Plants containing antimuscarinic agents

Latin name Common name Toxins

Atropa belladonna Deadly nightshade Hyoscyamine, atropine

SPECIFIC SUBSTANCES

PlantsSally Bradberry

Allister Vale

Brugmansia

sanguinea

Angel’s trumpet Hyoscyamine, atropine

Datura stramonium Thorn apple,

jimsonweed

Hyoscyamine, atropine

Hyoscyamus niger Black henbane,

stinking nightshade,

poison tobacco

Hyoscyamine

Solanum dulcamara Woody nightshade Solanum alkaloids,

e.g. solanine

Solanum nigrum Black nightshade Solanum alkaloids

Solanum

pseudocapsicum

Christmas cherry,

Jerusalem cherry

Solanum alkaloids

Solanum tuberosum Potato Solanum alkaloids

Table 1

AbstractLife-threatening poisoning from plant ingestions is rare though many

plants contain potentially toxic substances. These include antimuscarinic

agents, calcium oxalate crystals, cardioactive glycosides, pro-convulsants,

cyanogenic compounds, mitotic inhibitors, nicotine-like alkaloids, alkylat-

ing agent precursors, sodium channel activators and toxic proteins

(toxalbumins). Management is generally supportive though some specific

therapies exist, such as digoxin-specific antibody fragments in the

treatment of digitalis and oleander poisoning.

Keywords alkaloids; alkylating; antimuscarinic; calcium oxalate;

cardiotoxic; cyanogenic; nicotine; pro-convulsant; sodium channel;

toxalbumin; veno-occlusive

Plants containing calcium oxalate crystals

There are many potentially poisonous plants, though cases of

severe human poisoning are rare.1e5 Although many plants

contain gastrointestinal toxins, these rarely give rise to life-

threatening sequelae. In contrast, other botanical poisons may

cause specific organ damage and death may occur from only

small ingestions of yew (Genus Taxus), oleander (Thevetia

peruviana (yellow oleander) and Nerium oleander) and cowbane

(Genus Cicuta).

From a toxicological perspective, poisonous plants are most

appropriately considered by reference to the nature of the toxins

they contain.

Plants containing antimuscarinic agents

Plants containing antimuscarinic agents (Table 1) belong to the

nightshade family, Solanaceae. Ingestion of species containing

hyoscyamine and/or atropine cause a classical antimuscarinic

syndrome with tachycardia, dry, warm skin, urinary retention,

absent bowel sounds, delirium, hallucinations and possibly

convulsions. 6 Central nervous system effects are generally less

common following ingestion of Solanum species, which

predominantly cause gastrointestinal upset. Features may persist

for hours to days.6 Management is supportive.

Sally Bradberry BSc MD MRCP FAACT is Deputy Director of the National

Poisons Information Service (Birmingham Unit) and West Midlands

Poisons Unit at City Hospital, Birmingham, UK. Competing interests:

none declared.

Allister Vale MD FRCP FRCPE FRCPG FFOM FAACT FBTS is Director of the National

Poisons Information Service (Birmingham Unit) and the West Midlands

Poisons Unit at City Hospital, Birmingham, UK. Competing interests:

none declared.

MEDICINE 40:3 151

Calcium oxalate crystals

Some plants contain needle-shaped crystals of calcium oxalate

(Table 2), which can be released by mechanical stimulation.

These crystals can penetrate mucous membranes and induce

histamine release. Pain and irritation follow skin or eye contact.

Following ingestion, inflammation may be sufficiently severe to

cause oropharyngeal oedema. Systemic toxicity with hypo-

calcaemia does not occur since the crystals are insoluble.

Management of skin and eye exposures involves decontamina-

tion by irrigation with adequate analgesia. Following ingestion,

the priority is to protect the patency of the airway. Endoscopic

examination may be required to assess the damage.

Cardiotoxic steroids

These fall into twomain groups, cardenolides and bufadienolides.

The best-known examples are the foxglove (Digitalis purpurea)

and yellow oleander (Thevetia peruviana), which contain carde-

nolide cardiac glycosides that inhibit Naþ/Kþ ATP-ase. Ingestion

causes a syndrome similar to digoxin poisoning. The diagnosis and

management of oleander poisoning has been reviewed recently.7

Arrhythmias and hyperkalaemia can be rapidly and safely

Latin name Common name

Caladium bicolor Angel wings, caladium

Caryota mitis Fishtail palm

Colocasia esculenta Elephant’s ear

Dieffenbachia species Dumb cane

Epipremnum aureum Amarillo, devil’s ivy

Monstera deliciosa Swiss cheese plant

Philodendron selloum Sweetheart vine

Spathiphyllum species Peace lily

Table 2

� 2011 Published by Elsevier Ltd.

Plants containing mitotic inhibitors

Latin name Common name Toxins

Catharanthus roseus Madagascar periwinkle Vincamine,

vincristine

Colchicum autumnale Autumn crocus,

meadow saffron

Colchicine

Gloriosa superba Glory lily Colchicine

Podophyllum peltatum May apple Podophyllotoxin

Vinca minor Lesser periwinkle Vincamine,

vincristine

Table 4

SPECIFIC SUBSTANCES

reversed by the administration of digoxin-specific antibody

fragments.8,9 The administration of multiple doses of activated

charcoal also improves survival.10

Plants containing pro-convulsants

Plants containing pro-convulsants include cowbane (Cicuta

virosa), fool’s parsley (Aethusa cynapium), buttercup (Ranunculus

acris), and strychnine (Strychnos nux-vomica). There is a wide

variation in the convulsant potency of their toxins. The precise

mechanisms of seizure induction have not been elucidated for all

toxins but include g-aminobutyric acid antagonism,11 excitatory

amino acid mimicry, imbalance of acetylcholine homeostasis,

hypoglycaemia and sodium channel disruption. The seizures

produced are usually generalized tonic-clonic in nature. Strychnine

antagonises the post-synaptic inhibitory amino acid, glycine, at the

spinal cord motor neurone, causing muscle hyperactivity without

loss of consciousness.12 Management is supportive with judicious

use of benzodiazepines, although these may not be effective.

Cyanogenic compounds

With the exception of Sambucus nigra all species listed in Table 3

belong to the rose family, Rosaceae. These plants contain two

principal cyanogenic glycosides, prunasin in the vegetative

organs and amygdalin exclusively in seeds. Plants contain only

very small amounts of these compounds, so cyanide poisoning is

likely only after massive ingestions of vegetation or chewing

multiple seeds. As cyanide release requires hydrolysis in the

gastrointestinal tract, features of poisoning may be delayed for

a few hours.13 Nausea, vomiting, epigastric pain, diarrhoea,

salivation, flushed face, headache and shivering may occur, with

hypotension, convulsions, metabolic acidosis, coma and respi-

ratory paralysis in severe cases. Fatalities have been reported.14

Mitotic inhibitors

Some plants (Table 4) contain mitotic inhibitors that interfere

with the polymerization of microtubules necessary for spindle

formation during cell division. Effects are most apparent in

rapidly dividing cells including those of the gastrointestinal and

haematological systems. Ingestion causes nausea and vomiting,

which may progress to gastrointestinal mucosal ulceration and

necrosis. Features of CNS toxicity include headache, ataxia,

seizures and encephalopathy. Multi-system organ failure ensues

in the most severe cases and fatalities have occurred.15,16

Plants containing cyanogenic compounds

Latin name Common name Toxins

Cotoneaster horizontalis Wall cotoneaster Prunasin, amygdalin

Malus sylvestris Crab apple Prunasin, amygdalin

Prunus laurocerasus Cherry laurel Prunasin, amygdalin

Prunus armeniaca Apricot Prunasin, amygdalin

Prunus domestica Plum Prunasin, amygdalin

Prunus dulcis var amara Bitter almond Prunasin, amygdalin

Sambucus nigra Elder Prunasin

Table 3

MEDICINE 40:3 152

Management is supportive including conventional treatment of

bone marrow failure, if required.

Nicotine-like alkaloids

Nicotine-like alkaloids stimulate nicotinic cholinergic receptors,

causing hypertension, tachycardia, sweating, hypersalivation,

vomiting, muscle fasciculation and weakness. Depolarizing

neuromuscular blockade, seizures and death may occur in severe

cases.17,18 Plants in this category include hemlock (Conium

maculatum), blue cohosh (Caulophyllum thalictroides), laburnum

(Laburnum anagyroides) and the tobacco plant (Nicotiana

tabacum). Management is supportive.

Alkylating agent precursors

The pyrrolizidine alkaloids in plants, such as ragwort (Senecio

jacobaea) and purple viper’s bugloss (Echium plantagineum), are

metabolized to pyrroles that damage hepatic sinusoidal and

pulmonary endothelial cells. Endothelial repair and hypertrophy

result in veno-occlusive disease. Symptoms are gradual in onset

with non-specific anorexia and abdominal pain progressing to

hepatic cirrhosis. Human poisonings have occurred from chronic

ingestion of herbal teas19 and from ingestion of grain contami-

nated with seeds of plants containing these alkaloids.

Sodium channel activators

Plants containing these agents (Table 5) cause persistent sodium

influx at neuronal and cardiac membranes by stabilization of the

open configuration of voltage-gated sodium channels. Membrane

Plants containing sodium channel activators

Latin name Common name Toxins

Aconitum napellus Monkshood Aconitine

Kalmia angustifolia Sheep laurel Grayanotoxin

Pieris japonica Pieris Grayanotoxin

Rhododendron ponticum Rhododendron Grayanotoxin

Veratrum album False hellebore Protoverine

Zigadenus paniculatus Death camus Zigadenine

Table 5

� 2011 Published by Elsevier Ltd.

Plants containing toxic proteins

Latin name Common name Toxins

Abrus precatorius Jequirity bean Abrin

Hura crepitans Sandbox tree Huratoxin

Jatropha cathartica Jicamilla Curcin

Momordica charantia Bitter gourd Momordin

Phoradendron tomentosum American mistletoe Phoratoxin

Ricinus communis Castor oil plant Ricin

Robinia pseudoacacia False acacia, Black locust Robin

Table 6

SPECIFIC SUBSTANCES

depolarization is prolonged, leading to seizures and arrhythmias.20

Other features include vomiting, colicky diarrhoea, paraesthesiae,

muscle fasciculations, weakness and paralysis.21 Management is

supportive. No specific therapy for arrhythmias has proved

superior, though based on the mechanism of toxicity, sodium

channel blocking drugs such as lidocaine, flecainide or amiodar-

one may be useful. Intravenous magnesium has also successfully

terminated ventricular tachycardia induced by these plants.22

Toxic proteins (toxalbumins)

Plants containing these toxins (Table 6) inhibit protein synthesis.

Ricin and abrin are discussed by Bradberry.23 A

REFERENCES

1 New York Botanical Garden. In: Nelson LS, Shih RD, Balick MJ, eds.

Handbook of poisonous and injurious plants. 2 edn. New York:

Springer, 2007.

2 Frohne D, Pf€ander HJ. Poisonous plants. A handbook for doctors,

pharmacists, toxicologists, biologists and veterinarians. 2 edn.

London: Manson Publishing, 2005.

3 Cooper MR, Johnson AW, Dauncey EA. Poisonous plants and fungi: an

illustrated guide. 2 edn. London: TSO, 2003.

4 Krenzelok EP, Mrvos R. Friends and foes in the plant world: a profile

of plant ingestions and fatalities. Clin Toxicol 2011; 49: 142e9.

5 Barceloux DG, Barceloux DG, eds. Medical toxicology of natural

substances: foods, fungi, medicinal herbs, plants and venomous

animals. Hoboken, New Jersey: John Wiley & Sons, 2008.

MEDICINE 40:3 153

6 Carstairs SD, Luk JY, Cantrell FL. A comprehensive review of

anticholinergic plant exposures in California, 1997e2008. Clin Toxicol

2010; 48: 628.

7 Bandara V, Weinstein SA, White J, Eddleston M. A review of the

natural history, toxinology, diagnosis and clinical management of

Nerium oleander (common oleander) and Thevetia peruviana

(yellow oleander) poisoning. Toxicon 2010; 56: 273e81.

8 Eddleston M, Rajapakse S, Rajakanthan, et al. Anti-digoxin Fab

fragments in cardiotoxicity induced by ingestion of yellow oleander:

a randomised controlled trial. Lancet 2000; 355: 967e71.

9 Rajapakse S. Management of yellow oleander poisoning. Clin Toxicol

2009; 47: 206e12.

10 de Silva HA, Fonseka MMD, Pathmeswaran A, et al. Multiple-dose

activated charcoal for treatment of yellow oleander poisoning:

a single-blind, randomised, placebo-controlled trial. Lancet 2003;

361: 1935e8.

11 Schep LJ, Slaughter RJ, Becket G, Beasley DM. Poisoning due to water

hemlock. Clin Toxicol 2009; 47: 270e8.

12 Shadnia S, Moiensadat M, Abdollahi M. A case of acute strychnine

poisoning. Vet Hum Toxicol 2004; 46: 76e9.

13 Cigolini D, Ricci G, Zannoni M, et al. Hydroxocobalamin treatment of

acute cyanide poisoning from apricot kernels. BMJ Case Rep 2011.

online early: doi:1 0.1136/bcr.03.2011.3932.

14 Lasch EE, El Shawa R. Multiple cases of cyanide poisoning by apricot

kernels in children from Gaza. Pediatrics 1981; 68: 5e7.

15 George P. Death related to herbal therapy for joint pains - a rare

case of Gloriosa superba poisoning. J Clin Diagn Res 2011; 5:

379e80.

16 Nagesh KR, Menezes RG, Rastogi P, et al. Suicidal plant poisoning

with. Colchicum autumnale. J Forensic Legal Med 2011; 18: 285e7.

17 Heath KB. A fatal case of apparent water hemlock poisoning. Vet

Hum Toxicol 2001; 43: 35e6.

18 Musshoff F, Madea B. Fatal cytisine intoxication and analysis of

biological samples with LC-MS/MS. Forensic Sci Int 2009; 186:

e1e4.

19 Kumana CR, Ng M, Lin HJ, et al. Hepatic veno-occlusive disease due

to toxic alkaloid herbal tea. Lancet 1983; 2: 1360e1.

20 Strzelecki A, Pichon N, Gaulier JM, et al. Acute toxic herbal intake in

a suicide attempt and fatal refractory ventricular arrhythmia. Basic

Clin Pharmacol Toxicol 2010; 107: 698e9.

21 Chan TYK. Aconite poisoning. Clin Toxicol 2009; 47: 279e85.

22 Travis AD, Gummin DD, McCann P, Knuths JR. Monkshood-induced

dysrhythmia treated with magnesium. J Toxicol Clin Toxicol 2002;

40: 646.

23 Bradberry S. Ricin and abrin. Medicine 2012; 40: 80e1.

� 2011 Published by Elsevier Ltd.