Bee Toxic Pesticides Found in Bee Friendly Plants sold at Garden Centers
TOXIC PLANTS
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TOXIC PLANTS
Christopher Holstege, MDAssociate Professor
Departments of Emergency Medicine& PediatricsBlue Ridge Poison Center
University of Virginia
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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.
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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
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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
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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.
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Hint: plant
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Hint: plant
often misidentified as water parsnip
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Hint: plant final
often misidentified as water parsnip
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Water Hemlock
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Water Hemlock
What is the Latin name?
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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.
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+
+
+
+
Cl- GABA
Intracellular space
Extracellular space
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+
+
+
+
Cl- GABA
Picrotoxin
Intracellular space
Extracellular space
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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
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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.
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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.
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Hint: grow taller than a carrot
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Hint: leaves are like a carrot
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Hint: stem is hallow
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Hint: stem is red speckled
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Hint: used to kill Socrates
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Poison Hemlock
NH
Coniine
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Poison Hemlock
NH
Coniine
What is the Latin name?
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Conium maculatum
NH
Coniine
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Conium maculatum
NH
Coniine
What three other plants have similar clinical effects?
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Hints: plant 1
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Hints: plant 1
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Hints: plant 1 final
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Tobacco
N
CH3
N
H
Nicotine
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Tobacco
N
CH3
N
H
Nicotine
What is the Latin name?
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Nicotiana tabacum
N
CH3
N
H
Nicotine
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Hint: plant 2
misidentified as colored greens
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Hint: plant 2 final
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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.
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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?
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Nicotiana glauca
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Hint: plant 3 final
Used by herbalist to help smokers quit
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Lobelia inflata
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Adrenal Gland
(
(
(
(
(
(
Central Nervous System
Muscle Motor End-Plate
Sympathetic Nervous System
Parasympathetic Nervous System
( )ACH ACH
(
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Adrenal Gland
(
(
(
(
(
(
Central Nervous System
Muscle Motor End-Plate
Sympathetic Nervous System
Parasympathetic Nervous System
( )ACH ACH
(
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Adrenal Gland
(
(
(
(
(
(
Central Nervous System
Muscle Motor End-Plate
Sympathetic Nervous System
Parasympathetic Nervous System
( )ACH ACH
(
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Adrenal Gland
(
(
(
(
(
(
Central Nervous System
Muscle Motor End-Plate
Sympathetic Nervous System
Parasympathetic Nervous System
( )ACH ACH
(
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Adrenal Gland
(
(
(
(
(
(
Central Nervous System
Muscle Motor End-Plate
Sympathetic Nervous System
Parasympathetic Nervous System
( )ACH ACH
(
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Adrenal Gland
(
(
(
(
(
(
Central Nervous System
Muscle Motor End-Plate
Sympathetic Nervous System
Parasympathetic Nervous System
( )ACH ACH
(
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• 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
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Case
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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.
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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.
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Hint: history final
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Castor Bean
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Castor Bean
What is the Latin name of the plant?
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Ricinus communis
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Ricinus communis
What plant is related to this plant and has a more potent toxin?
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Jequirity Pea
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Jequirity Pea
What is the Latin name of the plant?
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Abrus precatorius
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Toxalbumins
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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.
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Recent History
London, Jan 3, 2003
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Recent History
Greenville, Oct 15, 2003
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Recent History
Feb 4, 2004
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SS
SS
A chain
B chain
RIBO
A
B
AB
Ricin/Abrin
CellPenetration
Disruption ofribosomal protein synthesis
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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.
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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.
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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 –
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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…
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Foxglove
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Digitalis purpurea
What is the Latin name?
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Digitalis purpurea
What other plants have cardiac glycosides?
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Cardiac Glycosides
Nerium oleander Convallaria majalisThevetia peruviana
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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)
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O
O
O-C-CH3
O
O
Oleandrose
O
O
O
Digitoxose3
OH
Oleandrin
Digitoxin
CH3
CH3
OH
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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?
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Cardiac Glycosides
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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.
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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.
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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 …
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Hint: history
Used by Ben Franklin as a sneezing powder
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Hint: often mistaken for …
Leeks or Ramps (Allium tricoccum)
Skunk Cabbage (Lysichiton americanus)
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Hellebore
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Hellebore
What is the Latin name?
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Veratrum viride
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Veratrum viride
What other plant is considered a Veratrum alkaloid?
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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
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OH
OH OH
OH
OH
OH
OH
CH3
CH3
N
CH3
O OH
Protoverine
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Veratrum alkaloids
• Mechanism– opens sodium channels
– cellular depolarization
• Signs/Symptoms– GI distress
– coma
– seizures
– hypotension
– cardiac dysrhythmias
– sneezing powders
• Treatment– supportive
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Grayanotoxins
Mountain LaurelKalmia latifolia
AzaleasRhododendron spp.
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HO
HO
OH
OH
OHOR3
R3 = -COCH3
Grayanotoxin I
CH3
CH3
CH3
CH3
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Grayanotoxins
• Mechanism– opens sodium channels
– cellular depolarization
• Signs/Symptoms– GI distress
– coma
– seizures
– cardiac dysrhythmias
– Turkey Honey disease
• Treatment– supportive
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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
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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 ??????
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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
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Aconitine
Monk’s-hood(Aconitum napellus)
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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
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CH3CH2
CH2
OCH3
OCH3
OH
OCOCH3
OCH3
N
OH
OCOC6H5
OH
CH3O
Aconitine
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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
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Anticholinergics
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Anticholinergics
Jimson Weed(Datura stramonium)
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N
CH3
OOCCH
CH2OH
C6H5
N
CH3
OOCCH
CH2OH
C6H5
O
Scopolamine
Hyoscyamine
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• Jamestown weed, Virginia (1676)
• 0.1 mg atropine per seed
• Teas, seeds, smoking
• Anticholinergic poisoning
• Symptoms last for days
• Physostigmine for treatment
Anticholinergics
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Anticholinergics
Deadly Nightshade(Atropa bella-donna)
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Anticholinergics
Mayapple or American Mandrake
(Podophyllum peltatum)
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Anticholinergics
Mayapple or American Mandrake
(Podophyllum peltatum)
What other substance is in mandrake?
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Anticholinergics
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Saponin Glycosides
Pokeweed(Phytolacca americana)
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HO
HOCH2OH
COOH
COOCH3
Phytolaccagenin
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Watch church picnics!
• Rhubarb pie made for church picnic.
• Picnickers develop sore throat, n/v abd pain, paresthesias, hyperreflexia, muscle twitches, and muscle cramps.
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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?
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Rhubarb
• leafs contain soluble oxalates
• cooking does not detoxify
• readily absorbed resulting in systemic formation of calcium oxalate
• may produce hypocalcemia, kidney dysfunction
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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?
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Calcium Oxalate Crystals
DieffenbachiaPhilodendron
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Calcium Oxalate Crystals
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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
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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.
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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.
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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
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Toxicodendron radicus
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Toxicodendron toxicarium
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Toxicodendron vernix
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Toxicodendron
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Lathyrus odoratusSweet Pea
• Mechanism– Aminopropionitrile (glutamate)
– Upper motor neurons and anterior horn cells damaged
• Symptoms– skeletal deformities
– growth suppression
– muscle paralysis
• Treatment– remove
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Solanaceus Alkaloids
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Solanaceus Alkaloids
Solanum nigrumBlack nightshade
Solanum tuberosum
Solanum pseudocapsicumJerusalem cherry
Lycopersicon esculentum
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• 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