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PLANTS-PAEONOL

Classification   |    Detailed evidence-based information

Therapeutic Toxic Class

    A) Paeonol is found in Paeonia suffruticosa and other plants of the Paeonia spp. and is one of the major components in various oriental medicines.

Specific Substances

    1) 2-Hydroxy-4-methoxyacetophenone

Available Forms Sources

    A) SOURCES
    1) Paeonol may be extracted from the root bark of Paeonia suffruticosa (yield approximately 0.54%).
    2) The bark of P. suffruticosa is also called Monton Bark (Kawashima et al, 1985).
    B) USES
    1) Paeonol is one of the components of Keishibukuryo-Gan and Daiobotampi-To, two oriental medicines used for treatment of gynecologic disorders (Kawashima et al, 1985).

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Paeonol is a major component in moutan bark which is used in various oriental medicines. Its primary pharmacologic actions are as an antibacterial, CNS depressant, analgesic, antipyretic, anti-inflammatory, and diuretic.
    0.2.7) NEUROLOGIC
    A) Paeonol has been noted in animals to cause CNS depression as well as analgesia.
    0.2.8) GASTROINTESTINAL
    A) Gastroenteritis may result following large ingestions.
    0.2.10) GENITOURINARY
    A) Doses of 62.5 to 250 mg/kg orally has produced dose dependent diuresis in animals.
    0.2.14) DERMATOLOGIC
    A) Contact dermatitis has been reported from occupational contact.
    0.2.20) REPRODUCTIVE
    A) The bark of Paeonia suffruticosa is listed as pregnancy category 2b (not to used in pregnancy).

Laboratory Monitoring

    A) No toxic dose has been established.
    B) Paeonol may be identified by thin-layer chromatography.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) 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.
    B) RESPIRATORY SUPPORT: Appears to be the primary treatment necessary for projected CNS depression. The half-life is approximately 30 minutes and the onset of action is rapid.
    C) DIURESIS: This agent is a diuretic and may deplete electrolytes, although the effect does not appear to be as severe as with hydrochlorothiazide.

Range Of Toxicity

    A) THERAPEUTIC DOSE - The lowest effective diuretic dose was 62.5 mg/kg (in animals) which is slightly lower than the 125 to 500 mg/kg needed for anti-inflammatory actions.
    B) The LD50 orally in a mouse is 3,430 mg/kg.

Summary Of Exposure

    A) Paeonol is a major component in moutan bark which is used in various oriental medicines. Its primary pharmacologic actions are as an antibacterial, CNS depressant, analgesic, antipyretic, anti-inflammatory, and diuretic.

Neurologic

    3.7.1) SUMMARY
    A) Paeonol has been noted in animals to cause CNS depression as well as analgesia.
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CNS DEPRESSION
    a) Paeonol has been noted in animal studies to cause CNS depression as well as analgesia (Kawashima et al, 1985).

Gastrointestinal

    3.8.1) SUMMARY
    A) Gastroenteritis may result following large ingestions.
    3.8.2) CLINICAL EFFECTS
    A) GASTROENTERITIS
    1) Ingestion of flowers and seeds may result in gastroenteritis with nausea, abdominal pain, and diarrhea (Duke, 1985).

Genitourinary

    3.10.1) SUMMARY
    A) Doses of 62.5 to 250 mg/kg orally has produced dose dependent diuresis in animals.
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) POLYURIA
    a) When tested in animals, 62.5 to 250 mg/kg orally produced dose dependent diuresis. The 250 mg/kg dose was almost as effective as 10 mg/kg of hydrochlorothiazide in the tested animals (Kawashima et al, 1985).

Dermatologic

    3.14.1) SUMMARY
    A) Contact dermatitis has been reported from occupational contact.
    3.14.2) CLINICAL EFFECTS
    A) CONTACT DERMATITIS
    1) CASE REPORT - Acrovesicular dermatitis of 2.5 years duration was reported in a 36-year-old with a 12 year history of working in nurseries. For the past years he had been working with Paeonia officinalis and patch tested positive to extracts of leaf, shoots, and roots. The nature of the allergen was unknown (Bruynzeel, 1989).
    2) CASE REPORT - A 37-year-old male presented with a severe eczema and localized edema of the wrists, axillae, neck and face following an occupational exposure as a process operator in an insecticide plant. Patch tests were a strong positive to both 1% and 2% tetrachloroacetophenone (TCAP), a chemical closely related to Paenol plant extracts. Airborne contact was also considered likely as the patient walked through the plant and developed a facial rash (van Joost & Wiemer, 1991).

Reproductive

    3.20.1) SUMMARY
    A) The bark of Paeonia suffruticosa is listed as pregnancy category 2b (not to used in pregnancy).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) McGuffin et al (1997) list the bark of Paeonia suffruticosa as pregnancy category 2b (not to be used during pregnancy).

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No toxic dose has been established.
    B) Paeonol may be identified by thin-layer chromatography.

Methods

    A) CHROMATOGRAPHY
    1) May be identified by thin layer chromatography (Kawashima et al, 1985).

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) No toxic dose has been established.
    B) Paeonol may be identified by thin-layer chromatography.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) ANIMAL DATA: In animal studies, 62 to 500 mg/kg has been therapeutic and 3400 mg/kg was lethal. Amounts greater than 500 mg/kg may warrant decontamination.
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) 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) AIRWAY MANAGEMENT
    1) Airway management appears to be the primary treatment necessary for possible CNS depression. The half-life is approximately 30 minutes and the onset of action rapid.
    B) FLUID/ELECTROLYTE BALANCE REGULATION
    1) This agent is a diuretic, and may deplete electrolytes, although the effect does not appear to be as severe as with hydrochlorothiazide. Patients may need to be monitored for fluid and electrolyte balance.

Summary

    A) THERAPEUTIC DOSE - The lowest effective diuretic dose was 62.5 mg/kg (in animals) which is slightly lower than the 125 to 500 mg/kg needed for anti-inflammatory actions.
    B) The LD50 orally in a mouse is 3,430 mg/kg.

Maximum Tolerated Exposure

    A) ANIMAL DATA
    1) The lowest effective diuretic dose was 62.5 milligrams/kilogram (rat) which is slightly lower than the 125 to 500 milligrams/kilogram needed for anti-inflammatory actions or to decrease gastric secretions in rats (Kawashima et al, 1985).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (ORAL)MOUSE:
    1) 3, 430 mg/kg (Harada & Yamashita, 1969)

Pharmacologic Mechanism

    A) The sites of action of paeonol are unknown, but its diuretic actions are dissimilar to those of hydrochlorothiazide, suggesting a different mechanism. The decrease in potassium excretion at the highest dose suggests an interaction with aldosterone in the collecting ducts (Kawashima et al, 1985).
    B) Paeonol has been shown experimentally to have bacteriostatic, analgesic, antipyretic, central depressive, and anti-inflammatory properties (Ohta et al, 1961) Harda & Yamashita, 1969; (Harada et al, 1972).

Physical Characteristics

    A) liquid

Molecular Weight

    A) 166.17

General Bibliography

    1) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    2) Bruynzeel DP: Contact dermatitis due to Paeonia (peony) contact. Dermatitis 1989; 20:152.
    3) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    4) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    5) Duke JA: Handbook of Medicinal Herbs, CRC Press, Boca Raton, FL, 1985.
    6) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    7) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    8) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    9) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    10) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
    11) Harada M & Yamashita A: Yakugaku Zasshi 1969; 89:1205-1211.
    12) Harada M, Yamashita A, & Aburada M: Yakugaku Zasshi 1972; 92:750-756.
    13) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    14) Kawashima K, Miwa Y, & Kinudra M: Diuretic action of paeonol. Planta Medica 1985; 3:187-189.
    15) Mimura K & Baba S: Chem Pharm Bull 1980; 28:1704-1710.
    16) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    17) Ohta T, Mihashi S, & Saheki Y: Yakugaku Zasshi 1961; 14:100-101.
    18) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    19) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    20) Spiller HA & Rogers GC: Evaluation of administration of activated charcoal in the home. Pediatrics 2002; 108:E100.
    21) Thakore S & Murphy N: The potential role of prehospital administration of activated charcoal. Emerg Med J 2002; 19:63-65.