Neurotransmitters and Receptors in the Autonomic Nervous System, Exams of Nursing

Download Neurotransmitters and Receptors in the Autonomic Nervous System and more Exams Nursing in PDF only on Docsity! P a g e 1 | 36 1 1. Somatic Nervous System The division of the peripheral nervous sys- tem that controls the body's skeletal mus- cles. In this system, a single myelinated fiber carries signal from the CNS to skeletal muscle to produce contraction. ACh is the neurotransmitter. 2. Autonomic Nervous System the part of the peripheral nervous system that controls the glands and the muscles of the internal organs (such as the heart). Its sympathetic division arouses; its parasym- pathetic division calms. Two neurons are in series, which synapse in ganglia, inner- vate smooth muscle, heart, and glands. Only the pre-ganglionic fiber is myelinat- ed. ACh is neurotransmitter in all gan- glia and post-ganglionic parasympathetic fibers. Norepinephrine (NE) is neurotrans- mitter in most postganglionic sympathetic fibers. 3. Sympathetic Nervous System The division of the autonomic nervous sys- tem that arouses the body, mobilizing its energy in stressful situations. Preganglion- ic fibers exit CNS in the thoracic and lumbar P a g e 2 | 36 2 regions of the spinal cord. Most sympathet- ic ganglia are found in chains on each side of the spinal cord - "paravertebral ganglia". P a g e 5 | 36 5 maffin cells directly into the blood stream (Hence: epinephrine is a hormone not a neurotransmitter). 6. Sweat Glands Glands involved in temperature control. Postganglionic sympathetic fibers release ACh not norepinephrine to activate "ec- crine" sweat glands. 7. Cholinergic Terminals Terminals that release ACh. Steps of neu- rotransmission: storage of the transmitter. After synthesis in the cytosol, ACh is stored in vesicles where it accumulates to high concentration. Release of the transmitter. Arrival of the action potential depolarizes the membrane, which opens voltage-de- pendent Ca2+ channels. Influx of Ca2+ trig- gers exocytosis - ACh-containing vesicles fuse with the membrane and release their contents. This step is blocked by botulinum toxin. Empty vesicles are recycled. Activa- tion of œr2eceptors on the nerve terminal can inhibit further release of ACh - feed- back inhibition. P a g e 6 | 36 6 8. Adrenergic Terminals Terminals that release norepinephrine. 9. Choline Acetyltransferase The enzyme that transfers the acetate ion from acetyl coenzyme A to choline, produc- ing the neurotransmitter acetylcholine. 10. Acetylcholinesterase (AChE) The enzyme that breaks down acetyl- choline in the synaptic cleft. ACh will split into acetate + choline. About 50% of the choline re-enters the nerve terminal for resynthesis of ACh. 11. Butyryl-Cholinesterase (BChE) The enzyme that breaks down ACh enter- ing the bloodstream. 12. Cholinesterase Inhibitors Binds with the cholinesterase enzyme, pre- venting it from breaking down ACh. This P a g e 7 | 36 7 allows ACh to last longer in the synaptic cleft and exert its effects. P a g e 10 | 36 10 back inhibition. Activation of M3 receptors on target leads to increase in cell Ca2+. P a g e 11 | 36 11 19. Nicotinic Receptor Type of acetylcholine receptor protein that is characterized by also binding to nicotine and is an ionotropic receptor. Action po- tential going across preganglionic neuron causes opening of Ca2+ channels. Ca2+ triggers fusion of vesicles and release of ACh. Binding of two ACh opens the ion channel of this receptor (ligand-gated ion channel), and influx of Na+ triggers an action potential in the muscle. Agonists open the channel, and antagonists block the channel. They have 5 subunits. ACh is the only physiological agonist for these receptors. 20. ±1Receptor An adrenergic receptor located at smooth muscles (causes contraction --> vasocon- striction), pupils (contracts radial muscle - mydriasis), pylorus, urinary sphincter, and prostate. It also causes ejaculation from pe- nis. Mechanism: Leads to constriction and results in an increase in cytosolic Ca2+ (cause contraction). 21. • They are located at smooth muscles (causes contraction --> vasoconstriction), pupils (contracts radial muscle - P a g e 12 | 36 12 mydriasis), pylorus, urinary • Where are ±1receptors located? • What is their mechanism? P a g e 15 | 36 15 Causes smooth muscle relax- ation • Mechanism: results in an in- crease in cAMP. 28. ²3Receptors An adrenergic receptor located in adipose tissue (causes lipolysis) and in the urinary bladder. Mechanism: causes an increase in cAMP. 29. • Located in adipose tissue (causes lipolysis) and in the urinary bladder. • Causes an increase in cAMP. • Where are ²3receptors located? • What is their mechanism? 30. M2 Receptor A muscarinic receptor located in the heart, lungs, stomach, and pancreas. They are also located at end of pre-synaptic nerve terminals that cause inhibition. Mechanism: cause a decrease in cAMP. 31. • Located in the heart, lungs, stomach, and pancreas • Cause a decrease in cAMP. • Where are M2 receptors located? • What is their mechanism? 32. M3 Receptor A muscarinic receptor located in the lungs, smooth muscle, secretory glands, eyes (contracts circular muscle - leads to con- striction - miosis), GI tract, urinary bladder, and uterus. Mechanism: cause an increase in cytosolic Ca2+. 33. M3 and ±1Receptors Which receptors cause an increase in cy- tosolic Ca2+? 34. ²1, ²2a, nd D1 Receptors Which receptors cause an increase in cAMP? P a g e 16 | 36 16 35. M2, ±2a, nd D2 Receptors P a g e 17 | 36 17 Which receptors cause a decrease in cAMP? 36. ²2Receptor Which is the only adrenergic receptor that norepinephrine does not stimulate? 37. Nicotinic N The type of nicotinic receptor found in gan- glia of both the sympathetic and parasym- pathetic nervous systems. 38. Nicotinic M The type of nicotinic receptor found at the neuromuscular junction (NMJ). 39. Acetylcholine A physiological agonist at both muscarinic and nicotinic receptors, therefore, will have many effects. It is a quaternary compound (limited distribution, poor GI absorption). Has a very short half life (ester bond cleaved very rapidly by BChE). Has virtu- ally no therapeutic uses. Only use: instilled into anterior chamber of the eye to induce miosis during ophthalmic surgery - effects last only for about ten minutes. 40. • Quaternary compound (poor distribution, poor absorption). Ester bond broken down rapid- ly after use (by BChE), so virtu- ally no therapeutic uses • Only use: instilled into ante- rior chamber of the eye to in- duce miosis during ophthalmic surgery - effects last only for about ten minutes. • What is the MOA of acetylcholine? • Therapeutic use? 41. Nicotine A tertiary ammonium drug, very lipophilic so easily crosses mucosal membranes, P a g e 20 | 36 20 • Effects? • How to reverse actions during overdose? • Why does the mechanism of action limit potential use of drugs on these receptors? P a g e 21 | 36 21 striction, increased HR --> in- creases BP. It has parasympa- thetic effects in GI and urinary tracts - cause nausea, vom- iting, diarrhea, and urination. In skeletal muscle, depolariza- tion blockade results in flaccid paralysis including respiratory muscles - the channel is kept open! • Give anticonvulsant (e.g. di- azepam) for CNS effects, give atropine to antagonize mus- carinic effects, and provide me- chanical respiration. • Because the sympathetic and parasympathetic nervous sys- tems will both be affected. 43. Varenicline A partial NN agonist (efficacy significantly < nicotine). It blocks nicotine binding and activation of NN receptors in the mesolim- bic dopamine system. System underlies "reinforcement and reward" system. Uses: smoking cessation - gives you less of an effect than nicotine. Side effects: re-suicidal thoughts, aggressive and erratic behavior, and drowsiness. 44. • A partial NN agonist (effica- cy significantly < nicotine). It blocks nicotine binding and ac- tivation of NN receptors in the mesolimbic dopamine system. System underlies "reinforce- ment and reward" system. • Used for smoking cessation - gives you less of an effect than nicotine. P a g e 22 | 36 22 • What is the MOA of varenicline? • Use? • Side effects? P a g e 25 | 36 25 • Acetylcholinesterase in- hibitor 49. Both are Nm receptor antag- onists (block ACh from bind- ing), leading to paralysis. Both can be reversed by AChE in- hibitor. *Difference is tubocu- rarine causes histamine re- lease and pancuronium pre- vents histamine release.* What is the difference between tubocu- rarine and pancuronium? 50. Succinylcholine A depolarizing neuromuscular blocker (Nm agonist). Allows ACh to bind to receptor once causing a prolonged muscle contrac- tion. Causes repetitive firing of muscle to maintain tension. It is used for endotracheal intubation, endoscopy, and ECT. Side ef- fects: causes fasciculations (uncontrolled muscle contraction) before paralysis sets in, may produce bradycardia. It is a qua- ternary compound and has a short DOA due to rapid hydrolysis by BChE. It is re- sistant to AChE. It should not be used with AChE inhibitors because will make symp- toms worse. Can also have a genetic vari- ant of BChE, causing prolonged effects. This usually isn't a problem, except for those with a genetic variant of the RYAN- ODINE Receptor (the receptor that regu- lates opening of the sarcoplasmic reticu- lum to increase cytosol calcium). In those with a mutant ryanodine receptor, this can drastically increase skeletal muscle oxida- tive metabolism, overwhelming the body to supply oxygen to the muscles and organs. The muscles are essentially converting the energy to heat, leading to hyperthermia. P a g e 26 | 36 26 51. • A depolarizing neuromuscu- lar blocker (Nm agonist). Al- lows ACh to bind to receptor once causing a prolonged mus- cle contraction. Causes repeti- tive firing of muscle to maintain tension. It is used for endotra- cheal intubation, endoscopy, and ECT. • Fasciculations (uncontrolled contractions) • Broken down rapidly by BChE • Variant in BChE: lasts longer. Variant in Ryanodine: hyper- thermia • Makes symptoms worse if ad- ministered with AChE inhibitor • What is the MOA of succinylcholine? Uses? • What tends to happen during adminstra- tion? • Why does it have a short DOA? • What about patients with a genetic vari- ant? • What if administered with an AChE in- hibitor? 52. Botulinum Toxin A Nm antagonist that blocks release of ACh from all cholinergic nerve terminals pro- ducing paralysis. It is used for a local ef- fect; injected directly into desired muscle - has a prolonged action (about 3-4 months). Uses: excessive sweating, joint spasticity, migraines, decrease bladder contraction, cervical dystonia, spasticity (stroke). May cause botulinum or poisoning. 53. • Blocks release of ACh from all cholinergic nerve terminals producing paralysis. It is used for a local effect. • Lasts for about 3-4 months. • What is the MOA of botulinum toxin? • What is the DOA? 54. Methacholine A quaternary muscarinic receptor agonist that is used in diagnosis of bronchial sensi- tivity (used during pulmonary function test). It is administered by inhalation and doses are increased until FEV1 falls 20%. It is a P a g e 27 | 36 27 55. • Quaternary muscarinic recep- tor agonist, has a longer action the ACh because it is resistant to BChE and ACh. • Used in diagnosis of bronchial sensitivity (used dur- ing pulmonary function test). It is administered by inhalation and doses are increased until FEV1 falls 20%. 56. Betanechol (Remember: "Beth's bladder problems" 57. • Quaternary muscarinic recep- tor agonist, resistant to AChE and BChE. • Used for its effects on bladder and GI tract and is said to have minimal CV effects. *Treatment of urinary retention* (SC 2.5, oral 10-100mg) through M3 ac- tivation. Stimulation of GI motil- ity after surgery, increases LES pressure (oral administration). 58. Pilocarpine quaternary drug and is hydrolyzed by es- terases in the gut (resistant to BChE and AChE). • What is the MOA of metacholine? • Use? A quaternary muscarinic receptor agonists. Therefore poor GI absorption. Carbamate ester NOT hydrolyzed by BChE or AChE, hence action prolonged 1-2 hrs. It is used for its effects on bladder and GI tract and is said to have minimal CV effects. *Treat- ment of urinary retention* (SC 2.5, oral 10-100mg). Stimulation of GI motility after surgery, increases LES pressure (oral ad- ministration). • What is the MOA of betanechol? • Use? P a g e 30 | 36 30 ternary and does not enter the CNS. 63. Neostigmine, Pyridostigmine *Quaternary, intermediate-acting acetyl- cholinesterase inhibitors.* They are used for treatment of myasthenia gravis, reversal of neuromuscular blockade after surgery, protection against nerve gases, and can be administered orally (at high dose). Also can be IV, IM, SQ. 64. • *Quaternary, intermediate-act- ing acetylcholinesterase in- hibitors.* • Used for treatment of myasthenia gravis, reversal of neuromuscular blockade af- ter surgery, protection against nerve gases, and can be admin- istered orally (at high dose). Also can be IV, IM, SQ. • What is the MOA of neostigmine and pyri- dostigme? • Use? 65. Physostigmine *Tertiary, intermediate-acting acetyl- cholinesterase inhibitors.* Can cross BBB. Used topically for glaucoma (but not drug of choice). Not used for Alzheimer's like rivastigmine (because it has a much short- er half life). It also produces more nega- tive cholinergic side effects compared to rivastigmine. 66. • *Tertiary, intermediate-act- ing acetylcholinesterase in- hibitors.* Can cross BBB. • Used topically for glaucoma (but not drug of choice). Not used for Alzheimer's because of its shorter half life and it pro- P a g e 31 | 36 31 • What is the MOA of physostigmine? • Use? P a g e 32 | 36 32 duces more negative choliner- gic side effects). 67. • Organophosphate poison- ing causes excessive ACh build-up. • Use atropine to block mus- carinic receptors • Use pralidoxime through IV in- fusion to regenerate the acetyl- cholinesterase • Use diazepam to suppress convulsions How to treat organophosphate poisoning? 68. Echothiophate A quaternary organophosphate acetyl- cholinesterase inhibitor: less lipid soluble than most organophosphates. It is rarely used to treat glaucoma and ONLY in apha- kic patients because it can cause cataracts and retinal detachment. 69. • Quaternary organophosphate acetylcholinesterase inhibitor. • It is rarely used to treat glau- coma and ONLY in aphakic pa- tients because it can cause cataracts and retinal detach- ment. • What is the MOA of echothiophate? • Use? 70. Donpezil A tertiary, selectively reversible AChE in- hibitor. Has little evidence of hepatotoxici- ty. Does not block BChE. Fewer peripheral muscarinic side effects. Side effects: GI - nausea, vomiting, diarrhea most common. Used for Alzheimer's. 71. • A tertiary, selectively re- versible AChE inhibitor. Has lit- tle evidence of hepatotoxicity. • What is the MOA of donepezil? • Use? • Side effects? P a g e 35 | 36 35 76. • Tertiary acetylcholinesterase inhibitor, used to treat Alzheimer's. • Nausea, vomiting, diarrhea, anorexia, weight loss. Natural tertiary ammonium alkaloid from daffodil bulb. It has a reversible half-life of 7 hours. Biotransformation by cyp2D6 and cyp3A4. Side effects: nausea/vomiting, di- arrhea, anorexia, weight loss. It is used to treat Alzheimer's. • What is the MOA of galantamine? • Side effects? 77. Atropine A tertiary muscarinic antagonist that is used in treatment of poisoning by cholinesterase inhibitors and mus- carine-containing mushrooms. It is also used during surgery to decrease bronchial and salivary secretions, bronchodilation, block GI vagal reflexes, etc. 78. • A tertiary muscarinic antago- nist • Used in treatment of poi- soning by cholinesterase in- hibitors and muscarine-con- taining mushrooms. It is also used during surgery to de- crease bronchial and sali- vary secretions, bronchodila- tion, block GI vagal reflexes, etc. • Mimic sympathetic response (side effects) - poisoning • It is reversed by *physostig- mine* - an AChE inhibitor. • What is the MOA of atropine? • Use? • Side effects? • How is atropine poisoning treated? 79. Scopolamine A tertiary muscarinic antagonist that is used for motion sickness (prevents vomit- P a g e 36 | 36 36 80. • Tertiary muscarinic antago- nist • Used for motion sickness ing). It is available as a patch for topical absorption. It has typical anti-muscarinic side effects. • What is the MOA of scopolamine? • Use? 81. Oxybutynin and Tolterodine Drugs used for urge incontinence (over- active bladder); block muscarinic recep- tors and cause detrusor muscle relaxation. Side effects: can cause dry mouth. Tertiary anti-muscarinic. 82. • Tertiary anti-muscarinic drugs • Overactive bladder • Can cause dry mouth • What is the MOA of oxybutynin and tolterodine? • Use? • Side effects? 83. Tertiary drugs Physostigmine, donepezil, rivastigmine are all: 84. Quaternary drugs Edrophonium, pyridostigmine, and prali- doxime are all: