The Autonomic Nervous System

and Toxic Syndromes

S. Rutherfoord Rose
Virginia Poison Center
Division of Clinical Toxicology
Department of Emergency Medicine
VCU Health System
 Objectives
Š Review the anatomy and physiology of the
autonomic nervous system
Š Improve understanding of medications that
affect the autonomic nervous system
Š Use clinical findings to predict potential
causes of toxic syndromes
Š Go over a bunch of tox cases and make this
lecture slightly more enjoyable than a hernia
 Autonomic Nervous System

Š Temperature regulation
Š Fluid and electrolyte balance
Š Metabolism rate
Š Digestion and excretion
Š Cardiovascular function
 Autonomic Nervous System

Š Responsible for control of involuntary responses

Š Two functional divisions:
„ Sympathetic (adrenergic)
„ Parasympathetic (cholinergic)
Š Preganglionic fibers – from spinal cord to ganglia
Š Postganglionic fibers – from ganglia to target organs
Š Synapses – space between nerve cells (endings)
Š Neurotransmitters – chemical messengers
„ Norepinephrine (NE)
„ Acetylcholine (Ach)
 Autonomic Nervous System

A. Sympathetic (thoracolumbar)
• Peripheral neurotransmitter = norepinephrine
• Receptors: alpha (1 and 2) & beta (1 and 2)

B. Parasympathetic (craniosacral)
• Peripheral neurotransmitter = acetylcholine
• Cholinergic receptors: muscarinic and nicotinic
 Physiologic Receptors in the
Autonomic Nervous System
CHOLINERGIC (Acetylcholine)
Nicotinic: autonomic ganglia, adrenal
medulla, striated muscle
Muscarinic: heart, smooth muscle, glands

ADRENERGIC (epinephrine, norepinephrine)

Alpha – 1: blood vessels, eyes, reproductive organs
Alpha – 2: regulate neurotransmitter release
Beta – 1: heart and kidneys
Beta – 2: salivary glands, eyes, lungs, GI tract, arterioles of
hear, lungs, skin, skeletal muscle

DOPAMINERGIC
CNS and renal vasculature
Adrenergic Transmission
Parasympathetic Receptors
Autonomic NS Receptors
 Autonomic Pharmacology
Š Sympathetic
„ Agonist: sympathomimetic / adrenergic (epinephrine)
„ Antagonist: sympatholytic
z Alpha receptor blockers (phentolamine)
z Beta blockers (propranolol, metoprolol)
Š Parasympathetic
„ Agonist: cholinergic (acetylcholine)
„ Antagonist: parasympatholytic, anticholinergic
z Muscarinic receptor blocker (atropine)
z Nicotinic antagonist (neuromuscular blockers, ganglionic blockers)
 Toxic Syndromes

Š Physical signs
Š Patient symptoms
Š Characteristic odors, color
Š Laboratory findings
Š Suggests, but does not confirm, a diagnosis
 TOXIC SYNDROMES – CASE 1

A 34 y/o female presents with confusion, disorientation and

somnolence
HR 140 BP 130/80
RR 16 T 101.6

Pupils widely dilated, reactive

Skin hot, dry
Bowel sounds decreased
Mouth dry CLUE: depressed, took “sleeping
Speech slurred pills”
Diagnosis ???
 ANTICHOLINERGIC
SYNDROME
ƒ Antihistamines: pyrilamine, doxylamine,
diphenhydramine, dimenhydrinate
ƒ Phenothiazines, cyclic antidepressants
ƒ Antiparkinson agents: benztropine, trihexiphenidyl
ƒ Plants
z Jimson weed (Datura stramonium)
z Deadly nightshade (Atropa belladonna)

ƒ Some Mushrooms (muscimol, ibotenic acid)

ƒ Atropine, scopalamine
ƒ Antispasmodics (belladonna, hyoscamine)
 ANTICHOLINERGIC
SYNDROME
Blind as a bat

Dry as a bone

Red as a beet

Hot as Hades

Mad as a hatter
 TOXIC SYNDROMES – CASE 2

A 24 y/o male presents with seizures and coma.

HR 160
BP 190/100
RR 24
T 102
Pupils, dilated, reactive Marked diaphoresis
Bowel sound hypoactive

CLUE 1: EKG – narrow complex sinus tach

CLUE 2: Drug abuser
CLUE 3: HR & BP return to normal within 60 minutes
 SYMPATHOMIMETIC
SYNDROME
Š Mixed alpha and beta adrenergic effects
Š Clinical effects:
„ Tachycardia

„ Hypertension

„ CNS stimulation

„ Diaphoresis

„ Decreased GI motility

„ Miosis/Mydriasis
 SYMPATHOMIMETIC
SYNDROME
Dx: cocaine toxicity

Other agents:
¾ Amphetamines
¾ Ephedrine
¾ Pseudoephedrine
¾ Anoretics (Fen-Phen)
¾ Propylhexadrine
¾ Tyramine
 TOXIC SYNDROMES – CASE 3
A 22 y/o male presents with lethargy, confusion, and
complaining of severe crampy abdominal pain, vomiting
and severe diarrhea.
HR 60
BP 110/70
RR 28, labored
T 99
Diaphoretic, cyanotic, drooling
Marked respiratory distress with rales
Bowel sounds hyperactive
Incontinent of bowel and bladder

CLUE: depressed Orkin Man recently broke up with his girlfriend

 CHOLINERGIC SYNDROME

Š Excess acetylcholine at muscarinic and nicotinic receptors

Š Dx: Organophosphate insecticide

Š Other Agents:
„ Carbamate insecticides

„ Physostigmine

„ Nicotine insecticides

„ Tobacco

„ Mushroom (Clitocybe, Inocybe)

 CHOLINERGIC SYNDROME

D diarrhea, diaphoresis
U urination
M miosis
B bradycardia
B bronchorrhea
E emesis
L lacrimation
S salivation, sweating
 TOXIC SYNDROMES – CASE 4

A 19 y/o male presents with headache and lethargy.

No history of vomiting or diarrhea.
HR 60 BP 210/120
RR 16 T 99.9
Pupils dilated, sluggishly reactive
Skin slightly moist
Bowels sounds decreased
CLUE: 30 min later he develops È LOC and
hemiparesis. Hx of “street speed”.
 ALPHA ADRENERGIC
SYNDROME
Š Dx: Phenylpropanolamine (PPA) Overdose

Š Other agents:
„ Phenylephrine

„ Methoxamine

„ Imidazolines

z Tetrahydrozaline (Visine)
z Oxymetazoline

z Naphazoline

z Xylometazoline
 Alpha Adrenergic Drugs
ALPHA AGONISTS ALPHA ANTAGONISTS
Š Dobutamine Š Doxazosin (Cardura)
Š Dopamine Š Prazosin (Minipress)
Š Ephedrine Š Terazosin (Hytrin)
Š Epinephrine Š Phentolamine (Regitine)
Š Ergot alkaloids Š Phenoxybenzamine
Š Methoxamine (Vasoxyl) Š Tolazoline (Priscoline)
Š Phenylephrine (Neo-synephrine) Š Induramine (Baratol)
Š Phenylpropanolamine (PPA) Š Urapidil
Š Pseudoephedrine (Sudafed) Š Labetalol (alpha & beta)
 TOXIC SYNDROMES – CASE 5

A 2 y/o male presents with agitation and bizarre behavior.

HR 190
BP 80/60
RR 24
T 99.8

Tremulous, irritable
Pupils normal size, reactive
Skin and bowel sounds normal

CLUE: older sibling takes liquid medicine for asthma

 BETA-ADRENERGIC
SYNDROME
Š Dx: Albuterol overdose

Š Other agents:

„ Terbutaline
„ Metaproterenol
„ Isoproterenol
„ Theophylline
„ Caffeine
 Beta Adrenergic Drugs
BETA BLOCKERS
BETA AGONISTS Š Acebutolol (Sectral)
Š Albuterol (Proventil, Ventolin) Š Atenolol (Tenormin)
Š Bitolterol (Tornalate) Š Betaxolol (Kerlone)
Š Dobutamine Š Bisoprolol (Zebeta)
Š Dopamine Š Esmolol (Brevibloc)
Š Epinephrine Š Metoprolol (Lopressor)
Š Isoetharine (Bronkosol) Š Carteolol (Cartrol)
Š Isoproterenol (Isuprel) Š Nadolol (Corgard)
Š Metaproterenol (Alupent) Š Penbutolol (Levatol)
Š Norepinephrine Š Pindolol (Visken)
Š Ritodrine (Yutopar)] Š Propranolol (Inderal)
Š Salmeterol (Serevent) Š Sotalol (Betapace)
Š Terbutaline (Bricanyl, Brethrine) Š Timolol (Blocadren)
Š Labetalol (Normodyne, Trandate)
 Beta Blocker Toxicity

Š Bradycardia
Š Hypotension
Š A-V block
Š Heart failure
Š CNS depression
Š Seizures
 TOXIC SYNDROMES – CASE 6

A 2 y/o female presents with extreme lethargy.

HR 72 Dusky appearance
BP 70/50 Lips cyanotic
RR 10 Shallow respirations
T 98 Skin Dry
Bowel sounds decreased, present
CLUE 1: The child improves somewhat after a 2mg dose of
naloxone
CLUE 2: Grandfather, visiting at child’s house, takes blood
pressure medicine
 SYMPATHOLYTIC
SYNDROME

Š Clonidine
Š Methyldopa
Š Guanabenz
Š Sedative / hypnotics
Š Opioids
Š Alcohol
 Imidazolines

• Antihypertensives:
• Guanfacine (Tenex)
• Guanabenz (Wytensin)

• Decongestants
• Tetrahydrozoline (Visine)
• Oxymetazoline (Afrin)
• Naphazoline (Clear Eyes)
 TOXIC SYNDROMES – CASE 7

A 45 y/o male presents comatose and cyanotic.

HR 68 BP 110/60
RR 8, shallow T 97.8

Pupils constricted
Needle marks on left arm
Bowel sounds decreased

CLUE: wakes up after IV naloxone

 OPIOID SYNDROME

Š Dx: Heroin Overdose

Š Triad: coma, respiratory depression, miosis
Š Other agents
„ Opiates
„ Clonidine
„ GHB or analogue
 TOXIC SYNDROMES – CASE 8

A 35 y/o female presents with confusion and lethargy. No nausea or

vomiting.
HR 110
BP 120/80 PE unremarkable except for drowsy,
RR 32 confusion and tachypnea.
T 99
Labs: Na 142 Cl 96 BUN 27 Glucose 100
K 4.1 Bicarb 8 Cr 2.2
Other labs?
ABG: 7.02 / 96 / 25 Measured osmolality = 380. ETOH = 0.
CLUE 1: Ca oxylate crystals in urine
CLUE 2: Empty container of radiator antifreeze found in trash can at home.
 TOXIC SYNDROMES- CASE 9

The police bring in a 28 y/o female with drowsiness who says

she just wants to die. There is a suicide note.
HR 130 Skin warm and dry
BP 120/80 Bowel sounds decreased
RR 16 Pupils slightly,reactive
T 98
15 minutes later:
 TOXIC SYNDROMES- CASE 9

The police bring in a 28 y/o female with drowsiness who says she just
wants to die. There is a suicide note.
HR 130 Skin warm and dry
BP 120/80 Bowel sounds decreased
RR 16 Pupils slightly,reactive
T 98

CLUE: 15 minutes later she has a seizure lasting 2 minutes, after

which she is deeply comatose with agonal respirations. Cardiac
monitor shows wide complex tachycardia with a rate of 160.
BP 60/40.
 TCA Clinical Toxicity

Š Lethargy ± agitation
Š Sinus tachycardia

Š Then:
Š Seizures, hypotension, ventricular
dysrhythmias
 Cyclic Antidepressants

Š Inhibit catecholamine reuptake

„ NE, 5-HT, DA
Š Block ACHM receptors
Š Block fast Na+ cardiac channels
Š Block alpha- adrenergic receptors
Š Block K+ efflux from cardiac cells
Š Indirect GABA antagonist
Š Block H1 and H2 receptors
 TOXIC SYNDROMES – CASE 10

A 22 y/o female presents with a severe toothache for one week, and mild
nausea and vomiting for 3 days. She is seeking pain medication for the
persistent toothache. Her friends told her that her eyes were turning
yellow.

Vital signs normal

Mild scleral icterus
Right upper quadrant tenderness
Severely abcessed tooth

CLUE: taking 4-5 OTC pain pills at a time every 3 – 4 hours.

 TOXIC SYNDROMES – CASE 11

A depressed 17 y/o female presents with acute onset of nausea,

abdominal pain, hematemesis and diarrhea.
HR 115
BP initially normal but falls to 80/50
Anion gap metabolic acidosis is present

CLUE 1: pregnant
CLUE 2: X-ray shows radiopaque pills in stomach and
proximal small bowel
 Iron Poisoning

Š Direct GI irritant Æ corrosive

Š Decreased venous return Æ fall in CO
Š Elevated lactate, release of protons as Fe++
converted to Fe+++
Š Catalyzes free radical formation and lipid
peroxidation (hepatotoxicity)
Š Hyperglycemia, leukocytosis
 TOXIC SYNDROMES – CASE 12

A 44 y/o female presents with dyspnea, nausea, vomiting and

lethargy. It is difficult to obtain a history because the
patient is hard of hearing.
HR 96 BP 130/90
RR 28 T 100.6
PE: consistent with advanced rheumatoid arthritis

CLUE:
ABG: 7.48 / 98 / 22
Na 142 Cl 106 Bicarb 14 K 3.5
Salicylates
Š Analgesics
„ ASA, Fiorinal
„ Goody, BC powders
Š Pepto-Bismol
Š Topical liniment analgesics (Ben Gay)
Š Suppositories
Š Chewing gum
Š Flavorings (oil of wintergreen)
Š Plants (acacia, hyacinth, calycanthus)
Š Chinese / herbal products
 Salicylates
Š GI irritant
Š Stimulates respiratory center
z Hyperventilation/respiratory alkalosis
Š May alter capillary permeability
z Cerebral/pulmonary edema
Š Uncouples oxidative phosphorylation
z Causing lactic acidosis, ketoacidosis
Š Inhibits cyclo-oxygenase
z Loss of gastric mucosal barrier
z Platelet dysfunction
 TOXIC SYNDROME – CASE 13

A 44 y/o female presents with severe nausea and vomiting.

HR 140, irregular
BP 110/70
RR 18 Agitated, tremulous
T 99 Skin, pupils, bowel sounds are normal

Cardiac monitor shows sinus tach with narrow QRS complex and occasional
PADS and PVDS. Before any further information can be obtained the
patient has a seizure which is not controlled with diazepam and
phenytoin.

CLUE: husband had asthma

Hypokalemia
 Theophylline

ƒ Mechanism of Action
z Inhibition of phosphodieterase
z Adenosine receptor antagonism
z Release of catecholamines

ƒ Clinical Effects
z Gastric acid and pepsin secretion
z Stimulation of respiratory & vomiting centers in medulla
z Positive inotropic and chronotropic effects
z Reduction of peripheral arteriolar resistance
z Relaxation of bronchial smooth muscle
z Increase GFR and RBF
z CNS stimulation
 TOXIC SYNDROMES – CASE 14

A 48 y/o male alcoholic presents with confusion and blurred vision.

HR 100
BP 140/90
RR 32
T 99
Confused, lethargic, disoriented

Labs: Na 144 Cl 100 Bicarb 10

K 3.9 Glu 100 BUN 18
Cr 1.2
ETOH = 0 Measured osmolality = 350

CLUE: emesis has a bluish tint; urinalysis is normal

 TOXIC SYNDROMES – CASE 15

A 19 y/o male is brought in by 6 policemen for severe agitation

and disruptive behavior.

Hypertensive

Nystagmus

Severe agitation alternating with coma

 TOXIC SYNDROMES – CASE 16

A 55 y/o male alcoholic presents with lethargy, confusion, nausea, vomiting

and abdominal pain.
HR 95 – remainder of vital signs normal
Mild epigastric tenderness

Labs: Na 140 Cl 110 Bicarb 24

K 3.8 BUN 21 Cr 1.2
Glucose 100
ETOH = 0
Measured osmolality = 372

CLUE: urine is positive for acetone

A 4 y/o girl is found comatose in a closet in her home. She is
dressed in her mother’s clothes, shoes and jewelry. Also in
the closet are her doll, several suitcases and several cans of
cleaning fluids and pesticides.

In the ED, she is comatose, with a regular HR of 108 bpm and

BP 80 mm Hg by palpation. She has pinpoint pupils, dry
skin and clear lungs. No bowel sounds are audible.

The parents are certain that all medications in the home are
secured in a medicine cabinet, and all other toxic chemicals
are locked under the kitchen sink
The child is stabilized in the ED. The HR decreases to
96 and the BP rises to 90 mm Hg. She becomes
awake, alert and her pupils dilate to normal size after
receiving a dose of 2 mg naloxone IV.

The parents still emphatically deny the use of any

natural or synthetic opiates at home.

Upon returning home, the father, while searching

through the closet, discovers an open bottle of
Lomotil tablets in an open suitcase. The
antidiarrheal medication had been left there after a
foreign trip.
Lomotil

• Diphenoxylate 2.5mg + atropine 0.025mg

• Lethargy reported after ingestion of 1 tablet
• CNS depression may be delayed up to 18 hours
• Treatment is supportive
• Naloxone for opioid effects
• Physostigmine has been used for anticholinergic toxicity
A mother runs into your office with her 2 year-
old son, anxiously stating that he is difficult to
arouse. He awoke that morning and had
breakfast as usual, then “fell asleep” two
hours later. The child has now been
“sleeping” for about an hour.

No one witnessed trauma.

Only medications in the house are APAP and
ASA – both stored in the bathroom medicine
cabinet.
No history of previous similar episodes.
No family history of metabolic disorders.
Pulse 110, BP 90/60, RR 8, T 36 (96.8)
Obtunded, responding only to painful stimuli by
crying and moving purposelessly.
Skin cool, slightly diphoretic.
Pupils midsize, neuro exam non-focal and
symmetric, with slight hyporeflexia in all
extremities.

At the end of the exam the child has a

generalized, tonic-clonic seizure.
Chem-strip blood sugar = 20 mg%
Further history reveals that the parents had hosted a
party the night before that had continued late into the
night.
Summary
 Conclusions

Š Safe use of cardiovascular and other resuscitation

drugs requires understanding of autonomic
nervous system
Š Assessment for “toxidromes” can assist in
diagnosis of intoxication when lab testing is not
available
Š Call the Poison Center – it’s a free call and not a
sign of weakness!!