The Autonomic Nervous System Introduction. Autonomic Nervous System - Overview

Transcription

1 The Autonomic Nervous System Introduction Edward JN Ishac, Ph.D. Professor Smith Building, Room Department of Pharmacology and Toxicology Medical College of Virginia Campus of Virginia Commonwealth University Richmond, Virginia, USA Autonomic Nervous System Overview www2.courses.vcu.edu/ptxed/ptx/ 1. Tissues / Organs: receptors present, tissue / organ response 2. Transmitters: NE, Ach, synthesis, storage, release, regulation 3. Drugs: receptor selectivity, mechanism of action 4. Can predict: clinical application, side effects, toxicity, treatment of toxicity 5. Eye Anatomy: miosis, mydriasis, cycloplegia, wide vs narrowangle, Horner s syn. 6. General: learn by drug classes, important adverse reactions, not dosage 1

2 ANS Overview Tissues/Organs Sympathetic NS Parasympathetic NS Cardiovascular System Organ Action Receptor Action Receptor BP = CO X TPR, CO = SV X HR Eye: Radial m. Mydriasis Reflexes oppose direct action to correct BP change (not HR change) Circular m. Miosis M 2, Ciliary m. Receptor Action Heart: HR, force HR M 2 vasoconstriction TPR BP Vascular muscle Constrict (NO) HR CO BP, D 15 renal vasodilation TPR BP Bronchial m. M 2 (vagus) HR CO BP GItract motility, motility (NO) relaxation TPR BP Sphincter m. Genitourinary m. Cardiovascular Drug Effects Penis Ejaculation α Erection M Norepinephrine BP, HR (reflex) Uterus NO = Nitric oxide Isoproterenol BP (o/), HR, PP Pilomotor α 2 nd Messengers Epinephrine BP, HR, PP Sweat glands secretion 23 D 15 camp Mecamylamine BP, (o/+) HR Liver glucose M 135 IP 3 / Ca 2+ Propranolol BP (o/), HR Kidney renin α 2 M 24 D 234 camp Atropine BP (o/), HR Fat cell Lipolysis β 3 N n N m Na + in K+ out Phentolamine BP, HR (reflex), PP Summary Table Indented = similar action to parent compound Most important agent, important, least important [ ] = questionable therapeutic value I =drug interactions S = side effects T = toxicity CV = cardiovascular system CNS = central nervous system Agent (trade name ) Adrenoceptor Agonists Therapeutic Use Notes MAOI = Monoamine oxidase inhibitors TCA = Tricyclic antidepressants Norepinephrine (Levarterenol) Hypotension, pressor agent α / β 3 ( ) neuronal, noncirculating, I: MAOI, TCA Epinephrine (generic) Allergic reactions (DOC), shock, CPR α / (β 3 ) adrenal medulla, circulating; I: MAOI, TCA Dopamine (Intropin) Shock (DOC) / / D, NE precursor, renal vasodilatation? I: MAOI Isoproterenol (Isuprel) Asthma, cardiac stimulant β, synthetic, not endogenous; BP(, ) HR Phenylephrine Methoxamine (Neosynephrine) (Vasoxyl) Nasal decongestant, hypotension Hypotension, pressor agent Not commonly used for hypotension; S: CV, reflex bradycardia Metaraminol (Aramine) Hypotension, pressor agent α, orally active; NE or DA better choice Clonidine Guanfacine αmethyldopa (Catapres) (Tenex) (Aldomet) Hypertension α 2, cns sympathetic outflow, inhibit NE release, rebound HT; S: dry mouth, sedation, impotence. αmethyldopa is metabolized to αmethylne (α 2 agonist, positive Coombs test) Dobutamine (Dobutrex) CHF, cardiac stimulant, iv infusion, tolerance, desensitization Prenalterol Albuterol Ritodrine Metaproterenol (Proventil, Ventolin) (Yutopar) (Alupent) Asthma bronchodilator Premature labor Asthma selective, Oral 12 hrs onset 46 hrs duration, Inhalation 510 min onset 34 hrs duration; S: cardiovascular; less via inhalation Note: Terbutaline not FDA approved for premature labor (cheaper, longer lasting than Ritodrine) Terbutaline (Brethaire) Asthma, (premature labor) 2

3 Autonomic Nervous System Autonomic Nervous System SYMPATHETIC Thoracolumbar T112, L13 PARASYMPATHETIC Craniosacral Cranial N. III, VII, IX, X Sacral S23 Flight or Fight BP, HR, GIT Feeding & Breeding BP, HR, GIT FUNCTIONS CONTROLLED Respiration Circulation Body Temperature Metabolism Sweating Secretions CENTRAL INVOLVEMENT Hypothalamus Integration, body temp & water balance Medulla BP, respiration Cerebral cortex somatic NS & ANS integration 3

4 Activation of SNS and release of NE & EPI from nerve endings and adrenal gland Increase blood flow, BP, HR, glucose, pupil dilation Decrease activity of digestive & immune system Fight or Flight Exam Stress Normal BP: 120 / 80 mmhg HR: 72 bpm Before exam: 140 / 99 mmhg HR: 97 bpm During exam: 179 / 149 mmhg HR: 110 bpm End of exam: 111 / 74 mmhg HR: 76 bpm 4

5 Neurons of the ANS Key Points Preganglionic fibers mylinated Postganglionic fibers non mylinated SNS pre : post 1:20 PNS pre : post 1:1 (exception 1:10,000 Auerbachs plexus) Key role of Ach Motor fiber not part of ANS Neurons of the ANS 5

6 Adrenoreceptors Alpha Beta Dopamine α 2 β 3 D 15 Vascular smooth muscle Nerve terminals Cardiac muscle Bronchial smooth muscle Fat cells Renal, vascular smooth muscle (D 1 ) Cholinoreceptors Muscarinic M 1 M 2 Ganglia cells Cardiac muscle Sweat glands Nicotinic M 4 /M 5 N N N M Ganglia cells Neuromuscular junction 6

7 ANS Diagram Key Points Division Anatomical Usually dual innervation Usually antagonistic Usually some ANS tone Usually one dominates Role of reflex responses Raynaud s Syndrome Excessive sympathetic tone in nerves supplying hands and feet. Minor cold, or even thought of cold, causes pronounced vasoconstriction that can be severe enough to cause necrosis of tissues Discoloration of the fingers and/or toes when the patient is exposed to changes in temperature (cold or hot) or emotional events Abnormal spasm of blood vessels causes diminished blood supply Initially, the digit(s) turn white because of diminished blood supply. Then turn blue because of prolonged lack of oxygen Finally turn red, the blood vessels reopen, causing a local "flushing" Threephase color sequence (white to blue to red) is typical Treatment: Ca++ blockers if severe 7