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ARNICA

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Arnica montana, the most popular source of arnica products, is an herbaceous perennial plant found in mountainous areas of Canada, the northern United States, and Europe. Arnica is available commercially in the form of liniments and massage oil for external application, and in very dilute homeopathic preparations for internal use. The flower heads and rootstock are cultivated for herbal medicinal use. Helenalin is considered the toxic principle of the plant. Ingestion of concentrated roots or flower may cause gastrointestinal irritation and CNS depression. Dermatitis is often seen following external use. Arnica is best known as a homeopathic remedy for muscle strain and soreness.

Specific Substances

    A) SYNONYMS
    1) Arnica
    2) Arnica chamissonis
    3) Arnica cordifolia Hook
    4) Arnica flowers
    5) Arnica fulgens
    6) Arnica latifolia
    7) Arnica montana
    8) Arnica root
    9) Arnica sororia Greene
    10) Arnica flos
    11) Common arnica
    12) European arnica
    13) EUROPEAN ARNICIA
    14) Kraftwurz
    15) Leopard's bane
    16) Mountain arnica
    17) Mountain daisy
    18) Mountain tobacco
    19) Mountain snuff
    20) Sneezewort
    21) Wolf's bane
    22) Wundkraut
    23) CAS 8057-65-6 (arnica montana oil)

Available Forms Sources

    A) FORMS
    1) Arnica is available in the following forms for herbal and homeopathic use: homeopathic solution, homeopathic injection, cream, gel, ointment (containing 15% to 20% tincture), tincture, and crude herb (Hanrahan, 2001; Schaffner, 1997).
    B) SOURCES
    1) The fresh or dried inflorescence of Arnica montana L or Arnica chamissonis Less. subsp. foliosa contain varying amounts of sesquiterpene lactones of the helenanolid type, predominantly ester derivatives of helenalin and 11,13-dihydrohelenalin, which are considered the major active constituents in arnica preparations (Schmidt et al, 2000; Blumenthal et al, 1998; Schaffner, 1997). The flower heads are used for extraction of the active sesquiterpene lactones (Schaffner, 1997).
    2) Two methods are reported for preparation of arnica extract. One involves hydroalcoholic maceration and gentle disintegration in soybean oil. The other method involves propylene glycol and butylene glycol extractions (Anon, 2001).
    C) USES
    1) In the United States, the FDA lists arnica as an unsafe herb; it is only allowed for food use as a flavoring agent in alcoholic beverages. Uses approved by the German Commission E include (Anon, 2000; Blumenthal et al, 1998):
    1) Fever and colds
    2) Cough/bronchitis
    3) Inflammation of mouth and pharynx
    4) Rheumatism
    5) Common cold
    6) Blunt injuries
    7) Infection tendencies
    2) Arnica preparations are used externally as antiphlogistic, antiseptic, and mild analgesic remedies for the supportive treatment of wear and tear effects, degeneration of the joints, rheumatic joint and muscle inflammations, sacroiliac pain, lumbago, myogelosis, muscular induration, injuries and accidents (hematoma, sprains, dislocations, bruising, edema associated with fractures), superficial phlebitis, thrombosis, arthralgia, furunculosis, inflammation of the mucous membranes of the oral and throat region, and inflammation caused by insect bites (Duke et al, 2002; Hanrahan, 2001; Schmidt et al, 2000; Bisset & Wichtl, 1994). Sesquiterpene lactones, especially helenalin, are known to have anti-inflammatory activity, with biological effects mediated through immunological processes; thus, arnica is widely used for pain and inflammation ((Hoffman, 2001)).
    3) Clinical studies demonstrated beneficial effects of homeopathic arnica therapy in the treatment of diabetic retinopathy (Zicari et al, 1998; (Zicari et al, 1997). Gonarthrosis has been treated effectively by intra-articular injections of a combination preparation containing arnica. Several double-blind, randomized, placebo-controlled studies failed to find beneficial effects of homeopathic arnica preparations in the prevention and treatment of tissue trauma with delayed onset muscle soreness (Ernst & Pittler, 1998). Homeopathic arnica preparations had no effect on surgically induced trauma after total abdominal hysterectomy or bilateral oral surgery. Very dilute homeopathic preparations are ingested for treatment of muscle/soft tissue trauma, vertigo, hoarseness, and seasickness (Hanrahan, 2001). Arnica has been given as a postpartum homeopathic preparation for treatment of perineal pain and for healing (Hofmeyr et al, 1990). Homeopathic arnica was shown to be ineffective for prevention of postoperative hematomas in a double-blind study (Ramelet et al, 2000).
    4) Arnica is also used in hair tonics, antidandruff preparations, perfumery, and cosmetics (Anon, 1998). In the United States, arnica may be used as a flavoring agent, up to a maximum of 0.03% (Daane, 2001).
    5) In general, herbal medications, with few exceptions, have a high safety profile. However, due to the unregulated nature of the herbal industry in the United States, it is advised to become intimately familiar with manufacturers and their products before recommending them for safe and effective use. Adulteration, in particular, has been a recurring problem.

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 large quantities of the herb, essential oil, or concentrated extract may result in toxic effects of vomiting, diarrhea, bleeding in susceptible persons, CNS depression, muscle weakness, hypertension and/or cardiotoxicity. Uterine contractions may occur. It is unlikely that ingestion of a homeopathic arnica (dilutions up to 10(30)) would cause any significant toxicity.
    B) Exposure to plant parts or topical preparations has resulted in contact dermatitis in susceptible individuals. Prolonged topical application of concentrated arnica herbal extract may result in blistering, skin ulcers, and necrosis.
    0.2.5) CARDIOVASCULAR
    A) Cardiotoxic effects of arnica ingestions have been reported. Increased blood pressure may result following significant overdose.
    0.2.6) RESPIRATORY
    A) Dyspnea has been reported following toxic ingestions.
    0.2.7) NEUROLOGIC
    A) CNS depression has been reported in children ingesting the flowers and roots.
    0.2.8) GASTROINTESTINAL
    A) Vomiting and diarrhea have been reported following toxic ingestions.
    0.2.10) GENITOURINARY
    A) Uterine contractions have been reported.
    0.2.14) DERMATOLOGIC
    A) Allergic contact dermatitis has been reported.
    0.2.20) REPRODUCTIVE
    A) Drinking arnica teas or tinctures may result in miscarriage.
    B) Reproductive/developmental toxicity data are not available for arnica montana extract.

Laboratory Monitoring

    A) Arnica plasma levels are not readily available nor useful in directing management following an overdose.
    B) Monitor vital signs in symptomatic patients following an overdose.
    C) Monitor fluid status as indicated in symptomatic patients.
    D) Monitor neurological function as indicated in symptomatic patients.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Treatment is SYMPTOMATIC and SUPPORTIVE.
    B) Gastrointestinal decontamination is generally NOT necessary.
    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) Ingestion of 70 grams of tincture was reported to cause death, however this case is poorly substantiated.

Clinical Effects

Summary Of Exposure

    A) Ingestion of large quantities of the herb, essential oil, or concentrated extract may result in toxic effects of vomiting, diarrhea, bleeding in susceptible persons, CNS depression, muscle weakness, hypertension and/or cardiotoxicity. Uterine contractions may occur. It is unlikely that ingestion of a homeopathic arnica (dilutions up to 10(30)) would cause any significant toxicity.
    B) Exposure to plant parts or topical preparations has resulted in contact dermatitis in susceptible individuals. Prolonged topical application of concentrated arnica herbal extract may result in blistering, skin ulcers, and necrosis.

Vital Signs

    3.3.4) BLOOD PRESSURE
    A) Increased blood pressure may result from a massive ingestion (Jellin et al, 2002).
    3.3.5) PULSE
    A) Increase or decrease in pulse rate may occur following large ingestions. Heart palpitations may occur. Abuse of the flower tincture or decoction used as an abortifacient has been reported to cause rapid pulse (Duke et al, 2002).

Heent

    3.4.3) EYES
    A) Direct contact with the eye has resulted in eyelid edema and hyperemia of the conjunctiva. It is not considered to be harmful to the cornea or conjunctiva (Anon, 2001; Grant & Schuman, 1993).
    3.4.5) NOSE
    A) When the flowerheads of Arnica montana are crushed and sniffed, sneezing may result (Hanrahan, 2001).
    3.4.6) THROAT
    A) Abuse of the flower tincture or decoction has been reported to cause bloody expectoration (Duke et al, 2002).
    B) Extensive oral mucosal ulcerations were reported in a patient following use of an undiluted commercial mouthwash containing 70% alcohol, oil of peppermint, and arnica. It is likely that the concentrated alcohol was the most significant contributing factor to mucosal irritation (Moghadam et al, 1999).

Cardiovascular

    3.5.1) SUMMARY
    A) Cardiotoxic effects of arnica ingestions have been reported. Increased blood pressure may result following significant overdose.
    3.5.2) CLINICAL EFFECTS
    A) CARDIAC ARREST
    1) Secondary sources report cardiac arrest and death following arnica ingestion, but no primary literature could be found to substantiate this (Duke et al, 2002; Anon, 1998; Bisset & Wichtl, 1994).
    a) It appears that helenalin, which shows a concentration-dependent inotropic effect, slows down the recovery kinetics of calcium, possibly due to a membrane-stabilizing action, which is responsible for the toxic cardiac effects of arnica (Bisset & Wichtl, 1994).
    B) PALPITATIONS
    1) Large ingestions may result in increase or decrease of pulse rate as well as heart palpitations (Duke et al, 2002). Accelerated heart rate has been reported following toxic ingestions (Anon, 2001).
    C) HYPERTENSIVE EPISODE
    1) When ingested in large quantity, arnica could result in increased blood pressure (Jellin et al, 2002; Daane, 2001).
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CARDIOTOXICITY
    a) Helenalin (constituent of arnica) concentrations ranging between 0.001 micromole (mcmol) and 0.1 mcmol produced a dose-dependent, irreversible positive inotropic effect on strips of the left atrium and papillary muscles from the left ventricle of the guinea-pig heart. This effect was found to be due to an inhibition of phosphodiesterase by helenalin resulting in an increase of cAMP and Ca2 positive influx (Robles, 1995).
    2) HYPERTENSION
    a) Alcoholic extracts of arnica fed to laboratory animals caused cardiotoxicity and significant increases in blood pressure (Tyler, 1993).

Respiratory

    3.6.1) SUMMARY
    A) Dyspnea has been reported following toxic ingestions.
    3.6.2) CLINICAL EFFECTS
    A) DYSPNEA
    1) Ingestions of toxic amounts may result in dyspnea (Jellin et al, 2002; Anon, 1998; Bisset & Wichtl, 1994). Respiratory dysfunction has been reported following abuse of the flower tincture or decoction used as an abortifacient (Duke et al, 2002).
    B) TACHYPNEA
    1) Ingestion of a toxic dose may result in a respiratory analeptic effect (Anon, 2000).

Neurologic

    3.7.1) SUMMARY
    A) CNS depression has been reported in children ingesting the flowers and roots.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) Although not likely at therapeutic doses, a massive oral dose of undiluted preparation may potentially result in CNS depression and reversible coma (Anon, 2000). There are reports of drowsiness and coma in children who have ingested the flowers and roots of the plant (Anon, 1998). Cerebral symptoms have been reported following abuse of the flower tincture or decoction used as an abortifacient (Duke et al, 2002).
    B) PARALYSIS
    1) Reports of muscle weakness and paralysis following toxic ingestions are found in the secondary literature, but no primary literature could be found to substantiate these assertions (Jellin, 2002; (Daane, 2001; Bisset & Wichtl, 1994).

Gastrointestinal

    3.8.1) SUMMARY
    A) Vomiting and diarrhea have been reported following toxic ingestions.
    3.8.2) CLINICAL EFFECTS
    A) GASTROENTERITIS
    1) Arnica toxic ingestion may result in gastroenteritis with abdominal pain, nausea, vomiting and diarrhea. Severe mucous membrane irritation with bleeding may occur with toxic oral doses (Anon, 2001; Hanrahan, 2001; Daane, 2001; Anon, 2000; Anon, 1998; Bisset & Wichtl, 1994). Vomiting and severe diarrhea have been reported following abuse of the flower tincture or decoction used as an abortifacient (Duke et al, 2002).

Genitourinary

    3.10.1) SUMMARY
    A) Uterine contractions have been reported.
    3.10.2) CLINICAL EFFECTS
    A) UTERINE SPASM
    1) Toxic ingestions may result in uterine contractions (Anon, 2000). The sesquiterpene lactones of arnica are responsible for its oxytocic activity (Duke et al, 2002; Anon, 1998; Bisset & Wichtl, 1994).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) HEMORRHAGE
    1) Theoretically, ingestion of concentrated arnica may produce an increased risk of bleeding. The inhibition of platelet aggregation seen with arnica is thought to be due to an interaction of helenalin and 11-alpha, 13- dihydrohelenaline with platelet sulfhydryl groups (Daane, 2001; Anon, 1998). Toxic doses have been reported to result in ecchymoses in susceptible persons (Hofmeyr et al, 1990).

Dermatologic

    3.14.1) SUMMARY
    A) Allergic contact dermatitis has been reported.
    3.14.2) CLINICAL EFFECTS
    A) CONTACT DERMATITIS
    1) Sesquiterpene lactones, particularly helenalin, which are constituents of arnica and the Compositae plants, are skin irritants and allergens and may cause contact dermatitis in susceptible individuals when handled or applied topically (Anon, 2001; Reider et al, 2001; Hanrahan, 2001; Anon, 1998; Spettoli et al, 1998; Tyler, 1993; Hausen, 1978; Hausen, 1978; Rudzki & Grzywa, 1977).
    a) Cases of occupational contact dermatitis due to arnica plants have been reported (Anon, 1998; Hausen, 1978).
    b) Skin patch testing has confirmed the sesquiterpene lactones as being responsible for the allergic contact dermatitis (Reider et al, 2001; Anon, 1998; Spettoli et al, 1998; Hausen, 1978).
    c) Arnica dermatitis is a delayed type IV allergy (Anon, 2001).
    2) CASE REPORT - Topical application of a cream containing 1.5% arnica resulted in leukemia-related Sweet's syndrome triggered by arnica. Application sites on the face and leg developed rapidly enlarging, necrotic lesions together with malaise and fever. Following surgical excision, a superficially ulcerated area was revealed (Delmonte et al, 1998).
    B) SKIN ULCER
    1) Following repeated contact, particularly with undiluted tinctures and high concentration liniments as well as contact with the plant, skin rashes with itching, blister formation, ulcers and superficial necroses may occur (Anon, 2001; Hanrahan, 2001; Anon, 2000; Blumenthal et al, 1998; Bisset & Wichtl, 1994).
    a) Prolonged topical administration on damaged skin, e.g., in injuries or ulcus cruris (indolent leg ulcers) may cause eczema and edematous dermatitis with the formation of pustules. High dose arnica therapy can result in primary toxic skin reactions with the formation of vesicles and necroses.
    C) FLUSHING
    1) Facial flushing has been reported following abuse of the flower tincture or decoction used as an abortifacient (Duke et al, 2002).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) MUSCLE PAIN
    1) Toxic doses of arnica extracts have been reported to result in muscle soreness and weakness (Anon, 2001; Hofmeyr et al, 1990).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) Individuals who are hypersensitive to arnica or to other members of the daisy family may develop rhinitis, conjunctivitis, urticaria, bronchospasm, and anaphylaxis following an exposure (Anon, 2000).

Reproductive

    3.20.1) SUMMARY
    A) Drinking arnica teas or tinctures may result in miscarriage.
    B) Reproductive/developmental toxicity data are not available for arnica montana extract.
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Internal use, Botanical Safety Handbook Class 2b (not to be used during pregnancy) (McGuffin et al, 1997).
    B) ABORTION
    1) Toxic ingestions may result in uterine contractions (Anon, 2000). The sesquiterpene lactones of arnica are responsible for its oxytocic activity (Duke et al, 2002; Anon, 1998; Bisset & Wichtl, 1994). Drinking arnica teas or tinctures may result in miscarriage (Schaffner, 1997).

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) No carcinogenic data is available for arnica montana extract (Anon, 2001).

Genotoxicity

    A) An arnica montana extract was found to elicit a positive mutagenic response in the Ames test (Salmonella typhimurium), possibly related to the flavonoid content of the extract (Anon, 2001).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Arnica plasma levels are not readily available nor useful in directing management following an overdose.
    B) Monitor vital signs in symptomatic patients following an overdose.
    C) Monitor fluid status as indicated in symptomatic patients.
    D) Monitor neurological function as indicated in symptomatic patients.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor fluid and electrolyte levels as indicated in patients with severe vomiting or diarrhea.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Monitor ECG in symptomatic patients.
    b) Monitor neurological function following a large acute exposure or in symptomatic patients.

Methods

    A) CHROMATOGRAPHY
    1) Identification of flavonoids and/or sesquiterpene lactones (toxic constituents) may be accomplished with thin layer chromatographic methods (Blumenthal et al, 1998; Rossetti et al, 1987).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Carefully observe patients with significant ingestion exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.

Monitoring

    A) Arnica plasma levels are not readily available nor useful in directing management following an overdose.
    B) Monitor vital signs in symptomatic patients following an overdose.
    C) Monitor fluid status as indicated in symptomatic patients.
    D) Monitor neurological function as indicated in symptomatic patients.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY -
    1) Gastrointestinal decontamination is generally NOT necessary, as significant toxicity is not expected after acute overdose. GI decontamination is recommended in symptomatic patients and those with significant coingestants.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Gastrointestinal decontamination is generally NOT necessary, as significant toxicity is not expected after acute overdose. Activated charcoal is recommended in symptomatic patients and those with significant coingestants.
    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) Treatment is SYMPTOMATIC and SUPPORTIVE. Monitor fluid status as indicated in patients with symptoms of severe diarrhea or vomiting. Monitor ECG in symptomatic patients.

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) Ingestion of 70 grams of tincture was reported to cause death, however this case is poorly substantiated.

Therapeutic Dose

    7.2.1) ADULT
    A) ROUTE OF ADMINISTRATION
    1) SUMMARY - Dosing of herbal preparations is highly dependent on a variety of factors, such as growing and harvesting conditions, plant parts and extraction methods used, and the dosage form chosen by the manufacturer. Standardization to single constituent markers has proven unreliable. Since no official standards have been established to date to regulate the production of herbal medicines in the United States, dosage ranges must be employed as guidelines.
    2) ORAL use of arnica flowers or arnica preparations is considered to be potentially unsafe and may cause severe adverse effects; therefore, it is generally recommended for external use only (Blumenthal et al, 1998).
    a) Tincture, coronary artery disease: 5-10 drops of tincture has been used for patients with coronary artery disease by physicians in Germany (Weiss, 1988).
    b) Tea, coronary artery disease: Tea is made by infusing 1 to 2 teaspoons of dried flowers in 1 cup of water (Weiss, 1988). The patient sips the tea throughout the day.
    c) Oral homeopathic dosages for arnica preparations range between C6 and C30 for delayed onset muscle soreness, D30 and C30 for surgical prophylaxis in patients undergoing total abdominal hysterectomy or bilateral oral surgery, and 3 pearls of arnica 5CH per day for therapy of diabetic retinopathy (Zicari et al, 1998; (Vickers et al, 1998) Zicari, 1997; (Vickers et al, 1997; Hart et al, 1997; Gulick et al, 1996; Loekken et al, 1995).
    3) TOPICAL - For wear and tear effects, degeneration of the joints, rheumatic joint and muscle inflammation, sacroiliac pain, lumbago, myogelosis, and muscular induration, twice daily topical administration of a 2 to 4 centimeters long ointment layer containing an oily extract of arnica flowers (5%) in the morning and in the evening onto the affected areas has been recommended (Fachinformation Arthrosenex(R) AR, 1998). The maximum strength of an ointment should not exceed 15% arnica oil or 20% to 25% arnica tincture (Anon, 2000; Blumenthal et al, 1998).
    7.2.2) PEDIATRIC
    A) ROUTE OF ADMINISTRATION
    1) TOPICAL - One-third to one-half the adult dose of topical preparations of arnica are used for minor wounds, bruises, and skin inflammation (Schilcher, 1997).

Minimum Lethal Exposure

    A) ROUTE OF EXPOSURE
    1) INGESTION - A secondary source reports a fatality following ingestion of 70 grams of arnica tincture, however no primary literature could be found to substantiate this (Duke et al, 2002).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) Sesquiterpene lactones, including helenalin, are found primarily in the leaves and flowers of the arnica plant. This is considered the toxic component and causes gastroenteritis, cardiotoxicity, dyspnea and CNS depression when ingested in large quantities (Duke et al, 2002).
    B) ANIMAL DATA
    1) Helenalin (constituent of arnica) concentrations ranging between 0.001 micromole (mcmol) and 0.1 mcmol produced a dose-dependent, irreversible positive inotropic effect on strips of the left atrium and papillary muscles from the left ventricle of the guinea-pig heart. This effect was found to be due to an inhibition of phosphodiesterase by helenalin resulting in an increase of cAMP and Ca2 positive influx (Robles, 1995).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ARNICA MONTANA OIL
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 31 mg/kg (RTECS, 2002)
    2) LD50- (ORAL)MOUSE:
    a) 123 mg/kg (RTECS, 2002)
    B) ARNICA RESINOID
    1) LD50- (ORAL)RAT:
    a) >5 g/kg (Anon, 2001)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) The mechanism of action and the active principle of arnica are yet not completely understood and are difficult to determine because of the complex composition of the extracts. Arnica and its preparations have demonstrated wound-healing, antiphlogistic, antiseptic, and mild analgesic properties in animal and in vitro studies. These effects were mainly attributed to the counterirritant sesquiterpene lactones helenalin and dihydrohelenalin (Anon, 2000) Williamson & Wyandt, 1998; Wichtl, 1997). Sesquiterpene lactones, especially helenalin, are known to have anti-inflammatory activity, with biological effects mediated through immunological processes ((Hoffman, 2001); Anon, 1998). Further in vitro and in vivo studies of arnica preparations or isolated ingredients have shown antiaggregatory, immunostimulatory, cytotoxic, cardiotonic, and antioxidative effects (Anon, 1998; Haraguchi et al, 1997; Woerdenbag et al, 1995; Robles et al, 1995).
    1) Helenalin inhibited the oxidative phosphorylation, chemotaxis, and mobility of human polymorphonuclear neutrophiles. It contributed to a reduction of the size of inflamed areas by stabilizing lysosomal membranes and was thought to possess therapeutic efficacy in the treatment of chronic arthritis (Fachinformation Arthrosenex(R) AR, 1998).
    2) Helenalin and its related esters are reported to have bactericidal (against salmonella) and fungicidal activity (Anon, 1998). Studies have shown that helenalin inhibits activation of the immune regulator NF-kB. Release of NF-kB can cause an overreaction of the immune system, which can endanger the healing process and lead to excessive inflammations. These overreactions may be avoided by helenalin through inhibition of NF-kB activation (Lyss et al, 1997).
    3) Various constituents of the plant appear to be responsible for different activities: phenols, phenol ethers and phenol esters are antiseptic; polyacetylenic and sesquiterpenic compounds are bacteriostatic and fungicidal; caffeic acid, chlorogenic acid and cynarine are choleretic, cholagogic and diuretics (Rossetti et al, 1987).
    B) Arnica preparations are reported to exhibit positive inotropic effects. Helenalin (constituent of arnica) concentrations ranging between 0.001 micromole (mcmol) and 0.1 mcmol produced a dose-dependent, irreversible positive inotropic effect on strips of the left atrium and papillary muscles from the left ventricle of the guinea-pig heart. This effect was found to be due to an inhibition of phosphodiesterase by helenalin resulting in an increase of cAMP and Ca2 positive influx (Robles, 1995).
    C) The sesquiterpene lactones, helenalin and dihydrohelenalin, displayed cytotoxic activity against the CLC4 and the COLO 320 cell lines (Woerdenbag et al, 1994).

Physicochemical

Physical Characteristics

    A) The medicinal parts of Arnica are derived from ethereal oil of the flowers, the dried flowers, the leaves collected before flowering and dried, the roots, and the dried rhizome and roots. The flower heads are aromatic; taste is bitter, somewhat pungent and spicy, and irritating (Anon, 2000; Bisset & Wichtl, 1994).

Molecular Weight

    A) Not applicable

References

General Bibliography

    1) Anon: Arnica, in: The Review of Natural Products, Facts and Comparisons, St Louis, MO, 1998.
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