Week 10 - PHCL 2600 Notes
Week 10 - PHCL 2600 Notes PHCL2600
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This page Class Notes was uploaded by Emily Notetaker on Sunday November 1, 2015. The Class Notes belongs to PHCL2600 at University of Toledo taught by Williams,F in Fall 2015. Since its upload, it has received 23 views. For similar materials see Funct Anat and Pathophysiol I in Pharmaceutical Sciences at University of Toledo.
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Date Created: 11/01/15
Lecture 1 0 Comparison of Nervous and Endocrine Systems Characteristics Nervous System Endocrine System Mediator molecules Site of mediator action Types of target cells Time to onset of action Duration of action Neurotransmitter released locally Hormones release into the blood circulation At synapse close to the release site Binds to receptors in post synaptic membrane Usually far from site of release Binds to receptors on or in target cells organ or tissue Muscle cells gland cells other neurons Cells throughout the body Within milliseconds Seconds to hours or days Generally brief action milliseconds Generally long action sec to days o The nervous and endocrine systems coordinate all body systems 0 Endocrine System 0 Consists of and containing hormonesecreting cells 0 I Pituitary thyroid adrenal parathyroid and pineal glands o I Hypothalamus thymus pancreas ovaries testes kidneys stomach liver small intestine skin heart adipose tissue and placenta o Endocrine System 0 Controls body activities 0 Function is mediated by molecules called 39 Controls volume control metabolism muscle contraction immune activities growth and development and reproduction o Slower responses effects last longer and broader in uence 0 Hormones o Body s chemical o by cells into the interstitial uid tissue uid and diffuse into the 0 Act 0n o In target tissues hormones bind to specific proteins called o Hormone Concentrations 0 Effects depend on the hormone concentration 0 Types 0 Normal range that produces normal response 0 Small amounts 9 nanomolar to picomolar o Abnormally high or low concentrations 0 Can elicit different responses to normal 39 0 Concentration When a hormone is taken as a drug or medication 0 Exaggerated or noncharacteristic effects 0 Possible adverse side effects Hormone Types 0 Two types 9 and 0 Most hormones are circulating hormones Circulating Hormones o Secreted into o Carried to distant 0 They bind to in target cells 0 They are inactivated by the liver and excreted by the kidney 0 thyroid hormones I Produced and secreted by the thyroid gland I They act on bones growth neurons and other target tissues Local Hormones Autocrines o Secreted into the I They do not enter the blood 0 Hormones act on the that secretes them I Short or no distance from the release site to the target cell 0 Cytokine interleukin1 I Released by monocytes and act on monocytes Local Hormones Paracrines o Secreted into the I They do not enter the blood 0 Act on neighboring cells 9 Diffuse short distance 0 Testosterone I Released from the testes I Acts on adjacent seminiferous tubules to stimulate spermatogenesis Chemical Classes of Hormones o The two classes 0 Classification is based on chemical structure 0 Classification I Watersoluble hormones o Amine 0 Peptideprotein 0 Eicosanoid I Lipidsoluble hormones 0 Steroid 0 Thyroid o Nitric oxide NO 0 WaterSoluble Hormones o Amine hormones I Synthesized by modification of certain amino acids I Examples 0 Norepinephrine epinephrine and dopamine from tyrosine 0 Histamine from histidine 0 Serotonin from tryptophane o Peptideprotein hormones I Amino acid polymers 0 Peptide lt 100 aa 0 Protein gt 100 aa I Examples 0 Oxytocin insulin growth hormone o Stored in secretory vesicles granules inside the cells 0 Stimulus of the cells cause their release I Bind to receptors on the surface of target cells 0 WaterSoluble Hormones o I Derived from fatty acid Arachidonic Acid I Local hormones and may also act as circulating hormones I Not Stored 0 Synthesized rapidly as needed 0 In response to stimuli I Inactive quickly near site of synthesis 0 I Prostaglandins and leukotrienes 0 In ammation 0 WaterSoluble Hormones Transport and Excretion o Free in plasma I Quickly broken down by enzymes or are taken up by tissues I Regulate activities With a rapid onset and a short duration 0 I Hormones are metabolized in liver and excreted by the kidneys o LipidSoluble Hormones o Stimulus causes synthesis and secretion into the blood I Bind to receptors in the cytoplasm or nucleus of the cell o I Synthesized from 39 0 Testosterone aldosterone cortisol estrogen o I Synthesized by attaching I T3 triiodothyrosine and T4 thyroxine o LipidSoluble Hormones Transport and Excretion o I They circulate bound to 0 TP makes them water soluble 0 Not quickly removed from the blood 0 Produce a prolonged effect 0 I Kidneys or liver Lecture 2 0 Carrier Proteins for Lipid Soluble Hormones 0 General carrier proteins I Albumin 0 Steroids 0 Some thyroid hormones I Transthyretin o Thyroid hormones 0 Some steroids 0 Specific carrier proteins I Cortisol binding globulin CBG 0 Cortisol and aldosterone I Thyroxine binding globulin TBG o Thyroid hormones I Sex steroid binding globulin TEBG 0 Testosterone and estradiol 0 They require carrier proteins to make them soluble 0 Control of Hormone Secretion o I Signals from nervous system I Chemical changes of molecules in the blood I Other hormones o I Negative feedback 9 most common I Positive feedback 0 Control of Hormone Secretion o 0 Most endocrine glands under 0 Cells can sense the magnitude of the biological effect produced by the hormone and decrease response 0 Based on magnitude of the effect produced by the hormone cell can decrease response 0 hypothalamuspituitaryorgan axis 0 Control of Hormone Secretion o I Less common 0 I Increases production and release of oxytocin to o Enhance milk production and release 0 Enhance contractions during childbirth o Hormone Activity 0 Hormones affect only specific target tissues 0 Only target tissues or cells With a receptor for a specific hormone respond to the hormone Response depends on both hormone and target cell 0 Target cells respond differently to the same hormone I Hormonal effects vary 0 Hormone Activity Receptor 0 o Hormone locks onto a specific receptor 0 Binding of hormone to the receptor unlock the cell s response producing an effect Lecture 30 Mmday b r 26 2MB 121 PM PHCL 2600 Fall 2015 From Bench to Bedside or firm Hecture to Hive Martirw J hilingen P harmD FCCM quotOn the up side you39re the healthiest patient on ICU quot PHCL 2600 Page 1 Neuromuscular Junction Presynaptic Axon of terminal Synap c vesicles Neuromuscular motor junction junction k Sarcotemm 39 Syrup Muscle fiber clequot Mitochondrion Postsynaptic Capillary Myofibrils membrane PHCL 2600 Page 2 pqgu og VOUS W 239 I Patient Case 9mm 0PM yogi 0 Vog l oldie l EFF a 72 up femaleF POD 10 sip GREG for CAD In the SICU intuljated and mechanically ventilated sedated and quotparalyzed Meals include mpri hinej CNS 04 Iorazepam urcuro iu quotquot antibiotics TlPNlr W hydrpc0rtisune and cum 9 DW m hiquotlaiisil iltempts to oi an patient are unsuccessful aAQCVease domg What happened fake Wmd Mum Neurollogic Medicatiwns liilililifl l llllil Ii Opiate EMElQESIC Stimulateg pentria p iuid rape t cauges CNS depressipn tum I in i u Nundepplari u 39 r i H 39 EFFEClI Elli Ac v PHCL 2600 Page 3 What Happened to EF Likel39y a combination at events aton Vegp n Critical iliness pelvneurepathy CIP 5550quot d g quot changesleadin tr n aicliuretulatlelnf elf drug n gta elites 39 1 cu e rena an Lire wf Decreased eliminatierlt Di vecurenium and mierphirie metabeiite Slow have 473 WWW A n Drugdrug and drugedisease imteract i eris E Merphime lere zepem int CNS depression 1 Vecurei1iiir hydrecertisene cel isti ri tebraimycin preliemged paralysisfmyepathy 2 0 m ptions for managing EF n Tim AIIGW For reversal qt problem and ci39iscnntiriuatie arid eliimiinatie erquot drugs 39 ects of veeure iu t P39Widestigiminer ED ver 5e Eff PHCL 2600 Page 4 What did we do I Time CD Trial of pyridostigmine gt Good ef cacy if problem is excessive blockade cholinergic side effects weenAN 19y No naloxone Good ef cacy however short duration and may preciitate oioid withdrawal Lows No flumazenil GD U M WW 0 Good ef cacy however also short duration may precipitate benzodiazepine withdrawal Takehomequot Points CNSactive medications may potentiate or antagonize effects of each other Systems eg CNS CV GI are interconnected Physiology and pharmacology must be considered within clinical context of situation Anatomy physiology pharmacology and pharmacy practice are all connected You must have a thorough understanding of anatomy physiology and pharmacology to be a good pharmacist PHCL and MBC courses are building blocks for PHPR courses With basic and pharmaceutical sciences back round and cliniclatl training pharmacists are expected to e the drug expe s PHCL 2600 Page 5 Lecture 31 Tuesday October 27 2015 1230 PM PHCL 2600 Page 1 Table 6 1 Responses of Effector Organs to Autonomic Nerve lmpulses 10232006 1121 AM McGrawHill s m Close Window Note Large images and tables on this page may necessitate printing in landscape mode Copyright 2006 The McGrawHill Companies All rights reserved Goodman amp Gilman39s Pharmacology gt II Drugs Acting at Synaptic and Neuroefiector Junctional Sittjb gt Chapter 6 Neurotransmissmn The Autonomic and Somatic Motor Nervous Systems fr Anatomy and General Functions of the Autonomic and Somatic Motor Nervous Systems gt Responses of Effector Organs to Autonomic Nerve lmpulses gt Table 6 1 Responses of Effector Organs to Autonomic Nerve Impulses ORGAN SYMPATHETIC ADRENERGIC PARASYMPATHETIC CHOLINERGIC SYSTEM EFFECTa RECEPTOR EFFECTB RECEPTOR TYPE TYPEquot Eye Radial muscle Contraction E 1 iris mydriasis Sphincter Contraction miosis M3 M2 muscle iris Ciliary muscle Relaxation for far 32 Contraction for near M3 M2 Lacrimal glands Secretion 393quot Secretion M3 M2 Heartc Sinoatrial node Increase in heart 31 gt 32 Decrease in heart rate M2 gtgt M3 rate Atria Increase in 51 gt 32 Decrease in contractility M2 gtgt M3 contractility and and shortened AP duration conduc on velocity Atrioventricular Increase in 31 gt 32 Decrease in conduction M2 gtgt M3 node automaticity and velocity AV block conduc on velocity HisPurkinje Increase in 51 gt 32 Little effect M2 gtgt M3 system automaticity and conduction velocity Ventricle Increase in 31 gt 32 Slight decrease in M2 gtgt M3 httpwwwaccessmedicinecomezproxymeduohioedulpopupaspxalD959769 contractility conduction velocity automaticity and PHCL 2600 Page 2 contractility Page 1 of 6 Table 61 Responses of Effector Organs to Autonomic Nerve Impulses Blood vessels Arteries and arteriolesd Coronary Skin and mucosa Skeletal muscle Cerebral Pulmonary Abdominal viscera Salivary glands Renal Veinsd Endothelium Lung Tracheal and bronchial smooth muscle Bronchial glands Stomach Motility and tone Sphincters Secretion rate of idioventricular pacemakers Constriction dilatione Constriction Constriction dilationeIf Constriction slight Constriction dilation Constriction dilation Constriction Constriction dilation Constriction dilation Relaxation Decreased secretion increased secretion Decrease usual ly Contraction usually Inhibition a1 a2 32 R1 2 a1 32 cL1 a1 Bz 0L1 Bz a1 02 a1a251 32 Cl1 0L2 32 52 011 1 0392 31 52 1 Cl2 httplwwwaccessmedicinecomezproxymeduohioedupopupaspxalD959769 PHCL 2600 Page 3 No innervation No innervation Dilationglh No innervationquot No innervation No innervation Dilationh No innervation Activation of NO synthase Contraction Stimulation Increasei Relaxation usually Stimulation 10232006 1121 AM M3 M3 M2 M3 M3 M2 M2 M3 M3 M2 M3 M2 Page 2 of 6 Intestine lirilet iliter anti telne Sphinctere Secretian Gaiitriadeier and create Kidney Re n iii eee retie n Urinanr bladder Detrueer T rigane and Sphincter Ureter Matility and tune UEEFUS Sex ergane maie Skin Pi lier39rreter m L eel ee Sweat gianee Spleen eepseie Dreereaeeh 1 Centrattienar Iinnibitierr Reilexetieni De i reeeeJir inereeee Relaxatien Centraetien Increase Pregnant ea n tire Ct i e n Reilaxetien Nenpregnant relenatien Ejeeuleten Cnntraetien Laeaheed eetretienk Gene re Iii nee eeeretien r Centraetien Reilaxatinni Table 6 11 Reeeenees ef Effecter Greene te atelierremit Nerve Irneeleee r1p Ell Elil2 El 1 ill e 111 l Ii 1 i 5392 httpwawtemceeeemediitinerernaee arewineclunhineidimmepu nese al 959mg PHCL 2600 Page 4 I nerea eelquot Relaxetien usually Stimuletien Centre etien Ne innervation Centre etien Rvexlaxat ien Increase r Variable Erectien IUEEZEIFEDUE 1121 AM M3 W112 are in MEF MEFME MBF Page 3 at E Table 61 Responses of Effector Organs to Autonomic Nerve Impulses Adrenal medulla Secretion of egineghrine and gorepinephrine Increased contractility Skeletal muscle glycogenolysis KJr uptake Liver Glycogenolysis and gluconeogenesis Pancreas Acini Decreased secretion Islets B cells Decreased secretion Increased secretion Fat cels UPOIYSlS thermogenesis Inhibition of lipolysis Salivary glands K and water secretion Nasopharyngea glands Pineal glands Melatonin synthesis Posterior pituitary DH secretion Autonomic nerve endings Sympathetic terminals Autoreceptor Inhibition of NE release Heteroreceptor 0L1 BZ Secretion II 2 B2 Cl lr Bl B2 B3 12 a 1 K and water secretion Secretion 2A gt 042C 123 Inhibition of NE release httplwwwaccessmedicinecomezproxymeduohioedupopupaspxalD959769 PHCL 2600 Page 5 10232006 1121 AM N 39132B43 M secondarily M3 M2 M3 M2 M3 M2 M2 M4 Page 4 of 6 Table 6 1 Respenses ef Elfecter Dreans te suitenemic Nerve Impulses ltifEiEfE iee 1121 AM Parasvmpathetic terminal AU SWEEE DEDF Inhibi tien ef ace reilease Mgr M4 lletererecepter Inhibitien ef tCh Its2a I lav2 release a espenses are designated te te previde an appresimate indicatien ef the impertance ref svmpathetic and parasvmpathetic nerve activitv in the centre at the varieus ergans and functiens listed bddrenergic recapters e1 I12 and subtvpes thereef Bl I352F i513 Chelinerdic recepters nicetinic N muscarinic hi with subtvpes 1 4 The recepter subtvpes are described mere fullv in Chatters Zr and m and in Tables 64 5 3 and 6 8 When a desigina39ti en ef subtvpe is net previdedr the nature ef the subtvpe has net been determined uneeuivecallv Univ the principal recepter subtvpes are shewn Transmitters ether than acetvlcheline and here tine hrine centribute te manv ef the respenses f339ln the heman heart the ratie at El te i5 is abeut 32 in atria and dirt in ventricles While his recepters predeminate M3 recepters are aise present Wane et al 2004 dThe predeminant e1 recepter subtvpe in meat bleed vessells beth arteries and veins is em see Table gag altheugh ether tel subtvpes are present in speciflc bleed vessels The tam is the predeminant subtvpe in the aerta Micheletti et al2filili3i EDiIEtl il39l predeminates in site ewind te metabelic auteregiulaterv mechanisms Jri iliverthe usual cencentratlen range ef phvslelegicallvr released circulating epinephrine tihe Brecepter respense vasedilatienl predeminates in bleed vessels ef skeletal musclie and liver EEiFECEDtDF respense vasecenstrictien in bleed vessels ef ether abdeminal viscera The renal and mlesienteric vessels alse centain specific depaminerdic recep ters whese activatien causes dilatien see review bv Geldberg et at 19TH g39Svmpathetic chelinergic neurens cause vasediilatien in skeletal muscle beds but this is net invelved in meat phvsielegical respenses illThe endetheli um ef mest bleed vessels releases ND which causes vaseclilatien in respense te muscarin ic stimuli i ieweverr unliite the recepters innervated bv svmpathetic chelinergic fibers in skeletal muscle bleed vessels these muscarinic recepters are net innervated and respend enlv te esegeneuslv added muscarinic agenists in tihe circulatien iquotiill i iile39 acirenergic fibers terminate at inhib iterv Elsii39ECEptDFS en smeeth muscle fibers and at inhibiterv earecepters en parasympathetic chelinergiicj escitaterv danglien cells ef the mventeric plexus the primarv inhibi terv respense is mediated we enteric neurens threueh new Pat recepters and peptide recepters jUterine respenses depend en stages ef menstrual cycle ameunt ef circulating estregen and re esterene and ether facters kFalms ef hands and same ether sites 39quotadrenergiic sweating39 39 Theireiis significant variatien amend species in the recepteir tvpes that mediatecertain metabeiic respenses all three 5 adrenergic recepters have been faced in human fat celils exdivatien cf 53 adrenergic recepters prexduces a vigereus thermegenic respense as well as lipelvsis The significance is unclear ectlvatien ef B adrenergic recepters alse inhibits leptin release frem ad39ipese tissue httpwawaccessmedlciheterneapresvmeduehieediufpepu pa5peaDEngEEl Page 5 ref IE PHCL 2600 Page 6 Table 6 11 RE EFDI ISES ref Effecter Dream te memmie Nerve Impul ee IDIEIMEDDE 1121 AM ADIHI emt diuret e hermene erginine veengreeeir u Cl ipt right 2 l The McGraJwHill Cle mtpamiiee ll rights lf39ESEWEd Privaex Notice Any we is 594 eject te the Terms ef Use and Notice dditieme Credits and Comment Im Fetmetien quot Mammal 3 silverch ir mmindium rutam A rhMc r w m empenmj httpIfwwwuemcee5Smediicinemmezerenemeduehieeldmmepu pe5mlteD959EEl Page E at E PHCL 2600 Page 7
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