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Drug Abuse and Misuse Carl B. Goodman, Ph.D. Professor of Pharmacology College of Pharmacy & Pharmaceutical Sciences Florida A&M University 308E FSH-SRC Tallahassee, FL 32307 850-599-3128 [email protected] The Drug Problem 60 million people in the USA alone are addicted to alcohol, nicotine or both; 5.5 million are addicted to illegal drugs and millions to legal pharmaceuticals. It is important to note at the outset that the legal status of a drug says nothing about its safety or the health risks associated with it…for the most part, a drug's legal status was determined before we knew much about the risks associated with it. If You Never Have Then You Know Someone Family Acceptance Peer Pressure Life Circumstances/Environment Violence – Wall Street Society Acceptance Movies and TV Shows Sports and Money Movies/Sports/Music ABUSED DRUGS alcohol nicotine caffeine and other OTC stimulants cocaine amphetamine and related legend stimulants opioids sedative hypnotics cannabis, entactogens, phencyclidine solvents and inhalants anabolic steroids street drugs administered intravenously; common diluents, fillers, contaminants. What Is Drug Addiction? Drug addiction is a complex brain disease. It is characterized by compulsive, at times uncontrollable, drug craving, seeking, and use that persist even in the face of extremely negative consequences. Drug seeking becomes compulsive, in large part as a result of the effects of prolonged drug use on brain functioning and on behavior. For many people, drug addiction becomes chronic, with relapses possible even after long periods of abstinence. The Brain Key Drug Abuse Terms Withdrawal: Presence and severity of characteristic withdrawal symptoms. Reinforcement: A measure of the substance's ability, in human and animal tests, to get users to take it again and again, and in preference to other substances. Tolerance: How much of the substance is needed to satisfy increasing cravings for it, and the level of stable need that is eventually reached. Dependence: How difficult it is for the user to quit, the relapse rate, the percentage of people who eventually become dependent, the rating users give their own need for the substance and the degree to which the substance will be used in the face of evidence that it causes harm. Intoxication: Though not usually counted as a measure of addiction in itself, the level of intoxication is associated with addiction and increases the personal and social damage a substance may do. Routes of Drug Administration Routes of Drug Administration Drugs are consumed by people in the following ways: Ingestion: swallowing drugs is convenient but a major drawback is that the timing and magnitude of the drug effects are greatly influenced by food in the stomach; some drugs are deactivated before they can be absorbed from the digestive tract and thus cannot be administered by this route; most drugs are absorbed from the small intestine, but those with small molecules (e.g., alcohol) can be absorbed through the stomach wall, and thus they act more rapidly Inhalation: many inhaled chemicals are absorbed directly into the bloodstream from the lungs (e.g., chemicals in tobacco and marijuana smoke); lung damage is a serious risk from the repeated inhalation of chemicals Mucous membranes: some drugs (e.g., cocaine) are readily absorbed through the mucous membranes of the nose, mouth, or rectum; this method of administration is problematic as these membranes can be easily damaged Injection; SC, IM, or IV: addicts typically favor the IV route, which is particularly dangerous; because it is fast and direct, there is a risk of death from overdose, impure drugs, or allergic reactions; there are only a few sites on the body appropriate for IV injection, thus addicts frequently develop infections and scar tissue at these sites Mechanisms of Psychoactive Drug Action 1. In order to produce psychoactive effects, drugs must enter the nervous system; fortunately, many drugs that are potentially dangerous neurotoxins do not readily penetrate the neurons of the CNS due to the blood-brain barrier; it is mediated by the particularly small pores in the walls of CNS blood vessels 2. Once a psychoactive drug has penetrated the CNS, it can influence neural activity in numerous ways; e.g., it can act diffusely on neural membranes or interact specifically with particular classes of neurotransmitters and receptors 3. The effects of psychoactive drugs are terminated by their metabolism, i.e., by their conversion to nonactive metabolites; most drugs are metabolized by liver enzymes; only small amounts of unmetabolized active drugs are eliminated in sweat, breath, urine, etc. Drug Tolerance Drug tolerance is any diminution of a drug's effect that results from prior exposure to the drug Tolerance can be measured in two ways: (1) by measuring the decrease in the response elicited by the same dose of the drug, or (2) by measuring the increase in the amount of drug required to produce the same effect; in effect, drug tolerance is a shift in the dose-response curve to the right It is common to think of tolerance effects as being of two different types: 1. Metabolic tolerance (any tolerance effect that results from a decrease in the amount of the drug reaching the target cells) or Functional tolerance (any tolerance that results from a decrease in the ability of the drug to influence the target cells) 2. Tolerance to most psychoactive drugs is primarily functional; an important thing to remember about functional tolerance is that it often develops for some effects of a drug but not others Addiction Physical Dependence: Biochemical level changes Patterns of addictive behavior: Eliminating physical dependence on a substance does not "cure" the addiction. Psychological Addiction Analogy of your first love to explain how addicts feel. Remember the first time they fell in love- and 1) Whole life began to focus on, and revolve around……. 2) “Broking the rules" ….. And perhaps exercised less than perfect judgement in the matter. This is compared with the addict's attitude towards their drug of choice- they are "in love" with the drug, and use of the drug and obtaining more becomes the center of their existence, very much like that person became the center of their lives. Scheduled Drug Lists Schedule I The drug or other substance has a high potential for abuse. The drug or other substance has no currently accepted medical use in treatment in the United States. There is a lack of accepted safety for use of the drug or other substance under medical supervision. Examples of Schedule I substances include heroin, lysergic acid diethylamide (LSD), marijuana, and methaqualone. Schedule II The drug or other substance has a high potential for abuse. The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions. Abuse of the drug or other substance may lead to severe psychological or physical dependence. Examples of Schedule II substances include morphine, phencyclidine (PCP), cocaine, methadone, and methamphetamine. Scheduled Drug Lists Schedule III The drug or other substance has less potential for abuse than the drugs or other substances in schedules I and II. The drug or other substance has a currently accepted medical use in treatment in the United States. Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence. Anabolic steroids, codeine and hydrocodone with aspirin or Tylenol®, and some barbiturates are examples of Schedule III substances. Schedule IV The drug or other substance has a low potential for abuse relative to the drugs or other substances in Schedule III. The drug or other substance has a currently accepted medical use in treatment in the United States. Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in Schedule III. Examples of drugs included in schedule IV are Darvon®, Talwin®, Equanil®, Valium®, and Xanax®. Scheduled Drug Lists Schedule V The drug or other substance has a low potential for abuse relative to the drugs or other substances in Schedule IV. The drug or other substance has a currently accepted medical use in treatment in the United States. Abuse of the drug or other substances may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in Schedule IV. Cough medicines with codeine are examples of Schedule V drugs. Commonly Abused Drugs CNS Stimulants Nicotine Caffeine Cocaine Amphetamines Methcathinone Methylphenidate Anorecitc Drugs Khat CNS STIMULANTS Cocaine: Made from the leaf of the coca plant, this drug often comes in the form of a white powder that some people inhale through their nose. Crack: A form of cocaine that can be smoked. Amphetamines: Often called "speed," these pills are sometimes prescribed by doctors for medical problems. Methamphetamine: A powerful form of amphetamine that comes in clear crystals (called "ice") or powder (called "crank") that is smoked or injected. Cocaine Cocaine and other stimulants have the same general effect, but differ greatly in their potency May be inhaled, absorbed across mucosal membranes, or ingested orally Cocaine is very addictive; it acts by blocking catecholamine reuptake It is a general stimulant, producing a feeling of energy, well-being, and selfconfidence; extremely high doses can lead to cocaine psychosis characterized by sleeplessness, nausea, restlessness and psychotic behavior. Very high doses can produce stroke, seizures, and respiratory arrest; withdrawal symptoms are mild. Clinically, cocaine derivatives are effective as local anesthetics Some Effects of Cocaine Use Tobacco It is used more than any other drug except caffeine; usually inhaled or absorbed through oral mucosa Nicotine is the major psychoactive ingredient; 4,000 other known chemicals are in tobacco Tobacco is highly addictive (e.g., patients with Buerger's disease will still smoke, even after their limbs are amputated) Effects ranging from nausea to relaxation Consequences of smoking range from coughing to failure of the cardiorespiratory system to cancer CNS Depressants Barbiturates Benzodiazepines Flunitrazepam Gamma Hydroxybutyric Acid Paraldehyde Chloral Hydrate Glutethimide and Methaqualone Meprobamate Alcohol It is consumed by 66% of the US population and 15 million are addicted Orally ingested; at most doses it is a depressant resulting in impaired function and is implicated in almost 50% of traffic fatalities It is believed to act primarily at the GABA-A receptor complex Alcohol is a small molecule and thus crosses the blood-brain barrier resulting in brain damage such as seen in Korsakoff's syndrome Alcohol also crosses the placenta and can result in birth defects such as Fetal Alcohol Syndrome. Very severe withdrawal effects; delerium tremens represent the 3rd stage of withdrawal, and may be lethal. Opiates Opiates include morphine and heroin; these are unmatched as analgesics and are very addictive Act at receptors for endogenous opiate neurotransmitters that are located throughout the brain Elicits moderately severe withdrawal symptoms but these are not lethal Over 2 million Americans use heroin to experience a rush of pleasure and drowsy euphoria Tolerance leads to an ever greater use of the drug which has many crime implications Common IV transmitted diseases and opiate side effects= Respiratory Depression can be seen with lethal doses Cannabis Marijuana Hashish Hashish Oil Synthetic THC Dentification Marijuana & Hashish It elicits psychoactive responses largely due to its active ingredient is tetrahydrocannabinol –THC; Hashish is more potent resin of marijuana plant - 7-14% THC content. Hallucinogen - distorts perceptions of time and space Little physical dependence or physical withdrawal May be inhaled or ingested orally (usually baked into an oil-rich substrate to aid absorption) Act at THC receptors throughout the brain Effects range from increases appetite, craving sweets to very relaxed states to periods of impaired judgement and short-term memory impairment A possible negative consequence is lung damage due to inhaling the drug Marijuana & Hashish Acts like depressant Clinically, marijuana has been shown to block the nausea of cancer and AIDS drugs, stimulate appetite, and decrease the severity of Glaucoma Stimulates dopamine and serotonin, influences GABA, and acetylcholine High doses - toxic psychosis Max effect - 30 minutes Effects last up to 3 hrs. Half-life - 19 hrs May be found in blood up to 50 hrs THC stored in fat cells Some Effects of Long-Term Use with Marijuana Use Hallucinogens Disrupt serotonin functioning Elevation of some bodily functions Altered sense of reality - sight and sound Enhanced emotionality Indoles & Catechols Hallucinogens Indoles LSD and psilocybin Similar chemical structure as indolin (serotonin NT) Ingestion - orally Max. effect - 1 hr. Half-life - 3 hrs Tolerance develops quickly Cross tolerance Little physical dependence or withdrawal Not generally toxic Catechols Hallucinogenic effects similar to indoles Similar to structure of dopamine & norepinephrine NT Peyote, mescaline, PCP Max effect - 1/2 - 2 hrs. Halflife - 6 hrs. Ingestion - smoke, snorted, oral or injection Adverse affects Anabolic Steroids Steroids are synthetic substances similar to the male sex hormone testosterone. They do have legitimate medical uses. Sometimes doctors prescribe anabolic steroids to help people with certain kinds of anemia and men who don't produce enough testosterone on their own. Most common anabolic steroids taken today: anadrol, oxandrin, dianabol, winstrol, decadurabolin, and equipoise. Anabolic Steroids Side Effects Side Effects: Baldness can be caused by steroid abuse. Because of how steroids act on the limbic system in the brain, mood swings, including homicidal rage can occur. Taking roids can cause pimples to pop up. Females who take steroids can become more masculine. Their voices can deepen. A condition called atherosclerosis can be caused by steroid use. This condition can lead to a heart attack or stroke. When hormone production is disrupted, males can develop breasts, a condition called gynecomastia. Tumors and blood-filled cysts can develop on the liver of steroid users. Increased levels of hormones signal bones to stop growing. Anabolic Steroids Inhalants Most inhalants are common household products that, when inhaled, cause a psychoactive (mind-altering) effect. There are literally hundreds of inhalants, including everyday products such as nail polish remover, glue, gasoline, household cleaners, and nitrous oxide ("laughing gas," which can be found in whipped cream dispensers and is often inhaled via a balloon). Inhalants also include fluorinated hydrocarbons found in aerosols such as hairspray, spray paint, and household cleaners. Although the wide range of chemicals found in different products can have different effects, inhalants generally fall into three categories: 1) Solvents 2) Gases 3) Nitrites Types of Inhalants Solvents include: Certain industrial or household products, such as paint thinner, nail polish remover, degreaser, dry-cleaning fluid, gasoline, and glue Some art or office supplies, such as correction fluid, felt-tip marker fluid, and electronic contact cleaner Gases include: Some household or commercial products, such as butane lighters, propane tanks, whipped cream dispensers, and refrigerant gases Certain household aerosol propellants, such as those found in spray paint, hair spray, deodorant spray, and fabric protector spray. Medical anesthetic gases, such as ether, chloroform, halothane, and nitrous oxide Nitrites include: Cyclohexyl nitrite (found in substances marketed as room deodorizers) Amyl nitrite (used for medical purposes) Butyl nitrite (previously used in perfumes and antifreeze, but now an illegal substance) Inhalants How Are They Used? Inhalants can be breathed in through the nose or mouth in a variety of ways: "Sniffing" or "snorting" fumes from containers Spraying aerosols directly into the nose or mouth Sniffing or inhaling fumes from substances sprayed or placed into a plastic or paper bag ("bagging") "Huffing" from an inhalant-soaked rag stuffed in the mouth Inhaling from balloons filled with nitrous oxide What Are the Common Street Names? Laughing gas (nitrous oxide) Snappers (amyl nitrite) Poppers (amyl nitrite and butyl nitrite) Whippets (fluorinated hydrocarbons, found in whipped cream dispensers) Bold or Rush (nitrites) Club Drugs Effects: Chronic use of MDMA may lead to changes in brain function. GHB abuse can cause coma and seizures. High doses of ketamine can cause delirium, amnesia, and other problems. Mixed with alcohol, Rohypnol can incapacitate users and cause amnesia. Statistics and Trends: According to the 2004 National Survey on Drug Use and Health, more than 11 million people have tried MDMA, more than 11 million have tried methamphetamine, and more than 23 million have tried LSD at least once. Club Drugs Brief Description: Typically used by teenagers and young adults at bars, clubs, concerts, and parties. The most common club drugs include Ecstasy (MDMA), GHB, Rohypnol, ketamine, methamphetamine, and acid (LSD). Street Names: XTC, X (MDMA) Special K, Vitamin K (ketamine) Liquid ecstasy, soap (GHB) Roofies (Rohypnol) MDMA (Ecstasy) MDMA (3-4 methylenedioxymethamphetamine) is a synthetic, psychoactive drug chemically similar to the stimulant methamphetamine and the hallucinogen mescaline. Street names for MDMA include "ecstasy," "XTC," and "hug drug." MDMA produces both amphetamine-like stimulation and mild mescaline-like hallucinations. After oral administration at doses ranging from 50 to 200 mg, effects are felt within 30 to 45 minutes, peak at 60 to 90 minutes, and last for 4 to 6 hours. In high doses, MDMA can interfere with the body's ability to regulate temperature. On rare but unpredictable occasions, this can lead to a sharp increase in body temperature (hyperthermia), resulting in liver, kidney, and cardiovascular system failure, and death. Because MDMA can interfere with its own metabolism (breakdown within the body), potentially harmful levels can be reached by repeated drug use within short intervals. GHB, Ketamine, and Rohypnol GHB and Rohypnol are predominantly central nervous system depressants. Because they are often colorless, tasteless, and odorless, they can be added to beverages and ingested unknowingly. These drugs emerged several years ago as "date rape" drugs.***** Because of concern about their abuse, Congress passed the "Drug-Induced Rape Prevention and Punishment Act of 1996" in October 1996. This legislation increased Federal penalties for use of any controlled substance to aid in sexual assault. GHB Since about 1990, GHB (gamma hydroxybutyrate) has been used in the U.S. for its euphoric, sedative, and anabolic (body building) effects. It is a central nervous system depressant that was widely available over-the-counter in health food stores during the 1980s and until 1992. It was purchased largely by body builders to aid in fat reduction and muscle building. Street names include "liquid ecstasy," "soap," "easy lay," "vita-G," and "Georgia home boy." Coma and seizures can occur following use of GHB. Combining use with other drugs such as alcohol can result in nausea and breathing difficulties. GHB may also produce withdrawal effects, including insomnia, anxiety, tremors, and sweating. GHB and two of its precursors, gamma butyrolactone (GBL) and 1,4 butanediol (BD), have been involved in poisonings, overdoses, date rapes, and deaths. Ketamine Ketamine is an anesthetic that has been approved for both human and animal use in medical settings since 1970; about 90 percent of the ketamine legally sold is intended for veterinary use. It can be injected or snorted. Ketamine is also known as "special K" or "vitamin K." Certain doses of ketamine can cause dream-like states and hallucinations. In high doses, ketamine can cause delirium, amnesia, impaired motor function, high blood pressure, depression, and potentially fatal respiratory problems. Rohypnol Rohypnol, a trade name for flunitrazepam, belongs to a class of drugs known as benzodiazepines. When mixed with alcohol, Rohypnol can incapacitate victims and prevent them from resisting sexual assault. It can produce "anterograde amnesia," which means individuals may not remember events they experienced while under the effects of the drug. Also, Rohypnol may be lethal when mixed with alcohol and/or other depressants. Rohypnol is not approved for use in the United States, and its importation is banned. Illicit use of Rohypnol started appearing in the United States in the early 1990s, where it became known as "rophies," "roofies," "roach," and "rope." Abuse of two other similar drugs appears to have replaced Rohypnol abuse in some regions of the country. These are clonazepam, marketed in the U.S. as Klonopin and in Mexico as Rivotril, and alprazolam, marketed as Xanax. Drugs Used to Treat Dependence and Addiction Naloxone Naltrexone Buprenorphine Varenicline/Cytisine Rimonabant Acamprosate Oxazepam/Lorazepam