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PLANTS-GOLDEN SEAL

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Golden Seal belongs to the Buttercup family, Ranunculaceae, though its leaves and fruit somewhat resemble those of the Raspberry and the Rubus genus generally.

Specific Substances

    1) GOLDEN SEAL
    2) Hydrastis canadensis
    3) Yellow root
    4) Orange root
    5) Yellow puccoon
    6) Ground raspberry
    7) Wild curcuma
    8) Turmeric root
    9) Indian dye
    10) Eye root
    11) Eye balm
    12) Indian paint
    13) Jaundice root
    14) Warnera
    15) Gelbwurzel
    16) Canadische
    17) Hydrastis
    18) Indian turmeric (rhizome)
    19) 1,6-HEPTADIENE-3,5-DIONE, 1,7-BIS(4-HYDROXY-3-METHOXYPHENYL)
    20) 1,7-BIS(4-HYDROXY-3-METHOXYPHENYL)-1,6-HEPTADIENE-3,5-DIONE
    21) C.I. 75300
    22) C.I. NATURAL YELLOW 3
    23) CAS 33171-04-9
    24) CAS 458-37-7
    25) CAS 8024-37-1
    26) CURCUMA
    27) CURCUMA OIL
    28) CURCUMIN
    29) CURCUMINE
    30) DIFERULOYLMETHANE
    31) HAIDR
    32) HALAD
    33) HALDAR
    34) HALUD
    35) INDIAN SAFFRON
    36) INDIAN TURMERIC
    37) KACHA HALDI
    38) KURKUMIN (CZECH)
    39) MERITA EARTH
    40) NCI-C61325
    41) OIL OF TURMERIC
    42) OILS, CURCUMA
    43) SOUCHET
    44) TURMERIC OIL
    45) TURMERIC OLEORESIN
    46) YELLOW GINGER
    47) YO-KIN
    48) ZLUT PRIRODNI 3 (CZECH)

Available Forms Sources

    A) FORMS
    1) AVAILABLE FORMS (Grieve, 1971)
    1) Powdered Root
    2) Fluid Extract
    3) Tincture
    4) Solid Extract
    B) USES
    1) ALLEGED HERBAL USES (Krochmal & Krochmal, 1973; Lewis & Elvin-Lewis, 1977; Lust, 1974)
    1) Tonic
    2) Poultice for eyes
    3) Poultice for skin lesions
    4) Laxative
    5) Hemorrhoids
    6) Reduce uterine bleeding
    7) Employed as a natural yellow dye
    8) Treatment for stomach and liver aliments
    9) Antibacterial action
    10) Amoebicidal properties
    2) The dried plant and its extracts were official through USP IX.
    3) LIMITED INDICATIONS - Its been suggested that because of its minor actions on circulation, and its effects on uterine tone, contractility, and on the central nervous system, that goldenseal is too unpredictable to be of therapeutic benefit (Tyler, 1993).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Golden seal (hydrastis) contains several alkaloids. In higher doses, hydrastine can cause hypertension, seizures, hyperreflexia and respiratory failure. Fatalities may occur from CNS stimulation and respiratory failure.
    B) Oral and gastrointestinal irritation (nausea, vomiting, diarrhea) occur at larger doses.
    C) Moderate dosing of hydrastine can result in peripheral vasoconstriction and increased cardiac output.
    D) Small amounts of the herb can be ingested, as with minor oral irritations, with no side effects reported.
    0.2.5) CARDIOVASCULAR
    A) Hypotension may be associated with berberine exposure, and hydrastine has been associated with hypertension.
    0.2.6) RESPIRATORY
    A) A metabolite of hydrastine has caused respiratory paralysis without narcosis in animals.
    0.2.7) NEUROLOGIC
    A) Hydrastine may cause seizures in toxic doses.
    0.2.8) GASTROINTESTINAL
    A) Nausea, vomiting and diarrhea, as well as, mucous membrane irritation may occur after ingestion of these products.
    0.2.10) GENITOURINARY
    A) Both hydrastine and berberine increase the tonus and stimulate uterine contractions. Higher doses relax uterine muscle.
    0.2.20) REPRODUCTIVE
    A) Goldenseal should be avoided during pregnancy.
    0.2.21) CARCINOGENICITY
    A) No information concerning golden seal as a human carcinogen was located (US DHHS, 1994; IARC, 1987; RTECS , 1995; IRIS , 1995).

Laboratory Monitoring

    A) Therapeutic/toxic levels have not been established.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) The alkaloids of the golden seal are concentrated in the root; the leaves, flower, and fruit contain only traces. "Tasting" the plant may be considered harmless.
    B) In large doses, CNS stimulation (seizures) and hypertension can occur; respiratory failure produced by the plant may be fatal.
    C) Treatment should be symptomatic and supportive.
    D) 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.
    E) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
    F) 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.
    G) Hypertension may occur secondary to hydrastine activity.
    H) RESPIRATORY DEPRESSION : Although not seen in humans, respiratory depression may be a problem and respiratory support should be available in serious intoxications.

Range Of Toxicity

    A) In animals, 1 mg/kg will produce a slight increase then decrease in blood pressure, while 2 mg/kg will produce significant, prolonged hypotension.
    B) LD50 reported in the mouse was greater than 2 grams/kilogram following oral ingestion.

Clinical Effects

Respiratory

    3.6.1) SUMMARY
    A) A metabolite of hydrastine has caused respiratory paralysis without narcosis in animals.
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RESPIRATORY DEPRESSION
    a) Oxidation of hydrastine produces hydrastinine, which when used experimentally in animals caused death by respiratory paralysis without narcosis (Sollmann, 1957; Laidlaw, 1910).

Neurologic

    3.7.1) SUMMARY
    A) Hydrastine may cause seizures in toxic doses.
    3.7.2) CLINICAL EFFECTS
    A) SEIZURE
    1) Hydrastine may cause seizures in toxic doses (Osol & Farrar, 1955).
    B) ABSENCE OF SENSATION
    1) Hydrastine has a weak local anesthetic action (Sollmann, 1957).

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea, vomiting and diarrhea, as well as, mucous membrane irritation may occur after ingestion of these products.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA, VOMITING AND DIARRHEA
    1) Large doses of the plant may cause mucosal irritation resulting in symptoms of nausea, vomiting and diarrhea (Hardin & Arena, 1974; DerMarderosian, 1994).
    B) GASTROINTESTINAL IRRITATION
    1) Exposures may cause irritation and hypersecretion of mucous membranes (Millspaugh, 1974; Westbrooks & Preacher, 1986; Tyler, 1994), but case reports are lacking.
    2) Some sources state that severe ulceration of both internal & external sources are possible, but, again, no specific cases are cited (Duke, 1985).
    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) ILEUS
    a) Tests done on animals demonstrated depression of intestinal smooth muscle (Sollmann, 1957).

Genitourinary

    3.10.1) SUMMARY
    A) Both hydrastine and berberine increase the tonus and stimulate uterine contractions. Higher doses relax uterine muscle.
    3.10.2) CLINICAL EFFECTS
    A) MICTURITION FINDING
    1) Golden Seal was thought to reduce urinary spasms, but this has not been shown clinically (Osol & Farrar, 1955).
    B) UTERINE SPASM
    1) Both hydrastine and berberine increase the tonus and stimulate uterine contractions. Higher concentrations relax uterine muscle (Osol & Farrar, 1955; (Laidlaw, 1910).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) COAG./BLEEDING TESTS ABNORMAL
    1) Frey (1909) and Hanzlik (1918) demonstrated that hydrastine was not styptic on wounds and may, in fact, increase bleeding. There is currently no evidence that goldenseal is beneficial in controlling internal bleeding (Tyler, 1994).

Musculoskeletal

    3.15.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPOTONIA
    a) Goldenseal may depress skeletal muscle (Sollmann, 1957).

Immunologic

    3.19.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) IMMUNE SYSTEM DISORDER
    a) Berberine sulfate has inhibited the activities of tumor promoters in vitro and in a mouse skin model of two-stage carcinogenesis (Nishino et al, 1986). The anti-inflammatory activity of berberine sulfate has been postulated as a factor which is associated with the antitumor-promoting activity.

Reproductive

    3.20.1) SUMMARY
    A) Goldenseal should be avoided during pregnancy.
    3.20.3) EFFECTS IN PREGNANCY
    A) HUMANS
    1) Goldenseal should be avoided during pregnancy (DerMarderosian, 1994).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) No information concerning golden seal as a human carcinogen was located (US DHHS, 1994; IARC, 1987; RTECS , 1995; IRIS , 1995).
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) Berberine sulfate inhibited the effects of the tumor-promoting chemicals teleocidin and 12-O-tetradecanoylphorbol-13-acetate in murine fibroblasts. Berberine sulfate also reduced the number of tumors and the percent of mice with tumors following treatment with teleocidin (promoter) and 7,12-dimethylbenz[a]anthracene (initiator) in a mouse skin model of two-stage carcinogenesis (Nishino et al, 1986).

Summary Of Exposure

    A) Golden seal (hydrastis) contains several alkaloids. In higher doses, hydrastine can cause hypertension, seizures, hyperreflexia and respiratory failure. Fatalities may occur from CNS stimulation and respiratory failure.
    B) Oral and gastrointestinal irritation (nausea, vomiting, diarrhea) occur at larger doses.
    C) Moderate dosing of hydrastine can result in peripheral vasoconstriction and increased cardiac output.
    D) Small amounts of the herb can be ingested, as with minor oral irritations, with no side effects reported.

Vital Signs

    3.3.2) RESPIRATIONS
    A) Respirations may be depressed.
    3.3.4) BLOOD PRESSURE
    A) Hypotension or hypertension may occur.

Heent

    3.4.3) EYES
    A) Pupillary dilation has been reported with 10% solutions of the alkaloid hydrastinine (DerMarderosian, 1994).
    3.4.6) THROAT
    A) Large doses of goldenseal may cause throat and mouth irritation (DerMarderosian, 1994).

Cardiovascular

    3.5.1) SUMMARY
    A) Hypotension may be associated with berberine exposure, and hydrastine has been associated with hypertension.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) Although it was earlier assumed that hydrastine may cause hypotension (Osol & Farrar, 1955), the alkaloid berberine (up to 6%) found in goldenseal is responsible for causing hypotension (DerMarderosian, 1994).
    B) HYPERTENSIVE EPISODE
    1) Hydrastine has the ability to constrict peripheral blood vessels; ingestion may result in an increase in blood pressure (DerMarderosian, 1994).
    C) CARDIOMYOPATHY
    1) Hydrastine is related to protopine alkaloids and may cause cardiac muscle depression (Sollmann, 1957).
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPOTENSION
    a) Animal studies have shown a slight decrease in blood pressure in small doses and a larger decrease with larger doses of hydrastine (Lieb, 1914). Orally, the blood pressure effect was minimal or nonexistent (Williams, 1908).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Therapeutic/toxic levels have not been established.
    4.1.2) SERUM/BLOOD
    A) TOXICITY
    1) Therapeutic/toxic levels have not been established.
    B) LABORATORY TEST INTERFERENCE
    1) At one time, it was thought that golden seal either purged the body of morphine or prevented its detection. There is no specific basis to substantiate this.
    a) Goldenseal has also been used to prevent the detection of other illicit drugs such as marijuana or cocaine in urine samples (DerMarderosian, 1994).
    2) Golden seal tea may be added to urine samples by illicit drug users in an attempt to falsify drug screening results. An in vitro study reported that golden seal tea can produce false negative results in a enzyme immunoassay (EMIT d.a.u) for urinary THC (Mikkelsen & Ash, 1988).
    3) The minimum concentration of golden seal tea which produced false-negative assay results for the levels of THC tested was 15 mg/mL (15 g/L). The concentrations of golden seal tea tested did not affect the results of urinary screens for amphetamines, barbiturates, benzodiazepines, cocaine or opiates.
    4) The addition of golden seal tea to urine causes a dark brown appearance which should alert the laboratory technician to the likelihood of sample adulteration. The pH and relative density of the urine adulterated with golden seal tea may not differ from unadulterated urine.
    4.1.4) OTHER
    A) OTHER
    1) OTHER
    a) Although Goldenseal has the reputation that it can prevent the detection of morphine, marijuana, or cocaine in urine samples, studies do not indicate any scientific evidence of this phenomenon (DerMarderosian, 1994).

Methods

    A) OTHER
    1) A method for alkaloid extraction is described in Gillis & Langenhaw (1931).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Therapeutic/toxic levels have not been established.

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) 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) Uterine cramping is usually not a problem. Treatment is symptomatic and supportive.
    B) AIRWAY MANAGEMENT
    1) Patients may need respiratory support.
    C) NAUSEA AND VOMITING
    1) Vomiting is usually not severe, supportive measures are all that is indicated.
    D) MONITORING OF PATIENT
    1) Monitor vital signs. Hypotension or hypertension may occur. Hydrastine acts as a peripheral blood vessel constrictor which can increase blood pressure.
    E) 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).
    7) PHENYTOIN/FOSPHENYTOIN
    a) Benzodiazepines and/or barbiturates are preferred to phenytoin or fosphenytoin in the treatment of drug or withdrawal induced seizures (Wallace, 2005).
    b) PHENYTOIN
    1) PHENYTOIN INTRAVENOUS PUSH VERSUS INTRAVENOUS INFUSION
    a) Administer phenytoin undiluted, by very slow intravenous push or dilute 50 mg/mL solution in 50 to 100 mL of 0.9% saline.
    b) ADULT DOSE: A loading dose of 20 mg/kg IV; may administer an additional 5 to 10 mg/kg dose 10 minutes after loading dose. Rate of administration should not exceed 50 mg/minute (Brophy et al, 2012).
    c) PEDIATRIC DOSE: A loading dose of 20 mg/kg, at a rate not exceeding 1 to 3 mg/kg/min or 50 mg/min, whichever is slower (Loddenkemper & Goodkin, 2011; Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    d) CAUTIONS: Administer phenytoin while monitoring ECG. Stop or slow infusion if dysrhythmias or hypotension occur. Be careful not to extravasate. Follow each injection with injection of sterile saline through the same needle (Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    e) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over next 12 to 24 hours for maintenance of therapeutic concentrations. Therapeutic concentrations of 10 to 20 mcg/mL have been reported (Prod Info Dilantin(R) intravenous injection, intramuscular injection, 2013).
    c) FOSPHENYTOIN
    1) ADULT DOSE: A loading dose of 20 mg phenytoin equivalent/kg IV, at a rate not exceeding 150 mg phenytoin equivalent/minute; may give additional dose of 5 mg/kg 10 minutes after the loading infusion (Brophy et al, 2012).
    2) CHILD DOSE: 20 mg phenytoin equivalent/kg IV, at a rate of 3 mg phenytoin equivalent/kg/minute, up to a maximum of 150 mg phenytoin equivalent/minute (Loddenkemper & Goodkin, 2011).
    3) CAUTIONS: Perform continuous monitoring of ECG, respiratory function, and blood pressure throughout the period where maximal serum phenytoin concentrations occur (about 10 to 20 minutes after the end of fosphenytoin infusion) (Prod Info CEREBYX(R) intravenous injection, 2014).
    4) SERUM CONCENTRATION MONITORING: Monitor serum phenytoin concentrations over the next 12 to 24 hours; therapeutic levels 10 to 20 mcg/mL. Do not obtain serum phenytoin concentrations until at least 2 hours after infusion is complete to allow for conversion of fosphenytoin to phenytoin (Prod Info CEREBYX(R) intravenous injection, 2014).

Range Of Toxicity

Summary

    A) In animals, 1 mg/kg will produce a slight increase then decrease in blood pressure, while 2 mg/kg will produce significant, prolonged hypotension.
    B) LD50 reported in the mouse was greater than 2 grams/kilogram following oral ingestion.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) DOSES RECOMMENDED BY HERBALIST FOR ALLEGED USES -
    a) Powdered Root - 10 grains.
    b) Fluid Extract - 1 quarter to 1 teaspoonful.
    c) Tincture - 1/2 to 1 teaspoonful.
    d) Solid Extract - 5 to 8 grains.
    e) Reference: (Grieve, 1971).
    f) Canker Sores/Other Mouth Sores - 240 milliliters water with 2 teaspoonfuls (6 g) of goldenseal used as a mouthwash to alleviate pain (Tyler, 1994).
    B) NOT RECOMMENDED -
    1) More recent data would suggest that internal ingestion has little if any rational benefit (indications) (Tyler, 1994).

Minimum Lethal Exposure

    A) ANIMAL DATA
    1) In animal data, the LD50 was greater than 2 grams/kilogram for an oral ingestion (RTECS , 2000).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The primary uterine action is due to hydrastine, the other alkaloids are almost inert (Grieve, 1971). Berberine is the other agent primarily responsible for blood pressure effects (Williams, 1908).
    2) In animals, 1 mg/kg will produce a slight increase then decrease in blood pressure, while 2 mg/kg will produce significant and prolonged hypotension (Leib, 1914).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAPERITONEAL)MOUSE:
    1) 1500 mg/kg (RTECS, 2000)
    B) LD50- (ORAL)MOUSE:
    1) >2 gm/kg (RTECS, 2000)
    C) LD50- (INTRAPERITONEAL)RAT:
    1) 104 mg/kg (Poe & Johnson, 1954)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) HYDRASTINE - has constrictive effects on uterine muscle in low doses and will relax the uterus in high doses (Sollmann, 1957) Duke, 1985). It also has a depressant action on cardiac and smooth muscle as well as weak anesthetic actions. Hydrastine has been shown to have a strychine like effect in animals (Laidlaw, 1910).
    B) BERBERINE - acts as a "bitter". It is 7 times as potent on the circulatory system as hydrastine (Williams, 1908). Large doses will decrease temperature, increase peristalsis and kill by central paralysis. It is a mild local anesthetic (Sollmann, 1957).
    C) CANADINE - has actions similar to morphine, but the concentrations in Golden Seal are too low for effects to be considered in combination with the other two alkaloids (Sollmann, 1957).
    D) Antineoplastic Activity
    1) Berberine has shown some anticancer effects when tested against Bl, KB & PS tumors (Perdue & Hartwell, 1976).
    2) Canadine like alkaloids have displayed cytotoxicity in vitro against KB cells derived from human epidermoid carcinoma (Cushman et al, 1979).

Physicochemical

Physical Characteristics

    A) The dried rhizome of Golden Seal has a sweetish smell similar to licorice root (Grieve, 1971).
    B) The color of the rhizome is bright yellow when fresh, but dark yellow brown with age (Grieve, 1971).
    C) has a bitter taste (Spoerke, 1980)
    D) Hydrastine is an isoquinoline alkaloid.

Molecular Weight

    A) BERBERINE: 336.37
    B) CANADINE: 339.38
    C) HYDRASTINE: 383.39

References

General Bibliography

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