the autonomic nervous system - prehospital medicine · autonomic nervous system functions: ......
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The Autonomic Nervous SystemThe Autonomic Nervous System
Autonomic Nervous SystemAutonomic Nervous System
Functions:Functions:
Without conscious effort, Without conscious effort,
Continuously.Continuously.
Controls:Controls:
Activities in smooth & cardiac muscles and Activities in smooth & cardiac muscles and sweat glands.sweat glands.
Nervous SystemNervous SystemNervous System
Central N.S.
brain &spinal cord
Peripheral N.S.AfferentDivision (information in)
EfferentDivision
(orders out)
Somatic System
(skeletal muscles)
AutonomicsystemSympathetic Parasympathetic
Components of the ANSComponents of the ANS
The autonomic component is divided The autonomic component is divided anatomically into:anatomically into:
the nerve fibers that innervate target organs the nerve fibers that innervate target organs or tissues or tissues
and nerve fibers that innervate the adrenal and nerve fibers that innervate the adrenal medulla that causes the release of substances medulla that causes the release of substances called catecholamines that act upon the ANS.called catecholamines that act upon the ANS.
Autonomic Nervous SystemAutonomic Nervous System
The Autonomic System can be influenced or The Autonomic System can be influenced or manipulated in two ways:manipulated in two ways:
by hormones that are circulated through the blood stream by hormones that are circulated through the blood stream ((ieie. ADH);. ADH);
and by the stimulation or blocking of nerve impulses. An and by the stimulation or blocking of nerve impulses. An example is the transmission impulses from receptors in the example is the transmission impulses from receptors in the carotid sinus and aortic arch to control B/P.carotid sinus and aortic arch to control B/P.
Both play important roles in the reflex regulation of the Both play important roles in the reflex regulation of the systemsystem. .
Sympathetic NeuronsSympathetic Neurons
Sympathetic neurons exit the spinal cord Sympathetic neurons exit the spinal cord via the thoracic vertebrae and lumbar via the thoracic vertebrae and lumbar vertebrae. For this reason the vertebrae. For this reason the sympathetic division is sometimes called sympathetic division is sometimes called the the thoracolumbarthoracolumbar division.division.
Sympathetic DivisionSympathetic Division
Parasympathetic NeuronsParasympathetic Neurons
The parasympathetic system is also termed the The parasympathetic system is also termed the CranialCranial--SacralSacral system because of the location system because of the location on the spinal cord that these nerves are located. on the spinal cord that these nerves are located.
PreganglionicPreganglionic fibres arise from neurons in the fibres arise from neurons in the midbrain midbrain –– medulla & pons medulla & pons –– and the sacral area and the sacral area of he spinal cord. of he spinal cord.
The Vagus ( X ) nerve carries about The Vagus ( X ) nerve carries about ¾¾ of all of all Parasympathetic fibres.Parasympathetic fibres.
Parasympathetic DivisionParasympathetic Division
Anatomy
• Sympathetic
• Parasympathetic
- “thoracolumbar”- T1-L3 (F, F, F)
- “craniosacral”- brainstem &S2-S4 (R & D)
Actions: Sympathetic vs. Actions: Sympathetic vs. ParasympatheticParasympathetic
Site Sympathetic Sympathetic ParasympatheticParasympathetic
Eye Dilate Constrict
Trachea/ BronchiTrachea/ Bronchi DilateDilate Constrict, increase Constrict, increase secretionssecretions
HeartHeart Increase HR, Increase HR, contractilitycontractility
Decrease rate, Decrease rate, contractilitycontractility
GI TractGI Tract Decrease GI MotilityDecrease GI Motility Increase MotilityIncrease Motility
Blood Supply to Blood Supply to MusclesMuscles
IncreasedIncreased No effectNo effect
Blood Supply to Blood Supply to Skin/Mucous Skin/Mucous MembranceMembrance/GI Tract/GI Tract
ConstrictConstrict No effectNo effect
ExceptionsExceptions
All systems dual innervation (both sympathetic and parasympathetic fibres).
Exceptions:
Adrenal medulla
Sweat glands and piloerector muscles
Ventricles of Heart
ALL ARE SYMPATHETIC INNERVATION ONLY
Structure of a typical neuronStructure of a typical neuron
Axon End Terminal; Meet Axon End Terminal; Meet DendriteDendrite
Slide #3 (BASIC)
Actual PhotographActual Photograph
Neurons and NeurotransmittersNeurons and Neurotransmitters
Two of the most frequently discussed Two of the most frequently discussed neurotransmitters:neurotransmitters:
Epinephrine and NorepinephrineEpinephrine and Norepinephrine
binds to:binds to:
alpha (alpha (11 22 ))
beta (beta (11 2 2 ))--note NE binds B1 onlynote NE binds B1 only
AcetylcholineAcetylcholine
nicotinic
muscarinic
Other NeurotransmittersOther Neurotransmitters
serotoninserotonin (5(5--HT)HT)
melatoninmelatonin
GlutamateGlutamate
gamma gamma aminobutyricaminobutyric acidacid (GABA), (GABA), aspartateaspartate
glycineglycine
histaminehistamine
AdenosineAdenosine, , ATPATP, , GTPGTP, and their derivatives , and their derivatives
Neurotransmitters send chemical messages.
NorepinephrineNorepinephrine
The major postganglionic neurotransmitter The major postganglionic neurotransmitter of the SNS.of the SNS.
It is produced from building blocks that It is produced from building blocks that are present in the end terminal of the are present in the end terminal of the neuron.neuron.
Adrenal medulla: 80% NE
EPI
Storage and ReleaseStorage and Release
Neurotransmitters are Neurotransmitters are taken up for storage taken up for storage at terminal endings of at terminal endings of nerves.nerves.
Nerve impulse Nerve impulse prompts prompts exocytosisexocytosis of of vesicles containing vesicles containing neurotransmitter.neurotransmitter.
ExocytosisExocytosis
ExocytosisExocytosis
NorepinephrineNorepinephrine
Following its use as a neurotransmitter, Following its use as a neurotransmitter, Norepinephrine is removed by:Norepinephrine is removed by:
Reuptake into the terminal nerve ending by Reuptake into the terminal nerve ending by active transport active transport –– 5050--80%. 80%.
Na+,K+Na+,K+--ATPaseATPase is the pump responsible for this reuptake. is the pump responsible for this reuptake.
Pump inhibited by cocaine, Pump inhibited by cocaine, TCAsTCAs..
Diffusion away from the nerve endings into the Diffusion away from the nerve endings into the surrounding body fluids.surrounding body fluids.
Destruction by enzymes such as MAO & COMT.Destruction by enzymes such as MAO & COMT.
Synthesis of AcetylcholineSynthesis of Acetylcholine
Acetylcholine is the major preganglionic Acetylcholine is the major preganglionic neurotransmitter of both the SNS and PNS and neurotransmitter of both the SNS and PNS and is the neurotransmitter of the postganglionic is the neurotransmitter of the postganglionic side of the PNS. side of the PNS.
It is also the neurotransmitter for the somatic It is also the neurotransmitter for the somatic system with striated skeletal muscle.system with striated skeletal muscle.
The only exception to this is the The only exception to this is the neurotransmitter for the neurotransmitter for the pilomotorpilomotor and sweat and sweat glands innervated by the SNS. Acetylcholine is glands innervated by the SNS. Acetylcholine is the neurotransmitter responsible at this end the neurotransmitter responsible at this end also, not Norepinephrine. This distinction is also, not Norepinephrine. This distinction is important when you start to study important when you start to study toxidromestoxidromes. .
Synthesis of AcetylcholineSynthesis of Acetylcholine
The process of synthesizing acetylcholine The process of synthesizing acetylcholine requires a catalyst to enable the reaction to requires a catalyst to enable the reaction to occur. occur.
This enzyme is This enzyme is cholinecholine acetyltransferaseacetyltransferase. .
On the opposite end, when acetylcholine is On the opposite end, when acetylcholine is broken down, it requires cholinesterase to broken down, it requires cholinesterase to facilitate the process. facilitate the process.
Acetyl coenzyme A binds with Acetyl coenzyme A binds with cholinecholine in the in the presence of catalyst presence of catalyst cholinecholine acetyltransferaseacetyltransferase to form acetylcholine.to form acetylcholine.
Acetylcholine is brokenAcetylcholine is broken--down by down by cholinesterase.cholinesterase.
ANS ReceptorsANS Receptors
The parasympathetic system is The parasympathetic system is referred to as the cholinergic referred to as the cholinergic system system –– this is because the major this is because the major neurotransmitter for the PNS is neurotransmitter for the PNS is acetylcholine.acetylcholine.
So why is the sympathetic system So why is the sympathetic system called the adrenergic system?called the adrenergic system?
There are two major receptors in the There are two major receptors in the PNS:PNS:
ANS ReceptorsANS Receptors
MuscarinicMuscarinic which are in the postganglionic PNS which are in the postganglionic PNS on the target end organs.on the target end organs.
NicotinicNicotinic, which are in the preganglionic side of , which are in the preganglionic side of both the SNS and the PNS.both the SNS and the PNS.
Some of the drugs that we administer affect Some of the drugs that we administer affect these receptors specifically: atropine blocks these receptors specifically: atropine blocks muscarinic receptors specifically and other muscarinic receptors specifically and other agents (curare) block nicotinic receptors in agents (curare) block nicotinic receptors in skeletal muscleskeletal muscle
Receptors ( I )Receptors ( I )
Adrenergic ( SNS ):Adrenergic ( SNS ):
11
blood vesselsblood vessels
constrictionconstriction
22
11
heartheart
HR, contractility, & HR, contractility, & conduction conduction
22
bronchial/vascular s.m.bronchial/vascular s.m.
dilationdilation
Cholinergic ( PNS ):Cholinergic ( PNS ):
Muscarinic:Muscarinic:
endend--organs organs ( Parasympathetic )( Parasympathetic )
stimulate accordinglystimulate accordingly
Nicotinic:Nicotinic:
gangliaganglia
stimulate poststimulate post-- ganglion neuronganglion neuron
musclesmuscles
stimulate contractionstimulate contraction
alpha ( alpha (
) and beta ( ) and beta (
) ) Receptors:Receptors:Alpha ReceptorsAlpha Receptors
Alpha 1Alpha 1 receptors:receptors:
Found predominately outside of the heart & major Found predominately outside of the heart & major organs.organs.
Influence smooth muscle found in the peripheral Influence smooth muscle found in the peripheral vasculature, intestinal tract and eyes.vasculature, intestinal tract and eyes.
Alpha 1:Alpha 1:
Vasoconstriction, pupil dilation, intestinal relaxation, Vasoconstriction, pupil dilation, intestinal relaxation, etc.etc.
Alpha ReceptorsAlpha Receptors
Alpha 2Alpha 2 receptors:receptors:
Act as a mediator of neurotransmitter production Act as a mediator of neurotransmitter production –– as neurotransmitter is released from the neuron, as neurotransmitter is released from the neuron, receptor sites on the neuron become filled receptor sites on the neuron become filled –– when when sufficient numbers have been occupied, a message sufficient numbers have been occupied, a message is sent to reduce or turnis sent to reduce or turn--off the production of off the production of neurotransmitter neurotransmitter –– this is sometimes referred to as this is sometimes referred to as a feedback loop mechanism.a feedback loop mechanism.
Alpha 2:Alpha 2:
Preganglionic receptor that regulates the release of Preganglionic receptor that regulates the release of neurotransmitter through a feedback loop.neurotransmitter through a feedback loop.
alpha ( alpha (
) and beta ( ) and beta (
) ) Receptors:Receptors:
Beta ReceptorsBeta Receptors
Beta 1Beta 1 receptors:receptors:
Found in the heart Found in the heart –– stimulation or stimulation or excitement of these receptors leads to an excitement of these receptors leads to an increase in heart rate (chronotropic), in force increase in heart rate (chronotropic), in force of contraction (of contraction (inotropicinotropic), and rate of nerve ), and rate of nerve impulse conduction (impulse conduction (dromotropicdromotropic).).
alpha ( alpha (
) and beta ( ) and beta (
) ) Receptors:Receptors:
alpha ( alpha (
) and beta ( ) and beta (
) ) Receptors:Receptors:Beta ReceptorsBeta Receptors
Beta 2Beta 2 receptors:receptors:
Found primarily in the pulmonary smooth muscle lining the Found primarily in the pulmonary smooth muscle lining the lower airways of the lungs and in the peripheral vasculature lower airways of the lungs and in the peripheral vasculature –– it is also thought that beta 2 cells in the liver regulate the it is also thought that beta 2 cells in the liver regulate the release of glycogen stores.release of glycogen stores.
Beta 2:Beta 2:
Primarily bronchodilation and peripheral vasodilation with Primarily bronchodilation and peripheral vasodilation with increased glycogen release.increased glycogen release.
IF you have trouble remembering where the beta 1 and beta 2 IF you have trouble remembering where the beta 1 and beta 2 receptors are located, receptors are located,
then just think of 1 heart = beta 1; and 2 lungs = beta 2.then just think of 1 heart = beta 1; and 2 lungs = beta 2.
Before We ContinueBefore We Continue
Pharmacology ofPharmacology of Synaptic TransmissionSynaptic Transmission
Drugs that facilitate a neurotransmitterDrugs that facilitate a neurotransmitter’’s s effects are called effects are called agonistsagonists; drugs that ; drugs that reduce a neurotransmitterreduce a neurotransmitter’’s effect are s effect are called called antagonistsantagonists
Drugs act upon one or more of the steps Drugs act upon one or more of the steps in neurotransmitter action; the exact in neurotransmitter action; the exact mechanism varies from drug to drugmechanism varies from drug to drug
Pharmacology ofPharmacology of Synaptic TransmissionSynaptic Transmission
For example, For example, cocainecocaine is a catecholamine is a catecholamine agonist that acts by blocking the reuptake agonist that acts by blocking the reuptake of dopamine and norepinephrineof dopamine and norepinephrine
Pharmacology ofPharmacology of Synaptic TransmissionSynaptic Transmission
By contrast, By contrast, valiumvalium is a GABA agonist is a GABA agonist that acts by increasing the binding of that acts by increasing the binding of GABA to its receptorGABA to its receptor
GABA is an inhibitory neurotransmitter (itGABA is an inhibitory neurotransmitter (it’’s s receptor allows Clreceptor allows Cl-- in, hyperpolarizing, in, hyperpolarizing, IPSPsIPSPs))
Pharmacology ofPharmacology of Synaptic TransmissionSynaptic Transmission
AtropineAtropine and and curarecurare are both ACh are both ACh antagonists;antagonists;
atropine blocks atropine blocks muscarinemuscarine receptors, not receptors, not allowing acetylcholine to bind allowing acetylcholine to bind
whereas curare paralyzes by blocking nicotinic whereas curare paralyzes by blocking nicotinic receptors, not allowing acetylcholine to bindreceptors, not allowing acetylcholine to bind
ToxicologyToxicology
DefinitionsDefinitions
ToxidromeToxidrome: a set of signs and symptoms : a set of signs and symptoms induced by ingestion of a toxic substance.induced by ingestion of a toxic substance.
Toxicology: The science of poisons, : The science of poisons, including their source, chemical including their source, chemical composition, action, tests, and antidotes.composition, action, tests, and antidotes.
ToxicodynamicsToxicodynamics: the study of the effects : the study of the effects of the toxic substance at the molecular of the toxic substance at the molecular level.level.
Major Toxic SyndromesMajor Toxic Syndromes
Cholinergic/AnticholinesteraseCholinergic/Anticholinesterase
AnticholinergicAnticholinergic
HallucinogenicHallucinogenic
OpiateOpiate
Sedative/hypnoticSedative/hypnotic
SympathomimeticSympathomimetic
Drug WithdrawalDrug Withdrawal
Cholinergic & Cholinergic & AnticholinesteraseAnticholinesterase
Organophosphate Organophosphate insecticides are examples insecticides are examples of cholinesterase of cholinesterase inhibitors.inhibitors.
Muscarinic signs and Muscarinic signs and symptoms may be symptoms may be remembered by using remembered by using one of the following one of the following mnemonicsmnemonics::
DUMBBELSDUMBBELS SLUDGESLUDGE
Cholinergic & Cholinergic & AnticholinesteraseAnticholinesterase
DDiarrheaiarrhea
UUrinationrination
MMiosisiosis
BBronchorrhearonchorrhea
BBradycardiaradycardia
EEmesismesis
LLacrimationacrimation
SSalivationalivation
SSalivationalivation
LLacrimationacrimation
UUrinationrination
DDefecationefecation
GG.I. Cramps.I. Cramps
EEmesismesis
Cholinergic & Cholinergic & AnticholinesteraseAnticholinesterase
Nicotinic signs can be remembered Nicotinic signs can be remembered using the using the MTWHFMTWHF mnemonic :mnemonic :
MMydriasisydriasisTTachycardiaachycardiaWWeaknesseaknessHHypertension/Hypoglycemiaypertension/HypoglycemiaFFasiculationsasiculations
Cholinergic & Cholinergic & AnticholinesteraseAnticholinesterase
Central signs may include:Central signs may include:-- CConfusiononfusion-- CConvulsionsonvulsions-- CComaoma
AnticholinergicsAnticholinergics
-- TCATCA-- AntihistaminesAntihistamines-- Belladonna alkaloids Belladonna alkaloids
(atropine/scopolamine)(atropine/scopolamine)-- MushroomsMushrooms-- AntipsychoticsAntipsychotics
-- OTC sleep meds.OTC sleep meds.
-- OTC cold meds.OTC cold meds.
-- ScopolamineScopolamine
-- Jimson WeedJimson Weed
Anticholinergic ToxidromesAnticholinergic Toxidromes
Red As A BeetRed As A Beet
Hot as a HareHot as a Hare
Mad as A HatterMad as A Hatter
Dry as a BoneDry as a Bone
Blind as a BatBlind as a Bat
AnticholinergicsAnticholinergics Signs include:Signs include:
Peripheral:Peripheral:-- flushed skin flushed skin -- mydriasis mydriasis -- hyperpyrexia hyperpyrexia -- dry skin & mucous dry skin & mucous
membranes membranes -- thirstthirst-- urinary retentionurinary retention
Central:Central:-- anxiety, confusionanxiety, confusion-- agitationagitation-- dysphagiadysphagia-- deliriumdelirium-- ataxiaataxia-- lethargylethargy-- respiratory failurerespiratory failure-- coma, deathcoma, death
AnticholinergicsAnticholinergics
Vital signs:Vital signs:
Increased pulse, increased respiratory Increased pulse, increased respiratory rate, increased B/P, increased temp.rate, increased B/P, increased temp.
These patients have many of the same signs These patients have many of the same signs as seen in as seen in sympathomimeticsympathomimetic & withdrawal.& withdrawal.
It is useful to note that these patients It is useful to note that these patients dondon’’t sweat or have bowel sounds.t sweat or have bowel sounds.
SympathomimeticsSympathomimetics
CocaineCocaine
MethamphetamineMethamphetamine
Methylphenidate Methylphenidate (Ritalin) (Ritalin)
SympathomimeticsSympathomimetics
HypertensionHypertension
TachycardiaTachycardia
Psychomotor AgitationPsychomotor Agitation
HyperthermiaHyperthermia
DiaphoresisDiaphoresis
MydriasisMydriasis
Causes of Adrenergic StateThink I’m not SAD
Sympathomimetics AnticholinergicsDrug withdrawal Hallucinogens
OpiatesOpiates
MiosisMiosis
Respiratory depressionRespiratory depression
BradycardiaBradycardia
HypotensionHypotension
SedationSedation
Decreased GI motilityDecreased GI motility
HypothermiaHypothermia
Pulmonary edemaPulmonary edema
SeizuresSeizures
NarcoticsNarcotics
Narcotics:Narcotics:-- Heroin, Morphine, Codeine, Heroin, Morphine, Codeine,
MeperidineMeperidine
Signs may include:Signs may include:-- CNS depressionCNS depression-- Respiratory depressionRespiratory depression-- Pulmonary edemaPulmonary edema-- HypotensionHypotension-- Miosis ( except Demerol )Miosis ( except Demerol )-- SeizuresSeizures
NarcoticsNarcotics
Miosis seen in approximately 90% of Narcotic Miosis seen in approximately 90% of Narcotic O.D. , unless hypoxic or mixed overdose O.D. , unless hypoxic or mixed overdose (exceptions are Demerol and Talwin). (exceptions are Demerol and Talwin).
If vomiting occurs with these patients, good If vomiting occurs with these patients, good chance of aspiration. chance of aspiration.
NonNon--cardiogenic pulmonary edema can be an cardiogenic pulmonary edema can be an extremely rapid onset, is usually fulminatingextremely rapid onset, is usually fulminating..
Longer half/life than Longer half/life than narcannarcan
BarbituatesBarbituates
Barbituates:Barbituates:Phenobarbital Long lastingPhenobarbital Long lastingButabarbitalButabarbital IntermediateIntermediateSecobarbitalSecobarbital Short actingShort acting
Overdose:Overdose:
No antidoteNo antidote
Skin Skin bullaebullae presentationpresentation
Narcotic Overdose: Special Narcotic Overdose: Special casescases
Pupils largePupils large
MeperedineMeperedine (Demerol)(Demerol)
LomotilLomotil
Narcan may not work:Narcan may not work:
FentanylFentanyl
Rigid chest syndromeRigid chest syndrome
Long acting agentsLong acting agents
methadonemethadone
MSMS--ContinContin
OxycontinOxycontinJanis Joplin
Narcotic Overdose: Narcotic Overdose: Atypical toxicity seenAtypical toxicity seen
SeizuresSeizures
MeperedineMeperedine (Demerol)(Demerol)
Tramadol (Ultram) Tramadol (Ultram)
Pentazocine (Talwin)Pentazocine (Talwin)
ProxypheneProxyphene (Darvocet)(Darvocet)
Ventricular Ventricular arrythmiasarrythmias
ProxypheneProxyphene (Darvocet)(Darvocet)
Serotonin syndromeSerotonin syndrome
MeperedineMeperedine
DextromorphanDextromorphan
Narcotic WithdrawalNarcotic Withdrawal
Vital Signs:Vital Signs:
Increased respiratory rate, increased Increased respiratory rate, increased pulse, increased B/P, increased temp.pulse, increased B/P, increased temp.
Signs may include:Signs may include:-- AgitationAgitation-- YawnYawn-- VomitingVomiting-- Cold turkey skinCold turkey skin-- Normal mental statusNormal mental status
Narcotic WithdrawalNarcotic Withdrawal
Cholinergic + +Cholinergic + +
Progression of signs & symptoms:Progression of signs & symptoms:
Yawn, Yawn, lacrimationlacrimation, , rhinnorhearhinnorhea, diaphoretic, , diaphoretic, restless, insomnia.restless, insomnia.
Mydriasis, Mydriasis, goosebumpsgoosebumps, aching, nausea., aching, nausea.
Anorexia, vomiting, diarrhea, ( after 2 Anorexia, vomiting, diarrhea, ( after 2 --3 3 days ).days ).
DishevelledDishevelled appearance, fever, increased B/P.appearance, fever, increased B/P.
Toxins and their AntidotesToxins and their Antidotes
AcetaminophenAcetaminophen NN--acetylcysteineacetylcysteine
Physostigmine
AtropineAtropine(muscarinic effects)(muscarinic effects)
PralidoximePralidoxime(nicotinic effects)(nicotinic effects)
AnticholinergicsAnticholinergics
AnticholinesterasesAnticholinesterases//CholinergicsCholinergics
Toxins and their AntidotesToxins and their Antidotes
BenzodiazepinesBenzodiazepines
BotulismBotulism
BetaBeta--blockersblockers
Calcium channel blockersCalcium channel blockers
Carbon monoxideCarbon monoxide
Cyanide, NitritesCyanide, Nitrites
FlumazenilFlumazenil
BotulinumBotulinum antitoxinantitoxin
GlucagonGlucagon
CalciumCalcium
Hyperbaric OHyperbaric O 22 , O, O 22
Sodium Sodium thiosulfatethiosulfate
Toxins and their AntidotesToxins and their Antidotes
EthanolEthanol
MethyleneMethylene blueblue
NaloxoneNaloxone
NaHCO3NaHCO3
Vitamin KVitamin K
MethanolMethanol
MethemoglobinMethemoglobin
OpioidsOpioids
TricyclicTricyclic antidepressantsantidepressants
Warfarin Warfarin
Pupillary ReactionsPupillary Reactions
Drugs that can Drugs that can cause Miosis:cause Miosis:
Narcotics Narcotics ( except Demerol )( except Demerol )
Cholinergic & Cholinergic & AnticholinesteraseAnticholinesterase OrganophosphatesOrganophosphates
PhencyclidinePhencyclidine ( PCP )( PCP )
MushroomsMushrooms
PhenothiazinesPhenothiazines
Drugs that can Drugs that can cause Mydriasis:cause Mydriasis:
AnticholinergicsAnticholinergics
SympathomimeticsSympathomimetics
Drug withdrawalDrug withdrawal
DemerolDemerol
Cholinergic & Cholinergic & AnticholinesteraseAnticholinesterase
Drugs that can cause Drugs that can cause Pulmonary EdemaPulmonary Edema
Drugs that cause pulmonary edema:Drugs that cause pulmonary edema:
-- SalicylatesSalicylates-- Narcotics ( especially Heroin )Narcotics ( especially Heroin )-- Carbon monoxideCarbon monoxide-- Sedative Sedative -- hypnoticshypnotics-- OrganophosphatesOrganophosphates
ToxidromesToxidromes
If patient presents If patient presents with:with:
pinpoint pupilspinpoint pupils
CNS depressionCNS depression
respiratory respiratory depressiondepression
Think NarcoticsThink Narcotics
If patient presents If patient presents with:with:
dilated pupilsdilated pupils
dry skindry skin
decreased GI decreased GI motilitymotility
dysrhythmiasdysrhythmias
↑↑
respirations, pulse, respirations, pulse, B/P, temperatureB/P, temperature
Think Think Anticholinergic Anticholinergic SyndromeSyndrome
ToxidromesToxidromes
If patient presents If patient presents with:with:
pinpoint pupilspinpoint pupils
sweatingsweating
increased secretions increased secretions -- SLUDGESLUDGE
increased GI motilityincreased GI motility
Think Cholinergic SyndromeThink Cholinergic Syndrome
ToxidromesToxidromes
If patient presents with:If patient presents with:
pallorpallor
diaphoresisdiaphoresis
nausea / vomiting / diarrheanausea / vomiting / diarrhea
hyperadrenergichyperadrenergic ( SNS ) ( SNS )
↑↑
respirations, pulse, B/P, temperaturerespirations, pulse, B/P, temperature
bowel sounds present bowel sounds present Think Think Sympathomimetic / Drug WithdrawalSympathomimetic / Drug Withdrawal
3,4 3,4 MethylenedioxymethamphetamineMethylenedioxymethamphetamine
OverviewOverview
Stimulant/hallucinogenStimulant/hallucinogen
19501950’’ss--armyarmy
19701970’’s therapy tools therapy tool
Route of admin.Route of admin.
DoseDose
5050--100mg/tablet100mg/tablet
Effective dose is Effective dose is 11--2mg/kg2mg/kg
Onset 30Onset 30--60 min.60 min.
Effects last 3Effects last 3--4 hours4 hours
Effects of EcstasyEffects of Ecstasy
TachycardiaTachycardia
MydriasisMydriasis
HypertensionHypertension
HyperthermiaHyperthermia
Muscle CrampsMuscle Cramps
HallucinationsHallucinations
SweatingSweating
DehydrationDehydration
But Wait, ThereBut Wait, There’’s Mores More
RhabdomyolysisRhabdomyolysis
Cardiac ArrhythmiasCardiac Arrhythmias
CVAsCVAs
SeizuresSeizures
ComaComa
DeathDeath
Ecstasy destroys neurons.
Treatment PearlsTreatment Pearls
CC--spinespine
ABCsABCs
BenzodiazepinesBenzodiazepines
IV fluidsIV fluids
CoolingCooling
Cause of most Cause of most fatalities?fatalities?
Physiology ofEcstasy
End Terminal and VesiclesEnd Terminal and Vesicles
Receptors & ReReceptors & Re--uptakeuptake
Serotonin/Receptor BindingSerotonin/Receptor Binding
GimmeGimme an an ““E!E!””
Serotonin Reuptake Serotonin Reuptake TransportersTransporters
Monoamine Monoamine OxidaseOxidase
DonDon’’t Bring Me Downt Bring Me Down
Depressed? You Bet!Depressed? You Bet!
Funny, I crave turkeyFunny, I crave turkey
Receptor DownReceptor Down--regulationregulation
NeurotoxicityNeurotoxicity--Current TheoryCurrent Theory
ShrinkageShrinkage
How Ecstasy WorksHow Ecstasy Works
Transporter Working BackwardsTransporter Working Backwards
End ResultEnd Result
Ecstasy + Prozac = Nothing!Ecstasy + Prozac = Nothing!
Which one is Real?Which one is Real?
TimelineTimeline
3000 BC3000 BC--Coca chewing Coca chewing practiced in S. Americapracticed in S. America
1500s Incan coca 1500s Incan coca plantations controlled by plantations controlled by SpanishSpanish
15751575--Labourers in Labourers in Spanish silver mines Spanish silver mines chewed cocachewed coca
1855 Cocaine extracted 1855 Cocaine extracted from coca leavesfrom coca leaves
1862 Merck produces 1862 Merck produces ¼¼ pound of cocainepound of cocaine
1884 Freud advocates 1884 Freud advocates use to treat variety of use to treat variety of conditionsconditions
1884 Merck produces 1884 Merck produces 3179 pounds of cocaine3179 pounds of cocaine
1886 Merck produces 1886 Merck produces 158352 pounds158352 pounds
TimelineTimeline
1886 Coca Cola 1886 Coca Cola introducedintroduced
1901 Coca Cola removes 1901 Coca Cola removes coca from their coca from their forumulaforumula
1910 First reports of 1910 First reports of nasal damage in literaturenasal damage in literature
1912 US government 1912 US government reports 5000 cocaine reports 5000 cocaine related fatalities/yearrelated fatalities/year
The Harrison Narcotics The Harrison Narcotics Act of 1914 banned Act of 1914 banned nonprescriptionnonprescription use of use of cocainecocaine--containing containing products products
19201920--1970 cocaine use 1970 cocaine use diminishesdiminishes
1970 Cocaine becomes 1970 Cocaine becomes schedule II substanceschedule II substance
1984 One kg costs 1984 One kg costs $25000$25000
Norepinephrine Everywhere!Norepinephrine Everywhere!
2525--100mg/line100mg/line
CocaCoca--Cola had Cola had 80mg/bottle80mg/bottle
Cocaine EffectsCocaine Effects
Think Think hyperadrenergichyperadrenergic
Blocks reuptake of Blocks reuptake of norepinephrinenorepinephrine
Stimulates release of Stimulates release of norepinephrine, norepinephrine, dopamine and dopamine and serotoninserotonin
Side EffectsSide Effects
CVACVA
HyperthermiaHyperthermia
rhabdomyolysisrhabdomyolysis
MIMI
CADCAD
TachycardiaTachycardia
Route Onset Peak Effect (min)
Duration (min)
Half-Life (min)
Inhalation 7 s 1-5 20 40-60
IV 15 s 3-5 20-30 40-60
Nasal 3 min 15 45-90 60-90
Oral 10 min 60 60 60-90
Onset of EffectsOnset of Effects
plus
MethamphetamineMethamphetamine
Figure 1 www.dea.gov
First synthesized 1887
Initial application 1920s as nasal decongestant (Benzedrine)
WW II used as stimulant
Popular with students and truckers in the 1950’s (Dexedrine)
Schedule II in 1971
Off-white/pinkish or yellowish powder, 5-20% purity
MethamphetamineMethamphetamine--An OverviewAn Overview
MethamphetamineMethamphetamine--An OverviewAn Overview
StimulantStimulant
Effects last up to 12 hours (cocaine 20 min)Effects last up to 12 hours (cocaine 20 min)
Ice, crystal meth (ephedrine reduction) Average dose 50 Ice, crystal meth (ephedrine reduction) Average dose 50 –– 200 mg200 mg
Onset of actionOnset of action
Oral: 30Oral: 30--60 min60 min
Nasal: 15Nasal: 15--20 min20 min
Inhaled or injected: 1Inhaled or injected: 1--3 min3 min
Elimination halfElimination half--life and duration of action: 4 life and duration of action: 4 –– 6 hours6 hours
White, yellow, light brown, dark brown powderWhite, yellow, light brown, dark brown powder
Whiter is cleanerWhiter is cleaner
Pills, capsules, injected, smokedPills, capsules, injected, smoked
Methamphetamine UsersMethamphetamine Users
TweakersTweakers
Long time, habitual meth Long time, habitual meth usersusers
Attempt to maintain Attempt to maintain steady state of meth in steady state of meth in their bloodstreamtheir bloodstream
May be sleep deprivedMay be sleep deprived
Frustrated, unpredictable Frustrated, unpredictable and dangerousand dangerous
May appear May appear ““supersuper-- exaggerated normalexaggerated normal””
TweakersTweakers
Eyes clear, speech concise, movements briskEyes clear, speech concise, movements brisk
Eyes look normal but on close exam may be moving Eyes look normal but on close exam may be moving 10X faster than normal may appear to roll10X faster than normal may appear to roll
Movements may be exaggerated (Movements may be exaggerated (overstimulatedoverstimulated))
Thought process scattered, paranoidThought process scattered, paranoid
Requires little provocation to react violently, may be Requires little provocation to react violently, may be hallucinatinghallucinating
Items Found in LabsItems Found in Labs
Lab glasswareLab glassware
Heat sourceHeat source
Red phosphorusRed phosphorus-- striker striker plates/road flaresplates/road flares
Starter fluid (ether)Starter fluid (ether)
Muriatic/hydrochloric Muriatic/hydrochloric acidacid--hardware storeshardware stores
Sodium hydroxide (lye): Sodium hydroxide (lye): "Drano" "Drano"
Sulfuric acid: battery acid Sulfuric acid: battery acid or drain cleanersor drain cleaners
Anhydrous ammoniaAnhydrous ammonia-- farmerfarmer’’s cos co--opop
Coleman fuelColeman fuel
Other solvents and Other solvents and containerscontainers
Toluene: paint thinnerToluene: paint thinner
Methanol: gas tank antiMethanol: gas tank anti-- freezefreeze
Iodine crystalsIodine crystals
Lithium: camera batteriesLithium: camera batteries
Methamphetamine ProductionMethamphetamine Production
Cold MethodCold Method
ephedrine (ephedrine (sudafedsudafed))
Mix with water, denatured alcohol, methanol or Mix with water, denatured alcohol, methanol or other solvent.other solvent.
Add iodine, red phosphorus (Add iodine, red phosphorus (phogenephogene gas) and gas) and water, heat to boiling 6water, heat to boiling 6--8 hours8 hours
red red phorphorusphorphorus, lye, lye
ether, toluene or Coleman fuel.ether, toluene or Coleman fuel.
Cold MethodCold Method
Nazi MethodNazi Method
Heat the Heat the ephedrine/pseudoephephedrine/pseudoeph edrine mixture in a edrine mixture in a dish on a heat source.dish on a heat source.
Explosion riskExplosion risk
sodium metal, lithium sodium metal, lithium wirewire
anhydrous ammoniaanhydrous ammonia
Signs of UsageSigns of Usage
Think Think hyperadrenergichyperadrenergic!!
BradycardiaBradycardia??
AtherosclerosisAtherosclerosis
SeizuresSeizures
HyperthermiaHyperthermia
Long Term UsageLong Term Usage
Depletion in the neurons of these Depletion in the neurons of these neurotransmitters, especially dopamine, neurotransmitters, especially dopamine, can have permanent effects in the braincan have permanent effects in the brain
SlownessSlowness
ParkinsonParkinson’’s like movement disorderss like movement disorders-- tremor tremor and rigidityand rigidity
Thinking problemsThinking problems
Treatment PearlsTreatment Pearls
BenzodiazepinesBenzodiazepines
Placental vasoconstrictionPlacental vasoconstriction
Cooling techniquesCooling techniques
Decrease BP=Decrease ICPDecrease BP=Decrease ICP
HistoryHistory
19601960’’s s anaestheticanaesthetic--issuesissues
19801980’’s bodybuildings bodybuilding--issuesissues
19901990’’s ravess raves--issuesissues
How it WorksHow it Works
Naturally Naturally occuringoccuring
GABA in brainGABA in brain
Dopamine responseDopamine response-- dose dependantdose dependant
HghHgh in ratsin rats
Dose Dependant EffectsDose Dependant Effects
10mg/kg10mg/kg--amnesia, amnesia, drowsinessdrowsiness
20mg/kg20mg/kg--sleep, delta sleep, delta waveswaves
5050--70mg/kg70mg/kg-- hypnosis, comahypnosis, coma
Note: no analgesia or Note: no analgesia or muscle relaxationmuscle relaxation
Treatment PearlsTreatment Pearls
Manage airway Manage airway appropriatelyappropriately
NarcanNarcan??
BradycardiaBradycardia
HypotensionHypotension
Watch for Watch for myoclonusmyoclonus
HallucinogensHallucinogens
MescalineMescaline
DISSOCIATIVE DRUGSDISSOCIATIVE DRUGSKetamineKetaminePhenycyclidinePhenycyclidine (PCP)(PCP)PhenylcyclohexylpyrolidinePhenylcyclohexylpyrolidine (PHP)(PHP)
Acts on all six neurotransmitter systemsActs on all six neurotransmitter systems
AnticholinergicAnticholinergic: dry skin, : dry skin, miosismiosis Dopaminergic/AdrenergicDopaminergic/Adrenergic:agitation:agitation, delusions, delusionsOpioidOpioid:pain:pain perception alterationsperception alterationsSerotinergicSerotinergic: perceptual changes: perceptual changesGABA receptor inhibitionGABA receptor inhibition: excitation: excitation
TreatmentTreatment
HaloperidolHaloperidol
PresynapticPresynaptic dopamine antagonistdopamine antagonist
Shifts the dopamineShifts the dopamine--acetylcholine activity ratio in acetylcholine activity ratio in the limbic systemthe limbic system
Therefore can counteract the dopamine stimulation Therefore can counteract the dopamine stimulation and cholinergic antagonism of the drugand cholinergic antagonism of the drug
UsageUsage
First tried in humansFirst tried in humans
Never mindNever mind……..what ..what about using it to about using it to neuter fluffy?neuter fluffy?
ActionsActions
11--5 minutes for onset5 minutes for onset
3030--45 minutes duration of effect45 minutes duration of effect
Provides analgesia and Provides analgesia and anaesthesiaanaesthesia
KK--holehole
Treatment PearlsTreatment Pearls
Watch the Watch the laryngospasmlaryngospasm
Minimize tactile stimulation to diminish Minimize tactile stimulation to diminish psychosispsychosis
Watch for transient spikes in BPWatch for transient spikes in BP
Jimson WeedJimson Weed
Jimson Weed
DextromethorphanDextromethorphan
Stages of Stages of AnaesthesiaAnaesthesia
Drowsiness, confusion, analgesiaDrowsiness, confusion, analgesia
Euphoria, excitement, spontaneous muscle Euphoria, excitement, spontaneous muscle movements, hallucinationsmovements, hallucinations
Loss of consciousnessLoss of consciousness
Negative Side EffectsNegative Side Effects
FrostbiteFrostbite
Malignant HyperthermiaMalignant Hyperthermia
Does not combine with hemoglobinDoes not combine with hemoglobin
Injuries from fallingInjuries from falling