Page 1 Misuse and Abuse of OTC and Prescription Drugs Lisa Booze, PharmD, CSPI lbooze@rx.umaryland.edu This program has been brought to you by PharmCon Misuse and Abuse of OTC and Prescription Drugs Accreditation: Pharmacists: 0798-0000-09-054-L01-P CE Credits: 1.0 contact hour Target Audience: Pharmacists Program Overview: The goal of this program is to supply program participants with up-to-date information on the epidemiology, etiology, and pathophysiology of Parkinson's disease. Participants will also gain knowledge on the symptoms and comorbidities of Parkinson's disease and currently available treatment options. Objectives: Outline the symptoms of Parkinson's disease, including the difference between motor and non-motor symptoms Recognize the possible comorbidities often linked with Parkinson's disease PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education This program has been brought to you by PharmCon Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity. Misuse and Abuse of OTC and Prescription Drugs Speaker: Dr. Lisa Booze is the Clinical Coordinator and a Certified Specialist in Poison Information at the Maryland Poison Center, a division of the University Of Maryland School Of Pharmacy. She is responsible for developing and implementing toxicology continuing education programs for health professionals in Maryland. She is a co-coordinator of the Poison Center Surveillance for Chemical and Bioterrorism and Public Health Program, supported by the Maryland Department of Health and Mental Hygiene. Dr. Booze is a member of the American Association of Poison Control Centers, the American Academy of Clinical Toxicology, and the Expert Consensus Panel that develops Out-of-Hospital Management Guidelines for U.S. poison centers. Speaker Disclosure: Dr Booze has no actual or potential conflicts of interest in relation to this program This program has been brought to you by PharmCon PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity. Why Do People Misuse Drugs? Do not follow directions Do not read ingredients take multiple products with the same ingredient Take drugs not prescribed for them OTC s are perceived safe even in large doses Dependence Abuse
Page 2 Therapeutic Errors 10.2% of calls to U.S. poison centers (255,732 cases) (NPDS 2007) Examples: Inadvertent double-dose Wrong medication taken/given Doses taken too close together Confused units of measure > 1 product with same ingredient OTC Drug Misuse 1/3 of those surveyed reported having misused OTC medications Higher dose 22% Longer course 17% Different purpose 11% 35% of those misusing OTC s reported at least 1 adverse effect Only 68% report reading instructions and warnings all of the time Generation Rx: Pharming Misuse/abuse of Rx and OTC s is equal to or greater than the abuse of illegal drugs 20% of the U.S. population has taken Rx drugs for nonmedical reasons (NIDA 2005) 61% of teens surveyed believe that Rx pain relievers are easier to get than illegal drugs, and 41% believe they are safer than illegal drugs (Partnership for a Drug Free America 2008) 35 30 25 20 15 10 5 0 Lifetime Trial 2008 Teens % of Teens Who Have Ever Tried: Marijuana Rx Drugs Crack/ Cocaine Inhalants Cough Ecstasy Medicine 2008 Partnership Attitude Tracking Study LSD Meth Ketamine Heroin GHB
Page 3 15% of 12 th Graders Have Used Rx Drugs Nonmedically in the Past Year! Any prescription drug 15.4% Opioids 9.2% Amphetamines 7.5% Sedatives 6.2% Tranquilizers 6.2% Where People Obtain Pain Relievers Drug Dealer/Stranger 3.9% More than One Doctor 1.6% One Doctor 19.1% Bought on Internet 0.1% Other 4.9% Free from Friend/Relative 55.7% Monitoring the Future Survey 2007 Bought/Took from Friend/Relative 14.8% 2006 National Survey on Drug Use and Health Complications from Rx and OTC Drug Misuse and Abuse Physical dependence Tolerance to therapeutic effect Inappropriate treatment of medical problems Drug interactions Adverse effects Unintentional overdoses Drug-Related Emergency Department Visits (DAWN 2006) 741,425 ED visits for non-medical use of Rx or OTC pharmaceuticals CNS agents (50%) 247,669 opioids Psychotherapeutic agents (44%) 195,625 benzodiazepines
Page 4 Unintentional Drug Overdose Deaths Unintentional drug poisoning mortality rates increased 68.3% from 1999-2004 19,838 deaths in 2004 2 nd only to motor vehicle accidents Rx opioids deaths increased by 160% from 1999-2004 CDC MMWR 2007:56 (05);93-96. Prescription Drugs Opioids 24% increase in U.S. ED visits due to nonmedical use of opioids (2004-2005, DAWN) Correlation between sales & usage of opioid pain meds and drug overdose death rates (DEA, CDC)
Page 5 Rx Opioid OD 16 year old male and a friend are found unconscious by his parents on his bedroom floor. Another friend witnessed each crushing and snorting a tablet a few hours before. 16 yo: Unresponsive to pain, RR 6, P 76, BP 100/56, pulse ox 90%, lungs clear, skin cool, pale and dry, pupils 2 mm & minimally responsive, ECG: NSR Rx Opioid Abuse EMS gave 0.4 mg naloxone x 2; respirations increased to 12, responded to pain and verbal stimuli. Upon awakening, he admitted to buying Oxycontin from a neighbor who takes it for cancer pain. He crushed and snorted 1 tablet. Friend could not be resuscitated. Oxycodone Drug Abuse Warning Network (DAWN): the number of ER visits involving oxycodone misuse increased about 10-fold between 1996 and 2004. Usually in combination with acetaminophen misuse acetaminophen toxicity OxyContin Controlled release form of oxycodone Wide range of strengths (10 mg-80 mg) Overdoses with as little as 1 tablet
Page 6 Why OxyContin? Chewing or crushing tablets removes extended release mechanism Crushing tablets and snorting powder Water soluble injected Perceived safe: purity and dose are reliable Hydrocodone Most common opioid in ED visits In combination with acetaminophen or ibuprofen (Vicodin, Lortab, Vicoprofen ) APAP toxicity Schedule III or IV fewer barriers to obtain the drug Methadone Analgesic, opioid addiction treatment Long duration of action: 24-36 hours Old drug but overdoses and fatalities increasing dramatically in some areas From 1999-2005, methadone-related deaths increased from 4% of all poisoning deaths to 14% (2004-2005: doubled) 70-80% of methadone-related deaths are unintentional Fentanyl 80-100 times more potent than morphine OD s after chewing fentanyl patches OD s from not removing old patches before applying new patches 2006: illicit fentanyl OD s and deaths Negative opiate screen
Page 7 Buprenorphine Subutex (2mg, 8mg) and Suboxone (with naloxone, 2mg/0.5mg, 8mg/2mg) SL tablets Approved for office-based opioid dependence High affinity for opioid receptor but has a ceiling effect Is diverted and abused by those who are addicted to low doses of opiates To get high or to self-treat withdrawal Buprenorphine If used after withdrawal begins lessens withdrawal symptoms If used soon after or before opioid use withdrawal If on Suboxone and then use heroin no effect from heroin If crushed and used IV withdrawal Less toxic than other opioids in OD s Opioid Toxidrome Lethargy, coma Respiratory depression Constricted pupils Hypotension, bradycardia, hypothermia Naloxone Used diagnostically; reverses CNS and respiratory depression 0.4-2.0 mg IV, IM, intranasal Might require higher doses Short duration: 1.5 hours Infusion for long-acting opioids Can precipitate withdrawal
Page 8 Stimulants Amphetamines Adderall Methylphenidate (Ritalin) Pseudoephedrine, phenylephrine Caffeine Herbal stimulants Stimulant Abuse/Misuse 33% increase in US ED visits due to nonmedical use of stimulants (2004-2005, DAWN) Prescription stimulants are referred to as the new caffeine Stimulant Abuse/Misuse ~ 8% of college students report using prescription stimulants that were not prescribed for them (U of Mich 2005) Reasons: Helps me concentrate 58% Helps increase my alertness 43% Gives me a high 43% Counteracts the effects of other drugs 8% Other reasons 14% Adderall The Drug of Choice 5.9% students reported using Rx stimulants not prescribed for them 75% favor Adderall because Easily accessible Everybody has a friend that is prescribed Adderall Causes fewer emotional ups and downs Believed to work better overall (Pharmacotherapy 2006; 26:1501)
Page 9 Adderall The Drug of Choice Adderall was perceived by 90% of students to be easy to obtain Only behind alcohol (100%) and marijuana (95%) Ritalin - 70% of students Used instead of coffee or energy drinks because they are more effective, last longer, safe, and have less calories. (DEWS Investigates, October 2006) But is Adderall use associated with other drug use? Yes, according to the 2009 National Survey on Drug Use and Health Unintentional Pediatric Stimulant Overdoses Parents giving excessive amounts to children to calm them, toddlers with access to meds PCC in Detroit reported 251 cases of pediatric methylphenidate overdoses in 2 years; 6-11 year olds many therapeutic errors (Arch Ped Adol Med 2000, 154:1199) Stimulants - Mechanism Sympathomimetics Stimulate alpha and beta adrenergic receptors Central nervous system stimulation Stimulate the release of and/or block the reuptake of neurotransmitters (norepinephrine, serotonin, dopamine)
Page 10 Stimulant Toxidrome Agitation, hallucinations, paranoia Tremor, seizures Tachycardia, hypertension, chest pain, MI Hyperthermia Warm skin, diaphoresis Dilated pupils CV collapse Hemorrhagic stroke OTC Drugs Acetaminophen Found in more than 600 OTC & Rx products Take > 1 product with acetaminophen Take too much, too often Chronic Acetaminophen Case A 62 year old man with chronic alcohol abuse and arthritis is admitted to the hospital with a history of a recent increase in alcohol consumption and chronic ingestion of 6-8 g per day of acetaminophen for about a week.
Page 11 Acetaminophen Metabolism Chronic Acetaminophen Case Initial laboratory values: bilirubin 3.6 mg/dl (nl 0.2-1), AST 2870 IU/L (nl 1-30), ALT 2300 IU/L (nl 1-30) and INR 3.0 The plasma acetaminophen level on admission was 73 mcg/ml AST/ALT increased to >7000 Recovered in 7 days with antidotal treatment and supportive care Acetaminophen CYP450 NAPQI 5-15% Cellular toxicity Glutathione 5% 40-67% Unchanged APAP APAP glucuronide 20-46% APAP sulfate Cysteine, mercaptate conjugates Acetaminophen Acute toxic dose children > 200 mg/kg adults > 10 g Toxicity with chronic use > 100-200 mg/kg/day in children > 4-10 g/day in adults Risk factors: chronic alcoholism, enzymeinducing drugs, malnutrition, liver disease Acetaminophen Liver Failure Cases On The Rise 662 acute liver failure patients at 22 transplant centers from 1998-2003 275 (42%) from APAP 1998: 28% due to APAP 2003: 51% due to APAP Larson, et al. Hepatology 2005; 42(6):1364
Page 12 Acetaminophen Liver Failure Cases On The Rise Phase I: up to 24 hours (if acute) 44% of APAP cases were suicide attempts 48% were unintentional OD s 63% of unintentional OD s were with APAP/narcotic combinations 38% took > 2 APAP products Larson, et al. Hepatology 2005; 42(6):1364 Nausea Vomiting Malaise Lethargy Chronic overdoses might not exhibit GI effects Phase II: up to 4 days GI symptoms subside RUQ pain Elevated liver function tests Prolonged INR PHASE III: 3-5 days markedly elevated liver enzymes (>10,000 U/L), bilirubin and INR jaundice hypoglycemia coagulation defects metabolic acidosis encephalopathy renal failure death
Page 13 PHASE IV: 4 days - 2 weeks resolution of hepatic and renal dysfunction no permanent sequelae Assessment & Treatment Plasma levels, history Activated Charcoal for recent acute OD s Acetylcysteine Liver Transplant Mechanism of Action of Acetylcysteine EARLY glutathione precursor glutathione substitute increases sulfate conjugation LATE improves microcirculatory blood flow scavenges oxygen free radicals Acetylcysteine Oral or intravenous administration Delay decreases effectiveness Most effective if initiated within 8-10 hours of overdose Initiate based on history, toxic APAP level or abnormal LFT s
Page 14 Oral N-Acetylcysteine 140 mg/kg po load; 70 mg/kg po q4h X 17 doses (72 hours total) Some patients may be treated with a shorter course (36 hours) Adverse effects: nausea, vomiting Intravenous Acetylcysteine (Acetadote ) 300 mg/kg, divided in 3 doses, over 21 hours total Longer infusion sometimes required, especially for chronic OD s or late presenters Adverse effects: flushing, urticaria, angioedema, respiratory distress, hypotension Cough & Cold Meds Antihistamines H 1 receptor antagonists chlorpheniramine, brompheniramine, diphenhydramine, doxylamine, loratadine Older antihistamines bind to peripheral and central H 1 receptors, and cholinergic, - and -adrenergic receptor sites 2 nd generation are peripherally selective
Page 15 Diphenhydramine Misuse A 45 year old is questioned by the pharmacist when he was noticed buying Unisom SleepGels weekly. He revealed a 6 month history of using Unisom SleepGels to relieve aggressive feelings... up to 60 capsules (3000 mg) daily. He reported a pleasant feeling in his head & abdomen, a calming effect, staring into space more often, blurred vision and dry mouth. Anticholinergic Toxidrome Mad as a hatter, hot as a hare, dry as a bone, red as a beet, blind as a bat Confusion, hallucinations, coma Hyperthermia Dry, flushed, warm skin Dilated pupils Hypertension, tachycardia Urinary retention Diphenhydramine Used in excessive amounts for sleep or as a sedative Abused dose (hallucinations): 150-700 mg Acute toxic dose: >7.5 mg/kg (or > 300 mg) Sodium channel blockade QRS, QT prolongation Cough Medicine Abuse A 16 year old girl was found sleeping on the lawn outside of her home when her parents came home from work. When awakened, she was confused and hallucinating. She admitted to ingesting 20 Triple C tablets after school to get high. HR 150, BP 170/100, RR 18, pupils are 5 mm & reactive with horizontal nystagmus.
Page 16 Dextromethorphan Semi-synthetic opioid Abuse or misuse by teens increased >300% from 2000 to 2003 (U.S. poison centers) DXM, dex, C-C-C, Robo, Red Devils, Triple C > 80% cases are with Coricidin products Abused dose = > 200-400 mg (range of 100-1200 mg) Dextromethorphan Effects are similar to phencyclidine (PCP) Produces hallucinations, CNS depression, seizures Hypertension, tachycardia, agitation, ataxia often seen Treatment Naloxone?? What Pharmacists Can Do Provide clear advice on how to take medications Do not take multiple products with the same ingredient Do not take more than is prescribed; always read labels OTC s are generally not meant to be taken chronically What Pharmacists Can Do Counsel patients on how to safeguard their medicines at home. Educate patients on how to dispose of their meds. Watch for escalating use of OTC or Rx drugs. Look for fake or altered prescriptions, prescriptions from multiple doctors (doctor shopping), an increase in sales of cough and cold meds. Be wary of reports of missing drugs. Control access to some OTC s.
Page 17 Notes Notes Notes