Devon A. Sherwood, PharmD, BCPP Assistant Professor University of New England College of Pharmacy Describe the epidemiology and overall impact of medications commonly abused. Explain the pathophysiology of abuse and dependence for commonly abused drugs. List common over-the-counter (OTC) and prescription (Rx) drugs of abuse. Identify side effect profiles and withdrawal symptoms of OTC and Rx drugs of abuse. Review available options for detoxification therapy and abstinence maintenance regarding common drugs of abuse. Which of the following increases the risk of abuse potential? A. Rapid absorption B. Potency of drug C. Lipophilicity and distribution leads to abrupt offset D. Short-half life / duration of effect E. All of the above Which of the following should not be recommended for opiate abstinence? A. Clonidine B. Methadone C. Suboxone D. Naltrexone Laxative Abuse: True or False? Effective for weight control True False Physical dependency does not occur True False Long term abuse may contribute to colon cancer True False Which of the following herbals when abused is known to cause hallucinations? A. Ma-huang B. Kratom C. Nutmeg D. Betel nut E. Kava Which of the following herbals has effects on mu and delta receptors, causing analgesic and addictive properties similar to opiates? A. Salvia B. Morning Glory C. Kratom D. Yohimbine E. Khat In 2010, 23.1 million Americans aged 12 or older (9.1% of US population) needed specialized treatment for a substance abuse problem, but only 2.6 million (11.2%) received it. It is estimated 22.6 million Americans aged 12 or older (8.9%) were current (past month) illicit drug users Includes marijuana/hashish, cocaine/crack, heroin, hallucinogens, inhalants or prescription-type psychotherapeutics used nonmedically. 1.) National Survey of Drug Use and Health, SAMHSA, 2013 2.) National Survey on Drug Use and Health 2013; National Institute on Drug Abuse (NIDA), National Institute of Health (NIH) 3.) Monitoring the Future; University of Michigan - http://www.monitoringthefuture.org/ First Specific Drug Associated with Initiation of Illicit Drug Use among Past Year Illicit Drug Initiates Aged 12 or older: 2010 Results from the 2010 National Survey on Drug Use and Health, US Department of Health and Human Services, 2012; http://oas.samhsa.gov/NSDUH/2k10NSDUH/2k 10Results.htm#Fig5-1 The incidence of nonmedical usage of psychotropic drugs has been increasing over the past 10 years NSDUH Report from April 11, 2013 identified an increase in nonmedical prescription drug use from the 2011 survey: 15.7 million (6.3% of US population) use in last year 6.7 million (2.7% US population) use in last month 1.) National Survey of Drug Use and Health, SAMHSA, 2012 2.) National Survey on Drug Use and Health 2010; National Institute on Drug Abuse (NIDA), National Institute of Health (NIH) In 2010, about 7 million persons (2.7% of US population) were current users in the past month of psychotherapeutic drugs taken nonmedically 5.1 million = pain relievers 2.2 million = tranquilizers 1.1 million = stimulants 0.4 million = sedatives. National Survey on Drug Use and Health 2010; National Institute on Drug Abuse (NIDA), National Institute of Health (NIH) NIDA-NIH: http://www.nida.nih.gov/tib/prescription.html Monitoring the Future Study (NIH grant in 2011) Drug Name 8th grade 10th grade 12th grade Marijuana/Hashish 12.5% 28.8% 36.4% Vicodin® 2.1% 5.9% 8.1% Amphetamines 3.5% 6.6% 8.2% Tranquilizers 2.0% 4.5% 5.6% OxyContin® 1.8% 3.9% 4.9% OTC Cough/Cold 2.7% 5.5% 5.3% Salvia 1.6% 3.9% 5.9% Any prescription drug abused in 12th grade = 15.2% 1.) National Survey on Drug Use and Health 2011; National Institute on Drug Abuse (NIDA), National Institute of Health (NIH) 2.) Monitoring the Future; University of Michigan - http://www.monitoringthefuture.org/ Substance Use Disorders: Dependence Abuse Substance Induced Disorders Intoxication Withdrawal Polysubstance Dependance A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by one or more of the following (one symptom in 12 months): 1.) Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home 2.) Recurrent substance use in physically hazardous situations 3.) Recurrent substance-related legal problems 4.) Continued substance use despite having persistant or recurrent social or interpersonal problems caused or exacerbated by the effects of substance abuse A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by three or more of the following, occurring at any time in the same 12-month period: 1.) Tolerance: A need for markedly increased amounts of the substance to achieve intoxication or desired effect, or markedly diminished effect with continued use of the same amount of the substance 2.) Withdrawal: As manifested by the characteristic withdrawal syndrome for the substance, or the same (or closely related) substance is taken to relieve or avoid withdrawal symptoms. 3.) Substance is taken in larger amounts or over a longer period than was intended 4.) Persistent desire or unsuccessful efforts to cut down or control substance use 5.) A great deal of time is spent in activities necessary to obtain the substance 6.) Important social, occupational, or recreational activities are given up or reduced because of substance use. 7.) The substance use continues despite knowledge of having a persistent or recurrent physical or psychological problem that is likely caused or exacerbated by the substance. Ineffective parenting Chaotic home environment Lack of mutual attachments/nurturing Inappropriate behavior in the classroom Failure in school performance Poor social coping skills Affiliations with deviant peers Perceptions of approval of drug-using behaviors in the school, peer, and community environments www.drugabuse.gov Strong family bonds Parental monitoring Parental involvement Success in school performance Prosocial institutions (ie. family, school, religious organizations) Conventional norms about drug use http://www.yanksarecoming.com/wpcontent/uploads/2009/12/BubbleBoy1.jpg www.drugabuse.gov DRUG ADDICTION IS A COMPLEX ILLNESS www.drugabuse.gov www.drugabuse.gov www.drugabuse.gov www.drugabuse.gov www.drugabuse.gov www.drugabuse.gov Opiates Anxiolytics / sedatives Benzodiazapines Barbiturates Non-benzodiazepines Stimulants Studies have shown properly using opiates exactly as prescribed is safe, manages pain effectively, and has a low chance of addiction. Taken by persons not prescribed the medication, using more than recommended or using an alternate route than prescribed (snorting, smoking or injecting) carries a high risk of addiction and/or overdosage NIDA Infofacts: Prescription and Over the Counter Medications; http://www.nida.nih.gov/infofacts/PainMed.html NIDA-NIH: http://www.nida.nih.gov/tib/prescription.html Opiate enters the brain and influences a range of mechanisms Slows the heart beat Constricts the pupils Mu, delta & kappa agonists Boosts the activity of dopamine Pleasure circuit Blocks pain Decreases breathing Sometimes causing breathing cessation Potentially death Pharmacotherapy: A Pathophysiologic Approach General effects Sedation Anxiety Lack of interest Slurred speech Withdrawal “Flu-like” symptoms: Runny nose Tear secretion Yawning Sneezing Nausea Vomiting Diarrhea Mydriasis One of the most commonly abused prescription drugs 80mg Oxycontin tablet = 16 Percocet tablets Propagated by illicit transactions, theft, and overprescribing (ie. “Pain clinics”) Sustained-release delivery is thwarted by cracking, chewing, smoking and injecting http://www.prescriptionbuyers.com/freeboard/ubbthreads.php/topics/1045193/NEW_OXYCONTIN_MARKINGS_SEPT_20. Accessed April 1, 2012. Physical/Psychological addiction Injection-related problems Infectious diseases HIV / AIDS Hepatitis B and C Collapsed veins Bacterial infections Abscesses Physical injuries Detoxification Taper off opiate + opiate substitute Clonidine (Catapres®) Buprenorphine Formulations (Buprenex®, Suboxone®) Maintenance of Opiate Abstinence Methadone Buprenorphine/Naloxone Naltrexone Attenuates the sympathetic response to withdrawal Causes a rapid and significant decrease in withdrawal signs and symptoms Usual oral dose is 0.1-0.2mg Q6h PO Watch BP! Use methadone as an opiate substitute Medication is taken orally Suppresses withdrawal for 24 to 36 hours and relieves cravings Detox: 15-40 mg/day not to exceed 21 days Maintenance: 20-120 mg/day Physicians must be credentialed to do office-based detoxification No more than 30 patients at a time for the first year licensed, then can petition for up to 100 patients per the DATA 2000 waiver Buprenorphine/Naloxone (Suboxone®) approved in October 2002 Use buprenorphine monotherapy only in pregnancy http://samhsa.gov: Buprenorphine Clinical Guide A mixed opiate agonist / antagonist Ceiling effect if dosed too high Safer for respiratory depression Suboxone® is a 4:1 ratio of buprenorphine to naloxone (if taken po only!!) Usual dose 4-24mg sublingually daily Safe and effective for office-based detox 16mg buprenorphine daily Up to 21% avoided outside opiates vs. 5.8% on placebo (p<0.001) Retention rates in programs < methadone High dose buprenorphine may suppress heroin use > methadone Doses > 8mg/d have best success QOD dosing also successful NEJM 2003;349:949-958. / Cochrane Database of Systematic Reviews 2003;(2):CD002207. / Addiction 2003;98(4):441-452. Competitive antagonists at opioid receptor sites Not to be used during active withdrawal Studies with long acting depot form Vivitrol® in Russia demonstrated extraordinary outcomes regarding drug abstinance, treatment retention, and decreased cravings Must wait 7-14 days or withdrawal will occur Reduces opiate cravings Increases risk for unintentional overdoses Studies show a reduction in (re)incarcerations when used with behavior therapy Compliance and motivation are major factors 32-58% successful in compliant patients Abstinence rates diminish over time Cochrane Database of Systematic Reviews 2003;(2):CD001333. Drug & Alcohol Dependence 1997;47(2):77-86. / Drugs 1988;35(3):192-213. Which of the following should not be recommended for opiate abstinence? A. Clonidine B. Methadone C. Suboxone D. Naltrexone Short acting opiate receptor blocker Not used for abstinence Counteracts the effects of opiods and can be used to treat overdose Dosing for overdose of opiate: 0.4 – 2mg IV, repeat every 2 to 3 min prn No response after 10mg = reconsider diagnosis! May administer IM or SUBQ if IV route is unavailable Micromedex Healthcare Series: Drugdex® Drug Point Hypnotic Drugs: Dose-response relationships Respiratory Depression BARBS Coma/ Anesthesia BDZs Ataxia Sedation Anticonvulsant Anxiolytic DOSE Katzung BG. Basic & Clinical Pharmacology. 10th ed. New York, NY: McGraw Hill; 2007 Goodman LS, Gilman A, Brunton LL. Goodman & Gilman's Manual of Pharmacology and Therapeutics. 11th ed. New York, NY : McGraw Hill; 2008. Enhance GABA GABA decreases brain activity of NT’s = drowsiness or calming effect Prescribed to treat anxiety, acute stress reactions, panic attacks, convulsions, and sleep disorders. Short-term relief from sleep problems due to tolerance and addiction potential Rapid absorption leads to quick onset Potency of drug Lipophilicity and distribution leads to abrupt offset Short-half life / duration of effect Intradose withdrawal Which of the following increase the risk of abuse potential? A. Rapid absorption B. Potency of drug C. Lipophilicity and distribution leads to abrupt offset D. Short-half life / duration of effect E. All of the above Agitation Increased anxiety Loss of appetite Diaphoresis Nausea Fatigue and lethargy Dizziness Psychosis Insomnia Seizures Poor concentration Headaches Increased acuity of senses Paresthesias Photophobia Dysphoria Confusion Based on: Drug variables Higher doses Longer duration of BZD treatment Drug half-life Rapid tapering Clinical variables Higher pre-taper anxiety and depression More personality pathology ie. neuroticism, dependency Panic disorder diagnosis History of recreational alcohol or drug abuse Inpatient versus outpatient treatment Detoxification is similar to alcohol treatment Length of treatment may be longer because onset of withdrawal symptoms may be delayed up to 7 days after discontinuing the drug After the acute withdrawal phase, minor abstinence symptoms may last for weeks Anxiety, insomnia, irritability, sensitivity to light & sound, and muscle spasms Success best if CBT is adjunctive Am J Psychiatry 2004;161:332-342. In case of overdosage, flumazenil (Romazicon®) can be used: 0.2mg IV over 30min, increase to 0.3 if no effect after another 30 min, Further doses of 0.5mg over 30min up to max of 3mg if no response, or max of 5mg if partial reponse Micromedex Healthcare Series: Drugdex® Drug Point Cocaine Methamphetamine Dextroamphetamine (Dexedrine®) Methylphenidate (Concerta®, Methylin®, Ritalin®) Amphetamines (Adderall®) Modafinil (Provigil®) OTC: Watch for ephedrine-related compounds! Ma-huang, psuedoephedrine Mechanism of Action: Increase the release and block reabsorption of dopamine Dopamine is involved in reward, motivation, experiencing pleasure, and motor function. Levels too high in the brain reward center = euphoria and add to addiction potential. The more rapid dopamine is released to reward centers of the brain, it higher chance of stimulant abuse. www.drugabuse.gov www.drugabuse.gov Poll from Nature in the April 2008 newsletter revealed 20% of researchers utilized a CPEM 1400 people from over 60 countries responded Nature 452, 674-675 (2008) Taken repeatedly or in high doses, stimulants can cause: Anxiety Paranoia Dangerously high body temperatures Irregular heartbeat Seizures Depression Common OTC & Herbal Drugs of Abuse Dextromethorphan Antihistamines: Diphenhydramine Dimenhydrinate Laxatives Synthetic Cannabinoids: K2, Spice, others… “Opiate Like” Compound: Kratom Bath Salts Dextromethorphan Synthetic opioid dextro-isomer of levorphanol MOA: Decreases sensitivity of cough receptors & interrupts cough impulse transmission Indication: Antitussive/Cough suppressant, T ½ = 2-4 hrs; renal excretion Popular products of abuse: Coricidin, Corcidin C&C, Robitussin DM Street names: Dex, DXM, CCC, Triple C, Robo, Skittles, Poor Man’s PCP Dextromethorphan Withdrawal symptoms: Dysphoria, intense cravings Tolerance develops with continued use Max dose = 120mg/day 100-200mg 200-400mg mild stimulant effect with hyperexcitability mild hallucinations, slurred speech and memory impairment 300-600mg ‘out-of-body’ state with altered senses and nystagmus full dissociative phase 600-1500mg Dextromethorphan Acute overdose: CNS depression, coma, hypotension, tachycardia and respiratory distress are noted Polyingestion increases risk of cardiorespiratory complications and can be fatal Use supportive measures Dehydration fluids Hyperthermia Cooling/Sedatives Agitation BZD Chronic (over 2-4 weeks): toxic syndrome (“bromism”) characterized by irritability, headache, confusion, anorexia, slurred speech and lethargy Timeline of Dextromethorphan (DM) abuse as reported by new DAWN-ED: National Estimates of Non-Medical Dextromethorphan ED Visits . Emergency Department Visits 12000 10000 8000 6000 ED Visits 4000 2000 0 2004 2005 2006 2007 2008 Prevalence of Dextromethorphan abuse True prevalence of DM misuse is unknown NSDUH suggests it is most common in 12 – 20yo Since 2006, SAMHSA's NSDUH reported a 17.2% decrease in usage in 2011. The NSDUH Report - - Misuse of Over-the-Counter Cough and Cold Medications among Persons Aged 12 to 25 Trends in Annual use of OTC Cough & Cold meds among 8th, 10th, and 12th Graders 2006 2007 2008 2009 2010 2011 2012 8th grade 4.2 4.0 3.6 3.8 3.2 2.7 3.0 10th grade 12th grade 5.3 5.4 5.3 6.0 5.1 5.5 4.7 6.9 5.8 5.5 5.9 6.6 5.3 5.6 Monitoring the Future 2012 Executive Report 2009 Annual prevalence of use of OTC Cold & Cough meds among 8th, 10th, and 12th Graders: Racial and Gender comparisons OTC Cold & Cough Medicines 8th 10th 12th Total 4 6 6 Male Female 3.7 3.8 5.9 6.0 8.1 * 4.1 White Black Hispanic 3.7 2.7 3.6 6.4 2.1 5.5 5.9 4.5 6.0 Source. The Monitoring the Future study, the University of Michigan, 2009 Anti-histamine abuse Benadryl (Diphenhydramine, DP) H1 receptor antagonist Indication: Allergic rhinitis, Insomnia Dramamine (Dimenhydrinate, DMH) = diphenhydramine + 8-chlorotheophylline H1 receptor antagonist + methylxanthine (55% / 45%) Indication: Motion sickness Anti-histamine abuse Abuse potential due to Hallucinogenic/Euphoric Sedative/Anxiolytic properties Risk factors History of illicit drug use History of psychiatric disorder Anti-histamine abuse Acute overdose 750-1250 mg DMH ~ 800mg = hallucinations, tactile and visual sensations, catatonic stupor ~1250mg = confusion, violence (750mg DMH = 400mg DP) Illicit drug users Chronic use Tolerance develops overtime Withdrawal: Depressed affect, lethargy, irritability, loss of appetite and amnesia. agitation, hostility, clumsiness, nausea and craving Psychiatric patients **Treatment is supportive and symptomatic; there is no specific antidote** Laxative abuse Presentation & Diagnosis: High clinical suspicion Objective evidence should be collected Self-report may be difficult Signs melanosis coli serum electrolytes (↓ K+) fecal electrolytes (↑ Mg) Symptoms alternating diarrhea/constipation GI cramping GI pain Laxative Abuse Long term complications: Internal organ damage Cathartic colon or megacolon = Stretched or “lazy” colon, colon infection Irritable Bowel Syndrome (IBS) Liver damage (rare) May increase risk of colon cancer Prevalence of laxative abuse in the general population and adolescents Lifetime occurrence of laxative abuse: 4.18% (general population) Lifetime occurrence of laxative abuse: 14.94% (bulimia nervosa) 3-fold increase Ranges from 18% - 75% Prevalence of laxative abuse in adolescent females: 3.2 - 5.5% (high school) 0 - 1.8% (middle school, 13–15 yoa) 32% (anorexia nervosa) Laxative Abuse: True or False? Effective for weight control True False Physical dependency does not occur True False Long term abuse may contribute to colon cancer True False Percentage of 12th Graders in Each Category of an Illicit Drug Use Index Who Have Tried Various Over-the-Counter Stimulants, 2007 Source. The Monitoring the Future study, the University of Michigan, 2007 Nonprescription Diet Pills: Trends in Lifetime and Annual Prevalence of Use by Gender and Race in Grade 12 Nonprescription Diet Pills Prevalence of use 2006 2007 Total 13.7 10.4 Males 7.0 5.1 Females 18.3 14.3 Total 9.4 6.7 Males 5.7 3.4 Females 12.5 9.2 White 10.7 9.3 Black 4.2 3.2 Hispanic 7.7 4.9 Lifetime Annual Annual Level of significance of difference between the two most recent classes: s = .05, ss = .01, sss = .001 Source. The Monitoring the Future study, the University of Michigan, 2007 Stimulants/Diet pills Phenylpropanolamine (Rx only in US) Ephedrine – Watch for herbal supplements! Ma-huang still available Pseudoephedrine Caffeinated products Caffeine Stimulants/Diet pills Xanthine (adenosine receptor antagonism) Found in diet pills, stay-awake pills, energy drinks, etc Guarana (herbal product) Alcoholic energy drinks: “Four loko” teen/college student deaths No longer has caffeine, others available Bath Salts: Not part of your spa package! Concentrated version of the stimulant in Khat Methendioxypyrovalerone (MDPV), mephedrone, & methylone are the most common ingredients Often found in plant foods or insect repellant http://womenscenter.missouri.edu/wpcontent/uploads/2010/11/National+Bubble+Bath+D Recent News: Bath Salts Most commonly known as Bliss, Ivory Wave, Purple Wave & Vanilla Sky Others: Blue Silk, Bolivian Bath, Cloud Nine, Drone, Energy-1, Lunar Wave, Meow Meow, Ocean Burst, Pure Ivory, Red Dove, Snow Leopard, Stardust, White Dove, White Knight, White Lightning October 1, 2011: DEA made possession and sale of the 3 common ingredients illegal temporarily illegal Calls to Poison Control Centers for Human Exposure to Bath Salts, 2010 to January 2012 Maine Law – LD 1589 The bill made the following changes to state law: Possession increased from a civil violation to a Class D misdemeanor crime, punishable by up to a year in jail. Unlawful trafficking of the drug increased from a Class E misdemeanor to a Class B felony, punishable by up to 10 years in prison. Aggravated trafficking increased from a Class C to a Class A felony, with a maximum penalty of 25 years. Unlawful furnishing and aggravated furnishing increased from Class E and D misdemeanors respectively to Class C and B felonies. Maine County Statistics Common Adverse Effects of Bath Salts Acute: Tachycardia Hypertension Hyperthermia Vasoconstriction Muscle spasm/tremor Seizures Rhabdomylysis Behavioral/Psychiatric: Severe Panic Attacks Psychosis (hallucinations & delusions) Paranoia Agitation Insomnia Irritability Violent Behavior Suicides are reported Herbal Drugs of Abuse - Hallucinogens Common Name/Active Ingredient Salvia divinorum - Salvinorin A Morning Glory - LSA (lysergic acid) Hawaiian baby woodrose - LSA Nutmeg - Myristicin, elemicin Peyote - Mescaline Ayahuasca - DMT (N, N-dimethyltryptamine) Jimsonweed - Atropine, scopolamine, hyoscopamine Anticholinergic effects Absinthe – Thujone Known for its euphoric effects Herbal Drugs of Abuse – Stimulants, etc. Common Name/Active Ingredient Stimulants: Ma-huang - Ephedra alkaloids Khat - Cathinone, cathine Betel nut - Arecoline Yohimbine - Yohimbine Guarana – Caffeine, xanthine alkaloids Miscellaneous effects: Kava – Kavalactones Anxiolytic Cloves – Eugenol, nicotine Analgesic, stimulant Kratom – Mitragynine, 7-hydroxymitragynine Analgesic, euphoric properties Which of the following herbals when abused is known to cause hallucinations? A. Ma-huang B. Kratom C. Nutmeg D. Betel nut E. Kava Notable Herbal Products of Abuse Salvia divinorum Active compound: Salvinorin A Potent hallucinogen Rapid onset and duration Overdose and dependence True risk is unknown Illegal in most states Maine prohibited sale to minors < 18yo Synthetic cannabinoids Most commonly known as K2 or Spice Other names: Bliss, Black Mamba, Bombay Blue, Blaze, Genie, Spice, Zohai, JWH -018, -073, -250, Yucatan Fire, Skunk, Moon Rocks March 1, 2011: DEA published a final order in the Federal Register temporarily placing five synthetic cannabinoids as Schedule I in the CSA Calls Received by U.S. Poison Control Centers for Human Exposure to Synthetic Marijuana, 2010 to July 2012 The number of calls in 2011 were more than double that in 2010 6,959 3,821 2,906 SOURCE: American Association of Poison Control Centers, Spice Data, updated August 2012. Kratom Mitragyna speciosa korthals species Botanical Classification: In the Rubiaciae family (Similar to the cofffee plant) Opiate like substance with analgesic properties MOA: Acts on mu-opiod receptor Used in Southeast Asia for opiate withdrawal symptoms, constipation, anxiolytic Which of the following herbals has effects on mu and delta receptors, causing analgesic and addictive properties similar to opiates? A. Salvia B. Morning Glory C. Kratom D. Yohimbine E. Khat Treatment = less expensive than alternatives Not treating or incarcerating = greater costs Ie.) avg methadone maintenance x 1 year = $4,700 per person avg imprisonment costs = $18,400 per person Every $1 yields up to $7 in reduced crime related costs Savings can exceed costs 12:1 when healthcare costs are included Reduced interpersonal conflicts Increased workplace productivity Fewer drug-related accidents www.drugabuse.gov NIDA 2012: http://www.drugabuse.gov/publications/topics-in-brief/medications-development-nida www.drugabuse.gov