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PLANTS-AMARYLLIDACEAE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) The Amaryllidaceae plant family are herbaceous perennials that produce bulbs. These plants contain toxic phenanthridine derivative alkaloids, the most common of which is lycorine (Frohne & Pfander, 1983).
    B) Some of these plants also contain oxalates and allergens (Mitchell & Rook, 1979).

Specific Substances

    1) Zephyranthes spp.

Available Forms Sources

    A) SOURCES
    1) NARCISSUS species are known to contain Amaryllidaceae alkaloids. N. radinganorum is known to contain homolycorine, 8-0-demethylhomolycorine, 9-0-demethylmaritidine (Bastida et al, 1988).
    B) USES
    1) GALANTHAMINE (one of the Amaryllidaceae alkaloids) is available pharmaceutically as Nivalin (Pharmachim of Bulgaria), and as a component of Energix.
    2) It possesses anticholinesterase properties similar to that of physostigmine (Mihailova et al, 1989). In Eastern Europe and the USSR, galanthamine has been used to treat pareses, paralysis, Alzheimer's disease, and myasthenia gravis (Mihailova et al, 1989).
    3) Several clinical trials (open and placebo-controlled) have shown that galanthamine is able to produce an improvement in cognitive function (or slow deterioration) in individuals with a mild form of Alzheimer's disease (Bruneton, 1999).
    4) It appears to have the ability to amplify nerve-muscle transfer (Bastida et al, 1990).
    5) Over two hundred different plants were tested for galanthamine content. The greatest quantity was 0.45% found in the leaves of Leucojum aestivum (Poulev et al, 1989).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Ingestion of parts of the plants of the Amaryllidaceae family may cause nausea, vomiting, abdominal pain, and diarrhea. Although hypotension, liver damage and CNS symptoms have been described after ingestions of significant amounts in animals, they are generally not reported in humans.
    1) The most toxic part is the bulb, especially the outer scale leaves.
    B) The duration of gastrointestinal symptoms in humans is about 3 hours.
    0.2.4) HEENT
    A) Allergic conjunctivitis and swelling of the eyelids have been reported.
    0.2.5) CARDIOVASCULAR
    A) Hypotension has been reported in animal experiments.
    0.2.6) RESPIRATORY
    A) Occupational asthma was reported in one worker following repeated exposure to amaryllis.
    0.2.7) NEUROLOGIC
    A) CNS depression has been reported in animal studies, and one text mentions that central paralysis is possible if large amounts are ingested and absorbed. Seizures have been reported in poisoned animals.
    0.2.8) GASTROINTESTINAL
    A) The most common symptoms are nausea, vomiting, and diarrhea, which have occurred following animal and human exposures.
    0.2.9) HEPATIC
    A) Hepatic damage has been reported in animal studies, but has not been reported following human exposure.
    0.2.12) FLUID-ELECTROLYTE
    A) Vomiting and diarrhea are usually self-limited following ingestion. Monitor fluid balance and electrolytes following significant GI loss.
    0.2.14) DERMATOLOGIC
    A) Both allergic and contact dermatitis may be seen after exposure to plants in this family. Not all of the symptoms may be due to the alkaloids, since some species (like the daffodil) contain oxalates as well.
    0.2.19) IMMUNOLOGIC
    A) Some members of the Amaryllidaceae family may contain allergens which may cause skin, eye, and respiratory symptoms in susceptible individuals.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Laboratory Monitoring

    A) If fluid loss is extensive, monitor fluid and electrolytes. No specific tests for the alkaloids are generally available for hospital use.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Treatment is symptomatic and supportive. Medical intervention is seldom required for most exposures which involve ingestion of a bulb or less.
    B) Emesis is the early and often the only symptom of ingestion. Unless large amounts (in excess of 1 bulb for a daffodil) are ingested, gastric decontamination is probably not required.
    C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    D) Replace fluids as required. There are no specific antidotes.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) TOXICITY: No specific toxic dose has been established. Ingestion of one or more bulbs of daffodils may cause gastrointestinal symptoms, even in adults.

Clinical Effects

Summary Of Exposure

    A) Ingestion of parts of the plants of the Amaryllidaceae family may cause nausea, vomiting, abdominal pain, and diarrhea. Although hypotension, liver damage and CNS symptoms have been described after ingestions of significant amounts in animals, they are generally not reported in humans.
    1) The most toxic part is the bulb, especially the outer scale leaves.
    B) The duration of gastrointestinal symptoms in humans is about 3 hours.

Heent

    3.4.1) SUMMARY
    A) Allergic conjunctivitis and swelling of the eyelids have been reported.
    3.4.3) EYES
    A) CASE REPORT: Allergic conjunctivitis and swelling of the eyelids were reported in an individual who raised Narcissus as cut flowers (Goncalo et al, 1987).

Cardiovascular

    3.5.1) SUMMARY
    A) Hypotension has been reported in animal experiments.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypotension has been reported in animal poisonings but has not been seen in human exposures (Wilson, 1924).

Respiratory

    3.6.1) SUMMARY
    A) Occupational asthma was reported in one worker following repeated exposure to amaryllis.
    3.6.2) CLINICAL EFFECTS
    A) RESPIRATORY FAILURE
    1) WITH POISONING/EXPOSURE
    a) ASTHMA
    1) CASE REPORT/CHRONIC EXPOSURE: A 50-year-old horticulturist developed occupational IgE-mediated asthma following exposure to amaryllis (genus Hippeastrum, family Amaryllidaceae) (Jansen et al, 1996). Symptoms of rhinitis and shortness of breath developed approximately one year after working in a greenhouse.

Neurologic

    3.7.1) SUMMARY
    A) CNS depression has been reported in animal studies, and one text mentions that central paralysis is possible if large amounts are ingested and absorbed. Seizures have been reported in poisoned animals.
    3.7.2) CLINICAL EFFECTS
    A) PARALYSIS
    1) WITH POISONING/EXPOSURE
    a) Central paralysis may be seen after ingestion of large amounts (Frohne & Pfander, 1983).
    B) DIZZINESS
    1) WITH POISONING/EXPOSURE
    a) Dizziness has been observed following ingestion (Cooper & Johnson, 1984).
    C) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Seizures and trembling are symptoms reported by Hardin & Arena (1974), but it is not mentioned whether these symptoms occurred in humans or animals.
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SEIZURES
    a) Seizures and sedation have been reported in animals (Wilson, 1924).
    2) SOMNOLENCE
    a) Sedation was a symptom reported by Wilson (1924) in animal poisonings.

Gastrointestinal

    3.8.1) SUMMARY
    A) The most common symptoms are nausea, vomiting, and diarrhea, which have occurred following animal and human exposures.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: Accidental ingestions resulting in nausea and vomiting have occurred when various parts of the plant have been mistaken for leeks, shallots or an oriental species that was supposedly edible (Bruneton, 1999). Cases of accidental exposure have been documented in Great Britain and the United States.
    b) SYMPTOMS: Nausea, vomiting, and abdominal pain occurred after ingestion (Frohne & Pfander, 1983; Litovitz & Fahey, 1982), and lasted up to 3 hours (Litovitz & Fahey, 1982).
    c) CASE SERIES: A group of students each inadvertently ingested a Narcissus tazetta bulb (assuming they were eating green onions) and most (8 of 10 children) developed vomiting approximately 30 minutes after exposure and were treated with IV fluids. The adult accompanying them also ingested the bulb and had vomiting and abdominal pain that responded to metoclopramide and IV fluid replacement. Following 4 hours of observation no further symptoms were reported and all cases were discharged (Hussein & Yassin, 2014).
    B) DIARRHEA
    1) WITH POISONING/EXPOSURE
    a) Profuse diarrhea has occurred after acute exposure (Frohne & Pfander, 1983) and resolved with symptomatic care (Bruneton, 1999).
    C) EXCESSIVE SALIVATION
    1) WITH POISONING/EXPOSURE
    a) Salivation may be seen after ingestion (Frohne & Pfander, 1983).

Hepatic

    3.9.1) SUMMARY
    A) Hepatic damage has been reported in animal studies, but has not been reported following human exposure.
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATOCELLULAR DAMAGE
    a) Hepatic degradation was reported in animal overdoses, but has not been observed following human exposure (Wilson, 1924).

Dermatologic

    3.14.1) SUMMARY
    A) Both allergic and contact dermatitis may be seen after exposure to plants in this family. Not all of the symptoms may be due to the alkaloids, since some species (like the daffodil) contain oxalates as well.
    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Many of these plants (such as daffodil) contain oxalates as well, and the mechanical irritation of the oxalate crystals may aid in absorption of the alkaloids (Frohne & Pfander, 1983).
    b) Both contact and allergic dermatitis which may have been reported, but are not common (Goncalo et al, 1987).
    c) In a study of occupational exposure in florists, the most commonly suspected cause of dermatitis was associated with the handling of daffodils (Merrick et al, 1991).
    d) SYMPTOMS: Lesions are generally limited to the hands and fingers, but secondary contact may spread to the face and neck (Bruneton, 1999). Most cases resolve when contact with the bulbs is discontinued.
    B) EXCESSIVE SWEATING
    1) WITH POISONING/EXPOSURE
    a) Sweating may occur shortly after ingestion (Frohne & Pfander, 1983).

Immunologic

    3.19.1) SUMMARY
    A) Some members of the Amaryllidaceae family may contain allergens which may cause skin, eye, and respiratory symptoms in susceptible individuals.
    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) WITH POISONING/EXPOSURE
    a) Most cases of narcissus dermatitis are due to direct irritancy, but some cases of positive patch testing and allergic sensitivity have occurred (Gude et al, 1988).
    b) IgE-mediated asthma was confirmed in one horticulturist following repeated exposure to amaryllis (genus Hippeastrum, family Amaryllidaceae) (Jansen et al, 1996).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) If fluid loss is extensive, monitor fluid and electrolytes. No specific tests for the alkaloids are generally available for hospital use.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor fluid and electrolyte loss if vomiting and diarrhea are extensive.

Methods

    A) CHROMATOGRAPHY
    1) GALANTHAMINE can be determined in human plasma and urine by an HPLC method described by Tencheva et al (1987). A radioimmunoassay has also been developed which can measure within the range of 0.5 to 100 nanograms. As little as 3.5 picograms may be detected (Poulev et al, 1989; Tanahashi et al, 1990).
    B) INHALANT ALLERGEN TESTING
    1) Jansen et al (1996) reported that total IgE and allergen-specific IgE titers were determined in one case report using the CAP system (Kabi Pharmacia, The Netherlands) and RAST testing. The patient was diagnosed with IgE-mediated asthma secondary to amaryllis exposure.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) If fluid loss is extensive, monitor fluid and electrolytes. No specific tests for the alkaloids are generally available for hospital use.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Emesis occurs early and often is the only symptom of ingestion. Unless large amounts (in excess of 1 bulb for a daffodil) are ingested, gastric decontamination is probably not required.
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Emesis is the early and often the only symptom of ingestion. Unless large amounts (in excess of 1 bulb for a daffodil) are ingested, gastric decontamination is probably not required.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) There is no specific antidote, treatment is symptomatic and supportive. Seizures and hypotension have been seen in animals, so the treatments are listed below. At the time of this review, these effects have NOT been reported in human exposures.
    B) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    C) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

    A) SUMMARY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Abstracts

Case Reports

    A) ACUTE EFFECTS
    1) A family of 4 adults were hospitalized after eating a soup made from young jonquil leaves mistaken for leeks. One hour after ingesting the soup they developed gastric burning, nausea, vomiting, and profuse diarrhea.
    2) Blood pressure and heart rate were within normal limits, but one patient mentioned a feeling of lethargy or somnolence. Treatment consisted of rehydration, oral antacids and antidiarrheals. Electrolytes were monitored, but only minor disturbances were found.
    3) The patients were followed for 15 days, the only abnormality was a feeling of nausea in one of the patients for 10 days (Vigneau et al, 1984).
    B) ADULT
    1) A Vietnamese couple were taken to the hospital after having consumed the stems and flowers of jonquils. The plants had been mistaken for Chinese Lilies, which are often eaten in Southeast Asia. After cooking the jonquils, the leaves and flowers were mixed in a salad with meat and lard.
    2) They each ingested about 3 or 4 teaspoonfuls of this mixture. Within one half hour, nausea and vomiting developed followed in another half hour by profuse diarrhea and cramping. Blood pressure was normal, and the heart rate was about 90 beats per minute.
    3) Treatment was symptomatic. The patients were monitored for cardiac, hepatic, and neurologic changes, but none were noted in the next 24 hours or upon reexamination 15 days later (Vigneau et al, 1984).

Range Of Toxicity

Summary

    A) TOXICITY: No specific toxic dose has been established. Ingestion of one or more bulbs of daffodils may cause gastrointestinal symptoms, even in adults.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) ORAL
    a) The recommended starting oral dose of galantamine in adults is 4 milligrams twice daily. After a minimum of 4 weeks of treatment, this dose is well tolerated, the dose should be increased to 8 milligrams twice daily. Further increases to 12 milligrams twice daily should be attempted only after a minimum of 4 weeks at the previous dose (Prod Info Reminyl(R), galantamine hydrobromide, 2001).
    2) PARENTERAL
    a) The recommended parenteral dose of galantamine in adults is 1.25 to 15 milligrams daily, administered subcutaneously. Treatment should be initiated with the lowest possible dose, with gradual increases to the optimal dose. When advancing to higher daily doses, the increases should be administered in two to three divided doses (ABDA-Datenbank, 1996).
    3) MAXIMUM DOSE - The maximum daily dose of galantamine is 25 milligrams in adults (ABDA-Datenbank, 1996).

Minimum Lethal Exposure

    A) SUMMARY
    1) A minimum lethal dose has not been established.

Maximum Tolerated Exposure

    A) SUMMARY
    1) Ingestion of even one bulb or less may cause gastrointestinal symptoms in an adult (Litovitz & Fehey, 1982).
    B) CASE REPORTS
    1) CASE REPORT: IgE-mediated asthma was reported in one horticulturist following approximately one year of being occupationally exposed to amaryllis (Jansen et al, 1996).
    2) CASE SERIES: A group of students each inadvertently ingested a Narcissus tazetta bulb (assuming they were eating green onions) and most (8 of 10 children) developed vomiting approximately 30 minutes after exposure and were treated with IV fluids. The adult accompanying them also ingested the bulb and had vomiting and abdominal pain that responded to metoclopramide and IV fluid replacement. Following 4 hours of observation no further symptoms were reported and all cases were discharged (Hussein & Yassin, 2014).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LYCORIN
    1) LD50- (SUBCUTANEOUS)MOUSE:
    a) 145 mg/kg (RTECS, 2000)
    B) NARCICLASINE
    1) LD50- (SUBCUTANEOUS)MOUSE:
    a) 5 mg/kg (Ceriotti, 1967)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Various Amaryllidaceae alkaloids have cytotoxic and antileukemic activity, and have been tested in mice. The most active alkaloids are pretazettine and its stereoisomer precriwelline, with haemanthamine, crinamine and 6-hydroxycrinamide also having some activity (Furusawa et al, 1980). The narcissus spp. is the most commonly cultivated in this genus and contains (like many other species) alkaloids, including homolycorine, haemanthamine, galanthamine, oduline, and masonine (Bruneton, 1999).
    B) The Amaryllidaceae alkaloids are specific protein inhibitors (Jimenez et al, 1976), as well as antivirals (Ieven et al, 1978; Ieven et al, 1979).
    C) These agents have antiviral activity against herpes viruses, antimitotic activity, antileukemic activity, antitumor activity and spasmolytic actions (Gude et al, 1988).
    D) GALANTHAMINE - possesses anticholinesterase actions similar to physostigmine (Nesterenko, 1965). It also has anti-morphine, anti-curare, and memory-influencing effects (Paskov, 1962; (Cozanitis, 1971; Krauz, 1974; Chaplygina & Iljuchenok, 1976). It also has anticholinergic and analgesic effects (Bastida et al, 1990).
    E) NARCICLASINE is an antimitotic agent which appears to act essentially as a metaphasic or a preprophasic poison. A colchicine effect is seen at 0.5 mg/kg (Ceriotti, 1967).
    F) CLINICAL STUDIES - Several clinical trials (open and placebo-controlled) have shown that galanthamine may improve cognitive function (or slow deterioration) in some individuals with mild Alzheimer's disease (Bruneton, 1999).

Animal Toxicology

Clinical Effects

    11.1.11) REPTILE
    A) REPTILE
    1) A TORTOISE developed loss of appetite and lethargy after eating the leaves of a wild daffodil. A postmortem showed severe gastritis and ulceration of mucous membranes (Cooper & Johnson, 1984).

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