Ipecac

Scientific Name(s): Cephalelis ipecacuanha A. Rich. (Rio Ipecac) and C. acuminata H. Karst (Cartagena ipecac). 1 Family: Rubiaceae

Common Name(s): Ipecac , ipecacuanha , golden root , Rio or Brazilian ipecac , Matto Grosso ipecac , Costa Rica ipecac

Uses

Ipecac has been used as an emetic and treatment for dysentery. It has amebicidal components. It currently is not recommended as an emetic for childhood poisonings. Activated charcoal now is the treatment of choice. Always consult a health care professional or poison control center when an accidental poisoning occurs.

Dosing

Ipecac syrup, which contains total alkaloids123 to 157 mg per 100 mL, has been used to induce vomiting. The usual dose range for the syrup is 10 to 30 mL, yielding a dose of alkaloids of 12 to 48 mg. Do not confuse the syrup with the fluid extract of ipecac, which is 14 times stronger. Cumulative toxicity requires administration of emetine for amebic dysentery in low doses for a short time with intervals of several weeks before further treatment.

Contraindications

Do not administer ipecac when a patient has a decreased level of consciousness or has ingested either a corrosive substance or hydrocarbon with a high aspiration potential.

Pregnancy/Lactation

Documented adverse effects include uterine stimulation. Avoid use.

Interactions

None well documented.

Adverse Reactions

Repeated exposure to powdered ipecac may cause rhinitis or asthma. Emetine can irritate skin if applied topically. Diarrhea, lethargy, drowsiness, and prolonged vomiting may occur.

Toxicology

Ipecac extracts may be highly toxic; do not confuse with syrup of ipecac. Emetine is a cardiotoxin and has been associated with serious cardiotoxicity.

Botany

Also known as Psychotria ipecacuanha , ipecac is a small perennial tropical plant that grows to about 60 cm in height. Horizontal roots extend from its slender underground stem. At maturity, the roots have a dark brown or red covering, a bitter taste, and a musty odor. The plant is native to the humid forests of Bolivia and Brazil where large plantations have been established to commercialize the collection of ipecac root. Much of the root crop continues to be harvested from the wild, particularly in South America. 1 India also is an important producer of ipecac.

History

Brazilian Indians valued ipecac as a remedy for dysentery and this information was brought to Europe by Portuguese missionaries. 2 , 3 It was used by the physician Jean Helvetius in 1686 to cure the son of Louis XIV of amebic dysentery. 3 It remained a secret remedy until Helvetius sold it to the French government, which in 1688 subsequently disclosed that the composition of the dysentery remedy contained a large amount of ipecacuanha. 3 The French chemist Pierre Joseph Pelletier extracted the alkaloid substance from the ipecacuanha in 1817 and named it emetine, believing the mixed alkaloids to be 1 compound. Two English chemists, Paul and Cownley, later demonstrated in 1894 that there were actually 2 distinct alkaloids, emetine and cephaeline. 3 The dried root and rhizome are the sources of the medicinal products. Ipecac has been widely used in its syrup form as a potent and effective emetic. Ipecac powder has been used to induce sweating at the onset of influenza, and small amounts of the extract have been incorporated into cough syrups as expectorants. Emetine, derived from the root, has been used for more than a century to treat dysentery. 4 In October 1965, the Food and Drug Administration ruled that 30 mL (1 oz) bottles of ipecac syrup could be dispensed without a prescription. Ipecac syrup is part of public health strategies for childhood poisoning prevention, but it no longer is routinely recommended. 3

Chemistry

The root and rhizomes of ipecac contain a number of closely related isoquinoline alkaloids in a total concentration of up to 2.5% by weight of the root, primarily emetine, cephaeline, and psychotrine. 4 Because leaves contain less than 0.5% emetine, they are usually not processed commercially. More than a half dozen other alkaloids are found in different parts of the plant. Emetine may be manufactured commercially by the chemical modification of either cephaeline or psychotrine.

Uses and Pharmacology

Ipecac alkaloids are rapidly absorbed and quickly enter the systemic circulation. 5 Response will vary among patients depending on the amount and identity of ingested material, as well as other clinical factors. One study has shown variations in the absorption patterns of ipecac syrup in a number of subjects. There is extensive distribution throughout the body and little of either alkaloid appears in the urine within 3 hours of administration. 6 The main excretion route for ipecac alkaloids is biliary. 7 It has been shown in 1 study that ipecac alkaloids may be detectable in urine several weeks after ingestion. 8 These findings have important implications for the investigation of ipecac syrup abuse and the identification of Munchausen syndrome by proxy or eating disorders using ipecac syrup. 6 , 8

The focus of present studies is the emetic potential of ipecac syrup, but there are limitations to these studies. They often are small and it is difficult to extrapolate data from simulated overdoses in volunteers who are using nontoxic amounts to overdose patients who are ingesting large toxic doses; dissolution, absorption, and gastric emptying rates are affected by the amount ingested. Also, overdose patients may take multiple drugs or other substances, and individual patient characteristics affect the outcome. Each situation must be individually assessed to determine if ipecac syrup is appropriate, dependent on substance ingested, time since ingestion, and clinical status of the patient.

Emetic

Emetine's primary central action is on the chemoreceptor trigger zone. Various mechanisms for emesis by ipecac have been proposed. 8 One study suggested an important role for 5-HT 3 receptors, as well as ipecac's high affinity for 5-HT 4 receptors. Cephaeline is about twice as potent as emetine in causing emesis. 9

Debate surrounds the use of ipecac and which patients will most benefit from it compared with other available treatments. 3 , 10 Though 1 study found no apparent benefit in patient outcome when syrup of ipecac was used in the home, there may be a benefit in certain poisonings. This remains to be proven. 11

Administer ipecac should to an alert, conscious patient who has ingested a potentially toxic amount of a poison. 12 Do not administer ipecac to a patient who has ingested either a corrosive substance or hydrocarbon with a high aspiration potential (eg, gasoline). 12

Maximum benefit can be expected in those patients who present soon after poison ingestion. 3 , 10 A 2004 ipecac syrup position paper recommends that it only be administered within 60 minutes of ingesting poison. 12

Animal data

There are limited studies in animals, but it was found that the amount of ingested material removed by ipecac-induced emesis depended on the time elapsed between the dosing and the onset of emesis. 12 There are limitations to the extrapolation of data from animal studies to the human model. 3

Clinical data

Ipecac syrup induces vomiting in 15 to 60 minutes and is most effective when accompanied by fluid intake. 13 It has been shown that the recovery of ingested substance is highly variable and decreases over time. There is no evidence from clinical studies that ipecac improves the outcome of poisoned patients. There are insufficient data to either support or exclude ipecac administration soon after poison ingestion. 12

Amebicide

Both cephaeline and emetine are active amebicides, although emetine is more active. Emetine inhibits cell protein synthesis. 13

Animal data

Research reveals no data regarding the use of ipecac as an amebicide in animals.

Clinical data

Emetine injected intramuscularly is distributed systemically. Emetine kills motile trophozoites of Entamoeba histolytica in doses smaller than those effective against cysts. 13 The drug does not reach high levels in the gut and therefore is not effective against amebic dysentery. It is useful for amebic abscesses and hepatitis.

Dosage

Ipecac is not currently recommended as an emetic for childhood poisonings. Activated charcoal now is the treatment of choice. Always refer to a health care professional or poison control center when an accidental poisoning occurs. Do not confuse the syrup with the fluid extract of ipecac, which is 14 times stronger. 14 Ipecac syrup, which contains total alkaloids 123 to 157 mg per 100 mL, has been used to induce vomiting. The usual dose range for the syrup is 10 to 30 mL, yielding a dose of alkaloids 12 to 48 mg. Follow ipecac administration in adults with 240 mL of water and 120 to 240 mL of water in children. The dose may be repeated if emesis does not occur in 20 to 30 minutes. For children 6 to 12 months of age, ipecac 5 to 10 mL with 120 to 240 mL of water usually is a sufficient dose. 12 In patients younger than 6 months of age, administer ipecac syrup only under physician supervision. Cumulative toxicity requires administration of emetine for amebic dysentery in low doses for short periods of time with intervals of several weeks between treatments.

Pregnancy/Lactation

Documented adverse effects include uterine stimulation. 15 Avoid use.

Interactions

None well documented.

Adverse Reactions

Powdered ipecac is a respiratory irritant. Pharmacists may develop rhinitis or asthma following repeated exposure to the powder during compounding procedures. Emetine can irritate skin if applied topically. 4 The most common complications of ipecac syrup are diarrhea, lethargy, drowsiness, and prolonged vomiting. 10 , 12 More severe complications include gastric rupture and Mallory-Weiss syndrome. 3

Toxicology

Ipecac extracts can be highly toxic when given either acutely or chronically. 4 Cephaeline is more toxic than emetine, causing more nausea and vomiting. Emetine, which constitutes more than half of the total ipecac content, has been associated with serious cardiotoxicity. 16 , 17 If given for a prolonged period of time or in total doses exceeding 1 g, emetine cause myositis at the injection site, GI and nervous system symptoms, hematuria, and circulatory collapse. Therefore, to treat amebic dysentery, emetine is given in low doses for a short period of time with several weeks between treatment regimens. The synthetic compound 2,3-dihydroemetine often is used to treat amebiasis. It may lead to less cardiotoxicity, but may be less effective than emetine. 4 , 13

Ipecac cardiomyopathy may be reversible, but it is unclear at which point the damage to myocardium is reversible. Further study is needed. 16 In animal studies, emetine has been shown to cause cardiac toxicity. A high level of emetine was evident in the heart. 7 One case of ipecac abuse demonstrated reversible left ventricular dysfunction over a 10-day period. Another case described a woman who ingested ipecac syrup 200 mL/wk for 3 months who developed myopathy, which resolved 4 months after stopping ipecac use. 16 , 18 This myopathy may be accompanied by cardiomyopathy. 19

Fluid extract of ipecac largely is not used because of the high number of fatal overdoses that occurred when the product was mistaken for syrup of ipecac. The fluid extract is 14 times more concentrated than the syrup. As little as 10 mL may be fatal. 17 The United States Pharmacopeia has not listed ipecac fluid extract since 1970, and it is unavailable commercially. 3 , 8 By comparison, syrup of ipecac has been used as a first-aid emetic. As much as 105 mL of the syrup has been retained in a child with only minor changes in the ECG. At least 1 fatality has been reported with the syrup in a 26-year-old woman who ingested 3 to 4 bottles of the syrup each night over a 3-month period. 20

Bibliography

1. Dobelis IN. Magic and Medicine of Plants . Pleasantville, NY: Reader's Digest Association; 1986.
2. Evans, WC. Trease and Evans' Pharmacognosy . 13th ed. London: Balliere Tindall; 1989.
3. Quang LS, Woolf AD. Past, present and future role of ipecac syrup. Curr Opin Pediatr . 2000;12:153-162.
4. Morton JF. Major Medicinal Plants . Springfield, IL: Charles C. Thomas; 1977.
5. Endo T, Nemoto M, Ogawa T, et al. Pharmacological aspects of ipecac syrup (TJN-119)-induced emesis in ferrets. Res Commun Mol Pathol Pharmacol . 2000;108:187-200.
6. Scharman EJ, Hutzler JM, Rosencrance JG, Tracy TS. Single dose pharmacokinetics of syrup of ipecac. Ther Drug Monit . 2000;22:566-573.
7. Asano T, Ishihara K, Wakui Y, et al. Absorption, distribution and excretion of 3H-labeled cephaeline- and emetine-spiked ipecac syrup in rats. Eur J Drug Metab Pharmacokinet . 2002;27:17-27.
8. Yamashita M, Yamashita M, Azuma J. Urinary excretion of ipecac alkaloids in human volunteers. Vet Hum Toxicol . 2002;44:257-259.
9. Hasegawa M, Sasaki T, Sadakane K, et al. Studies for the emetic mechanisms of ipecac syrup (TJN-119) and its active components in ferrets: involvement of 5-hydroxytryptamine receptors. Jpn J Pharmacol . 2002;89:113-119.
10. Bond GR. The role of activated charcoal and gastric emptying in gastrointestinal decontamination: a state-of-the-art review. Ann Emerg Med . 2002;39:273-286.
11. Bond GR. Home syrup of ipecac use does not reduce emergency department use or improve outcome. Pediatrics . 2003;112:1061-1064.
12. Position paper: Ipecac syrup. J Toxicol Clin Toxicol . 2004;42:133-143.
13. Bowman WC. Textbook of Pharmacology . 2nd ed. St. Louis, MO: Blackwell Mosby Book Distributors; 1980.
14. Minton N, Swift R, Lawlor C, Mant T, Henry J. Ipecacuanha-induced emesis: a human model for testing antiemetic drug activity. Clin Pharmacol Ther . 1993;54:53-57.
15. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG . 2002;109:227-235.
16. Ho PC, Dweik R, Cohen MC. Rapidly reversible cardiomyopathy associated with chronic ipecac ingestion. Clin Cardiol . 1998;21:780-783.
17. King WD. Syrup of ipecac: a drug review. Clin Toxicol . 1980;17:353-358.
18. Thyagarajan D, Day BJ, Wodak J, Gilligan B, Dennett X. Emetine myopathy in a patient with an eating disorder. Med J Aust . 1993;159:757-760.
19. Dresser LP, Massey EW, Johnson EE, Bossen E. Ipecac myopathy and cardiomyopathy. J Neurol Neurosurg Psychiatry . 1993;56:560-562.
20. Adler AG, Walinsky P, Krall RA, Cho SY. Death resulting from ipecac syrup poisoning. JAMA . 1980;243:1927-1928.

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