Charge (BZP) 18.May.2012-Expires: 7 days - Do not archive DESCRIPTION SUBSTANCE NAME Benzylpiperazine (BZP)   SUBSTANCE CLASS Psychoactive Central Stimulant Piperazine-Based Hallucinogenic Stimulant   USES While piperazine-based hallucinogenics or stimulants are not currently used therapeutically, they are misused. It is believed to have a similar action as the hallucinogenic-amphetamines, explaining the reason for its abuse. It is less potent than methamphetamine or MDMA, but is being sold in continuously increasing doses, making the effects more consistent with these more potent drugs.[1]   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.   Some names for piperazine-based designer drugs are actually street names that refer to the imprint on the tablet, rather than a brand name. These pills are sometimes sold to a consumer as MDMA (Ecstasy) but may contain anywhere between zero to 500 mg of benzylpiperazine (BZP) plus trifluoromethylphenylpiperazine (TFMPP). Generally, tablets and capsules contain Benzylpiperazine (BZP). These capsules can range from 70 to 1000 mg BZP. Some products contain BZP in combination with Trifluoromethylphenylpiperazine (TFMPP), generally in a ratio of 2:1 (e.g. 200 mg BZP plus 100 mg TFMPP).   Some products may contain flipiperazine (PFPP), m-chlorophenylpiperazine (MCPP), p-methoxyphenylpiperazine (MEOPP) or methylenedioxybenzylpiperazine (MDBP).   Some products come with separate "recovery" capsules containing 5-hydroxytryptophan (5-HTP), which is a serotonin precursor and causes serotonergic symptoms. These capsules generally contain between 50 and 500 mg of 5-HTP.   Some capsules claim to contain an "anti-seizing" agent, which is actually therapeutically inactive.   ACTIVE INGREDIENT Charge Capsule: 105mg() Benzylpiperazine  (equivalent to mg )()   Recommended dose is 1 to 2 capsules, then another 1 to 2 after 2 hours. Maximum dose 3 capsules. Available in packets of 6 or 18.   Warning: Note: tablets claim to contain "500 mg". However, this refers to total mg of all ingredients, not active ingredients, and is effectively a meaningless statement.   INTERVENTION CRITERIA Intervention Level Child Observation is recommended: For any exposure to a piperazine based hallucinogenic stimulant (Note: the interval for useful decontamination is very limited.) Adult Observation is recommended: > 400 mg of a piperazine-based hallucinogenic stimulant is ingested Symptomatic patients (other than mild) Exposures with intent to self-harm   (Note: the interval for useful decontamination is very limited.)   Observation Period Observation at Home In the case of standard release formulations, if the patient does not require medical observation they can be monitored at home for 4 hours in the care of a reliable observer.   Medical attention should be sought if ANY symptoms occur, including: Euphoria Confusion/agitation Anxiety Increased heart rate Palpitations Chest pain Gastrointestinal upset Fever Tremor   Medical Observation If medical observation is required the patient must be monitored for 4 hours following exposure for onset or worsening of symptoms.   Once the patient remains asymptomatic for 4 hours and any necessary decontamination or investigations have been carried out: Discharge into the care of a reliable observer, or Refer for psychological assessment (if the overdose was intentional)   Investigations Serum levels do not aid management.   Heart rate Blood pressure Body temperature 12 lead ECG Blood glucose Serum sodium Admission Criteria Admission to a hospital facility is required for those suffering significant signs of toxicity including: Agitation - sufficient to impair ability to function alone Paranoia Vomiting Abdominal pain Palpitations Chest pain Hyperthermia Seizure Cardiac dysrhythmia, including supraventricular tachycardias Evidence of hepatotoxicity   Admission into an intensive care facility is required for those suffering severe overdose or complications.   TREATMENT TREATMENT SUMMARY Piperazine based hallucinogenic stimulants are considered to possess an hallucinogenic-amphetamine-like effect.   The majority of hallucinogenic-amphetamine presentations will recover with a period of observation, calming environment and, if required, benzodiazepine. Gastrointestinal decontamination is unlikely to be beneficial. Stimulant abuse may be via intravenous injection of ground tablets. Pulmonary granuloma formation in chronic abusers predisposes to reduced pulmonary function,[2] vascular obliteration, pulmonary hypertension, and cor pulmonale.[3][4]   Patients may become dehydrated and require significant volume replacement – however, it is imperative to recognize those suffering hyponatremia as administration of fluids may prove fatal. Serum sodium must be measured, and CT brain scan undertaken to exclude cerebral edema in those with CNS signs.   The severely toxic may suffer seizure or cardiovascular abnormality. Chest pain may indicate an acute coronary syndrome (arteriospasm) which will likely settle if the patient is calmed with a benzodiazpeine, nitrate, or in severe cases a vasodilator such as phentolamine. Hyperthermia should be immediately and actively managed, and the patient carefully monitored for further complications including rhabdomyolysis, DIC, and renal failure. Hepatotoxicity is well recognized, and while recovery is usual, fulminant hepatic failure requiring liver transplant may manifest. Serotonin syndrome should be considered, especially in those using other serotonergic compounds either therapeutically or recreationally.   Emergency Stabilization Ensure adequate cardiorespiratory function Cardiac arrest Seizure Emergency monitoring Decontamination Ingestion Single dose activated charcoal Antidote(s) None recommended Enhanced Elimination Not recommended Supportive Care Monitoring Neurologic Seizure Intracranial hemorrhage Serotonin toxicity Delirium Fluid and electrolytes Hyponatremia Dehydration Hyperkalemia Cardiovascular Tachycardia Hypertension Acute coronary syndrome Cardiac dysrhythmia Metabolic Hyperthermia Metabolic acidosis Musculoskeletal Rhabdomyolysis Respiratory Non-cardiogenic pulmonary edema Renal Acute renal failure Hepatic Hepatotoxicity Other Movement disorder Ocular Corrosive eye injury Dermatologic Skin burn EMERGENCY STABILIZATION A range of acute cardiovascular emergencies may occur due to vasospasm or vascular rupture. Such events include hemorrhagic or ischemic stroke, cardiac dysrhythmia/arrest, dissection of large vessels including the aorta.   Hyponatremia may occur and initially present as seizure. Should respiratory arrest develop likelihood of recovery is remote.[5]   Ensure Adequate Cardiopulmonary Function Ensure the airway is protected if compromised (intubation may be necessary).   Cardiovascular Immediately establish secure intravenous access.   Cardiac Arrest Prolonged cardiac resuscitation following standard ACLS protocols is warranted as recovery with a good neurological outcome is occasionally reported in poisoned patients receiving CPR for periods of 3 to 5 hours.[6]   Seizure Most toxic seizures are short-lived and often do not require intervention.   Administer a benzodiazepine as first-line treatment to patients with seizure activity.   Blood glucose concentration should be promptly determined. If the result indicates hypoglycemia, or is unobtainable, 50% dextrose should be administered IV (preceded by thiamine in adults).   Emergency Monitoring Respiratory rate Heart rate Blood pressure State of hydration 12 lead ECG Serum electrolytes - especially sodium Blood glucose Neurological status   DECONTAMINATION Efficacy of gastrointestinal decontamination is questionable as amphetamines and amphetamine-like compounds are rapidly absorbed; and the patient likely a late presenter and less than co-operative.   Ingestion Single Dose Activated Charcoal Administration of activated charcoal may be considered if a patient has ingested a potentially toxic amount up to 1 hour previously.[7]   Single dose activated charcoal[8] CHILD 1 to 2 g/kg orally ADULT 50 to 100 g orally   Nasogastric Intubation Nasogastric instillation of activated charcoal is not recommended unless the ingestion is considered potentially severely toxic and oral administration is not successful. Accurate placement of the nasogastric tube and protection of the airway must be ensured.   Whole Bowel Irrigation Whole bowel irrigation is not recommended for this drug unless a potentially severely toxic dose of an enteric coated or modified release (e.g. sustained release) formulation has been ingested,[9] or the quantity of compound is too great for activated charcoal alone to be an effective decontaminant (ratio of charcoal to compound is less than ten to one). Due to the risk of pulmonary aspiration ensure that the airway is fully protected if whole bowel irrigation is used.   The only irrigant recommended is an iso-osmotic polyethylene glycol electrolyte solution administered at the following rates until the rectal effluent is clear.[10]   CHILD 9 months to 6 years: 20 mL/kg/h orally or via NG tube 6 to 12 years: 20 mL/kg/h orally or via NG tube ADOLESCENT or ADULT 1,500 to 2,000 mL/h orally or via NG tube   SIGNS AND SYMPTOMS Piperazines have a stimulant effects, as a result of increased monoamine (dopamine, serotonin, noradrenaline) availability.[11]   Piperazine toxicity commonly causes tachycardia, hypertension, palpitations, gastrointestinal upset (nausea, abdominal pain, vomiting, diarrhea), dehydration, headache, anxiety, fever and agitation.[12][13][14] Mydriasis, blurred vision, sweating, tremor, ataxia and confusion are relatively common. Nystagmus, trismus and paresthesia may uncommonly occur.[12][15] Hallucinations, hyperventilation, shortness of breath and flushed skin are rare.   In more severe cases, seizures, collapse, myoclonic jerking and extrapyramidal features (choreoathetoid movements, dystonic reactions) may occur.[12] Serotonin syndrome has also been reported.[16] Hypertension can be severe.[12] If prolonged or severe, fever and excessive motor activity may lead to hyperthermia, metabolic acidosis, disseminated intravascular coagulation and renal failure. Renal failure has been reported on one occasion,[17] as has psychosis.[18] Given piperazine's mechanism of action, theoretical concerns are cardiac dysrhythmia, acute hepatitis/liver failure, and death.[19]   Hypersensitivity reactions, such as bronchospasm, Stevens-Johnson syndrome, acute hepatitis, thrombocytopenia, hemolytic anemia and angioedema have occurred in individuals taking piperazine therapeutically.[15]   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.   Onset/Duration of Symptoms Onset of affect is usually delayed about 2 hours post-ingestion.[1][20] Effects generally persist for about 12 to 24 hours, but may occur for up to 72 hours following use.[12] There may be a role for monoamine depletion/withdrawal in prolonged toxicity. Routes of Exposure Benzylpiperazine (BZP) liquid and dust is known to be corrosive. This may cause burns to the gastrointestinal tract if swallowed or to the eye or skin if these areas are contaminated. Piperazine based hallucinogenic stimulants are also smoked by some individuals and there is also the potential for effects similar to inhalation of a corrosive (or acid) gas to manifest.   Tablets are often dissolved and directly injected. Due to the bulk of these tablets being composed of non-water soluble agents such as talc there is a high rate of complications following granuloma formation and vascular obliteration.[4][3] While the lung is a particular target with resultant pulmonary hypertension/cor pulmonale, other organs can be affected. Infection following such abuse is also a concern.[2]   Severity of Poisoning Mild Hallucinogenic Amphetamine Toxicity Moderate Hallucinogenic Amphetamine Toxicity Severe Hallucinogenic Amphetamine Toxicity Euphoria Increased alertness Mydriasis Bruxism (grinding of teeth) Altered mental status Muscle aches Tachycardia Hypertension Agitation Paranoia Hallucinations Diaphoresis Vomiting Abdominal pain Palpitations Chest pain Hyperthermia Hyponatremia Metabolic acidosis Rhabdomyolysis DIC (disseminated intravascular coagulation) Acute renal failure Coma   CHRONIC EFFECTS Hypersensitivity reactions, such as bronchospasm, Stevens-Johnson syndrome, acute hepatitis, thrombocytopenia, hemolytic anemia and angioedema have occurred in individuals taking piperazine therapeutically.[15]   Given their mechanism of action, theoretical concerns following chronic us/abuse of piperazines would be similar to hallucinogenic amphetamines.   Respiratory Injection of ground tablets is a common form of abuse of this drug. As the bulk of the tablet is composed of non-water soluble agents such as talc, chronic abuse can lead to foreign body granuloma formation and vascular obliteration.[3] The lung is the particular target and a range of abnormalities in pulmonary function have been noted;[2] pulmonary hypertension/cor pulmonale may also result and can be fatal.   Tachypnea Dyspnea Pleuritic chest pain Pulmonary function testing abnormalities[2] Obstructive pattern Restrictive pattern Hypoxia when breathing room air Diffusing capacity less than 60% Pulmonary granuloma Pulmonary hypertension Cor pulmonale   Neurologic If large amounts of amphetamine or amphetamine-like compounds are consumed over a long period of time, amphetamine psychosis can develop, which is similar to paranoid schizophrenia. The psychosis is manifested by hallucinations, delusions and paranoia. Symptoms usually disappear within a few weeks after drug use stops.   A range of sequelae have been noted following chronic human abuse including: Choreoathetoid movements[21] Hallucinations Visual Tactile Olfactory Auditory (less common)   A lasting paranoid psychotic reaction may develop,[22] and behavior can become destructive and violent. While the majority of patients recover within 10 days, effects persist for more than 6 months in 10% of cases.[23][24][25] Single re-exposures may produce acute exacerbations even after long periods of abstinence.   Cardiovascular Chronic oral amphetamine abuse has been associated with: Cardiomyopathy Vascular spasm Aortic dissection[26]   Chronic intravenous abuse with:[27] Widespread necrotising angiitis Aneurysm Sacculations Segmental stenosis Thrombosis Hypertension Vascular rupture Pulmonary edema Renal failure   Accidental intra-arterial injection can cause a more localized but severe arterial vasospasm.[28][29] Pulmonary hypertension has occurred after chronic inhalation of an amphetamine.[30]   Injection of crushed and dissolved tablets also risks bacteremia and bacterial endocarditis;[3] vasculitis[31] and intracranial hemorrhage; pulmonary granuloma and pulmonary hypertension with cor pulmonale.[3][4]   Gastrointestinal Anorexia and weight loss Ischemic colitis Other Diffuse hair loss has been associated with long-term amphetamine use.[32][33]   Amphetamine and amphetamine-like compounds have rarely produced aplastic anemia and a fatal pancytopenia after prolonged use.[34]   Infections such as hepatitis B and C and HIV are possible complications of intravenous use of amphetamine and amphetamine-like compounds.[34]   Tolerance Tolerance can develop to the anorectic and various autonomic effects including body temperature, blood pressure, heart rate and respirations.[35]   Withdrawal Syndrome Acute withdrawal may precipitate severe depression and suicidal thoughts. Symptoms usually peak after 2 to 3 days and are seldom directly life-threatening.   Physical symptoms associated with withdrawal are:[36] Abdominal cramps Anxiety Craving Diaphoresis Dyspnea Exhaustion Gastroenteritis Headache Increased appetite Irritability Lethargy Mental confusion Moderate to severe depression Psychotic reaction Restlessness Insomnia   REFERENCES [1] Bye C, Munro-Faure AD, Peck AW, Young PA. A comparison of the effects of 1-benzylpiperazine and dexamphetamine on human performance tests. Eur J Clin Pharmacol 1973 Oct; 6 (3): 163-9. [2] Parran TV Jr, Jasinski DR. Intravenous methylphenidate abuse. Prototype for prescription drug abuse. Arch Intern Med 1991 Apr; 151 (4): 781-3. [3] Hahn HH, Schweid AI, Beaty HN. Complications of injecting dissolved methylphenidate tablets. Arch Intern Med 1969 Jun; 123 (6): 656-9. [4] Lewman LV. Fatal pulmonary hypertension from intravenous injection of methylphenidate (Ritalin) tablets. Hum Pathol 1972 Mar; 3 (1): 67-70. [5] Hartung TK, Schofield E, Short AI, Parr MJ, Henry JA. Hyponatraemic states following 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') ingestion. QJM 2002 Jul; 95 (7): 431-7. [6] Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 8: advanced challenges in resuscitation: section 2: toxicology in ECC. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Circulation 2000 Aug 22; 102 (8 Suppl): I223-8. [7] Chyka PA, Seger D, Krenzelok EP, Vale JA. Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43 (2): 61-87. [8] Fountain JS, Beasley DM. Activated charcoal supercedes ipecac as gastric decontaminant. N Z Med J 1998 Oct 23; 111 (1076): 402-4. [9] Position paper: whole bowel irrigation. J Toxicol Clin Toxicol 2004; 42 (6): 843-54. [10] Tenenbein M. Whole bowel irrigation as a gastrointestinal decontamination procedure after acute poisoning. Med Toxicol Adverse Drug Exp 1988 Mar-Apr; 3 (2): 77-84. [11] Baumann MH, Clark RD, Budzynski AG, Partilla JS, Blough BE, Rothman RB. N-substituted piperazines abused by humans mimic the molecular mechanism of 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy'). Neuropsychopharmacology 2005 Mar; 30 (3): 550-60. [12] Gee P, Richardson S, Woltersdorf W, Moore G. Toxic effects of BZP-based herbal party pills in humans: a prospective study in Christchurch, New Zealand. N Z Med J 2005 Dec 16; 118 (1227): U1784. [13] Wilkins C, Girling M, Sweetsur P, Huckle T, Huakau J. Legal party pill use in New Zealand: prevalence of use, availability, health harms and ‘gateway effects’ of benzylpiperazine (BZP) and triflourophenylmethylpiperazine (TFMPP). Centre for Social and Health Outcomes Research (SHORE) & Te Ropu Whariki, Massey University: 2006. http://www.ndp.govt.nz/legalpartypills/documents/legal-party-pill-use-nz.pdf [14] Theron L, Jansen K, Miles J. Benzylpiperizine-based party pills' impact on the Auckland City Hospital Emergency Department Overdose Database (2002-2004) compared with ecstasy (MDMA or methylene dioxymethamphetamine), gamma hydroxybutyrate (GHB), amphetamines, cocaine, and alcohol. N Z Med J 2007 Feb 16; 120 (1249): U2416. [15] Sweetman SC, editor. Martindale. The complete drug reference. 33rd ed. London: Pharmaceutical Press; 2002. p. 105-6. [16] Klaassen T, Ho Pian KL, Westenberg HG, den Boer JA, van Praag HM. Serotonin syndrome after challenge with the 5-HT agonist meta-chlorophenylpiperazine. Psychiatry Res 1998 Jul 13; 79 (3): 207-12. [17] Alansari M, Hamilton D. Nephrotoxicity of BZP-based herbal party pills: a New Zealand case report. N Z Med J 2006 May 5; 119 (1233): U1959. [18] Austin H, Monasterio E. Acute psychosis following ingestion of 'Rapture'. Australas Psychiatry 2004 Dec; 12 (4): 406-8. [19] Greene SL, Dargan PI, O'connor N, Jones AL, Kerins M. Multiple toxicity from 3,4-methylenedioxymethamphetamine ("ecstasy"). Am J Emerg Med 2003 Mar; 21 (2): 121-4. [20] Campbell H, Cline W, Evans M, Lloyd J, Peck AW. Comparison of the effects of dexamphetamine and 1-benzylpiperazine in former addicts. Eur J Clin Pharmacol 1973 Oct; 6 (3): 170-6. [21] Lundh H, Tunving K. An extrapyramidal choreiform syndrome caused by amphetamine addiction. J Neurol Neurosurg Psychiatry 1981 Aug; 44 (8): 728-30. [22] Sato M. A lasting vulnerability to psychosis in patients with previous methamphetamine psychosis. Ann N Y Acad Sci 1992 Jun 28; 654 (): 160-70. [23] Schaffer CB, Pauli MW. Psychotic reaction caused by proprietary oral diet agents. Am J Psychiatry 1980 Oct; 137 (10): 1256-7. [24] Ando K, Hironaka N, Yanagita T. Psychotic manifestations in amphetamine abuse--experimental study on the mechanism of psychotic recurrence. Psychopharmacol Bull 1986; 22 (3): 763-7. [25] Iwanami A, Kato N, Nakatani Y. P300 in methamphetamine psychosis. Biol Psychiatry 1991 Oct 1; 30 (7): 726-30. [26] Davis GG, Swalwell CI. Acute aortic dissections and ruptured berry aneurysms associated with methamphetamine abuse. J Forensic Sci 1994 Nov; 39 (6): 1481-5. [27] Citron BP, Halpern M, McCarron M, Lundberg GD, McCormick R, Pincus IJ, Tatter D, Haverback BJ. Necrotizing angiitis associated with drug abuse. N Engl J Med 1970 Nov 5; 283 (19): 1003-11. [28] Hawkins LG, Lischer CG, Sweeney M. The main line accidental intra-arterial drug injection. Clin Orthop Relat Res 1973 Jul-Aug; (94): 268-74. [29] Birkhahn HJ, Heifetz M. Accidental intra-arterial injection of amphetamine: an unusual hazard of drug addiction. Case report. Br J Anaesth 1973 Jul; 45 (7): 761-3. [30] Schaiberger PH, Kennedy TC, Miller FC, Gal J, Petty TL. Pulmonary hypertension associated with long-term inhalation of "crank" methamphetamine. Chest 1993 Aug; 104 (2): 614-6. [31] Cahill DW, Knipp H, Mosser J. Intracranial hemorrhage with amphetamine abuse. [Letter] Neurology 1981 Aug; 31 (8): 1058-9. [32] Eckert J, Church RE, Ebling FJ, Munro DS. Hair loss in women. Br J Dermatol 1967 Oct; 79 (10): 543-8. [33] Alexander S. Diffuse alopecia in women. Trans St Johns Hosp Dermatol Soc 1965; 51 (1): 99-102. [34] McEvoy GK, editor. AHFS drug information. Bethesda (MD): American Society of Health-System Pharmacists; 1997. p. 1764-6. [35] Robinson TE, Becker JB. Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res 1986 Jun; 396 (2): 157-98. [36] OSWALD I, THACORE VR. Amphetamine and phenmetrazine addiction. Physiological abnormalities in the abstinence syndrome. Br Med J 1963 Aug 17; 5354 (): 427-31. Do Not Archive. This document is current on day of issue, NZ: 18.May.2012

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