BBS B3M1 Case 3 (Fight or Flight) PDF

Basic Biomedical Sciences I Case 3: “Fight or Flight” Block 3 Module 1 AUTONOMIC NERVOUS SYSTEM The axons are often small, myelinated nerve fibers known as B The primary function of the ANS or visceral motor system is the...

Basic Biomedical Sciences I Case 3: “Fight or Flight” Block 3 Module 1 AUTONOMIC NERVOUS SYSTEM The axons are often small, myelinated nerve fibers known as B The primary function of the ANS or visceral motor system is the fibers. However, some axons are unmyelinated C fibers. They regulation of the cardiovascular, respiratory, digestive, urinary and leave the spinal cord in the ventral root and enter the paravertebral reproductive organs. ganglion at the same segmental level through a white These organs are the main effectors against perturbing influences, communicating ramus. White rami are found only in T1 to L2. The both external and internal. preganglionic axons may synapse on postganglionic neurons in In general, the visceral motor neurons innervate smooth and this ganglion, or they may pass through the ganglion and enter cardiac muscles and glandular epithelium, or structures made up either the sympathetic chain or a splanchnic nerve. Preganglionic of combinations of these tissues. axons in the paravertebral sympathetic chain of ganglia may travel o For example, a sudden increase in systemic blood pressure rostrally or caudally to a nearby or distant paravertebral ganglion activates the baroreceptors, which in turn adjust the ANS and and then synapse. restore the blood pressure toward its previous level. If the synapse is in a paravertebral ganglion, the postganglionic The ANS ensures that tissues of the body receive appropriate axon often passes through gray communicating ramus to enter a nutrients, electrolytes and oxygen and that functions such as spinal nerve. Each of the 31 pairs of spinal nerves has a gray osmolarity and temperature are properly regulated. ramus. Postganglionic axons are distributed through the peripheral The ANS also participates in appropriate coordinated responses to nerves to effects such as piloerector muscles, blood vessels, sweat external stimuli. glands, located in the skin, muscle and joints. Postganglionic axons o For example, the ANS helps regulate pupil size in response are generally unmyelinated (C Fibers), although some exceptions to different intensities of ambient light. exist. o An extreme example is the “fight or flight” response that Preganglionic axons in a splanchnic nerve often travel to occurs when a threat intensively activates the sympathetic prevertebral ganglion and synapse, or they may pass through the nervous system. ganglion and an autonomic plexus and end in a more distant o Accompanying the autonomic motor fibers in peripheral ganglion. nerves are different fibers that originate from sensory The sympathetic chain extends from the cervical to coccygeal receptors in the viscera. levels of the spinal cord. This arrangement serves as a distribution o Many of these receptors trigger reflexes, but the activity of system, enabling preganglionic neurons, which are limited to some evokes sensory experiences, such as pain, hunger, thoracic and upper lumbar segments, to activate postganglionic thirst, nausea, and a sense of visceral distention. neurons that innervate all body segments. However, there are The ANS is further divided into Sympathetic and Parasympathetic fewer paravertebral ganglia fuses during development. For Nervous System example, the superior cervical ganglia represent the fused ganglia of C1 to C4; the middle cervical ganglia is the fused ganglia of C5- GENERAL ORGANIZATION OF THE SYMPATHETIC AND C6; and the inferior cervical ganglia is from C7-C8. The term PARASYMPATHETIC NERVOUS SYSTEM stellate ganglion refers to a fusion of the inferior cervical ganglia The functional unit of the sympathetic and parasympathetic with the ganglia T1. nervous system is a two-neuron motor pathway, which consists of Generally, the sympathetic preganglionic neurons are distributed to a preganglionic neuron, whose cell body is located in the CNS, and ipsilateral ganglia and thus control autonomic function on the same a postganglionic neuron, whose cell body is in one of the autonomic side. An important exception is that the sympathetic innervation of ganglia. The enteric nervous system includes neurons and nerve the intestine and of the pelvic viscera is bilateral. fibers in the myenteric and submucosal plexuses, which are located in the wall of the gastrointestinal tract. The sympathetic preganglionic neurons are found in the brainstem and in the sacral spinal cord. Parasympathetic postganglionic neurons are found in parasympathetic ganglia near or actually within the walls of the target organs. Sympathetic preganglionic neurons are concentrated in the intermediolateral cell column in the thoracic and upper lumbar segments of the spinal cord. Some of the neurons may also be found in the 8th cervical (C8) segment. In addition to this, groups of sympathetic preganglionic neurons are found in other locations, including lateral funiculus, the intermediate region, and other parts of lamina X dorsal to the central canal in the spinal cord. BBS I Block 3 Module 1 Nervous System 1 of 7 Location of Parasympathetic Postganglionic Neurons o Activity of these sensory receptors never reaches the level of Found in the Intermediate region of the S3 and S4 segments of consciousness. Instead, afferent fibers form the afferent limb sacral spinal cord of reflex arcs Found in several cranial nerve nuclei in the brainstem: o Both viscerovisceral and viscerosomatic reflexes are elicited o Edinger-Westphal Nuclei (CNIII) by these fibers o Superior (CNVII) Visceral reflexes operate at a subconscious level and they are very o Inferior (CNIX) important for homeostatic regulation and adjustment to external o Salivatory nuclei stimuli o Dorsal Motor Nucleus Visceral afferent fibers contain many neuropeptides or combination o Nucleus Ambiguus of these, including angiotensin II, argininevasopressin, bombesin, calcitonin gene-related peptide, cholecystokinin, substance P, Location of Postganglionic Parasympathetic cells enkephalin, oxytocin, somatostatin, and vasoactive intestinal Cranial Ganglia peptide. o Ciliary ganglion Visceral afferent fibers that mediate sensation include nociceptors ▪ Preganglionic input is from Edinger-Westphal nucleus that travel in sympathetic nerves, such as the splanchnic nerves (CNIII) Visceral pain is caused by: ▪ Innervates the papillary sphincter and ciliary muscle of o Excessive distention of hollow viscera the eye o Contraction against an obstruction o Pterygopalatine ganglia o Ischemia ▪ Supplies the lacrimal glands Origin of Visceral Pain ▪ Supplies glands in the nasal and oral pharynx o Difficult to identify because of diffuse nature and tendency to o Submandibular ganglia be referred to somatic structures ▪ Input from the superior salivatory nucleus Visceral Nociceptors in sympathetic nerves reach the spinal cord ▪ Projects to the submandibular and sublingual glands via: and glands in the oral cavity o Sympathetic chain o Otic ganglion o White ramus ▪ Input from the inferior salivatory nucleus o Dorsal Roots ▪ Innervates the parotid salivary glands and glands in the mouth Terminals of nociceptive afferent fibers distribute widely in the superficial dorsal horn and also in lamina V and X of the spinal gray Other parasympathetic postganglionic neurons are located near or matter in the walls of visceral organs in the thoracic, abdominal, and pelvic cavities. They activate not only local interneurons, which participate in reflex arcs, but also projection cells, which include spinothalamic tract Neurons of the enteric plexus include cells that can be considered cells that signal pain to the brain parasympathetic postganglionic neurons o These cells receive input from the vagus or pelvic nerves COMPARISON OF THE SYMPATHETIC AND PARASYMPATHETIC The vagus nerve innervates the heart, lungs, bronchi, liver, DIVISIONS OF THE AUTONOMIC OUTFLOW pancreas & all of the gastrointestinal tract from the esophagus to Feature Sympathetic Parasympathetic splenic flexure of the colon (Thoracolumbar) (Craniosacral) The remainder of the colon and rectum, as well as the urinary Location of Spinal segments T1 to Spinal segments S2 to bladder and reproductive organs is supplied by sacral Preganglionic T2 mainly S4, intermediate gray: parasympathetic preganglionic neurons that distribute through the bodies intermediolateral cell general visceral efferent column nuclei of cranial nerves pelvic nerves to postganglionic neuron in the pelvic ganglia II, VII, IX, X Parasympathetic preganglionic neurons project to the viscera of Location of While rami T1 to L2, Pelvic nerves, carnival the thorax and part of abdomen are located in the dorsal motor Preganglionic sympathetic trunks nerves III, VII, IX, X nucleus and and the nucleus ambiguus of the vagus nerve fibers splanchnic nerves Location of Paravertebral ganglia, Ganglion cell clusters in Dorsal motor nucleus postganglionic cell prevertebral walls of viscera, cranial o Largely secretomotor bodies ganglia (celiac, nerve autonomic ganglia ▪ Activates glands aorticorenal, superior ciliary -III: o Supplies visceral organs in the: mesenteric, pterygopalatine and inferior mesenteric) submandibular- VII; otic- ▪ Neck (pharynx, larynx) IX) ▪ Thoracic cavity Location of Fibers to structures of Within the viscera of the → Trachea postganglionic body wall and limbs in body cavities; short → Bronchi nerve fibers gray rami and spinal nerves or plexuses → Lungs nerves, plexuses extending from cranial associated with arteries ganglia to target organs; → Heart supplying visceral often accompany → Esophagus structures of the head trigeminal nerve ▪ Abdominal cavity and body cavities branches in head → GI tract Target Effectors Smooth muscle, cardiac Mostly viscera of the muscle, and secretory head and the thoracic, → Liver cells through body abdominal, and pelvic → Pancreas cavities o Electrical stimulation of dorsal motor nucleus causes gastric Primary Acetylcholine Acetylcholine acid secretion neurotransmitter of ▪ Secretion of insulin and glucagons by the pancreas preganglionic neurons Nucleus ambiguus Primary Norepinephrine; cells Acetylcholine o Visceromotor neurotransmitter of supplying sweat glands ▪ Modifies the activity of cardiac muscle postganglionic use acetylcholine neurons Visceral Afferent Fibers Neuropeptides of Neuropeptide Y and Vasoactive intestinal Visceral afferent fibers are accompanied by visceral afferent fibers postganglionic others peptide and others o Most of the afferent fibers supply information that originates neurons General Mobilization of resources Promotion of restorative from sensory receptors in the viscera physiologic effects for intensive activity processes BBS I Block 3 Module 1 Nervous System 2 of 7 Enteric Nervous System state. In each organ, the resulting effects are likely to be entirely Located in the walls of the GI tract different from those in other organs. o Contains about 100 million neurons SYMPATHETIC POSTGANGLIONIC NEURONS Subdivisions: They typically release norepinephrine, which excites some effector o Myenteric plexus cells but inhibits other effector cells. The receptors on the target ▪ Lies between the longitudinal and circular muscles cells may be either alpha- or beta-adrenergic receptors. These are layers of the gut further subdivided into Alpha 1, Alpha 2, Beta 1, Beta 2. ▪ Neurons control GI motility Alpha 1 (A1): located postsynaptically, but Alpha 2 (A2) receptors o Submucosal plexus may be either presynaptic or postsynaptic. Receptors located ▪ Lies in the submucosa of the gut presynaptically are generally called AUTORECEPTORS; they ▪ Neurons regulate body fluid homeostasis usually inhibit transmitter release. The effects of agents that excite Activity is modulated by the sympathetic nervous system A1 or A2 can be distinguished by using antagonists to block these o Sympathetic postganglionic neurons w/ Norepinephrine receptors specifically. For example, prazosin is a selective A1 ▪ Inhibit intestinal motility antagonist, and yohimbine is a selective A2 antagonist. The effects o Sympathetic postganglionic neurons w/ Norepinephrine AND of A1 receptors mediated by activation of inositol triphosphate- neuropeptide Y diacylglycerol second messenger system. On the other hand, A2 ▪ Regulate blood flow receptors decrease the rate of synthesis of camp through the action o Sympathetic postganglionic neurons w/ Norepinephrine AND on a G protein. somatostatin B receptors are subdivided into B1 and B2 receptors on the basis ▪ Control intestinal secretion of the ability of antagonists to block them. The proteins that make NEUROTRANSMITTERS IN AUTONOMIC GANGLIA up the two types of B receptors are similar, with seven membrane- Classic transmitter is Acetylcholine and it has 2 classes: spanning regions connected by intracellular and extracellular o Nicotinic receptors domains. Agonist drugs that work on B receptors activate a G ▪ Can be blocked by agents such as curare or protein, which stimulates adenyl cyclase to increase CAMP hexamethonium concentration. B receptors can also be antagonized by the action o Muscarinic receptors of A2 receptors. The number of B receptors. The number of B ▪ Can be blocked by agents such as atropine receptors can be regulated. o Both mediate excitatory postsynaptic potentials, but at PARASYMPATHETIC POSTGANGLIONIC NEURONS DIFFERENT RATES The neurotransmitter used is acetylcholine. o Stimulation of preganglionic neurons elicits a fast excitatory Parasympathetic postganglionic actions are mediated by postsynaptic potential muscarinic receptors. At least two types of muscarinic receptors, ▪ Activation of nicotinic receptors caused by opening of M1 and M2, can be distinguished on the basis of the action of the ion channels action of the antagonist pirenzepine. M1 receptors have a high o Followed by a slow EPSP (mediated by muscarinic affinity for pirenzepine and their activation enhances the secretion receptors) of gastric acid. M2 receptors have a low affinity and their activation Besides Ach, sympathetic preganglionic; neurons may release slows the heart. A subtype of M2 activates glands such as lacrimal enkephalin, substance P, Luteinizing Hormone releasing hormone, and submaxillary glands. neurotensin, or somatostatin Muscarinic receptors have diverse actions: MECHANISM OF ACTION 1. Some of their effects are mediated by specific second BINDING WITH RECEPTOR PROTEINS messenger systems. For example, Cardiac M2 muscarinic o Before acetylcholine, morphine, or epinephrine secreted at receptors may act by way of the inositol triphosphate an autonomic nerve ending can stimulate an effector organ, system, and they may also inhibit adenylyl cyclase and it must first bind with specific receptors on the effector. The thus CAMP synthesis. receptor is on the outside of the cell membrane, bound as a 2. They also open or close ion channels, particularly prosthetic group to a protein molecule that penetrates all the potassium and calcium channels. way through the cell membrane, when the transmitter 3. They relax vascular smooth muscle by an effect on substance binds with the receptor, this cause a endothelial cells, which produce endothelium-derived conformational change in the structure of the protein relaxing factor. molecule, in turn, the altered protein molecule excites or EFFECTS OF SYMPATHETIC AND PARASYMPATHETIC inhibits the cell, most often by (1) causing change in cell STIMULATION ON SPECIFIC ORGANS membrane permeability to one or more ions or (2) activating EYES or inactivating an enzyme attached to the other end of the o Sympathetic stimulation contracts the meridional fibers of the receptor protein where it protrudes into the interior of the cell. iris that dilate the pupil SECOND MESSENGER MECHANISM o Parasympathetic stimulation contracts the circular muscle of o Receptor action by altering Intracellular “second messenger” the circular muscle of the iris to constrict the pupil. enzymes. Another way a receptor often functions is to GLANDS activate or inactivate an enzyme (or other intracellular o The nasal, lacrimal, salivary, and many gastrointestinal chemical) inside the cell. The enzyme often is attached to the glands are strongly stimulated by the parasympathetic receptor protein where the receptor protrudes into the system, usually resulting in copious quantities of watery interiors of the cell. For instance, binding of norepinephrine secretion. with its receptor on the outside of many cells increases the o Sympathetic stimulation has a direct effect on glandular cells activity of the enzyme adenylyl cyclase in the inside of the in causing formation of a concentrated secretion that cell, and this causes formation of cyclic adenosine contains extra enzymes and mucus. It also causes monophosphate (cAMP). The cAMO in turn can initiate any vasoconstriction of the blood vessels that supply the glands one of many different intracellular actions, the exact effect and, in this way, often reduces their rates of secretion. depending on the chemical machinery of the effector cell. o The sweat glands secrete large quantities of sweat when the It is easy to understand how an autonomic transmitter substance sympathetic nerves are stimulated, but no effect is caused by can cause inhibition in some organs or excitation in others. This is stimulating the parasympathetics. usually determined by the nature of the receptor protein in the cell o The apocrine glands in the axillae secrete a thick, odoriferous membrane and the effects of receptor binding on its formational secretion as a result of sympathetic stimulation, but they do not respond to parasympathetic stimulation. BBS I Block 3 Module 1 Nervous System 3 of 7  GASTROINTESTINAL SYSTEM discharge simultaneously as a complete unit, a phenomenon called o The gastrointestinal system has its own intrinsic set of nerves mass discharge. This frequently occurs when the hypothalamus is known as the intramural plexus or the intestinal enteric activated by fright or fear or severe pain. The result is a widespread nervous system, located in the walls of the gut. reaction throughout the body called the alarm or stress response, o However, both parasympathetic and sympathetic stimulation which we shall discuss shortly. can affect gastrointestinal activity, mainly by increasing or At other times, activation occurs in isolated portions of the decreasing specific actions in the intramural plexus. sympathetic nervous system, mainly in response to reflexes that o Parasympathetic stimulation, in general, increases the involve the spinal cord. The most important of these are the overall degree of activity of the gastrointestinal tract by following: promoting peristalsis and relaxing the sphincters, thus 1. In the process of heat regulation, the sympathetics control allowing rapid propulsion of contents along the tract. sweating and blood flow in the skin without affecting other o This propulsive effect is associated with simultaneous organs innervated by the sympathetics. increases in rates of secretion by many of the gastrointestinal 2. During muscular activity in some animals, specific glands. sympathetic cholinergic vasodilator fibers to the skeletal HEART muscles are stimulated independently, apart from the o In general, sympathetic stimulation increases the overall remainder of the sympathetic system. activity of the heart. 3. Many “local reflexes” involving sensory afferent fibers that o This is accomplished by increasing both the rate and the travel centrally in the sympathetic nerves to the force of heart contraction. sympathetic ganglia and spinal cord cause highly localized o Parasympathetic stimulation causes mainly the opposite reflex responses. For instance, heating a local skin area effect. causes local vasodilation and enhanced local sweating, o To express these effects in another way, sympathetic whereas cooling causes the opposite effects. stimulation increases the effectiveness of the heart as a 4. Many of the sympathetic reflexes that control pump, as is required during heavy exercise, whereas gastrointestinal function are discrete, operating sometimes parasympathetic stimulation decreases its pumping by way of nerve pathways that do not even enter the spinal capability but allows the heart some degree of rest between cord, merely passing from the gut to the sympathetic bursts of strenuous activity. ganglia, mainly the prevertebral ganglia, and then back to SYSTEMIC BLOOD VESSELS the gut through the sympathetic nerves to control motor or o Most systemic blood vessels, especially those of the secretory activity. abdominal viscera and the skin of the limbs, are constricted PARASYMPATHETIC SYSTEM USUALLY by sympathetic stimulation. CAUSES SPECIFIC LOCALIZED RESPONSES o Parasympathetic stimulation has almost no effects on most In contrast to the common mass discharge response of the blood vessels except to dilate vessels in certain restricted sympathetic system, control functions of the Parasympathetic areas, such as in the blush area of the face. System are more likely to be highly specific. o Under some conditions, the beta functions of the o Ex: parasympathetic cardiovascular reflexes usually act only sympathetics causes vascular dilation instead of the usual on the heart to increase or decrease its rate of beating. sympathetic vascular constriction, but this occurs rarely Likewise, other parasympathetic reflexes cause secretion except after drugs have paralyzed the sympathetic alpha mainly by the mouth glands, sometimes by the stomach vasoconstrictor effects, which in blood vessels, are usually glands. Finally, the rectal emptying reflex does not affect far dominant over the beta effects. other parts of the bowel to a major extent. ARTERIAL PRESSURE Yet there is often association between closely allied o The arterial pressure is determined by two factors, propulsion parasympathetic functions of blood by the heart and resistance to flow of this blood o Ex: Salivary secretion can occur independently of gastric through the blood vessels. secretion, and pancreatic secretion occurs at the same time. o Sympathetic stimulation increases both propulsion by the Also the rectal emptying reflex often initiates a urinary heart and resistance to flow, which usually causes a marked bladder emptying reflex, resulting in simultaneous emptying acute increase in arterial pressure but often very little change of both the bladder and rectum. Conversely, the bladder in long-term pressure unless the sympathetics stimulate the emptying reflex can help initiate rectal emptying. kidneys to retain salt and water at the same time. o Conversely, moderate parasympathetic stimulation ALARM OR STRESS RESPONSE OF THE SNS decreases the pumping by the heart but has virtually no effect When large portions of the sympathetic nervous system discharge on peripheral resistance. at the same time– that is, a mass discharge–these increases in OTHER ORGANS many ways the ability of the body to perform vigorous muscle o Most of the endodermal structures such as the ducts of the activity. liver, gallbladder, ureter, urinary bladder, and bronchi are Summarize ways: inhibited by sympathetic stimulation but excited by 1. Increased arterial pressure parasympathetic stimulation 2. Increased blood flow to active muscles concurrent with o Sympathetic stimulation has multiple metabolic effects such decreased blood flow to organs such as the as release of glucose from the liver, increase in blood gastrointestinal tract and the kidneys that are not needed glucose concentration, increase in glycogenolysis, increase for rapid motor activity in skeletal muscle strength, increase in basal metabolic rate, 3. Increased rates of cellular metabolism throughout the body and increase in mental activity 4. Increased blood glucose concentration o Both are involved in the execution of the male and female 5. Increased glycolysis in liver and muscles sexual acts 6. Increased muscle strength 7. Increased mental activity SYMPATHETIC SYSTEM OFTEN RESPONDS 8. Increased rate of blood coagulation BY MASS DISCHARGE he sum of these effects permits a person to perform far more Stimulation of discrete organs in some instances and mass strenuous physical activity than would otherwise be possible. stimulation in other instances by the sympathetic and Because its mental or physical stress that excites the sympathetic parasympathetic systems system. This system provides extra activation of the body in states The Sympathetic System often responds by mass discharge. In any of stress–sympathetic stress response. instance, almost all portions of the sympathetic nervous system BBS I Block 3 Module 1 Nervous System 4 of 7  The sympathetic system is especially strongly activated in many Nicotinic receptors are found in the autonomic ganglia at the emotional states. For instance, in the state of rage, which is synapses between the preganglionic and postganglionic neurons stimulated by the hypothalamus, signals are transmitted downward of both the sympathetic and parasympathetic systems through reticular formation of the brain stem and into the spinal cord ADRENERGIC RECEPTORS – to cause massive sympathetic discharge– sympathetic alarm ALPHA AND BETA RECEPTORS reaction. Its also called the fight or flight reaction. There are also two major types of adrenergic receptors, alpha METABOLISM OF CHEMICAL MEDIATORS IN ANS receptors and beta receptors. (The beta receptors in turn are SYNTHESIS OF ACETYLCHOLINE, DESTRUCTION, AND divided into beta1 and beta2, there is a division of alpha1 receptors DURATION OF ACTION into alpha2 receptors Acetylcholine is synthesized in terminal endings and varicosities of Norepinephrine and epinephrine, both of which are secreted into the cholinergic nerve fibers where it is stored in vesicles in highly the blood by the adrenal medulla, have slightly different effects in concentrated form until it is released. The basic chemical reaction exciting the alpha and beta receptors. Norepinephrine excites of the synthesis is the following: mainly alpha receptors but excites the beta receptors to a lesser Acetyl-CoA + Choline — Choline acetyltransferase → Acetylcholine extent as well. Conversely, epinephrine excites both types of receptors approximately equally. Therefore, the relative effects of Once acetylcholine is secreted into a tissue by a cholinergic nerve norepinephrine and epinephrine on different effector organs are ending, it persists in the tissue for a few seconds while it performs determined by the types of receptors in the organs. If they are all its nerve signal transmitter function. Then it is split into an acetate beta receptors, epinephrine will be the more effective excitant. ion and choline, catalyzed by the enzyme acetylcholinesterase that Table 60-1 gives the distribution of alpha and beta receptors in the is bound with collagen and glycosaminoglycans in the local organs and systems controlled by the sympathetics. Note that connective tissue. This is the same mechanism for acetylcholine certain alpha functions are excitatory, whereas others are inhibitory. signal transmission and subsequent acetylcholine destruction that Likewise certain beta functions are excitatory and others are occurs at the neuromuscular junctions of skeletal nerve fibers, the inhibitory. Therefore, alpha and beta receptors are not necessarily choline that is formed is then transported back into the terminal associated with excitation or inhibition but simply with the affinity of nerve ending, where it is used again and again for synthesis of new the hormone for the receptors in the given effector organ. ACH. A synthetic hormone chemically similar to epinephrine and SYNTHESIS OF NOREPINEPHRINE, norepinephrine, isopropyl norepinephrine, has an extremely strong REMOVAL, AND DURATION OF ACTION action on beta receptors but essentially no action on alpha Begins in the axoplasm of the terminal endings of adrenergic nerve receptors fibers but is completed inside the secretory vesicles. The basic ALPHA RECEPTOR BETA-1 RECEPTOR BETA-2 RECEPTOR steps are the following: Vasoconstriction Vasodilation o Tyrosine — Hydroxylation → DOPA Iris dilation Cardioacceleration o DOPA — Decarboxylation → Dopamine Intestinal relaxation Increased myocardial o Transport of dopamine into the vesicles strength Intestinal sphincter Intestinal relaxation o Dopamine — Hydroxylation → Norepinephrine contraction Uterus relaxation o In the adrenal medulla, this reaction goes still one step Pilomotor contraction Bronchodilation further to transform about 80% of the norepinephrine into Bladder sphincter Lipolysis Calorigenesis epinephrine, as follows: contraction Glycogenolysis ▪ Norepinephrine — Methylation → Epinephrine Bladder wall relaxation After secretion of norepinephrine by the terminal nerve endings, it PHARMACOLOGY OF THE ANS is removed from the secretory site in three ways: (1) reuptake into DRUGS THAT ACT ON ADRENERGIC EFFECTOR ORGANS the adrenergic nerve ending themselves by an active transport Sympathetic Drugs process accounting for removal of 50 to 80 percent of the secreted o From the foregoing discussion, it is obvious that intravenous norepinephrine. (2) diffusion away from the nerve endings into the injection of norepinephrine causes essentially the same surrounding body fluids and then into the blood-accounting for effects throughout the body as sympathetic stimulation. removal of most of the remaining norepinephrine and (3) Therefore, norepinephrine is called a sympathomimetic or destruction of small amount by tissue enzymes. adrenergic drug. Epinephrine and methoxamine are also Ordinarily, the norepinephrine secreted directly into a tissue sympathomimetic drugs, and there are many others. They remains active for only a few seconds, demonstrating that otis Differ From one another in the degree to which they stimulate reuptake and diffusion away from the tissue are rapid. However, different sympathetic effector organs and in their duration of the norepinephrine and epinephrine secreted into the blood by the action. Norepinephrine and epinephrine have actions as adrenal medullae remain active until they diffuse into some tissue, short as 1 to 2 minutes, whereas the actions of other where they can be destroyed by catechol-Omethyltransferase; this commonly used sympathomimetic drugs last for 30 minutes occurs mainly on the liver. Therefore, when secreted into the blood, to 2 hours both norepinephrine and epinephrine remain very active for 10 to DRUGS THAT CAUSE RELEASE OF NOREPINEPHRINE 30 seconds but their activity declines to extinction over 1 to several Certain drugs have an indirect sympathomimetic action instead of minutes. directly exciting adrenergic effector organs. These drugs include TYPES OF CHOLINERGIC AND ADRENERGIC RECEPTOR ephedrine, tyramine, and amphetamine. Their effect is to cause ACETYLCHOLINE RECEPTORS - MUSCARINIC AND release of norepinephrine from its storage vesicles in the NICOTINIC RECEPTORS sympathetic nerve endings. The released norepinephrine in turn Acetylcholine activates mainly two types of receptors. They are causes sympathetic effects. called muscarinic and nicotinic receptors. The reason of these DRUGS THAT BLOCK ADRENERGIC ACTIVITY names is that muscarine, a poison from toadstools, activates iny Adrenergic activity can be blocked at several points in the muscarinic receptors and will not activate nicotinic receptors, stimulatory process, as follows: whereas nicotine activates only nicotinic receptors; acetylcholine o The synthesis and storage of norepinephrine in the activates both of them sympathetic nerve endings can be prevented. The best- Muscarinic receptors are found on all effector cells that are known drug that causes this effect is reserpine. stimulated by the postganglionic cholinergic neurons either the o Release of norepinephrine from the sympathetic endings can parasympathetic nervous system or the sympathetic nervous be blocked. This is caused by guanethidine. system. BBS I Block 3 Module 1 Nervous System 5 of 7  o The sympathetic alpha receptors can be blocked. Two drugs that cause this effect are phenoxybenzamine and phentilamine. o The sympathetic beta receptors can be blocked. A drug that locks all beta receptors is propranolol. One that blocks only beta1 receptors is metoprolol. o Sympathetic activity can be blocked by drugs that block transmission of nerve impulses through the autonomic ganglia. An important drug for blockade of both sympathetic and parasympathetic transmission through the ganglia is hexamethonium. DRUGS THAT ACT ON CHOLINERGIC EFFECTOR ORGANS Parasympathetic Drugs (Cholinergic Drugs) o Acetylcholine injected intravenously usually does not cause exactly the same effects throughout the body as parasympathetic stimulation because most of the Ach is destroyed by cholinesterase in the blood and body fluids before it can reach all the effector organs. Yet a number of other drugs that are not so rapidly destroyed can produce typical widespread parasympathetic effects, and they are called parasympathomimetic drugs. o Pilocarpine and methacholine act directly on the muscarinic type of receptors. DRUGS THAT ACT ON CHOLINERGIC EFFECTOR ORGANS Anticholinesterase Drugs o They include neostigmine, pyridostigmine and ambedonium and these drugs inhibit acetylcholinesterase, thus preventing rapid destruction of the acetylcholine. As a consequence, the quantity of acetylcholine acting on the effector organs progressively increases with successive stimuli, and the degree of action also increases. DRUGS THAT BLOCK CHOLINERGIC ACTIVITY Antimuscarinic Drugs o Atropine and similar drugs, such as homatropine and scopolamine, block the action of acetylcholine on the muscarinic type of receptors. DRUGS THAT STIMULATE AUTONOMIC POSTGANGLIONIC NEURONS Nicotine is a drug that can stimulate postganglionic neurons in the same manner as acetylcholine. Therefore, drugs that cause autonomic effects by stimulating the postganglionic neurons are called nicotinic drugs. GANGLIONIC BLOCKING DRUGS Tetraethyl ammonium ion, hexamethonium ion, and pentolinium block acetylcholine stimulation of the postganglionic neurons in both sympathetic and parasympathetic systems simultaneously. But their sympathetic blocking activity usually far overshadows the effects of parasympathetic blockade. BBS I Block 3 Module 1 Nervous System 6 of 7 BBS I Block 3 Module 1 Nervous System 7 of 7