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HSCI180 CH6-7 Stimulants, Depresesants, Inhalants.docx

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Simon Fraser University
Health Sciences
HSCI 180
Julian Somers

CHAPTER 6–Stimulants Stimulants  Stimulants are substances that keep a person going mentally and physically  Cocaine and amphetamine are restricted stimulants  Caffeine and nicotine are readily available stimulants Cocaine  Stimulates CNS, create intense feelings of pleasure, increase alertness and decreases appetite and need for sleep  Cocaine is classified into Schedule I in the Controlled Drugs and Substances act Forms of Cocaine  In manufacturing illicit cocaine, coca leaves is mixed with an organic solvent.  After soaking, mixing and mashing, excess liquid is filtered leaving coca paste (can be mixed with tobacco and smoked).  The paste can be made into cocaine hydrochloride (most common form), a salt that dissolves easily in water and cannot be heated for inhalation. Either snort or inject this intravenously  Extract cocaine hydrochloride into a volatile organic solvent (eg ether) and extract it into freebase (can be heated and the vapors inhaled) – dangerous b/c flammable  Mix freebase with simple household chemicals (eg baking soda or water) then drying to form Crack or rock (lump of dried, smokeable cocaine) Pharmacology  Chemical structure of cocaine very complicated and does not structurally resemble any of the neurotransmitters, does not tell us how or why cocaine affects the brain  Mechanism of Action: Cocaine blocks reuptake of dopamine, serotonin, and norepinephrine  prolongs the effects of these neurotransmitters, contributes to pleasurable/euphoric effects of cocaine  Administration o Chewing or sucking coca leaves = Slow absorption and onset of effects o Snorting through nasal mucous membranes = Rapid absorption and onset of effects o Injected intravenously = Rapid and brief effects o Smoked = Rapid and brief effects  Elimination o Cocaine is metabolized by enzymes in the blood and liver o Half-life of about one hour o Major metabolites (detected by urine screening) have a half-life of eight hours History  Coca = a bush that grows in the Andes and produces cocaine. o It has been harvested for thousands of years and actively cultivated for over 800 years o Natives of the Andes chewed coca leaves to give them greater strength and endurance o The coca leaf was an important part of Inca culture (Used in religious ceremonies and as currency )  Angelo Mariani  Used coca leaf extract in many products including lozenges, tea, and, especially, coca wine  Coca extract was later used in the United States in early versions of Coca-Cola and in many patent medicines (eg Cocaine toothache drops)  Dr. W. S. Halsted  Experimented with ability of cocaine to produce local anesthesia. Delivered via newly developed hypodermic syringe o Cocaine was isolated before 1860 o Processing 500 kilograms of coca leaves yields 1 kilogram of cocaine  Sigmund Freud  Early psychiatric uses, studied use of cocaine as a treatment for depression and morphine dependence. Later opposed use of the drug after nursing a friend through cocaine psychosis  Past Use and Future Trends o 1880 introduced, mostly positive opinions o 1890 – dangers and side effects b/c well known o 1900s society turned against cocaine and passed laws to control it o Little cocaine use until 1970s o 1970s-1980s begin again and thought not capable of producing ‗real‘ dependency o 1980 eventually aware of all potential dangers o 2006 surveys indicate that about 2 percent of adults currently use cocaine  Down from a high of 7 to 9 percent in the 1980s  Usage rates of cocaine and amphetamine tend to cycle in opposition to each other  Prior to 1985, the major form of the drug available was cocaine hydrochloride, which was snorted o Cocaine was relatively expensive and its use was associated with status, wealth, and fame  Then an inexpensive ($5 to $10 a hit) form of smokable cocaine became available—crack o Smoked cocaine has a greater abuse potential than snorted cocaine Contemporary Legal Controls on Cocaine in Canada  Canada is a leading producer and exporter of illegal synthetic drugs o While heroin, cocaine and cannabis consumption have levelled off, the use of synthetic drugs like methamphetamine and ecstasy (MDMA) have increased rapidly o Ecstasy factories in Canada are the among the largest in North America and chemical precursors are readily available  Media and politicians focused on crack use among urban blacks (Associated with violence and dependency)  Anti-Drug Abuse Acts of 1986 and 1988 = Penalties for sale of crack cocaine significantly more severe than penalties associated with powder cocaine o Tougher penalties for first-time users of crack  Concerns about federal cocaine sentencing policy o Does it overstate the seriousness of most crack cocaine offenses? o Does it disproportionately affect the black community? Supply of Illicit Cocaine  Columbia remains the primary source of powder cocaine for Canadian market o A piece of crack costs $20 & a gram of powder cocaine ~80-110 $  Readily available in all major U.S. cities o Street cocaine averages about 50-75 percent pure o Most illicit cocaine comes from Columbia, Peru, Bolivia Benefits  Local anesthetic properties of cocaine were discovered in 1860, but the drug was not used medically until 1884, was an ingredient in many patent medicines in North America  Synthesized drugs have largely replaced cocaine for medical use  Cocaine remains in use for surgery in the nasal, laryngeal, and esophageal regions  Athletes and entertainers felt it produces a feeling of increased energy and well bein Causes for Concern:  Acute Toxicity o Acute cocaine toxicity causes profound CNS stimulation, which can lead to respiratory or cardiac arrest o Significant individual variation in the uptake and metabolism of cocaine o Difficult to estimate the size of a lethal dose o Rare, severe, and unpredictable reactions can cause cardiac failure o Cocaine + alcohol can cause the formation cocaethylene (even more toxic than cocaine)  Chronic Toxicity o Risks of regularly snorting cocaine = Paranoid psychosis, Damage to the heart muscle o Snorting irritates nasal septum, damages it and leading to inflamed runny nose  Dependence potential o Animal and human studies have shown that cocaine is a powerfully reinforcing drug o Some people experience withdrawal symptoms (cocaine craving, irritability, anxiety, depressed mood, increased appetite, exhaustion)  Cocaine use during pregnancy o Increased risk of miscarriage and torn placenta o No consistent negative associations between prenatal cocaine exposure and development of child Amphetamines  CNS Stimulants, increase energy, wakefulness, alertness, reduce hunger, and feelings of wellness  Amp are produced through chemical synthesis by pharmaceutical companies or in illicit laboratories on the street  Amp is classified into Schedule I in the Controlled Drugs and Substances act Pharmacology  Chemical structure of amphetamine is similar to the catecholamine (dop&norep) neurotransmitters o Ephedrine and PPA are less able to cross the barrier and so produce more peripheral than central nervous system effects  Mechanism of Action o Increase the release of monoamine neurotransmitters (dopamine, norepinephrine and serotonin), resulting in an increased concentration of these monoamines at the synapse. o Also block the reuptake o Amphetamine reduces monoamine metabolism by inhibiting monoamine oxidase  Absorption o Like cocaine, amphetamines are consumed via oral, intranasal, intravenous and inhalation routes. o Peak effects  1.5 hours after oral ingestion  5-20 minutes after intranasal administration  5-10 minutes following intravenous injection or smoking  Elimination o Half-life = 5-12 hours  Two days for complete elimination History  The Chinese used a medicinal tea made from what the called ma huang (In North America, called Ephedra) o Active ingredient = ephedrine (a sympathomimetic drug used to treat asthma) o Stimulates the sympathetic branch of the autonomic nervous system  New synthesized chemical similar to ephedrine, called amphetamine, was patented in 1932  Amphetamine was used medically  treated Asthma , Narcolepsy, Hyperactivity in children, Appetite suppressant, as a stimulant, Ideal for ‗cramming‘ because it allows them to sta awake for long periods  Use by soldiers in World War II to fight fatigue  Peak use 1950s-1970s o Readily available in Canada & abused by athletes, students and truck drivers o cocaine+ heroin injected together = speedball, Amphetamine+ heroin same effect, Amphetamine got street name speed o Most street amphetamines came from prescriptions  Recognize abuse by 1970s o Amphetamines became more tightly controlled o Many look-alikes appeared (replaced with caffeine or ephedrine) identical packaging o Some users switched back to cocaine (safer and cheaper)  Illicit manufacture of methamphetamine grew o Limited amphetamine availability increased the number of illicit laboratories making methamphetamine Methamphetamine (“crank”) is a derivative of amphetamine  Chemical Structure: Methamphetamine molecule simply has a methyl group added to the basic amphetamine structure. o Methamphetamine hydrochloride crystals (―Ice or crystal meth‖) = Smokeable  This allows it to cross the blood brain barrier more readily than amphetamine, increasing CNS potency  Manufacture of methamphetamine is dangerous and associated with toxic fumes and residue  Supplies of Illicit Methamphetamine o Average price range across Canada is between $80-$150 per gram o Canada has earned a reputation as an important methamphetamine source o Abuse rose dramatically during 1990s o Methamphetamine use in Canada is relatively low compared with other drugs of abuse. o Methamphetamine abuse began in the western United States and then spread east; it is also now considered a ―club drug‖ Benefits  Previous use for depression to temporarily elevate mood/feelings of fatigue o Adjunctive therapy- a treatment used together with primary treatment. o The benefit of amphetamines is that their effects occur rapidly compared with standard antidepressant medications. o But when drug over, mood drops often below predrug level  Weight control o Widely use to reduce food intake and body weight - Effect is real but small o Combination of fenfluramine and phentermine was associated with heart valve damage and lung disease in some people  Narcolepsy (uncontrolled daytime episodes of muscular weakness and falling asleep) o Stimulants used to keep patients awake during the day o Newer drug modafinil (Provigil) promotes wakefulness by increasing the activity of norepinephrine and dopamine  Low abuse potential / Doesn‘t induce tolerance  Treatment of attention-deficit hyperactivity disorder (ADHD) o Characterized by problems with inattention, hyperactivity, and impulsivity o Stimulant medications can reverse catecholamine-associated deficits that may underlie ADHD o Due to side effects and concerns about the risk of abuse, other treatments for ADHD are being studied o Methylphenidate (Ritalin) – treat ADHD  “Smart pills” o At a low level of arousal, may improve performance o At a high level of arousal, may decrease performance, especially on complex or difficult tasks that require concentration  Athletics o Under some circumstances, may produce slight improvements in athletic performance (competitions 1%) Causes for concern  Acute Toxicity o Acute behavioral toxicity = Increases in feelings of power, suspicion, paranoia  Potential risk of violent behavior (increased feelings of power and capability) o Small doses, complex decision making can be temporarily impaired o Very high doses may destroy catecholamine neurons o Contaminants formed during the manufacture of illicit methamphetamine may have toxic effects on brain cells  Chronic Toxicity from High-Dose Use o Paranoid psychosis - Two possible reasons for the psychosis  Heavy methamphetamine users have schizoid personalities.  Caused by sleep deprivation. o Higher risk among those who inject the drug  Dependence Potential o Often no obvious withdrawal symptoms, evidence show that withdrawal symdrome is limited o Symptoms include craving, lethargy, depressed mood o Produce psychological dependence / habit forming? Potential for abuse is limited. Must consider dose and route of administra
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