Gamma Hydroxybutyrate 18.May.2012-Expires: 7 days - Do not archive DESCRIPTION SUBSTANCE NAME Gamma Hydroxybutyrate   USES This substance is used either industrially or therapeutically, but can be subject to abuse. Treatment for narcolepsy Treatment for alcoholism Anesthetic agent Euphoric “Date rape” agent “Growth Hormone booster” “Aphrodisiac” “Muscle builder” (although effectiveness has never been proven)   INTERVENTION CRITERIA The correct identification of the substance is important. If the symptoms are inconsistent with those described, or the history is considered unreliable, other substances may need to be considered.   Intervention Level Child Medical observation is recommended: For any suspected exposure in children   The risks of decontamination outweigh any benefits, and should not be attempted.   Adult Medical observation is recommended: For any suspected ingestion   The risks of decontamination outweigh any benefits, and should not be attempted.   History of dose ingested is not a reliable guide to management.   Observation Period Observation at Home All patients require medical attention.   Medical Observation If medical observation is required the patient must be monitored for 6 hours following exposure for onset or worsening of symptoms.   If the patient is asymptomatic at the end of the observation period, and if they have been appropriately decontaminated and any investigations have been carried out, they may be: Discharged into the care of a reliable observer, or Referred for psychological assessment if the overdose was with intent of self-harm.   Investigations Levels Serum levels do not aid management.   Monitoring Monitor: Level of consciousness Heart rate Blood pressure Respirations Seizure activity   Admission Criteria Hospital admission is recommended with: Any symptomatic ingestion   The admission hospital may require the following resources: Advanced care facilities/Intensive Care Unit   TREATMENT TREATMENT SUMMARY Due to this drug's fast onset of action, gastrointestinal decontamination is not recommended.   Airways management is the mainstay of treatment and with adequate supportive care the prognosis is good. Intubation, and possibly ventilation, may be necessary due to respiratory depression and aspiration risk.   Profound coma is a well recognized consequence following ingestion of this compound and is generally short-term. While wakening may be hastened with use of physostigmine (an experimental antidote for this indication), patients will generally satisfactorily recover with adequate airways management alone.   Seizures may rarely occur and, in the presence of coma, indicate anoxia: manage the airway and ensure adequate ventilation. Should repetitive seizure occur in a well ventilated patient treat with a benzodiazepine, or if still refractory, a barbiturate. Other complications such as bradycardia, hypotension and gastrointestinal upset should be treated along usual guidelines. Myoclonic jerking is a recognized re-emergence phenomenon and single episodes do not require treatment.   A withdrawal syndrome is recognized after chronic abuse of this compound and may last 3 to 12 days. Benzodiazepines are usually effective to relieve symptoms. Weakness, headache, fatigue and nausea lasting 3 days after ingestion may occur. However, if significant CNS depressant effects persist beyond 8 hours, alternative causes should be investigated.   The correct identification of the substance is important. If the symptoms are inconsistent with those described, or the history is considered unreliable, other substances may need to be considered.   Emergency Stabilization Ensure adequate cardiorespiratory function Decontamination Ingestion Not recommended Antidote(s) Physostigmine (Experimental Antidote) Enhanced Elimination Not recommended Supportive Care Monitoring Respiratory Respiratory failure Pulmonary aspiration Neurologic Coma Seizure Cardiovascular Bradycardia Other Withdrawal syndrome EMERGENCY STABILIZATION Ensure Adequate Cardiopulmonary Function Ensure the airway is protected if compromised (intubation may be necessary).   DECONTAMINATION Ingestion Decontamination Not Recommended Absorption is too rapid for decontamination to be effective. Supportive care is likely to be successful without decontamination. ANTIDOTE(S) Physostigmine Physostigmine is viewed as an unproven experimental antidote for this intoxication. Neither naloxone nor flumazenil will reverse coma.[1][2]   Previously considered as an agent for reversal of gamma hydroxybutyric acid induced anesthesia,[3] this possible antidote has been reported as successful in a limited number of gamma hydroxybutyric acid overdose cases.[4] It may be considered in severe or life-threatening presentations.   Physostigmine dose:   CHILD: 0.02 mg/kg (maximum dose 0.5 mg) IV: slow push over 5 to 10 minutes   ADULT: 1 to 2 mg IV: slow push over 5 to 10 minutes.[5]   The dose may be repeated at 10 minute intervals if a severe or life-threatening condition continues.   As the duration of action of physostigmine is approximately 20 to 60 minutes, further doses may be required if severe or life-threatening symptoms recur.   ECG monitoring must be undertaken prior to and during this treatment and advanced life support must be available.   Do not administer physostigmine if:[6] The QRS is widened (greater than 100 msec) PR interval greater than 200 msec In the presence of right axis deviation   Physostigmine may exacerbate bradycardia and conduction delays, and too rapid administration may precipitate a seizure.[4]   Significant cholinergic effects (e.g. bradycardia, salivation, emesis, etc) subsequent to physostigmine use may be treated with atropine at a dose one half that of the administered physostigmine.[7]   ENHANCED ELIMINATION Enhanced Elimination Not Recommended Procedures for enhanced elimination of this compound are not recommended as it is rapidly metabolized. SUPPORTIVE CARE Monitoring Closely monitor: Level of consciousness Respiratory function Gag reflex For signs of withdrawal   Respiratory Respiratory Failure Monitoring for respiratory failure should include: Chest auscultation Oxygen saturation Arterial blood gases   Treat using standard protocols for respiratory failure.   Pulmonary Aspiration Aspiration is a significant risk. Monitor: Airway Breathing Pulse oximetry Arterial blood gases Chest x-ray   Manage pulmonary aspiration using standard protocols.   Neurologic Coma Profound coma is characteristic and generally short-term. Airway protection may be required, endo-tracheal intubation and even ventilation may on occasion be necessary.[8]   Closely monitor level of consciousness.   Follow standard protocols for the management of coma.   Seizures Myoclonic jerking is recognized as a re-emergence phenomenon (sometime mistaken for seizure activity) and does not require treatment. However, tonic-clonic seizures may occur and should be treated with standard protocols. Anoxia is an important precipitant and adequate airways and ventilation must be ensured.   Observe the patient closely for onset of seizure activity.   Toxic seizure may be managed following these (hyperlinked) recommendations.   Cardiovascular Bradycardia Monitor: Heart rate/rhythm Blood pressure ECG   Manage bradycardia following standard treatment protocols.   Other Withdrawal Syndrome A withdrawal syndrome related to gamma hydroxybutyrate is recognized with symptoms resolving in some 3 to 12 days.[9] Treatment with benzodiazepines has been reported as being sufficient to achieve regression of symptoms.[10]   Monitor for: Insomnia Confusion Hallucinations Autonomic instability Tachycardia Hypertension Diaphoresis Tremor Increased creatine phosphokinase   Follow standard protocols for the management of withdrawal.   DISCHARGE CRITERIA Patients may, if initially symptomatic, be discharged following 6 hours of observation subsequent to becoming stable and asymptomatic.[11]   SIGNS AND SYMPTOMS The correct identification of the substance is important. If the symptoms are inconsistent with those described, or the history is considered unreliable, other substances may need to be considered.   Other drug/compounds are commonly co-ingested with this substance and may significantly influence the clinical picture.   With mild toxicity, gastrointestinal upset may occur and CNS effects predominate including euphoria, CNS depression, headache, and occasionally miosis and nystagmus. Sudden drowsiness followed by profound coma is a characteristic presentation (a GCS of 3 is not uncommon). Recovery is sometimes accompanied by emergence phenomena including myoclonic jerking, transient confusion, and combativeness.   With serious toxicity, sudden, profound coma, seizures, and respiratory arrest may occur. Deaths are reported.[12][13] Complications may include bradycardia, hypotension, and hypothermia.   Persistent symptoms of weakness, headache, fatigue, and nausea lasting three days after ingestion has been noted,[14] and a withdrawal syndrome is described.[15][9]   Onset/Duration of Symptoms In the majority of cases signs and symptoms develop within 1 hour of ingestion and resolve within 8 hours of onset.[16][17][18] Recovery from coma, if it occurs, is typically rapid, and may be indicated by initial GCS score.[16]   Weakness, headache, fatigue, and nausea lasting three days after ingestion has been noted,[14] and a withdrawal syndrome lasting 3 to 12 days is described.[15][9]   Severity of Poisoning Mild Gamma-Hydroxybutyrate Toxicity Moderate Gamma-Hydroxybutyrate Toxicity Severe Gamma-Hydroxybutyrate Toxicity Euphoria Drowsiness Dizziness Headache Weakness Bradycardia Hypotension Myoclonic jerking Hypothermia (mild) Profound coma Seizure Respiratory arrest   ACUTE EFFECTS (ORGAN SYSTEM) Cardiovascular Bradycardia Hypotension Neurologic Euphoria Abrupt drowsiness Dizziness Headache Miosis Nystagmus Myoclonic jerking Tonic-clonic seizures Short-term coma Gastrointestinal Nausea Emesis Respiratory Apnea Cyanosis Respiratory arrest Metabolic Respiratory acidosis Hypothermia (mild) Other Withdrawal Syndrome Insomnia Confusion Hallucinations Autonomic instability Tachycardia Hypertension Diaphoresis Tremor Increased creatinine phosphokinase TOXICITY The correct identification of the substance is important. If the symptoms are inconsistent with those described, or the history is considered unreliable, other substances may need to be considered.   HUMAN Child The acute toxic dose in children has not been determined. Adult Toxicity of gamma hydroxybutyrate:[8]   10 mg/kg Amnesia and hypotonia 20-30 mg/kg A normal sequence of REM and non-REM sleep 50 mg/kg Anesthesia >50 mg/kg Decreased cardiac output, severe respiratory depression, seizure-like activity, coma   Other substances may be abused concomitantly with this compound greatly increasing toxicity.   Sodium hydroxide may be inappropriately used in the preparation of gamma hydroxybutyrate forming a caustic mixture.[13]   REPRODUCTION PREGNANCY The effects of exposure to this substance during pregnancy are unknown.   It is recommended that this substance should not be used during pregnancy. Gamma hydroxybutyrate is not reported as teratogenic when injected into fertile chicken eggs.[19] LACTATION It is unknown whether this compound is excreted in human breast milk.   It is recommended that this substance should not be used while breast feeding. TOXIC MECHANISM Gamma hydroxybutyrate (GHB) is a water-soluble four carbon molecule normally found in the human body. It is formed from the precursor molecule gamma butyrolactone (GBL) and is metabolized to succinic semialdehyde and the neurotransmitter gamma-aminobutyric acid (GABA).[11] The greatest concentration of GHB in humans is in the basal ganglia.   Mechanism of Action   HUMAN Gamma hydroxybutyrate (GHB) acts as: - An inhibitory neurotransmitter regulating dopaminergic neurons - A central nervous system depressant with euphoria-inducing capabilities Has a general anesthetic effect caused via: - Suppression of the entire cerebrospinal axis, and - Muscular relaxation by direct action on the spinal cord, rather than neuromuscular junction.[20]   ANIMAL GHB alters dopaminergic activity: Either by reducing dopaminergic activity in the basal ganglia - Possibly due to the inhibition of dopamine-releasing nerve cells Or by stimulating dopamine release However, the direction is dependent on several undefined variables.   GHB has binding affinity for two receptor sites in the central nervous system - GHB-specific receptor - The GABAB receptor GHB might mediate some of its effects (alteration in dopaminergic activity) through interaction with the GABAB receptor.[21]   THERAPEUTIC DRUG INFORMATION KINETICS ABSORPTION Oral Absorption Yes, rapidly Effect of Food May reduce rate Onset of Action 10 min to 1 hour Duration of Action ~ 2 to 3 hours Effects may not peak until 2 hours post ingestion Residual effects may be present for up to 24 hours Time to Peak Plasma Levels 20 to 60 minutes   METABOLISM Metabolism Hepatic Major Metabolic Pathways Parent: Following oxidation to succinate and entry into the Krebs cycle, gamma hydroxybutyrate is almost completely metabolized to water and carbon dioxide.[22][20] First Pass Metabolism Significant   ELIMINATION Excretion Urine 2 to 5% excreted unchanged[18][23] Lungs excreted as carbon dioxide Half-life Therapeutic 20 min   IDENTIFICATION PRODUCT INFORMATION This substance may be available in a stated dosage, however, this should be treated with some caution particularly if obtained illicitly, due to variables such as uncontrolled manufacturing process, inappropriate packaging, and product bulking.   OTHER NAME(S) Chemical Name Gamma hydroxybutyric acid:: 4-hydroxy butyrate,4-hydroxy butanoic acid,Gamma hydrate, Gamma hydroxybutyrate, Sodium oxybate, Sodium oxybutyrate.   “Street” Names Alcover Aminos Blue Thunder Cherry Menth Cherry Meth Date Rape Drug Easy Lay Everclear Fantasy Fingernail Polish Remover Flower Power G G caps G juice Gamma 10 Gamma Date Rape Drug Gamma hydrate Gammahydroxybutyrate Gamma-hydroxybutyric acid Gamma-OH GBH Georgia Home Boy GH Buddy GHB GHBees (GHB & 2C-B) Ghbers GHGold Gina Goop Great Hormones Great Hormones at Bedtime Grevious Bodily Harm Grievous Bodily Harm G-Riffick H2O Ink Jet Cartridge Cleaner Jib Liquid E Liquid Ecstasy Liquid Fantasy Liquid G Liquid X Max (GHB & Amphetamines) Nail Polish Remover Natural Sleep 500 Nectar Organic Quaalude Oxy-Sleep Paint Stripper Phantasy Plant Food PMSomax Puritech Rejoov Salty water Scoop Sleep-500 Soap Sodium oxybate Sodium oxybutyrate Somatomax Somsanit Swirl Thundar Tranquili G Vita-G Water White Magic Cleaner Womans Viagra   CODES CAS NUMBER Gamma Hydroxybutyrate: 591-81-1 Sodium Gamma Hydroxybutyrate: 502-85-2   MOLECULAR FORMULA GHB: C4H8O3   PHYSICOCHEMICAL PROPERTIES GAMMA HYDROXYBUTYRATE DESCRIPTION Liquid (colorless, odorless liquid with a salty taste free of suspended matter) or white crystalline powder PHYSICAL PROPERTIES Molecular Weight 104.11 126.1 (sodium salt) Solubility Water: soluble Alcohol: soluble Aromatic hydrocarbons: soluble Esters: soluble Ketone: soluble Attempts to avoid detection: Artificial flavoring Artificial coloring Mixed in: Fruit drinks Bottled water Sold as cleaning products, e.g. CD cleaner   Testing: Gamma butyrolactone (GBL) and 1,4 butanediol are rapidly metabolized to gamma hydroxybutyrate (GHB), therefore: Routine drug screen will not detect GHB Tests must be targeted specifically for GHB Urine testing should be used   REFERENCES [1] Gerra G, Caccavari R, Fontanesi B, Marcato A, Fertonani Affini G, Maestri D, Avanzini P, Lecchini R, Delsignore R, Mutti A. Flumazenil effects on growth hormone response to gamma-hydroxybutyric acid. Int Clin Psychopharmacol 1994 Sep; 9 (3): 211-5. [2] Li J, Stokes SA, Woeckener A. A tale of novel intoxication: seven cases of gamma-hydroxybutyric acid overdose. Ann Emerg Med 1998 Jun; 31 (6): 723-8. [3] Henderson RS, Holmes CM. Reversal of the anaesthetic action of sodium gamma-hydroxybutyrate. Anaesth Intensive Care 1976 Nov; 4 (4): 351-4. [4] Yates SW, Viera AJ. Physostigmine in the treatment of gamma-hydroxybutyric acid overdose. Mayo Clin Proc 2000 Apr; 75 (4): 401-2. [5] Bowden CA, Krenzelok EP. Clinical applications of commonly used contemporary antidotes. A US perspective. Drug Saf 1997 Jan; 16 (1): 9-47. [6] Burns MJ, Linden CH, Graudins A, Brown RM, Fletcher KE. A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning. Ann Emerg Med 2000 Apr; 35 (4): 374-81. [7] Rumack BH. Anticholinergic poisoning: treatment with physostigmine. Pediatrics 1973 Sep; 52 (3): 449-51. [8] Multistate outbreak of poisonings associated with illicit use of gamma hydroxy butyrate. MMWR Morb Mortal Wkly Rep 1990 Nov 30; 39 (47): 861-3. [9] Galloway GP, Frederick SL, Staggers FE Jr, Gonzales M, Stalcup SA, Smith DE. Gamma-hydroxybutyrate: an emerging drug of abuse that causes physical dependence. Addiction 1997 Jan; 92 (1): 89-96. [10] Addolorato G, Caputo F, Capristo E, Bernardi M, Stefanini GF, Gasbarrini G. A case of gamma-hydroxybutyric acid withdrawal syndrome during alcohol addiction treatment: utility of diazepam administration. Clin Neuropharmacol 1999 Jan-Feb; 22 (1): 60-2. [11] Li J, Stokes SA, Woeckener A. A tale of novel intoxication: a review of the effects of gamma-hydroxybutyric acid with recommendations for management. Ann Emerg Med 1998 Jun; 31 (6): 729-36. [12] Kraner J, Plassard J, McCoy D, Roraback J, Witeck M, Evans M. Fatal overdose from ingestion of 1,4-butanediol, a GHB precursor [abstract]. J Toxicol Clin Toxicol 2000; 38 (5): 534-5. [13] Gamma hydroxy butyrate use--New York and Texas, 1995-1996. MMWR Morb Mortal Wkly Rep 1997 Apr 4; 46 (13): 281-3. [14] Gilmore DA, Freed CR. Central nervous system depression and weakness following ingestion of gamma hydroxybutyrate [abstract]. Vet Hum Toxicol 1991; 33: 366. [15] Craig K, Gomez HF, McManus JL, Bania TC. Severe gamma-hydroxybutyrate withdrawal: a case report and literature review. J Emerg Med 2000 Jan; 18 (1): 65-70. [16] Chin RL, Sporer KA, Cullison B, Dyer JE, Wu TD. Clinical course of gamma-hydroxybutyrate overdose. Ann Emerg Med 1998 Jun; 31 (6): 716-22. [17] Viswanathan S, Chen C, Kolecki P. Revivarant (gamma-butyrolactone) poisoning. [Letter] Am J Emerg Med 2000 May; 18 (3): 358-9. [18] Dyer JE. gamma-Hydroxybutyrate: a health-food product producing coma and seizurelike activity. Am J Emerg Med 1991 Jul; 9 (4): 321-4. [19] Cavender FL, Sowinski EJ. Glycols. In: Clayton GD, Clayton FE, editors. Patty’s Industrial hygiene and toxicology, Volume II, Patr F. 4th Ed. New York: John Wiley & Sons, Inc.; 1994. p4645-719. [20] Doherty JD, Stout RW, Roth RH. Metabolism of (1-14C)gamma-hydroxybutyric acid by rat brain after intraventricular injection. Biochem Pharmacol 1975 Feb 15; 24 (4): 469-74. [21] Tunnicliff G. Sites of action of gamma-hydroxybutyrate (GHB)--a neuroactive drug with abuse potential. J Toxicol Clin Toxicol 1997; 35 (6): 581-90. [22] Vickers MD. Gammahydroxybutyric acid. Int Anesthesiol Clin 1969 Spring; 7 (1): 75-89. [23] HELRICH M, MCASLAN TC, SKOLNIK S, BESSMAN SP. CORRELATION OF BLOOD LEVELS OF 4-HYDROXYBUTYRATE WITH STATE OF CONSCIOUSNESS. Anesthesiology 1964 Nov-Dec; 25 (): 771-5. Do Not Archive. This document is current on day of issue, NZ: 18.May.2012

Disclaimer

All information contained on this database is as accurate and up-to-date as our resources allow. Since the University of Otago, the New Zealand National Poisons Centre and Intergen cannot anticipate or control the conditions under which this information may be used, each user should view the information in the specific context of the intended application.

The University of Otago, the New Zealand National Poisons Centre and Intergen will not be responsible for damages of any nature resulting from use or reliance upon this information.

© National Poisons Centre, New Zealand. Portions © Intergen.

If you would like further information about TOXINZ, or wish to make comment, please contact us on +64 3 479 7248 or email us at TOXINZ@otago.ac.nz.