systemic blood pressure so nicotine would cause an increase.

The sympathetic system causes pupillary dilation when norepinephrine binds to an adrenergic receptor in the radial fibers of the iris smooth muscle. Phenylephrine mimics this action by binding to the same receptor when drops are applied onto the surface of the eye in a doctor’s office. (credit: Corey Theiss / Vulegenda/Wikimedia Commons)

The plant from the genus Atropa, which is known as belladonna or deadly nightshade, was used cosmetically to dilate pupils, but can be fatal when ingested. The berries on the plant may seem attractive as a fruit, but they contain the same anticholinergic compounds as the rest of the plant.

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Script:
  1. The autonomic system is affected by a number of exogenous agents, including some that are therapeutic and some that are illicit.
  2. These drugs affect the autonomic system by mimicking or interfering with the endogenous agents or their receptors.
  3. A survey of how different drugs affect autonomic function illustrates the role that the neurotransmitters and hormones play in autonomic function.
  4. Drugs can be thought of as chemical tools to effect changes in the system with some precision, based on where those drugs are effective.
  5. Nicotine is not a drug that is used therapeutically, except for smoking cessation.
  6. When it is introduced into the body via products, it has broad effects on the autonomic system.
  7. Nicotine carries a risk for cardiovascular disease because of these broad effects.
  8. The drug stimulates both sympathetic and parasympathetic ganglia at the preganglionic fiber synapse.
  9. For most organ systems in the body, the competing input from the two postganglionic fibers will essentially cancel each other out.
  10. However, for the cardiovascular system, the results are different.
  11. Because there is essentially no parasympathetic influence on blood pressure for the entire body, the sympathetic input is increased by nicotine, causing an increase in blood pressure.
  12. Also, the influence that the autonomic system has on the heart is not the same as for other systems.
  13. Other organs have smooth muscle or glandular tissue that is activated or inhibited by the autonomic system.
  14. Cardiac muscle is intrinsically active and is modulated by the autonomic system.
  15. The contradictory signals do not just cancel each other out, they alter the regularity of the heart rate and can cause arrhythmias.
  16. Both hypertension and arrhythmias are risk factors for heart disease.
  17. Other drugs affect one division of the autonomic system or the other.
  18. The sympathetic system is affected by drugs that mimic the actions of adrenergic molecules which are norepinephrine and epinephrine.
  19. They are called sympathomimetic drugs.
  20. Drugs such as phenylephrine bind to the adrenergic receptors and stimulate target organs just as sympathetic activity would.
  21. Other drugs are sympatholytic because they block adrenergic activity and cancel the sympathetic influence on the target organ.
  22. Drugs that act on the parasympathetic system also work by either enhancing the postganglionic signal or blocking it.
  23. A muscarinic agonist or parasympathomimetic drug acts just like acetylcholine released by the parasympathetic postganglionic fiber.
  24. Anticholinergic drugs block muscarinic receptors, suppressing parasympathetic interaction with the organ.
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