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PLANTS-DRYOPTERIS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Dryopteris filix-mas is the botanic name for the male fern, a plant that has been used since antiquity against tapeworms. Although once used extensively, synthetic, safer agents are now used.

Specific Substances

    A) Dryopteris austriaca
    1) Finnish Broad Buckler Fern
    Dryopteris borreri
    1) Rusty male fern
    Dryopteris filix-mas (Linne)(Schott)
    1) Aspidio
    2) Aspidium
    3) Aspidium filix-mas
    4) Basket Fern
    5) Buckler fern
    6) European Aspidium
    7) Farnwurzel
    8) Felce maschio
    9) Filicis maris folium (Male fern leaf)
    10) Filicis maris herba (Male fern herb)
    11) Filicis maris rhizoma (Male fern rhizome)
    12) Filix Mas
    13) Fougere male
    14) Johanniswurzel
    15) Male fern
    16) Polypodium Filix-mas (Linn)
    17) Polystichum Filix-mas (Roth)
    18) Rizoma de helecho macho
    19) Rhizoma Filicis
    Dryopteris marginalis (L) (Asa Gray)
    1) American Aspidium
    2) Aspidium marginale (Sw)
    3) Leather Wood Fern
    4) Marginal Fern
    5) Polypodium marginale (L)

Available Forms Sources

    A) FORMS
    1) It may be found in capsules, in oil medium, or in pills of 12-gram doses for adults (Duke, 1985).
    B) SOURCES
    1) ASPIDIUM is the rhizome and leaf stem of various Dryopteris ferns. The underground parts are collected in the fall, dried, and preserved. Most aspidium is gathered in Europe (specifically Italy and Yugoslavia). Labor costs deter gathering the plant in the United States (Claus et al, 1970).
    a) Aspidium contains not less than 1.5 percent crude filicin (composed of a mixture of various dimeric, trimeric, and tetrameric butanone phloroglucides)(Claus et al, 1970; Reynolds, 2000).
    b) In the United States, the aspidium has frequently been contaminated by other plants. Althea leaves are used to give the green color characteristic of good quality aspidium. Osmunda claytoniana and Polystichum achrostichoides (Christmas Fern) have sometimes been substituted for Dryopteris species (Osol & Farrar, 1955).
    C) USES
    1) Male fern rhizome has anthelmintic properties and is cytotoxic (Blumenthal et al, 1998). Aspidium is used specifically against tapeworms, Taenia solium, Taenia saginata, Diphyllobothrium latum, and Hymenolepis nana (Osol & Farrar, 1955). Dryopteris dilatata is known to be four times as active as regular aspidium (Rosendahl, 1911).
    2) Male fern herb preparations are used externally for rheumatism, sciatica, muscle pain, neuralgia, earache and toothache, for teething in infants and sleep disorders (Blumenthal et al, 1998).
    3) Male fern has been used as an old folk remedy for cancerous tumors. It is also used in veterinary practice and as an insecticide (Duke, 1985).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) When used extensively, poisonings were not uncommon, both because of the small therapeutic index and because of individual patient sensitivity. There are few human cases now, but a few veterinary cases may be seen.
    B) Adverse effects include nausea, vomiting, diarrhea, headache, vertigo, delirium, visual disturbances (including blindness), tremors, convulsion, and cardiac or respiratory failure.
    C) Muscular weakness and coma may occur with large doses.
    0.2.4) HEENT
    A) Visual disturbances, which may end in permanent blindness (in a few cases), may be seen after serious poisonings with this plant. Visual disturbances have been seen in almost half of the cases.
    0.2.5) CARDIOVASCULAR
    A) Bradycardia and cardiac failure may be seen in poisoning cases.
    0.2.6) RESPIRATORY
    A) An ascending depression, involvement of the medulla, dyspnea, cyanosis, and respiratory depression may be seen in severe poisoning cases.
    0.2.7) NEUROLOGIC
    A) Headache, dizziness, seizures, and coma may be seen.
    0.2.8) GASTROINTESTINAL
    A) The compounds found in male fern are irritating to the gastrointestinal tract. Nausea, diarrhea, cramping, and vomiting may be seen.
    0.2.9) HEPATIC
    A) Liver damage and jaundice may occur in poisoning cases.
    0.2.10) GENITOURINARY
    A) Parenchymatous nephritis was noted in animals fatally poisoned.
    B) Albuminuria may occur with poisoning.
    C) Uterine muscle stimulation may be seen after exposure.
    0.2.12) FLUID-ELECTROLYTE
    A) If vomiting and diarrhea are severe, patients should be monitored for fluid and electrolyte loss.
    0.2.18) PSYCHIATRIC
    A) Mental disturbances (undefined) have been noted in poisoning cases.
    0.2.20) REPRODUCTIVE
    A) Specific information was not available. Since this agent stimulates uterine muscle, it should probably NOT be used during pregnancy.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Laboratory Monitoring

    A) Monitor hepatic and renal function in symptomatic patients.
    B) Monitor fluid and electrolyte status in patients with significant vomiting or diarrhea.
    C) Monitor for cardiac dysrhythmias and respiratory depression.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) There is no specific antidote. Management is directed at monitoring for cardiac abnormalities, potential kidney or liver damage, respiratory depression, and visual acuity. Conditions which develop are managed by symptomatic and supportive care. Do NOT use a fatty or oily cathartic, as it will increase absorption.
    B) Rehydrate patients losing fluids through vomiting or diarrhea.
    C) Monitor for cardiac dysrhythmias and respiratory depression.
    D) Patients should have visual acuity monitored during and for a short time after exposure. There is no specific antidote to reverse the effects.
    E) 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.
    F) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    G) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 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) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 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).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    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) Minimum lethal human exposure is unknown.

Clinical Effects

Summary Of Exposure

    A) When used extensively, poisonings were not uncommon, both because of the small therapeutic index and because of individual patient sensitivity. There are few human cases now, but a few veterinary cases may be seen.
    B) Adverse effects include nausea, vomiting, diarrhea, headache, vertigo, delirium, visual disturbances (including blindness), tremors, convulsion, and cardiac or respiratory failure.
    C) Muscular weakness and coma may occur with large doses.

Vital Signs

    3.3.3) TEMPERATURE
    A) Cold sweats may be seen in poisoning cases (Osol & Farrar, 1955).

Heent

    3.4.1) SUMMARY
    A) Visual disturbances, which may end in permanent blindness (in a few cases), may be seen after serious poisonings with this plant. Visual disturbances have been seen in almost half of the cases.
    3.4.3) EYES
    A) Visual disturbances, which may end in permanent blindness (in a few cases), may be seen after serious poisonings with this plant (Frohne & Pfander, 1984; Reynolds, 2000; Duke, 1985; Blumenthal et al, 1998). The blindness is a characteristic sign of poisoning by this plant in both man and animals (Cooper & Johnson, 1984). Visual disturbances have been seen in almost half of the cases (Osol & Farrar, 1955).

Cardiovascular

    3.5.1) SUMMARY
    A) Bradycardia and cardiac failure may be seen in poisoning cases.
    3.5.2) CLINICAL EFFECTS
    A) BRADYCARDIA
    1) Bradycardia may occur (Reynolds, 2000; Blumenthal et al, 1998).
    B) HEART FAILURE
    1) Cardiac failure may occur (Reynolds, 2000; Duke, 1985; Blumenthal et al, 1998).
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CARDIAC ARREST
    a) Cardiac arrest and asystole were seen in lower animals given the oleoresin hypodermically (Osol & Farrar, 1955).

Respiratory

    3.6.1) SUMMARY
    A) An ascending depression, involvement of the medulla, dyspnea, cyanosis, and respiratory depression may be seen in severe poisoning cases.
    3.6.2) CLINICAL EFFECTS
    A) ACUTE RESPIRATORY INSUFFICIENCY
    1) An ascending depression, involvement of the medulla, dyspnea, cyanosis, and respiratory depression may be seen in severe poisoning cases (Osol & Farrar, 1955; Reynolds, 2000) Duke, 1985; (Blumenthal et al, 1998).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) DYSPNEA
    a) Severe dyspnea was noted in lower animals given the oleoresin hypodermically (Osol & Farrar, 1955).

Neurologic

    3.7.1) SUMMARY
    A) Headache, dizziness, seizures, and coma may be seen.
    3.7.2) CLINICAL EFFECTS
    A) SEIZURE
    1) Stimulation of the spinal cord may result in tremors and seizures (Osol & Farrar, 1955; Reynolds, 2000; Duke, 1985; Blumenthal et al, 1998).
    B) HEADACHE
    1) Headache may be seen in poisoning cases (Osol & Farrar, 1955; Reynolds, 2000; Blumenthal et al, 1998).
    C) DIZZINESS
    1) Dizziness may be seen (Reynolds, 2000; Duke, 1985; Blumenthal et al, 1998).
    D) COMA
    1) Coma may be seen in poisoning cases (Reynolds, 2000).
    E) DELIRIUM
    1) Delirium may be seen (Duke, 1985).

Gastrointestinal

    3.8.1) SUMMARY
    A) The compounds found in male fern are irritating to the gastrointestinal tract. Nausea, diarrhea, cramping, and vomiting may be seen.
    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) The compounds found in male fern are irritating to the gastrointestinal tract, and nausea and vomiting may be seen (Frohne & Pfander, 1984; Reynolds, 2000; Blumenthal et al, 1998).
    B) ABDOMINAL PAIN
    1) Cramping may be seen in cases of poisoning by this plant (Frohne & Pfander, 1984; Reynolds, 2000; Blumenthal et al, 1998).
    C) DIARRHEA
    1) The irritating nature of male fern oleoresin may produce diarrhea (Duke, 1985; Blumenthal et al, 1998; Reynolds, 2000).

Hepatic

    3.9.1) SUMMARY
    A) Liver damage and jaundice may occur in poisoning cases.
    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) Liver damage and jaundice may occur in poisoning cases (Osol & Farrar, 1955; Reynolds, 2000; Blumenthal et al, 1998).

Genitourinary

    3.10.1) SUMMARY
    A) Parenchymatous nephritis was noted in animals fatally poisoned.
    B) Albuminuria may occur with poisoning.
    C) Uterine muscle stimulation may be seen after exposure.
    3.10.2) CLINICAL EFFECTS
    A) ALBUMINURIA
    1) Albuminuria may occur with poisoning (Reynolds, 2000) Blumenthal et al, 1998).
    B) UTERUS CONTRACTED
    1) Uterine muscle stimulation may be seen after exposure (Reynolds, 2000; Blumenthal et al, 1998).
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) NEPHRITIS
    a) Parenchymatous nephritis was noted in animals fatally poisoned (Osol & Farrar, 1955).

Reproductive

    3.20.1) SUMMARY
    A) Specific information was not available. Since this agent stimulates uterine muscle, it should probably NOT be used during pregnancy.
    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.
    2) Although specific information is not available, this agent does stimulate uterine muscle and should not be used in pregnancy.

Carcinogenicity

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

Genotoxicity

    A) At the time of this review, no data were available to assess the mutagenic or genotoxic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor hepatic and renal function in symptomatic patients.
    B) Monitor fluid and electrolyte status in patients with significant vomiting or diarrhea.
    C) Monitor for cardiac dysrhythmias and respiratory depression.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor hepatic and renal function in symptomatic patients.
    2) Monitor fluid and electrolyte status in patients with significant vomiting or diarrhea.
    3) Monitor for cardiac dysrhythmias and respiratory depression.
    4) Patients should have visual acuity monitored during and for a short time after exposure.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Monitor hepatic and renal function in symptomatic patients.
    B) Monitor fluid and electrolyte status in patients with significant vomiting or diarrhea.
    C) Monitor for cardiac dysrhythmias and respiratory depression.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) 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) ACTIVATED CHARCOAL
    1) Do not use a fatty or oily cathartic, as it will increase absorption.
    2) 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.
    3) 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).
    B) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    6.5.3) TREATMENT
    A) SUPPORT
    1) There is no antidote for overdose. Treatment is symptomatic and supportive.
    B) MONITORING OF PATIENT
    1) VISION TESTING: Eye toxicity with various degrees of loss of vision occurs in almost half the cases of overdose (Osol & Farrar, 1955). Patients should have visual acuity monitored during and for a short time after exposure. There is no specific antidote to reverse the effects.
    C) 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, 2010; 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).

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) DERMAL DECONTAMINATION
    1) 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.

Range Of Toxicity

Summary

    A) Minimum lethal human exposure is unknown.

Therapeutic Dose

    7.2.1) ADULT
    A) SPECIFIC SUBSTANCE
    1) ASPIDIUM POWDER -
    a) 4 to 8 grams (1 to 2 drachms) (Osol & Farrar, 1955)
    b) The oleoresin is a more consistent and chemically stable dosage preparation, and is generally preferred to the powder (Osol & Farrar, 1955).
    2) ASPIDIUM OLEORESIN -
    a) Aspidium, in the form of aspidium oleoresin or male fern oleoresin, has not less than 24 percent crude filicin (composed of a mixture of various dimeric, trimeric, and tetrameric butanone phloroglucides), and is used as a teniafuge in doses of 4 to 5 grams (60 grains) for an adult. Doses may range from 1 to 5 grams. This dose is preceded and followed by a cathartic. Castor oil is not recommended as the cathartic since it is thought to increase the absorption of filicin's components (Claus et al, 1970; Osol & Farrar, 1955).
    b) If the initial treatment is not successful, at least 10 days should elapse before administering a second dose (Claus et al, 1970).
    3) FILMARON -
    a) This is one of the active components of aspidium. It is used as a 10 percent solution mixed with castor oil (Osol & Farrar, 1955).
    b) The dose is 0.5 to 0.75 gram (about 7.5 to 12 grains) (Osol & Farrar, 1955).
    7.2.2) PEDIATRIC
    A) SPECIFIC SUBSTANCE
    1) ASPIDIUM OLEORESIN -
    a) Dose is 250 milligrams (about 4 minims) per year of age up to a maximum of 15 years (Osol & Farrar, 1955).
    b) The use of aspidium in children is hazardous (Osol & Farrar, 1955).

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) No specific maximum tolerated exposure amount has been determined, but the drug has a low therapeutic index, and amount not much greater than the therapeutic amounts would be expected to produce adverse effects or toxicity.

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Aspidium does not kill tapeworms, it paralyzes them, so that they may be washed out of the body (Osol & Farrar, 1955).

Toxicologic Mechanism

    A) The toxic component of male fern is the crude filicin which is composed of a mixture of various dimeric, trimeric, and tetrameric butanone phloroglucides. These phloroglucides are relatively unstable compounds composed of butyric or isobutyric acid combined with phloroglucinol or its various homologues (Pabst & Bliss, 1932; Robertson & Sandrock, 1933; Frohne & Pfander, 1984).
    B) These compounds have had a number of different names. Amorphous filic acid, crystalline filicic acid (also called filicin and filicinic acid), filic acid, aspidinin, albaspidin, aspidin, aspidinol, falvaspidinic acid, and filmaron (Osol & Farrar, 1955). The simplest of these compounds is aspidinol which has been shown to be a monomethyl ether of C-methylphloro-n-butyrophenone. Filicinic acid is a decomposition product of several aspidium chemicals (Robertson & Sandrock, 1933).
    C) The toxic compounds are found on the scales (which are really hairlike excretory cells) which are located on the frond bases and the rhizomes of the plant (Frohne & Pfander, 1984).
    D) RETINAL TOXICITY - Harnack (1912) has postulated that the retinal toxicity is due to spasm of the retinal vessels and subsequent optic atrophy.
    E) These ferns do contain thiaminase like Pteridium aquilinum (Braken Fern), but the thiamine deficiency seen in animals who have eaten Braken is not seen with Dryopteris species (Cooper & Johnson, 1984).
    F) Aspidium paralyzes the voluntary muscles of higher animals and the contractile tissues of invertebrates (Straub, 1902).

Animal Toxicology

Clinical Effects

    11.1.2) BOVINE/CATTLE
    A) Various outbreaks of poisoning by Dryopteris species have occurred, usually in winter when there is little in the way of other forage (Cooper & Johnson, 1984).
    B) SYMPTOMS -
    1) MORTALITY is usually low (Cooper & Johnson, 1984).
    2) BLINDNESS which is occasionally permanent, is a characteristic sign of poisoning by this plant in both man and animals. The blindness is often associated with widely dilated pupils (Cooper & Johnson, 1984). There are hemorrhages of the retina, edema of the optic disc, and optic nerve damage (Rosen et al, 1970).
    3) STAGGERING GAIT and hard dark brown stools are often seen. The animals may wish to stand or lie in water (MacLeod et al, 1978; Edgar & Thin, 1968; Murray, 1966).
    C) Postmortem examination of cattle killed by male fern showed the walls of the abomasum and small intestine to be thickened and inflamed, the rumen contents were very dry, the gall bladder was enlarged, there were numerous small hemorrhages of major blood vessels of the thorax, there were small hemorrhages of the heart, and the digestive tract had a number of ulcers (Edgar & Thin, 1968; MacLeod et al, 1978).

Treatment

    11.2.2) LIFE SUPPORT
    A) GENERAL
    1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.
    11.2.5) TREATMENT
    A) CATTLE
    1) Even though ruminal bacteria synthesize thiamine, thus making thiamine deficiency unlikely, vitamin B complex and calcium has been injected as treatment. There seems to be little effect on the animals from this treatment. Cathartics may be of some use in treating the constipation (Cooper & Johnson, 1984).

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