Identification

Name
Ipecac
Accession Number
DB13293
Type
Small Molecule
Groups
Approved, Withdrawn
Description

Ipecac is obtained from the plant Cephaelis ipecacuanha and contains a number of emetic alkaloids including emetine and cephaeline.[9] Ipecac was approved by Health Canada as an OTC but all those products are now discontinued.[7] The FDA does not have currently any approved product containing ipecac, however, ipecac as an ingredient is accepted to be sold over the counter in packages of 1 fluid ounce (30 ml) for the emergency use to cause vomiting in poisoning.[8]

Synonyms
  • Ipecac syrup
  • Ipecacuanha
  • Ipsatol
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ipecac SyrupSyrup140 mgOralD.C. Labs Limited1964-12-312003-07-11Canada
Ipecac Syrup 1.8gm/30ml USPSyrup1.8 gOralMeta Pharmaceuticals Inc.1991-12-311998-11-05Canada
PMS-ipecac SyrupSyrup7 %OralPharmascience Inc1988-12-312009-12-02Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Trousse Antipoison Pour Enfants LiqIpecac (30 ml) + Activated charcoal (120 ml)LiquidOralProdemdis Enr.1988-12-312010-07-15Canada
Categories
UNII
62I3C8233L
CAS number
8012-96-2
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

Ipecac is indicated as an emetic agent for the induction of vomiting in poisoning victims who ingested systemic poison in order to prevent absorption of the chemicals through the gastrointestinal tract. In low doses, ipecac was also used as an expectorant.[9]

Reports have suggested that ipecac was vastly used in patients with eating disorders to produce vomiting.[5]

Pharmacodynamics

An effective and safe dose of ipecac may cause vomiting within 20 minutes of the administration.[9] In prospective studies with children, the mean time to vomit was reported to be of 21.7 minutes.[10]

Mechanism of action

The emetic components of ipecac, emetine and cephaeline, act centrally and locally in the gastrointestinal tract to cause vomiting.[9] The mechanism by which ipecac performs his effect is by irritating the stomach lining and chemically stimulating the chemoreceptor trigger zone.[6]

Absorption

The main components of ipecac are rapidly absorbed from the GI tract, this absorption depends on the amount of emesis produced by the administered dose. The peak plasma concentration of 10-16 ng/ml is attained 20 minutes after first administration.[5] The bioavailability of ipecac is reduced over time from 67-11% after 5-60 minutes of administration.[3]

Volume of distribution

The volume of distribution is thought to be large based on the prolonged excretion.[5]

Protein binding

This pharmacokinetic property is not relevant as the absorbed dose of ipecac is minimal.

Metabolism

The main components of ipecac have been shown in microsomal enzyme systems that emetine is converted to cephaeline and 9-O-demethylemetine by CYP2D6. On the other hand, CYP3A4 produces the transformation of emetine to 9-O-demethylemetine and 10-O-demethylemetine. In preclinical studies, it was shown that cephaline is conjugated with glucuronice to form cephaeline-6'-O-glucuronide for biliary excretion whereas emetine gets demethylated to cephaline and 9-O-demethylemetine before glucuronidation.[5]

Route of elimination

Due to the emetic function, even 76% of the administered dose is vomited. From the absorbed dose, the elimination from plasma is relatively rapid. In some clinical trials, the alkaloids were not observed in plasma 6 hours after administration. When the patient does not vomit any part of the administered dose, there could be traces in plasma after 24 hours. The component alkaloids are eliminated via the bile and urine as it has been observed a persistence in urine after chronic administration.[5] Biliary and urinary excretion of ipecac corresponds to 57.5% and 16.5% of the administered dose respectively. From the excreted dose, unchanged cephaeline accountd for 42.4% of the eliminated dose in feces.[4]

Half life

The effect of ipecac is done in about 20 minutes and the elimination of the little-absorbed dose is reported to be very rapid. Thus, the half-life is thought to be of about 0.5-1 hour.[5]

Clearance

The urinary excretion of the main components of ipecac accounts for 75% of the administered dose 48 hours after initial administration.[6]

Toxicity

An overdose of an ipecac preparation may cause serious poisoning. If emesis is not provoked after two doses of ipecac, a gastric lavage is recommended.[9] The overdose of the components such as emetine is reported to cause the onset of myopathy. Chronic use of this drug has been indicated to produce muscle weakness, waddling gait, dyspnea, left atrial enlargement and reduced left ventricular ejection fraction.[5]

Affected organisms
  • Humans
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Ipecac can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Ipecac.
3,5-diiodothyropropionic acidThe metabolism of Ipecac can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Ipecac.
4-MethoxyamphetamineThe metabolism of Ipecac can be decreased when combined with 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of Ipecac can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Ipecac can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of Ipecac can be decreased when combined with 6-O-benzylguanine.
9-aminocamptothecinThe metabolism of Ipecac can be decreased when combined with 9-aminocamptothecin.
AbacavirAbacavir may decrease the excretion rate of Ipecac which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Lee MR: Ipecacuanha: the South American vomiting root. J R Coll Physicians Edinb. 2008 Dec;38(4):355-60. [PubMed:19227966]
  2. Axelsson P, Thorn SE, Wattwil M: Betamethasone does not prevent nausea and vomiting induced by ipecacuanha. Acta Anaesthesiol Scand. 2004 Nov;48(10):1283-6. [PubMed:15504189]
  3. Saincher A, Sitar DS, Tenenbein M: Efficacy of ipecac during the first hour after drug ingestion in human volunteers. J Toxicol Clin Toxicol. 1997;35(6):609-15. [PubMed:9365428]
  4. Asano T, Watanabe J, Sadakane C, Ishihara K, Hirakura K, Wakui Y, Yanagisawa T, Kimura M, Kamei H, Yoshida T, Fujii Y, Yamashita M: Biotransformation of the ipecac alkaloids cephaeline and emetine from ipecac syrup in rats. Eur J Drug Metab Pharmacokinet. 2002 Jan-Mar;27(1):29-35. [PubMed:11996324]
  5. Barceloux D.G. (2012). Medical toxicology of drug abuse: Synthesized chemicals and psychoactive plants.. Wiley.
  6. Benzoni T. and Gossman W. (2017). Ipecac. Treasure Island: StatPearls Publishing.
  7. Health Canada [Link]
  8. FDA code of federal regulations [Link]
  9. FDA federal register [Link]
  10. FDA Poisonous Plant Database [Link]
External Links
PubChem Substance
347911447
ChEMBL
CHEMBL2108372
Wikipedia
Ipecacuanha
ATC Codes
V03AB01 — IpecacuanhaR05CA04 — Ipecacuanha
MSDS
Download (46.5 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SyrupOral140 mg
SyrupOral1.8 g
SyrupOral7 %
LiquidOral
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
water solubilitySoluble'MSDS'
logP5.0Barceloux D. Medical Toxicology of Drug Abuse. (2012)
pKa6.64-6.77Purich D. The inhibitor index. (2017)
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Barceloux D.G. (2012). Medical toxicology of drug abuse: Synthesized chemicals and psychoactive plants.. Wiley.
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Asano T, Kushida H, Sadakane C, Ishihara K, Wakui Y, Yanagisawa T, Kimura M, Kamei H, Yoshida T: Metabolism of ipecac alkaloids cephaeline and emetine by human hepatic microsomal cytochrome P450s, and their inhibitory effects on P450 enzyme activities. Biol Pharm Bull. 2001 Jun;24(6):678-82. [PubMed:11411558]
  2. Barceloux D.G. (2012). Medical toxicology of drug abuse: Synthesized chemicals and psychoactive plants.. Wiley.

Drug created on June 23, 2017 14:39 / Updated on November 02, 2018 07:37