TOXIC PLANTS

TOXIC PLANTS

Christopher Holstege, MDAssociate Professor

Departments of Emergency Medicine& PediatricsBlue Ridge Poison Center

University of Virginia

Substances Most Frequently Involved in Human Exposures

1. Analgesics 10.5%

2. Cleaning Substances 9.5%

3. Cosmetics 9.4%

4. Plants 4.9%

5. Cough/Cold Products 4.5%

5. Bites and envenomations 4.2%

2000 annual report of the AAPCC TESSAm J Emerg Med 2004;19(5):337-395.

Toxic Plant Ingestions

• Most commonly affected:– Children (>75,000), hikers, abuse

– consumption as food or herbs by adults

• Total exposures for 2004: 106,385

• Total major outcomes: 94

• Total deaths: 6

Most Common Plant Exposures

• Pepper 4,984

• Philodendron 4,378

• Poinsettia 2,952

• Holly 2,871

• Dumbcane 2,648

• Peace lily 2,632

• Pokeweed 2,207

• Jade plant 1,715

• Poison ivy 1,478

Vet Hum Tox 2001;43(1):35-7

• 14 y/o native boy was harvesting with his family plants in a swampy area of northern Saskatchewan on Thanksgiving weekend.

• He ate root material from a presumed edible plant.

• Within minutes he began seizing, became cyanotic, and was found in cardiac arrest.

• EMS arrives and 22 min of resuscitation revises him.

• He continued with intermittent seizures.

• Declared brain dead 20 hours after eating it.

Hint: plant

Hint: plant

often misidentified as water parsnip

Hint: plant final

often misidentified as water parsnip

Water Hemlock

Water Hemlock

What is the Latin name?

Cicuta maculata

• Heath KB. A fatal case of apparent water hemlock poisoning. Vet Hum Toxicol. 2001 Feb;43(1):35-6.

• From the Centers for Disease Control and Prevention. Water hemlock poisoning--Maine, 1992. JAMA. 1994 May 18;271(19):1475.

• Landers D. Seizures and death on a white river float trip. Report of water hemlock poisoning. West J Med. 1985 May;142(5):637-40.

• Mack RB. Keats, Socrates and fool's parsley--water hemlock poisoning. N C Med J. 1985 Mar;46(3):163-4.

• Carlton BE. Water hemlock poisoning complicated by rhabdomyolysis and renal failure. Clin Toxicol. 1979;14(1):87-92.

+

+

+

+

Cl- GABA

Intracellular space

Extracellular space

+

+

+

+

Cl- GABA

Picrotoxin

Intracellular space

Extracellular space

HOCH2(CH2)2-(C C)2-(CH CH)3-CHCH2CH2CH3

OH

Cicutoxin

• Agonist activity at the picrotoxin site

• GABA receptor inhibition

• Symptoms– GI distress, diaphoresis, seizures, mydriasis,

rhabdomyolysis, renal failure

• Treatment– charcoal

– observation for 4 hours

– benzodiazepines & barbituates

WJM 1995;163(6):573-4

• 4 y/o boy and his father ingest the green tops of “wild carrots” growing in their backyard.

• Within 30 minutes, the child became sleepy and takes a nap, which is unusual for him.

• 2 hours later the father cannot wake him and there is emesis in the bed of green material.

• EMS is contacted.

WJM 1995;163(6):573-4

• P 100; RR 26

• Pupils miotic

• Disconjugate gaze

• Neck supple

• Withdraws from painful stimuli, + gag

• Labs are all normal

• Toxicology screen is negative

• CXR neg

• Lavage and activated charcoal.

Hint: grow taller than a carrot

Hint: leaves are like a carrot

Hint: stem is hallow

Hint: stem is red speckled

Hint: used to kill Socrates

Poison Hemlock

NH

Coniine

Poison Hemlock

NH

Coniine

What is the Latin name?

Conium maculatum

NH

Coniine

Conium maculatum

NH

Coniine

What three other plants have similar clinical effects?

Hints: plant 1

Hints: plant 1

Hints: plant 1 final

Tobacco

N

CH3

N

H

Nicotine

Tobacco

N

CH3

N

H

Nicotine

What is the Latin name?

Nicotiana tabacum

N

CH3

N

H

Nicotine

Hint: plant 2

misidentified as colored greens

Hint: plant 2 final

Tree tobacco

• Streenkamp PA. Accidental fatal poisoning by Nicotiana glauca: identification of anabasine by high performance liquid chromatography/photodiode array/mass spectrometry. Forensic Sci Int. 2002 Jul 17;127(3):208-17.

• Mizrachi N. Fatal poisoning from Nicotiana glauca leaves: identification of anabasine by gas-chromatography/mass spectrometry. J Forensic Sci. 2000 May;45(3):736-41.

• Mellick LB. Neuromuscular blockade after ingestion of tree tobacco (Nicotiana glauca). Ann Emerg Med. 1999 Jul;34(1):101-4.

• Sims DM. Another death due to ingestion of Nicotiana glauca. J Forensic Sci. 1999 Mar;44(2):447-9.

• Castorena JL. A fatal poisoning from Nicotiana glauca. J Toxicol Clin Toxicol. 1987;25(5):429-35.

Tree tobacco

• Streenkamp PA. Accidental fatal poisoning by Nicotiana glauca: identification of anabasine by high performance liquid chromatography/photodiode array/mass spectrometry. Forensic Sci Int. 2002 Jul 17;127(3):208-17.

• Mizrachi N. Fatal poisoning from Nicotiana glauca leaves: identification of anabasine by gas-chromatography/mass spectrometry. J Forensic Sci. 2000 May;45(3):736-41.

• Mellick LB. Neuromuscular blockade after ingestion of tree tobacco (Nicotiana glauca). Ann Emerg Med. 1999 Jul;34(1):101-4.

• Sims DM. Another death due to ingestion of Nicotiana glauca. J Forensic Sci. 1999 Mar;44(2):447-9.

• Castorena JL. A fatal poisoning from Nicotiana glauca. J Toxicol Clin Toxicol. 1987;25(5):429-35.

What is the Latin name?

Nicotiana glauca

Hint: plant 3 final

Used by herbalist to help smokers quit

Lobelia inflata

Adrenal Gland

(

(

(

(

(

(

Central Nervous System

Muscle Motor End-Plate

Sympathetic Nervous System

Parasympathetic Nervous System

( )ACH ACH

(

Adrenal Gland

(

(

(

(

(

(

Central Nervous System

Muscle Motor End-Plate

Sympathetic Nervous System

Parasympathetic Nervous System

( )ACH ACH

(

Adrenal Gland

(

(

(

(

(

(

Central Nervous System

Muscle Motor End-Plate

Sympathetic Nervous System

Parasympathetic Nervous System

( )ACH ACH

(

Adrenal Gland

(

(

(

(

(

(

Central Nervous System

Muscle Motor End-Plate

Sympathetic Nervous System

Parasympathetic Nervous System

( )ACH ACH

(

Adrenal Gland

(

(

(

(

(

(

Central Nervous System

Muscle Motor End-Plate

Sympathetic Nervous System

Parasympathetic Nervous System

( )ACH ACH

(

Adrenal Gland

(

(

(

(

(

(

Central Nervous System

Muscle Motor End-Plate

Sympathetic Nervous System

Parasympathetic Nervous System

( )ACH ACH

(

• Mechanism– stimulation of nicotinic acetylcholine receptors

• Signs/SymptomsSeizures

– cortex, thalamus, interpeduncular nucleus stimulation

Autonomic Ganglia Stimulation– sympathetic and parasympathetic stimulation

Neuromuscular Depolarizion

• Treatment– Atropine

– Benzodiazepines/Barbituates

nicotine/conine/lobeline

Case

Hint: history

• Bulgarian dissident Georgi Markov was killed by poison dart filled with this agent and fired from an umbrella in London in 1978.

• Markov, a communist defector working for the BBC World Service, left his office at Bush House in the UK capital on September 11 and walked across Waterloo Bridge to take the train home to Clapham in south-west London.

• As he waited at a bus stop moments into his journey home, he felt a sharp jab in his thigh and saw a man picking up an umbrella.

• He developed a high temperature and in four days was dead.

Hint: history final

• A post mortem, conducted with the help of scientists from the UK government's germ warfare centre at Porton Down, established that he had been killed by a 1.7 mm pellet containing a 0.2 milligram dose of this poison.

• No toxin was isolated. Because of the small volume and rapid demise of the patient, ricin was believed to be the only capable inciting agent.

• The coroner recreated the scenario by injecting a pig with a similar dose of ricin. The pig died in a similar manner 26 hours later.

• Markov's assassination was detected only because the pellet carrying the poison had not dissolved as expected.

Hint: history final

Castor Bean

Castor Bean

What is the Latin name of the plant?

Ricinus communis

Ricinus communis

What plant is related to this plant and has a more potent toxin?

Jequirity Pea

Jequirity Pea

What is the Latin name of the plant?

Abrus precatorius

Toxalbumins

Ricin

• Ricin, a highly potent toxin produced by castor beans, is classified by the Centers for Disease Control and Prevention as a level B biothreat because it is easily produced, readily available, and highly stable.

• There have been a number of attacks recently in the news where ricin was utilized.

Recent History

London, Jan 3, 2003

Recent History

Greenville, Oct 15, 2003

Recent History

Feb 4, 2004

SS

SS

A chain

B chain

RIBO

A

B

AB

Ricin/Abrin

CellPenetration

Disruption ofribosomal protein synthesis

Ricin Vaccine

Vitteta ES. A pilot clinical trial of a recombinant ricin vaccine in normal humans. Proc Natl Acad Sci U S A. 2006 Feb

14;103(7):2268-73. Epub 2006 Feb 3.

Mutant recombinant RTA (named RiVax) was expressed and produced in Escherichia coli and purified. When RiVax was injected i.m. into mice it protected them against a ricin challenge of 10 LD(50)s. Preclinical studies in both mice and rabbits demonstrated that RiVax was safe. Based on these results, three groups of five normal volunteers were injected three times at monthly intervals with 10, 33, or 100 mug of RiVax. The vaccine was safe and elicited ricin-neutralizing Abs in one of five individuals in the low-dose group, four of five in the intermediate-dose group, and five of five in the high-dose group. These results justify further development of the vaccine.

NEJM 2004;351(6):594-599.

History

• 53 y/o woman presents with persistent n/v. The vomiting has occurred every hour for 18 hours. She c/o mild chest and abdominal discomfort.

• PMH: irritable bowel syndrome & ADD.

• Meds: methylphenidate

• FH: brother with CAD before 50

• SH: past smoker, occ etoh

• Recently picked dandelion leaves from her partners inner city garden for a salad.

NEJM 2004;351(6):594-599.

Physical Exam

• P 36, BP supine 110/60, standing 90/50, 98%

• RUQ tenderness

Tests

• ECG: sinus bradycardia @ 36 & non-specific ST & T wave changes.

• Troponin - ; K 5.2 mmmol/L; Tox screen –

• CXR –

• US RUQ –

NEJM 2004;351(6):594-599.

• 0.5 mg atropine intravenous (P to 70s)

• Admitted

• Day 3– Digoxin level 1.3 ng/ml

– Digitoxin level 43 ng/ml (normal 10-32)

• She subsequently confirmed that she picked the dandelions from a patch of…

Foxglove

Digitalis purpurea

What is the Latin name?

Digitalis purpurea

What other plants have cardiac glycosides?

Cardiac Glycosides

Nerium oleander Convallaria majalisThevetia peruviana

Yellow Oleander

• Rural Sri Lanka

• One of the leading causes of overdose deaths

• 2002, 2189 patients at 2 hospitals

• 198 patients died (9/0% fatality rate)

O

O

O-C-CH3

O

O

Oleandrose

O

O

O

Digitoxose3

OH

Oleandrin

Digitoxin

CH3

CH3

OH

Cardiac Glycosides

• Mechanism– inhibit Na+/K+-ATPase pump activity

– increased vagal tone

• Signs/Symptoms– GI upset

– syncope

– AV block & dysrhythmias

– Death

• Management– correct K

What antidote can you give?

Cardiac Glycosides

A hike in the woods

• A 26 year old male was foraging for “ramps” and erroneously picked a different broad leaf with striations.

• Later that night, he cooked the green leaf into a spaghetti sauce and ingested it. He noticed a tingling sensation along his tongue and felt that his “throat was closing up”. He stopped eating the meal after approximately “4 bites” and spontaneously vomited within a half hour of the meal.

• He proceeded to the emergency department because of intractable vomiting and profound dizziness.

A hike in the woods

• BP:83/42, HR:42, RR:20, T: 36.2oC.

• He was in moderate distress with diaphoresis and mild abdominal tenderness.

• ECG showed sinus bradycardia, PR duration 188 msec, QRS duration 87 msec, and QTc duration 367 msec.

• The patient received 3 liters of normal saline and was admitted to a monitored bed. His initial lab work was significant for a digoxin level of 0.38, a normal chemistry.

A hike in the woods

• Aggressive measures were reserved because the patient’s mentation was normal, excellent urine output, and asymptomatic after the fluid resuscitation.

• The patients pulse and systolic blood pressure increased above 50 and 90 approximately 8 hours following the ingestion with no sequelae.

• After evaluation of the plant by a botanist, it was concluded that this green leaf was …

Hint: history

Used by Ben Franklin as a sneezing powder

Hint: often mistaken for …

Leeks or Ramps (Allium tricoccum)

Skunk Cabbage (Lysichiton americanus)

Hellebore

Hellebore

What is the Latin name?

Veratrum viride

Veratrum viride

What other plant is considered a Veratrum alkaloid?

Veratrum alkaloids

Death Camus(Zigadenus – 14 species)

• Used during Roman times as an arrow tip poison

• Often mistaken as wild onions out West

• In the lily family

• Remarkably similar to nontoxic wild onions – Cammassia quamash

OH

OH OH

OH

OH

OH

OH

CH3

CH3

N

CH3

O OH

Protoverine

Veratrum alkaloids

• Mechanism– opens sodium channels

– cellular depolarization

• Signs/Symptoms– GI distress

– coma

– seizures

– hypotension

– cardiac dysrhythmias

– sneezing powders

• Treatment– supportive

Grayanotoxins

Mountain LaurelKalmia latifolia

AzaleasRhododendron spp.

HO

HO

OH

OH

OHOR3

R3 = -COCH3

Grayanotoxin I

CH3

CH3

CH3

CH3

Grayanotoxins

• Mechanism– opens sodium channels

– cellular depolarization

• Signs/Symptoms– GI distress

– coma

– seizures

– cardiac dysrhythmias

– Turkey Honey disease

• Treatment– supportive

JAMA 1971;216(1):121-124

Dec 3 1881

• George Henry Lamson, MD– Morphine addict

– Sold surgical instruments for cash

• Visits brother-n-law, Percy John – boarding school

– Poliomyelitis; useless legs

– Gives capsule full of “sugar” to boy & raisin cake

– Tells headmaster: “Percy probably would not last much longer”

• 15 minutes later– Heartburn, malaise, “throat closing,” n/v, tetanic convulsions

• Dead 4 hours after ingestion

JAMA 1971;216(1):121-124

• Necropsy– No natural disease

• Vomitous– Isolated alkaloid

– Demonstrated effects on mice

– Tasted it

• Capsule = sugar

• Cake = raisins injected with ??????

JAMA 1971;216(1):121-124

• Necropsy– No natural disease

• Vomitous– Isolated alkaloid

– Demonstrated effects on mice

– Tasted it

• Capsule = sugar

• Cake = raisins injected with aconitine

• Executed April 1882

Aconitine

Monk’s-hood(Aconitum napellus)

Aconitine

• Mechanism– opens sodium channels

– cellular depolarization

– enhanced vagal tone

• Signs/Symptoms– GI distress

– coma

– seizures

– hypotension

– cardiac dysrhythmias: torsades, v-tach, brady, asystole

– herbal preparations

• Treatment– supportive

– lidocaine, amiodarone, potassium, magnesium

CH3CH2

CH2

OCH3

OCH3

OH

OCOCH3

OCH3

N

OH

OCOC6H5

OH

CH3O

Aconitine

Acta Ophthalmol Scand 2002;80:332-335

• 75 y/o woman c/o blurred vision of left eye

• Also c/o h/a for days

• On coumadin for previous pulmonary embolism

• Only finding on exam was mydriasis

• DDX: Adie’s tonic pupil, intracranial 3rd nerve

• CT head negative

• Picking flowers the day before

• Pilocarpine 1% showed no effect

Anticholinergics

Anticholinergics

Jimson Weed(Datura stramonium)

N

CH3

OOCCH

CH2OH

C6H5

N

CH3

OOCCH

CH2OH

C6H5

O

Scopolamine

Hyoscyamine

• Jamestown weed, Virginia (1676)

• 0.1 mg atropine per seed

• Teas, seeds, smoking

• Anticholinergic poisoning

• Symptoms last for days

• Physostigmine for treatment

Anticholinergics

Anticholinergics

Deadly Nightshade(Atropa bella-donna)

Anticholinergics

Mayapple or American Mandrake

(Podophyllum peltatum)

Anticholinergics

Mayapple or American Mandrake

(Podophyllum peltatum)

What other substance is in mandrake?

Anticholinergics

Saponin Glycosides

Pokeweed(Phytolacca americana)

HO

HOCH2OH

COOH

COOCH3

Phytolaccagenin

Watch church picnics!

• Rhubarb pie made for church picnic.

• Picnickers develop sore throat, n/v abd pain, paresthesias, hyperreflexia, muscle twitches, and muscle cramps.

Watch church picnics!

• Rhubarb pie made for church picnic.

• Picnickers develop sore throat, n/v abd pain, paresthesias, hyperreflexia, muscle twitches, and muscle cramps.

What electrolyte abnormality?

Rhubarb

• leafs contain soluble oxalates

• cooking does not detoxify

• readily absorbed resulting in systemic formation of calcium oxalate

• may produce hypocalcemia, kidney dysfunction

Rhubarb

• leafs contain soluble oxalates

• cooking does not detoxify

• readily absorbed resulting in systemic formation of calcium oxylate

• may produce hypocalcemia, kidney dysfunction

What other plants contain insoluble oxalate crystals?

Calcium Oxalate Crystals

DieffenbachiaPhilodendron

Calcium Oxalate Crystals

Blighia sapida

• Mechanism– eating unripe fruit

– Hypoglycins A & B

» inhibiton fatty acid beta-oxidation (fatty liver)

» inhibition of glucose-6-phosphase (hypoglycemia)

• Symptoms– Jamaican Vomiting Sickness described 1875

– weakness, headache, vomiting, coma, seizures

– Improvement followed by relapse

– Profound hypoglycemia

– Mortality rate of 80% prior to 1954

• Treatment– Glucose

– L-Carnitine

Run from the flames

• 9 y/o male presents with facial pain

• He was in his normal state of health until this morning when he awoke from sleep and noted a diffuse rash over his face with a marked burning sensation

• It has progressed through the day and involves only his face and neck and stops at his shirt neck line.

• He has had no fevers and his immunizations are up to date.

• He denies any other complaints.

• His best friend also awoke with the same rash.

Run from the flames

• The previous day, while playing on the school playground, they watched a neighboring farm burning brush. Smoke from the fire blew over the area where they were watching.

Toxicodendron

• Mechanism– urushiol: oily substance responsible for type 4

allergic rx

• Symptoms– skin inflammation, blistering

• Treatment– atarax

– prednisone taper over 2 weeks starting with 1-2mg/kg

Toxicodendron radicus

Toxicodendron toxicarium

Toxicodendron vernix

Toxicodendron

Lathyrus odoratusSweet Pea

• Mechanism– Aminopropionitrile (glutamate)

– Upper motor neurons and anterior horn cells damaged

• Symptoms– skeletal deformities

– growth suppression

– muscle paralysis

• Treatment– remove

Solanaceus Alkaloids

Solanaceus Alkaloids

Solanum nigrumBlack nightshade

Solanum tuberosum

Solanum pseudocapsicumJerusalem cherry

Lycopersicon esculentum

• Mechanism– solanine

» a glycosalkaloid (three sugars attached to a steroid)

» highest concentration in unripe fruit

» in vitro: inhibit cholinesterase & cardiac glycoside

• Symptoms– GI distress in 2-24 hrs after ingest and last for days

– delrium, hallucinations, coma, death

Solanaceus Alkaloids