eMedicine Specialties > Emergency Medicine > Toxicology

Plant Poisoning, Alkaloids - Quinolizidine and Isoquinoline

Author: David Vearrier, MD, Fellow, Department of Toxicology, Drexel University College of Medicine
Coauthor(s): Richard J Hamilton, MD, FAAEM, FACMT, Chairman, Department of Emergency Medicine, Drexel University College of Medicine
Contributor Information and Disclosures

Updated: Apr 13, 2009

Introduction

Background

Alkaloids are alkali-like compounds that form salts with acids and contain nitrogen, generally in heterocyclic and/or ring structures. Found in a wide variety of plants, animals, and fungi, many alkaloids have medicinal and toxic properties.

Quinolizidine and isoquinoline alkaloids are a widely distributed, heterogeneous group of alkaloids with members of each group having known toxicity to humans and domestic animals.

Plants containing quinolizidine alkaloids with known toxicity include the following:

• Baptisia species (false indigo)
• Cytisus species (scotch broom)
• Laburnum species (goldenchain, laburnum)
• Lupinus species (lupine, bluebonnet)
• Sophora species (mescal bean, frijolito)

Plants containing isoquinoline alkaloids with known toxicity include the following:

• Argemone species (prickly poppy)
• Chelidonium species (celandine poppy)
• Corydalis species (fitweed)
• Dicentra species (dutchman's breeches)
• Papaver species (poppy)
• Sanguinaria species (bloodroot)

Cytisine, a tricyclic quinolizidine alkaloid found in Baptisia, Cytisus, Laburnum, and Sophora species, has nicotinelike effects on the gastrointestinal (GI) tract and the central nervous system (CNS). These plants may be smoked recreationally for their stimulant effects and mild hallucinogenic properties. Mescal bean may have been used by Native American peoples for ceremonial and medicinal purposes. Sophora root is used in traditional Chinese medicine where it is known as "Ku Shen" and is used to treat dysentery, scabies, itchy rashes including eczema, skin lesions, jaundice, edema, urinary dysfunction, and vaginal discharge.

Lupinus species contain sparteine, a tetracyclic quinolizidine alkaloid, and lupinine, a bicyclic quinolizidine alkaloid. Lupinus species are broadly divided into bitter lupins that contain high levels of alkaloids in their seeds, and sweet lupins that contain lower levels of alkaloids and are cultivated for human consumption. Sweet lupins do contain sparteine and lupinine and must be soaked in water to prevent toxicity following ingestion. These two alkaloids are also found in other genera.

The toxic isoquinoline alkaloids include papaverine, sanguinarine, dihydrosanguinarine, protoverine, berberine, coptisine, protopine, and chelidonine. They act as GI tract irritants, CNS stimulants, and have varying degrees of neurologic effects, ranging from relaxation and euphoria to seizures. They are also vasodilatory. Prickly poppy is smoked as a euphoriant.

Papaverine, found in prickly poppy and bloodroot, has been used medically as a smooth muscle relaxant. Prickly poppy extracts act as capillary dilators and have been implicated in epidemic glaucoma in India.

Sanguinaria species (bloodroot) extract was Food and Drug Administration (FDA) approved and used commercially as a dental plaque inhibitor; however, it is no longer added to commercially available toothpaste and mouthwash due to concerns that chronic use may cause oral leukoplakia. Sanguinaria extract may still be purchased over the Internet, where it is marketed as a mouthwash for dental decay, as an escharotic for skin lesions including cancer, and as a tea for a variety of indications. It is not FDA approved for these uses.

Celandine extracts are used in the herbal treatment of gastrointestinal disorders, including dyspepsia, gallstone disease, and irritable bowel syndrome. Celandine extracts have been shown to increase the flow of bile acids and decrease right upper quadrant pain due to biliary dyskinesia. Celandine extract also has stimulatory effects on smooth muscle contraction in the stomach and spasmolytic effects in the small intestine, which may explain its beneficial effects in dyspepsia and irritable bowel syndrome.

Argemone oil poisoning is relatively common in India, where it is known as epidemic dropsy and is a result of argemone oil being added as an adulterant to mustard oil. In 1998, an epidemic of argemone oil poisoning in New Delhi led to 3000 victims and 60 deaths.¹ Argemone oil poisoning has also been reported after transcutaneous absorption from adulteration of mustard oil used in massages.

Pathophysiology

Cytisine is similar in action to nicotine. GI irritation is common, and toxic ingestions almost invariably result in emesis. Onset of symptoms is rapid. GI upset and vomiting start 45 minutes to 4 hours after ingestion. CNS effects include drowsiness, weakness, loss of coordination, muscle fasciculations, seizures, coma, and mydriasis. Some anticholinergic effects, such as urinary retention, may manifest. Respiratory failure, as in nicotine poisoning, is observed in patients with severe cases.

Cutaneous exposure to celandine and bloodroot extracts may cause a contact dermatitis, and ingestion of celandine extract is known to be hepatotoxic with numerous cases of acute cholestatic hepatitis reported in the literature. Rarely, necrotizing hepatitis has been reported. Celandine extract has also been implicated in a case of hemolytic anemia.²

Corydalis species (fitweed) ingestion has demonstrated delayed hepatotoxicity.

Argemone oil has been reported to cause oxidative stress by reducing levels of glutathione reductase and glucose-6-phosphate reductase in erythrocytes and glutathione, alpha-tocopherol, and glutathione-S-transferase in erythrocytes and liver.³ Sanguinarine and related isoquinoline alkaloids are the active toxins in argemone oil responsible for its adverse effects. Others postulate that sanguinarine toxicity is additionally mediated by inhibition of Na⁺ K⁺ ATPase, inhibition of DNA polymerase, inhibition of the cytochrome P-450 system, and accumulation of pyruvate due to increased rates of glycogenolysis.

Bloodroot extract, which contains the alkaloid sanguinarine, is a strong escharotic that causes cell cycle blockade and apoptosis, especially in cancerous cells.

Both argemone oil and isolated sanguinarine alkaloid have also been reported to be genotoxic in humans, and argemone oil consumption is linked with an elevated incidence of gallbladder carcinoma in India.

Sparteine has been reported to have cardiac, ganglioplegic, and oxytocic effects, while lupinine is anticholinergic. Both have been reported to cause sedation.

Ingestion of poppies may result in narcotic effects from opiate alkaloids and papaverine, as well as hypotension and cardiovascular collapse.

Frequency

United States

Most of the isoquinolines are noxious in smell and taste and discourage ingestion; thus, human toxicity is rare. Interestingly, some domestic species tolerate ingestion of isoquinoline and other alkaloids, and humans can ingest toxic alkaloids from the milk of a poisoned animal and manifest symptoms.

Isolated American and European case reports exist of toxicity following ingestion of improperly washed lupini beans.

Incidence of alkaloid poisoning is low and probably underreported.

International

As mentioned above, outbreaks of argemone oil poisoning are relatively common in India, where it has been used to adulterate more expensive mustard oil. Outbreaks have also been reported in Mauritius, Fiji, Madagascar, and South Africa.

Laburnum poisoning is reported widely in Great Britain and Europe; 50 cases were documented in 1979. One group in Germany, recorded 892 exposures between 1998 and 2004, and, of these, 45 demonstrated moderate or major effects.⁴ Concern regarding the toxicity of this plant may greatly exceed actual clinical effects in many cases.^5,6

Mortality/Morbidity

Mortality is rare. A single adult case of death by Laburnum poisoning was reported in a man with schizophrenia. Mescal bean and other quinolizidine and isoquinoline alkaloids have been documented with sporadic case reports of fatality. Epidemic outbreaks of argemone oil poisoning have led to numerous deaths.

Race

Isoquinoline and/or quinolizidine poisonings are not noted to have increased frequency in any particular race.

Sex

Effects of isoquinoline and/or quinolizidine poisoning are related to dose and not sex.

Age

The toxic alkaloids are concentrated in the pealike or brightly colored seeds in laburnum, mescal bean, and lupine, which children may consume resulting in serious morbidity and mortality.

Clinical

History

• For all ingestions, obtain as complete a history as possible, including the following:
  • Medications
  • Allergies
  • Suspected ingestion
  • Time of ingestion
  • Possible co-ingestions
• Identify the plant ingested if possible. An on-site plant reference text and established relationship with an emergency plant taxonomy consultant are useful resources.
  • Laburnum is a small tree, up to 30 feet tall, that bears golden sweet pea-shaped flowers and seeds in pealike pods. It is found in the southeastern United States and Europe.
  • Mescal bean is a shrub or small tree with purple flowers and bright red seeds. It is found in the southwestern United States and Mexico.
• Patients with cytisine ingestion may complain of vomiting, diarrhea, GI cramping, palpitations, confusion, tremor, and weakness.
• Following Sophora root ingestion, patients may complain of excessive salivation, abnormal gait, shortness of breath, muscle spasm, dizziness, palpitations, nausea, vomiting, and constipation. Reduced libido and impotence have been reported, though the association is confounded by other herbs in the formulation. Three case reports of adverse effects after ingestion of 60 g of Sophora root extract suggest that significant toxicity may occur at that dose.⁷
• Following argemone oil poisoning, patients may complain of whole body swelling, headache, vomiting, diarrhea, and shortness of breath.
• Following ingestion of Lupinus alkaloids, patients may complain of anticholinergic symptoms such as blurry vision, dry mouth, confusion, palpitations, flushing, and fever.
• Following ingestion of poppy seed tea, patients may complain of drowsiness and weakness, which can progress occasionally to respiratory arrest and death.⁸

Physical

• Cytisine ingestion causes a nicotinic toxidrome with hyperactive bowel sounds, vomiting, diarrhea, fasciculations, weakness, diaphoresis, seizures, coma, and mydriasis. 
• Sophora root ingestion may be associated with vomiting, CNS agitation or depression, ataxia, diaphoresis, seizures, and respiratory depression.
• Physical examination following argemone oil ingestion may reveal pitting edema of the extremities, rales or rhonchi consistent with pulmonary edema, and flushing of the skin. Hypotension, vomiting, and diarrhea may be present.
• Exposure to morphine and papaverine from poppy seeds can produce depressed mental status and respiratory failure, as well as miosis and mild hypotension and bradycardia typical of opioid toxidrome.⁸

Causes

Risk factors for quinolizidine and/or isoquinoline plant toxicity include use of medicinal herbs and/or preparations, recreational drug experimentation (most notably mescal bean and opium poppy), drinking of milk from animals that ingest toxic plants (rare), adulteration of mustard oil (international), and childhood ingestion of ornamental plants (most notably Laburnum).

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