11/11/04SUBSTANCE ABUSE: Opiates/Hallucinogens/ Gamma-hydroxybutyrate(GHB)/Inhalant AbuseJohn Gualtieri, PharmDClinical Assistant ProfessorDept. of Experimental and Clinical PharmacologyCollege of Pharmacy, University of MinnesotaOBJECTIVES1. Describe the pharmacology and pathophysiology of opiate drugs, hallucinogens and GHB.2. Be able to recognize the clinical manifestations of opiate, hallucinogen and GHB intoxication.3. Be familiar with the some of the street drug names associated with the opiates, hallucinogens and GHB.4. Identify potential pharmacotherapeutic and non-pharmacotherapeutic interventions used for the treatment ofthe opiate, hallucinogen and GHB intoxication.5. Identify potential pharmacotherapeutic interventions used for the treatment of the withdrawal from opiates.6. Understand the prevalence of inhalant abuse among young adolescents as well as the volatile substancescommonly abused.7. Describe the pharmacology and pathophysiology of some of the more common chemicals used by the volatilesubstance abuser.8. Be able to recognize the clinical manifestations of intoxication with some of the more common chemicals usedby the volatile substance abuser.OPIATESI. AVAILABLE FORMS• Natural opium, morphine, and codeine are derived from the Poppy Plant (Papaver somniferum). This was theflowering plant that knocked out Dorothy and the Gang as they were running across the field of flowers toward theWizard’s castle in the movie The Wizard of Oz.CHEMICAL NAMESSTREET DRUG NAMES OF NARCOTICSNatural OpiatesMorphine, codeineOpium; HashishSemisyntheticHeroin“Dope”, “Skag”, “Lady Jane”, “Speedball”, “Smack”, “Heaven”OxycodonePercodanHydromorphoneDilaudidSyntheticMeperidineDemerolMethadoneDolophineDiphenoxylateLomotilFentanylSublimaze, “China White”, “Tango and Cash”PropoxypheneDarvon, Darvocet (mixed with acetaminophen)II. SOCIAL IMPACTIt is estimated that 4 to 6.5 million Americans have recently abused narcotics and 2.5 million citizens have used heroinat some time in their lives. Heroin-related emergency room visits also continue to increase annually. Unlike thestimulants, opiates induce a profound physical dependence in addition to a strong psychological dependence. Thephysical dependence in the regular user and subsequent withdrawal syndrome generally requires more extensive21/11/04medical intervention and makes drug rehabilitation much more difficult and costly. John Belushi, a famousactor/comedian, reportedly died following the injection of a “speedball” which is a combination of cocaine and heroin.Kurt Cobain, the leader of the famous rock-band Nirvana, committed suicide following his long battle with depressionand heroin addiction.III. PHARMACOLOGY• Opiate agents exert their effects through the mu, kappa, sigma, delta, and epsilon endorphin receptors which in anaive person produce such classic effects as analgesia, sedation, euphoria, constipation (decreased bowelmotility), and miosis. With chronic use, receptor tolerance develops leading to the escalation of doses to achievethe same desired effect and physical dependence.IV. TOXICOLOGICAL EFFECTSClassic Opiate Toxicity• Consists primarily of CNS depression, respiratory depression, cardiovascular instability (i.e., hypotension), miosis,diminished bowel motility (constipation).Seizures• Seizure may occur with certain compounds [e.g., meperidine (Demerol), propoxyphene (Darvon)]. Patientschronically using meperidine, especially those with renal insufficiency, are at risk for developing normeperidinetoxicity. Normeperidine toxicity is associated with tremor, myoclonus, or seizures. This type of neurotoxicity isnot reversed with naloxone.• Tramadol overdose has also been associated with the development of seizures. Naloxone administration isineffective for tramadol-induced seizures and may even increase the risk of seizure development.Serotonergic Excess (‘Serotonin Syndrome’)• Meperidine, dextromethorphan, and tramadol all possess some serotonergic activity and all have been associatedwith the development of serotonin syndrome when taken with monamine oxidase inhibitors. Serotonin syndromeis characterized by the development of intense muscle rigidity, tremors, severe hyperthermia, altered mental status,and death. It is also confused with or misdiagnosed as Neuroleptic Malignant Syndrome (NMS).• Treatment is essentially supportive with emphasis placed on applying aggressive cooling measures and musclerelaxants to keep the body temperature down.Cardiac Arrhythmias• Intraventricular conduction delays, heart block, bigeminy, ventricular arrhythmia and non-specific ST-T waveabnormalities may result from propoxyphene overdose. Norpropoxyphene, a metabolite of propoxyphene isresponsible for this cardiotoxicity which cannot be reversed with naloxone. The norpropoxyphene blocks fastsodium channels of the myocardium producing a membrane stabilizing or ‘quinidine-like’effect similar to cocaineand the cyclic antidepressants.• Aggressive intravenous sodium bicarbonate therapy in conjunction with lidocaine therapy should be employed withevidence of propoxyphene-induced cardiotoxicity.Anticholinergic Toxicity• Lomotil is a commonly used antidiarrheal preparation that contains diphenoxylate(an opiate) and atropine.Excessive dosing of Lomotil, especially in children, may lead to severe opiate intoxication due to thediphenoxylate and anticholinergic poisoning due to the atropine.Pulmonary Edema• Noncardiogenic pulmonary edema may occur, often after resuscitation and administration of the opiate antagonist,naloxone. The exact etiology of this complication is not well known.31/11/04Miscellaneous• Abuse of dextromethorphan (DMX) in high doses (4 ounces of DM cough syrup) may produce an abuser ‘high’similar to phencyclidine. Movement disorders, phencyclidine-like psychosis, CNS depression and respiratorydepression have been associated with severe overdoses of dextromethorphan. Naloxone appears to reverse the CNSand respiratory depression.V. TREATMENT AND MONITORING• Consists primarily of supportive measures in combination with naloxone (Narcan), an opiate receptorantagonist.A. Basic and Advanced Life Support1. ABCs (airway, breathing, and circulation)2. Establish IV access3. Oxygen and assisted or mechanical ventilation as required.B. Oral Ingestion1. AC/C2. Serious opiate toxicity from ingestion is uncommon.C. Initial Monitoring