Autonomic Nervous System (Physiology)

AUTONOMIC NERVOUS SYSTEM 1. Afferent neuron ⚫ the neurons of which bring information from the periphery to the CNS. ⚫ Afferent neurons provide sensory input to modulate the function of the efferent division through reflex arcs. 2. Efferent neurons ⚫ carries nerve impulses from the CNS to the effector organs by way of two types of efferent neurons (the preganglionic neuron and the postganglionic neuron)  Efferent neurons divisions: A. Somatic Nervous System: ⚫ Carries nerve impulse to skeletal muscle (voluntary control) ⚫ No ganglia ⚫ A single myelinated motor neuron ⚫ Faster response B. Autonomic Nervous System (Involuntary control) I. Parasympathetic Nervous System II. Sympathetic Nervous System III. Enteric Nervous system: GIT, pancreas, and gallbladder, Glands, Smooth Muscle & Cardiac Muscle (Involuntary control).  ANS: 1. Sympathetic NS ⚫ Its function: adjusting in response to stressful situations, such as trauma, fear, hypoglycemia, cold, and exercise  Effects of stimulation of the sympathetic division:  diverting flow from the skin and internal organs.  To mobilize energy stores of the body.  Increase blood flow to skeletal muscles and the heart while diverting flow from the skin and internal organs.  Dilation of the pupils(mydriasis) and the bronchioles  Decrease GI motility  Fight or flight response The changes experienced by the body during emergencies have been referred to as the “fight or flight”.  ANS: 2. Parasympathetic NS ⚫ is involved with maintaining homeostasis within the body. ⚫ it maintains essential bodily functions, such as digestive processes and elimination of wastes ⚫ “rest and digest” situations. ⚫ Note: Dual innervation: Most organs in the body are innervated by both divisions of the ANS. PSNS acts opposite to SNS .  Where are nicotinic receptors found? Nicotinic receptors are found in: The somatic nervous system (neuromuscular junctions in skeletal muscles). The sympathetic and parasympathetic nervous system (autonomic ganglia).  ANS: 3. Enteric NS ⚫ collection of nerve fibers that innervate the gastrointestinal (GI) tract, pancreas, and gallbladder, ⚫ This system functions independently of the CNS and controls the motility, exocrine and endocrine secretions, and microcirculation of the GI tract. ⚫ It is modulated by both the sympathetic and parasympathetic nervous systems. Drug (Ach)  CHEMICAL SIGNALING BETWEEN CELLS ⚫ Hormones - chemicals released into the bloodstream ⇒ physiological effects on tissues - specific hormone receptors. ⚫ Local mediators - Most cells in the body secrete chemicals that act locally, and they don’t enter blood. E.g., histamine and prostaglandins. ⚫ Neurotransmitters: A specific chemical signals, released from the nerve terminals.  Neurotransmitters 1. Norepinephrine and epinephrine – ANS 2. Acetylcholine - ANS 3. Dopamine - CNS (low levels lead to Parkinson’s disease, depression) 4. Serotonin - CNS (low levels lead to depression) 5. Histamine - CNS 6. γ-aminobutyric acid (GABA)- CNS ⚫ Co-transmitters, such as adenosine, often accompany neurotransmitter on nerve stimulation and modulate the transmission process. o Neurotransmitters of ANS 1. Acetylcholine (ACh) (cholinergic) mediates the transmission of nerve impulses across:  autonomic ganglia in both sympathetic and parasympathetic NS.  at adrenal medulla.  Transmission from the postganglionic nerves to the effector organs in parasympathetic system,  transmission at the neuromuscular junction  A few sympathetic fibers, such as those involved in sweating (*), are cholinergic 2. Norepinephrine (NE) and epinephrine (E) (adrenergic)  Transmission from the postganglionic nerves to the effector organs in sympathetic system.  Cholinergic receptors (CHOLINOCEPTORS) A. Muscarinic receptors ⚫ G protein–coupled receptors. ⚫ Recognize muscarine, ACh, and weak affinity to nicotine NT. ⚫ five subclasses of muscarinic receptors: M1, M2, M3, M4, and M5. ⚫ Found on the effector organs of parasympathetic such as the gastric (M1), heart and smooth muscle (M2), bladder and exocrine glands and smooth muscle (M3) ⚫ When M receptor activated – G-protein – IP3 and DAG intracellular Ca2+ - cause hyperpolarization, secretion, or contraction. B. Nicotinic receptors ⚫ ligand-gated ion channel (Fastest channel) ⚫ Recognize nicotine, Ach, and weak affinity to muscarine NT. ⚫ Two types: Nm and Nn ⚫ Located in the CNS, adrenal medulla, autonomic ganglia (called Nn), and the neuromuscular junction (NMJ) called Nm.  Cholinergic agonists (parasympathomimetic) ⚫ ACh has both muscarinic and nicotinic activity. Its actions include:  Decrease in heart rate and cardiac output (BP = CO * PR)  Decrease in blood pressure (VASODILATION)? HOW?  Increases salivary secretion and intestinal secretions and motility  increases the tone of the detrusor urine muscle, causing expulsion of urine.  constriction of the pupillae sphincter muscle, causing miosis (marked constriction of the pupil). o What is the meaning of direct and indirect acting drugs?  Direct acting means that the drug directly binds to receptor.  Indirect acting means that the drug inhibit AchE enzyme thereby increase the level of Ach, so more effect occurs. 1-Direct-acting Agonist Drugs  Bethanechol: used for urinary retention (post operative)  Carbachol: as a miotic agent to treat glaucoma (decrease the IOP)  Pilocarpine: to treat glaucoma and lower IOP of both narrow-angle (or closed-angle) and wide-angle (also called open-angle) glaucoma.  Also, it is used for Xerostomia (dry mouth). o Two types of Glaucoma (for your knowledge)  Types of Glaucoma: 1. Open Angle Glaucoma –Excessive production of Aqueous Humor. Excessive β adrenergic receptor mediated production and secretion of aqueous humor from the ciliary body epithelium.  Best treated with beta-blockers: Reduce (Production, Synthesis or Secretion, Acetazolamide, Timolol, Betaxolol) 2. Closed Angle Glaucoma –Outflow obstruction of Aqueous Humor. Results from obstruction of canal of Schlemm through which aqueous humor was supposed to be filtrated out.  Caused by 1. Mydriatics: Anti-cholinergic drugs 2. Antidepressants: SSRI drugs  Treatment: Pilocarpine, Carbachol, ecothiopate and physostigmine.  NOTE: any drug cause mydriatics lead to glaucoma(⬆️IOP) while any drug cause miosis ⬇️IOP 2. Indirect-acting Cholinergic Agonists: Acetylcholinesterase Inhibitors (Reversible) Drugs inhibit AChE the enzyme that cleaves ACh to acetate and choline and terminate ACh action this results in the accumulation of ACh in the synaptic space–so prolong ACh action  Examples:  Physostigmine: used to stimulate the bladder and GI tract. (Post operative)  Neostigmine, ambenonium and Pyridostigmine: used to treat myasthenia gravis  Rivastigmine: to delay the progression of Alzheimer disease  Edrophonium It is used in the diagnosis of myasthenia gravis, which is an autoimmune disease caused by antibodies to the nicotinic receptor at NMJs.  NOTE: Neostigmine also used post operative as antidot for tubocurarine. 3. Indirect-acting cholinergic agonists: anticholinesterases (IRREVERSIBLE)  Echothiopate (eye drops): for the chronic treatment of open-angle glaucoma.  Long duration of action (1 week)  Toxicology of anticholinesterase agent Reactivation of acetylcholinesterase (Antidote)  Example: organophosphate (sarin gas) and insecticide poisoning  Treatment: Pralidoxime (PAM) antidote: can reactivate inhibited AChE: it displaces phosphate group and regenerate the enzyme  Ecothiophate  PAM/Atropine (according to time)  Sarine gas/insecticide Atropine  Antimuscarinic Agents 1. Atropine: (narrow TI)  used as an antispasmodic to reduce activity of the GI tract  used to reduce hypermotility states of the urinary bladder.  Used as antidote for cholinergic agonist  Antisecretory before surgery.  Contraindicated on narrow angle glaucoma  Note: atropine is derived from plant called atropa belladonna. 2. Scopolamine(hyoscine)  used for motion sickness  antispasmodic 3. Ipratropium  as bronchodilators for maintenance treatment of chronic obstructive pulmonary disease (COPD). (First line for COPD and second for Asthma.) 4. Benztropine  treatment of Parkinson disease. (Caused by dopamine deficiency).  Neuromuscular-blocking drugs nicotinic receptors antagonist 1. A. Nondepolarizing blockers (competitive)  Tubocurarine is the prototype agent in this class  interact with the nicotinic receptors to prevent the binding of Ach --- inhibit muscular contraction  Therapeutic uses: as adjuvant drugs in anesthesia during surgery to relax skeletal muscle and to facilitate intubation  Cause hepatotoxicity/allergy 2. Depolarizing agents  Succinylcholine  QUISTIONS: 1 Which of the following is correct regarding the autonomic nervous system (ANS)? A. Afferent neurons carry signals from the CNS to the effector organs. B. The neurotransmitter at the parasympathetic ganglion is norepinephrine (NE). C. The neurotransmitter at the sympathetic ganglion is acetylcholine (ACh). D. Sympathetic neurons release ACh in the effector organs. E. Parasympathetic neurons release NE in the effector organs. 2 Which of the following is correct regarding somatic motor neurons? A. The neurotransmitter at the somatic motor neuron ganglion is acetylcholine. B. The neurotransmitter at the somatic motor neuron ganglion is norepinephrine. C. Somatic motor neurons innervate smooth muscles. D. Somatic motor neurons do not have ganglia. E. Responses in the somatic motor neurons are generally slower than in the autonomic nervous system. 3 Which of the following physiological changes could happen when a person is attacked by a grizzly bear? A. Increase in heart rate. B. Increase in lacrimation (tears). C. Constriction of the pupil (miosis). D. Increase in gastric motility. 4 Which of the following changes could theoretically happen in a person when the parasympathetic system is inhibited using a pharmacological agent? A. Reduction in heart rate. B. Constriction of the pupil (miosis). C. Increase in gastric motility. D. Dry mouth (xerostomia). E. Contraction of detrusor muscle in the bladder. 5 Which of the following statements is correct regarding the sympathetic and parasympathetic systems? A. Acetylcholine activates muscarinic receptors. B. Acetylcholine activates adrenergic receptors. C. Norepinephrine activates muscarinic receptors. D. Activation of the sympathetic system causes a drop in blood pressure. 6 Which of the following statements concerning the parasympathetic nervous system is correct? A. The parasympathetic system uses norepinephrine as a neurotransmitter. B. The parasympathetic system often discharges as a single, functional system. C. The parasympathetic division is involved in accommodation of near vision, movement of food, and urination. D. The postganglionic fibers of the parasympathetic division are long compared to those of the sympathetic nervous system. E. The parasympathetic system controls the secretion of the adrenal medulla. 7 Which of the following is correct regarding neurotransmitters and neurotransmission? A. Neurotransmitters are released from the presynaptic nerve terminals. B. Neurotransmitter release is triggered by the arrival of action potentials in the postsynaptic cell. C. Intracellular calcium levels drop in the neuron before the neurotransmitter is released. D. Serotonin and dopamine are the primary neurotransmitters in the ANS. 8 An elderly man was brought to the emergency room after he ingested a large quantity of carvedilol tablets, a drug that blocks α1, β1, and β2 adrenergic receptors, which mainly mediate the cardiovascular effects of epinephrine and norepinephrine in the body. Which of the following symptoms would you expect in this patient? A. Increased heart rate (tachycardia). B. Reduced heart rate (bradycardia). C. Dilation of the pupil (mydriasis). D. Increased blood pressure. 9 All of the following statements regarding central control of autonomic functions are correct except: A. Baroreceptors are pressure sensors located at various cardiovascular sites. B. The parasympathetic system is activated by the CNS in response to a sudden drop in blood pressure. C. The parasympathetic system is activated by the CNS in response to a sudden increase in blood pressure. D. The sympathetic system is activated by the CNS in response to a sudden drop in blood pressure. 10 Which of the following is correct regarding membrane receptors and signal transduction? A. ANS neurotransmitters bind to membrane receptors on the effector cells, which leads to intracellular events. B. Cholinergic muscarinic receptors are examples of ionotropic receptors. C. Cholinergic nicotinic receptors are examples of metabotropic receptors. D. Metabotropic receptors activate ion channels directly Ans: 1-C 8-B 9-B 2-D 3-A 4-D 5-A 6-C 7-A 10-A 1 Botulinum toxin blocks the release of acetylcholine from cholinergic nerve terminals. Which of the following is a possible effect of botulinum toxin? A. Skeletal muscle paralysis. B. Improvement of myasthenia gravis symptoms. C. Increased salivation. D. Reduced heart rate. 2 A dentist would like to reduce salivation in a patient in preparation for an oral surgical procedure. Which of the following strategies will be useful in reducing salivation? A. Activate nicotinic receptors in the salivary glands. B. Block nicotinic receptors in the salivary glands. C. Activate muscarinic receptors in the salivary glands. D. Block muscarinic receptors in the salivary glands. 3 Which of the following is a systemic effect of a muscarinic agonist? A. Reduced heart rate (bradycardia). B. Increased blood pressure. C. Mydriasis (dilation of the pupil). D. Reduced urinary frequency. E. Constipation. 4 If an ophthalmologist wants to dilate the pupils for an eye examination, which of the following drugs/classes of drugs could be theoretically useful? A. Muscarinic receptor activator (agonist). B. Muscarinic receptor inhibitor (antagonist). C. Acetylcholine. D. Pilocarpine. E. Neostigmine. D. Dilation of the pupils (mydriasis). E. Dry mouth. 5 In Alzheimer’s disease, there is a deficiency of cholinergic neuronal function in the brain. Theoretically, which of the following strategies will be useful in treating the symptoms of Alzheimer’s disease? A. Muscarinic antagonists. B. Muscarinic agonists. C. Anticholinesterase agents. D. Pilocarpine. E. Neostigmine. A. Inhibiting cholinergic receptors in the brain. B. Inhibiting the release of acetylcholine in the brain. C. Inhibiting the acetylcholinesterase enzyme in the brain. D. Activating the acetylcholinesterase enzyme in the brain 9 Which of the following drugs or classes of drugs will be useful in treating the symptoms of myasthenia gravis? 6 An elderly female who lives in a farmhouse was brought to the emergency room in serious condition after ingesting a liquid from an unlabeled bottle found near her bed, apparently in a suicide attempt. She presented with diarrhea, frequent urination, convulsions, breathing difficulties, constricted pupils (miosis), and excessive salivation. Which of the following is correct regarding this patient? A. She most likely consumed an organophosphate pesticide. B. The symptoms are consistent with sympathetic activation. C. Her symptoms can be treated using an anticholinesterase agent. D. Her symptoms can be treated using a cholinergic agonist. 7 Sarin is a volatile nerve agent that inhibits cholinesterase enzymes. Which of the following symptoms would you expect to see in a patient exposed to sarin? A. Urinary retention. B. Tachycardia. C. Constriction of pupils (miosis). 8 Head and neck irradiation in cancer patients can decrease salivary secretion and cause dry mouth. All the following drugs or classes of drugs are theoretically useful in improving secretion of saliva in these patients except: A. Nicotinic antagonists. B. Muscarinic agonists. C. Muscarinic antagonists. D. Anticholinesterase agents. 10 Atropa belladonna is a plant that contains atropine (a muscarinic antagonist). Which of the following drugs or classes of drugs will be useful in treating poisoning with belladonna? A. Malathion. B. Physostigmine. C. Muscarinic antagonists. D. Nicotinic antagonists. Ans: 1-A 2-D 3-A 4-B 5-C 6-A 7-C 8-A 9- D 10-B 1 During an ophthalmic surgical procedure, the surgeon wanted to constrict the pupil of the patient using a miotic drug. However, he accidentally used another drug that caused dilation of the pupil (mydriasis) instead. Most likely, which of the following drugs did he use? A. β1 Agonist. B. Muscarinic agonist. C. Physostigmine. D. Ipratropium. E. Phentolamine. A. Acetylcholine. B. Pilocarpine. C. Tropicamide. D. Phentolamine. E. Bethanechol. 5 Which of the following drugs would be the most effective anti– motion sickness drug for a person planning to go on a cruise? 2 Sarin is a nerve gas that is an organophosphate cholinesterase inhibitor. Which of the following could be used as an antidote to sarin poisoning? A. Pilocarpine. B. Carbachol. C. Atropine. D. Physostigmine. E. Nicotine. 3 Atropine is one of the ingredients in the antidiarrheal combination diphenoxylate/atropine available in the United States. Which of the following effects is produced by atropine that contributes to its antidiarrheal effect? A. Increase in gastrointestinal motility. B. Reduction in gastrointestinal motility. C. Increase in salivation. D. Increase in acid secretion. 4 A patient with chronic obstructive pulmonary disease (COPD) was prescribed a β2 agonist for the relief of bronchospasm. However, the patient did not respond to this treatment. Which of the following drugs or classes of drugs would you suggest for this patient as the next option? A. Atropine. B. Tropicamide. C. Scopolamine. D. Darifenacin. E. Tiotropium. 6 Which of the following is correct regarding ganglion blocking drugs? A. Blockade of sympathetic ganglia could result in reduced blood pressure. B. Blockade of parasympathetic ganglia could result in reduced heart rate. C. Nicotine is a nondepolarizing ganglion blocker. D. Atropine is a nondepolarizing ganglion blocker. 7 Which of the following is correct regarding the neuromuscular blockers (NMBs)? A. Nondepolarizing NMBs are administered orally. B. Cholinesterase inhibitors reduce the effects of nondepolarizing NMBs. C. Nondepolarizing NMBs affect diaphragm muscles first. D. Effects of depolarizing neuromuscular blockers can be reversed using cholinesterase inhibitors. 8 Which of the following is correct regarding drug interactions with nondepolarizing neuromuscular blockers (NMBs)? A. Desflurane reduces the effects of nondepolarizing NMBs. B. Cholinesterase inhibitors increase the effects of nondepolarizing NMBs. C. Aminoglycosides increase the effects of nondepolarizing NMBs. D. Calcium channel blockers reduce the effects of nondepolarizing NMBs. 9 A patient was administered a neuromuscular blocker (NMB) prior to a surgical procedure to produce skeletal muscle paralysis. This NMB drug affected small, rapidly contracting muscles of the face and eyes first and diaphragm muscles last. The effect of this drug was easily reversed with neostigmine. Which of the following neuromuscular blockers was most likely administered to this patient? A. Rocuronium. B. Succinylcholine. C. Diazepam. D. Tubocurarine. 10 A patient was administered a neuromuscular blocker (NMB) prior to a surgical procedure to produce skeletal muscle paralysis. This NMB drug caused initial skeletal muscle fasciculations before the onset of paralysis. The effect of this drug could not be reversed with neostigmine. Which of the following neuromuscular blockers was most likely administered to this patient? A. Cisatracurium. B. Succinylcholine. C. Diazepam. D. Tubocurarine.