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Wilfrid Laurier University
Bruce Mc Kay

Licit drug- legal Illicit drug- illegal Instrumental use: socially accepted goal in mind Recreational use: sole purpose of getting intoxicated Deviant drug use: very few people approve of (ex. Meth) Drug misuse: in greater use than prescribed by doctor or other than intended by manufacturer Drug abuse: recurrent substance use in a manner, amount or situation such that it causes social, occupational, psychological or physical problems Drug dependence: so frequently it would be difficult to stop, tolerance, withdrawal, often taking more for longer than intended, unable to cut down, great deal of time spent obtaining, continue taking it despite knowing effects, important social, occupational, recreational activities given up Harm reduction: Canada’s Drug Strategy includes public education, safe injection sites, syringe exchange programs, methadone maintenance therapy, and designated driver/ alternative transportation programs Laws on drugs driven by concerns of: Toxicity, Dependence, Crime Drug toxicity: Physiological: has the capacity to kill you (ex stop the heart) Behavioural: dangerous behavior while using Acute toxicity: amphetamines can cause the heart to stop, alcohol can cause breathing to stop Chronic effects: heart disease, lung cancer, meth mouth DAWN- drug abuse warning network, reports number of drug related visits to ER, about half due to prescription drugs less than a third due to recreational drugs, CIH Canadian institute for health information keeps track of deaths Family: family adapts to the addiction of a member maybe making it hard to stop without disrupting the family, also runs in the family Most addictive: heroin, tobacco Medium: cocaine Least: hallucinogens, marijuana Most addictive: snorting, injecting Medium: smoking Least: eating Ch 3 - In 1900s fear of Chinese immigrants lead to first legislation of drugs in Opium Act - Proprietary medicine act: required documentation and approval of medicines prescribed by doctors - 1950’s media produces highly sensational accounts of evil drug users - 1996 Controlled drugs and substances act in Canada o Prohibits importation, sale possession etc of illegal drugs and drugs without a prescription o Summary conviction offences (less severe): police must see you do it, 6 months in prison o Indictable offence: must have warrants for arrest, over 6 months in prison or over $5000 in fines, hybrid offence (sentence to be determined) o Trafficking will result in criminal record, not expunged in US ever o Illegal for someone to attempt to obtain medication from a doctor without disclosing all other controlled substances obtained from other doctors in the last 30 days - Schedules o 1: MDMA, Rohypnol, Adderal, Cocaine, “hard drugs”, can have life imprisonment o 2: Cannabis and derivatives o 7, 8: hash and marijuana quantities o 3: Medical sedatives, hallucinogens, max 3 years for possession, 10 for trafficking, production, importing o 4: prescriptions, steroids, sedatives, legal with prescriptions o 5: laws, in transport over the border should be declared o 6: precursors- suspicious for making drugs, acetone, ethyl ether, lysergic acid, ephedrine - Clinical trial phases: o 1- initial safety, first administration to humans in healthy volunteers o 2- side effects and drug interaction studies o 3- usefulness of drug on patients o 4- trials after the drug has already received patent 2001 Canada implements Marijuana regulation category 1: painful medical conditions (MS, cancer, seizures, HIV/AIDS, arthritis, spinal cord injury) and category 2: conventional treatments failed - Neural system has glia cells (create blood-brain barrier that protects the brain from potentially toxic chemicals, a drug must be able to pass through this layer, must be lipophilic - dissolvable in oils and fats) and nerve cells. Dendrites, at the end of the neuron, have receptors that can activate or inhibit the action potential of a neuron. Axon extends from this conducting electrical signal to presynaptic terminals where chemical messengers are stored. - Peripheral nervous system: nerves outside the brain and spinal cord consisting of somatic and autonomic nervous system, Somatic: nerves carry sensory information (Acetylcholine: neurotransmitter in the somatic system to excite the muscle) Autonomic nervous system: controls involuntary functions such as heart rate o Parasympathetic: relaxed, has acetylcholine o Sympathetic: fight or flight, norepinephrine is the neurotransmitter - CNS Central Nervous System, brain and spinal cord o Hypothalamus: controls hormones for primal urges, eat, sleep, sex o Limbic system involved in emotion, memory, contains amygdala, nucleus accumbens and hippocampus o Dopaminergenic pathway, plays a large role in reward and reinforcement, compulsion, pleasure o Mid brain, pons, medulla play roles in sensory and motor reflexes, they also include most of the manufacture of neurotransmitters dopamine, norepinephrine and serotonin o Norepinephrine: arousal, attentiveness, food intake, body weight o Serotonin: mood, memory processing, sleep, cognition, link between serotonin system dysfunction in depression and suicide, also may be related to hallucinogenic drugs o GABA: most areas of CNS, inhibitory functions may be affected by sedative drugs o Glutamate: throughout the brain, makes cells more excitable o Endorphins: play a role in pain relief - Comparing potency: o ED effective dose, minimal dose of a particular drug to have effect in a given percentage of population o LD lethal dose, minimal dose of a particular drug capable of causing death in a given percentage of population - Higher the difference between ED and LD the safer it is TI (therapeutic index) called safety margin - Oral ingestion: slow absorption, reject poisons, stomach pump opportunity, no immediate effect - Injection: rapid effects, high concentration can be delivered, must have I.V. antidote if there is a mistake, damaged veins, blood borne disease transmission - Subcutaneous injection (under the skin) - Intramuscular: easier to do, absorption is more rapid, absorbed into capillaries, slower to act than IV but faster to administer - Inhalation: fast absorption time, shorter duration of a drug, lung/throat irritation tars/hydrocarbons - Topical application transdermal (across skin, slowly but stably), Intranasal (absorbs across mucous membranes rapidly) - Suppository/enema good for patients who can’t swallow or are vomiting Agonist: mimicks action of neurotransmitter and activates receptor Antagonist: occupies the receptor and prevents the neurotransmitter from activating it - Chemical name of a drug gives complete chemical description of the molecule - Generic names are official legal names - Brand name specifies formula and trademark - Prodrugs: only active after metabolized by liver, lasts longer - Pharmacodynamic tolerance: neuron’s sensitivity to drugs changes Ch 9 - alcohol first distilled in middle ages (brandy), Mid 1800s gin epidemic, average 5 drinks a day - The percentage of alcohol by volume is one half the proof number - Late 1700’s North Americans drank alcoholic beverages and most favoured them to water which was likely to be contaminated - Until demonization of alcohol, the temperance movement - Second half of 1800s refrigeration and immigration made the sale of beer easier - 1851 US prohibition begins - 1864 Dunkin act in Ontario any country may vote to be dry by majority - 1901 Canadian prohibition begins, numerous exceptions - Organized crime begins and Canada realizes that prohibition laws are unenforceable, repealed by 1948, as well as loss of income for the government without alcohol sales - Majority of alcohol is in tax dollars: domestic 77% spirits, 55% wine, 51% beer (without costs $7, $14, $15) Wine - Fermentation: a biological process by which sugars such as glucose from organic material are converted by yeast to ethanol and carbon dioxide Beer, similar to wine with barley and hops Liquor: - Starts similar to wines but yeast dies at a certain percentage so it must be distilled, boiled off and collect vapour, can be distilled to 95% ethanol - Under 16 drinks a week is healthy according to health Canada - Binge drinking for men: 5+ drinks in a row, female 4+ drinks in a row - Alcohol is removed by the liver 7-9g per hour - Alcohol increases the activity of one or two enzymes related to its oxidation, women have less of this enzyme, most Asians don’t have the enzyme that breaks down what alcohol turns into, causing it to have a worse effect - Increase in GABA, decrease in glutamate, widespread neuronal inhibition - BAC number of grams of alcohol in 100 mLs of blood - Dilation of peripheral blood vessels making loss of body heat but making the user feel warmer - Alcohol contains acetaldehyde quite toxic in small quantities and could be cause of nausea and headache in the morning - Fetal alcohol syndrome: o Growth retardation before or after birth, Abnormal features on face and head , small head, face and eyes, Evidence of brain abnormality - Withdrawal includes (can last several weeks) o Stage 1. Tremors, loss of appetite, insomnia, sweating rapid heartbeat o Stage 2. Hallucinations, auditory, visual, tactile: sensation of snakes or bugs crawling may be due to nervous system rebounding from constant inhibition by becoming overly excitable o Stage3. Delusions, disorientation usually followed by amnesia o Stage 4. Seizure activity Tobacco - Originally north American aboriginal peoples used tobacco in rituals - Chris Columbus “discovered” tobacco - Cigars are made of tightly rolled leaves, Cigarettes are made of shredded tobacco - 1930’s and 40’s began seeing cigarettes as a health problem, marketing of filter cigarettes begins - 1964 US surgeon general saw cigarettes as causing cancer, 1965 companies began having to include the warning on lables and television and radio ads were banned in 1971 - 1908 Act in Canada banned sales of cigarettes to those under 16 years not enforced, 1993 legal age becomes 18 - 1983 tobacco tax doubled but not much changes - 1989 cigarette manufacturers began needing to list amounts in each brand and warnings on packages as well as restriction on promotion - Since 1985 smoking prevalence has significantly dropped - 2000- 50% of packaging must be a warning (in Canada), 2011 75%, 2006: smoke-free Ontario act, cigarettes must be out of sight in stores - Chewing tobacco causes leukoplakia a whitening, thickening and hardening of tissue in the mouth considered a precancerous lesion, gums can recede and expose teeth to disease - Tobacco damages DNA - Most provinces now have laws prohibiting smoking in public places - Recent years cigarette promotions in other countries have increased the export of cigarettes from the US, developing countries smoke a lot as there is no regulation - For effect on fetuses there is a dose-response relationship, the more a woman smokes during pregnancy the lower the baby’s birth weight will be, babies become shorter and smaller, and born earlier, have neurological problems with reading and mathematical skills, miscarriages are also common,(similar to “crack babies”), SIDS increased risk of facial mal-formations when the father smokes - Birth control increases likelihood of sticky platelets causing blood clots - Nicotine is one of the most toxic drugs, deactivated in the liver, overdose causes seizures, mimics acetylcholine, also causes a release of adrenaline, passes blood brain barrier in 58 secs, used as insecticide, stimulates CNS - Smoking ruins cilliary escalator that clears toxins from lungs - CO attaches to hemoglobin better than O , slow a2phyxiation - Peak age to start is 6 to 7 grade, 80-90% start before age 18, 1 in 4 smoke - Smokers show reduction in MAO oxidase that breaks down dopamine. This may enhance the pleasurable effects of a dose of nicotine Ch 15 - 3 kinds of cannabis: sativa, indica, ruderalis - hashish (concentrated), ganja (dried flowering tops) and bhang (remainder of the plant) - Indica: 2-3’ high, historically had THC, potency varies on genetics and environmental conditions - Sativa 18’ high, less THC, hybridized with indica to increase THC, originated in Asian, historically grown for fibres for rope, up to 2lbs of bud - Up to 66 compounds in marijuana that are psychoactive - outdoor plants THC 5-15%, Hash up to 20% THC, Hash oil up to 60% THC (trichomes ground, mixed with ethanol to separate, then evaporated leaving oil) - Illegal for the last 90 years th - May 27 2002 Canadian government began a bill to decriminalize marijuana but it didn’t go through - 1970’s people began seeing that regular people were using marijuana and a more lax position was taken until Reagen admin in 1981 took a “get tough” attitude - comes from Middle East, Morocco, Afghanistan, Pakistan, Jamaica - Prevalence higher in males and age of initiation at average 15.6 years - Most widely consumed illicit drug in the world (about 50% of Canadians) - When smoked THC is rapidly absorbed into the blood and distributed first to the brain then to the rest of the body, peaking within 5-10 mins, metabolized by the liver, complete elimination may take 2 or 3 weeks - 1992 Anandamide- natural substance produced in the body with marijuana-like effects - In the brain works mostly on cerebellum (fine body movements), hippocampus (memory storage), cerebral cortex (higher cognitive functions), nucleus accumbens (involved in reward) - Acute administration to infrequent marijuana users shows: Slowed cognitive processing, Impaired short-term memory, Impaired inhibitory control, Loss of sustained concentration or vigilance, Impaired visuospatial processing, Fragmented speech, Impairment in attention - persistent users lose about 6 IQ points or persistent users since age 18 about 9 IQ points, loss in executive function and processing speed - Dronabinol: oral form of synthetic THC - Medicinal uses: Improve spasticity in MS patients, Delay disease progression in ALS, Management of glaucoma, Increases in airway conductance in asthma - Marijuana may decrease immune system - May cause amotivational syndrome: diminished motivation in habitual users - higher correlation with anxiety, depression and schizophrenia, abuse potential as quitting causes irritability, anxiety, loss of appetite Ch 6 - Inca empire in Peru used coca plants, holding a ball in the mouth almost continually - 1800’s as local anaesthetic, Canada banned coca additive in 1908 - Cocaine use is regionalized, either no one is doing it or many people - Freud touted as cure for many psychiatric ails including depression, morphine dependence until he saw his friend in the throws of withdrawal - Absorbs so well into mucous membranes still used as local anesthetic for surgery in nose, larynx or esophagus - 1960’s amphetamines become harder to obtain and cocaine use begins to increase - Before 1985 cocaine was a symbol of wealth and fame, majority of users snorted - “Free Base” no acid content, different chemical preparation - Late 1980’s crack was made, it was cheaper and gave everyone access - Columbia and Peru largest exporters, Mexico is a large transit country, by land is the most common smuggling method, Bolivia, Colombian cartels build submarines - Cocaine blocks the reuptake of dopamine, norepinephrine and serotonin - Metabolized by enzymes in blood and liver, rapidly removed - poisoning leads to profound CNS stimulation progressing to convulsions, lead to respiratory or cardiac arrest - Difficult to estimate lethal dose - Combination of cocaine and alcohol creates a chemical more toxic than the cocaine (cocaethylene) - Binge: irritability, restlessness and paranoia, full-blown psychosis with auditory hallucinations, formication hallucination (bugs under skin), depression, insomnia, decreased appetite, sneezing - Crack cocaine gives burst of energy, invincibility, well-being, prolonged wakefulness, appetite diminished, increased heart rate, pupils dilate - High addiction potential as it is powerfully reinforcing: if you raise a monkey in a loving environment with stimulus it doesn’t push cocaine lever to extent of addiction or death - spontaneous abortion or torn placenta are increased - Amphetamines: (originally tea, 1920’s synthesized from ephedrine) o Increased energy, wakefulness, feelings of wellness o was used to dilate bronchial passages in asthma patients o Currently used to treat hyperactive children o soldiers to keep awake o In 1950s-1970s used by athletes, truck drivers and students all legally manufactured and purchased o Most desired street version is methamphetamine, injected in liquid form, at one time used in patients who overdosed on sleeping pills to stimulate respiration, use declined until 1990s when illicitly manufactured as a crystallized form that was smoked under the names: crank, ice, glass o Canada currently limits the access to precursor chemicals that are needed in manufacture as well as those needed in its preparation o Amphetamines are close in molecular structure to dopamine and to norepinephrine, in the methamphetamine a methyl group improves crossing the blood-brain barrier o Complete elimination occurs within two days of the last dose o Abuse potential very high due to extreme feelings of euphoria o Higher doses the person is likely to panic and become suspicious to the point of paranoia o Impaired capacity to control or inhibit aggressive impulses, increased positive symptoms of psychosis, perception of the environment as a hostile and threatening place o Central effects of amphetamine: prolonged wakefulness, invincibility, increased attention, burst of energy o ADHD medication: better to cure hyperactivity than inattention, works only if parents are treated as well, 30% of meds used for non-medical purposes o Chronic Amphetamine use: formication hallucination, compulsive behavior (counting), psychosis- violent mood swings, bizarre delusions, paranoia, persist for weeks or months o Meth: ephedrine source currently cold medications, resembles dopamine Ch 11 Caffeine: Belongs to the xanthine family, more people use caffeine than any other psychoactive drug -related to alkaloids but uniquely soluble in water Theophylline Peak blood levels reached 30 mins after ingestion, half life about 3hrs. Loss of tolerance can take more than 2 months of abstinence. Withdrawal: headache, fatigue, dysphoric mood, flu-like somatic symptoms. Blocks the brains receptors for adenosine which produces behavioural sedation by inhibiting, releases norepinephrine, dopamine, mesolimbic pathways involved in reward. Low doses- increased activity in CNS, short term memory and attention. Pregnant mice have indicated that large doses of caffeine can produce skeletal abnormalities in babies. In females can reduce her chances of becoming pregnant, increase chances of miscarriage, slows growth of fetus so it weighs less at birth 10g (100 cups of coffee) required for caffeine intoxication leading to death by convulsions and respiratory arrest. Symptoms: Irritability, anxiety, restlessness, confusion, delirium, headache, insomnia,Visual flashes, ringing ears, Increased skins sensitivity, irregular heatbeat, Abdominal pain, nausea, vomiting, dehydration, fever, Seizures, trembling, twitching, overextension, rapid breathing Theophylline- in tea Theobromine- in chocolate Coffee: Egypt and other Arabic companies in Middle East use and spread to Europe in seventeenth century Spreads quickly in US because seen as opposition to tea and British, Commercial roasting NYC 1790 Latin America is world’s largest producer, Brazil leading, then Vietnam, Colombia and Indonesia third Coffea Arabica beans: milder, more expensive Coffea robusta: stronger and bitter, used in instant coffee, higher caffeine content less expensive Decaf: 1970’s people begin to remove caffeine, unroasted beans soaked in organic solvent methylene chloride (a carcinogen) which evaporates during roasting. Caffeine removed is put into soft drinks Tea: Invented in China -British levied tax on tea and chocolate, this tax extended to Canadian and American colonies, US begins smuggling tea so Britain gives East India Trading company the right to sell tea without taxes, American merchants would make no profit on this tea and the Boston harbor turns brown with tea China, Sri Lanka, India or Indonesia, pluckers only use bud leaf or first two leaves at each growth Leaves are dried and crushed then fermented until the leaves turn copper Green tea: same leaves but non-oxidized Oolong tea: partially oxidized tea 40-60mg per cup Chocolate: Aztecs created, Dutch took this liquid and removed the fat cocoa butter, mixed with sugar and chocolate powder it can easily be formed into bars, Swiss invented milk chocolate. Introduced to Europe almost a century before coffee and tea, use spread very slowly, Spanish kept preparation a secret until 1600s A large part of the crop comes from Africa 200 mg of theobromide, only 4mgof caffeine Pop: Coca-cola: originally marketed as tonic coca leaves and cola nut, leaves imported by pharmaceutical company in NJ, cocaine extracted for medical use Energy drinks:- Jolt first in 1985 Guarana extract guaranine is caffeine from a different plant, Health Canada doesn’t regulate Red Bull ingredients -sugar, caffeine and taurine together have positive synergistic effects on reaction time, memory and mood. With alcohol produces false sense of sobriety, more likely to drink and drive, drink more for longer. Ch 7 inhalants: Volatile solvents: liquid state that dissolves other substances Sniffing, Huffing (soak shirtsleeve or sock in solvent and place it over nose or mouth), Bagging (filling a bag and placing over nose, mouth or head) Depresses CNS similar to alcohol or benzodiazepines, activates the brain’s dopaminergenic system. Quickly absorbed into blood stream through lungs and travels to brain and organs. Almost immediate, lasts a few minutes. Euphoria, light-headedness, distorted vision, impulsiveness or lack of inhibition. Physical symptoms: ataxia (inability to co-ordinate muscle movements), nausea and vomiting, dizziness and flushing. Once the high passes becomes depressant, drowsy and physically ill. Risks: -sudden heart failure due to rush of adrenaline, suicide, suffocation, overdose, frostbite and burns -Risks to mothers similar to Fetal alcohol syndrome Long term risks: -anxiety, irritability, bone marrow and blood damage, CNS damage, nose bleeds, damage to heart and lungs, sneezing, coughing, hearing loss, liver and kidney damage, loss of STM, spasms, weightloss, low energy Use is higher in younger grades, poor Hispanic youth and on aboriginal reserves Use not currently controlled by Canadian federal Law but some provincial or municipal laws Gaseous anesthetics: nitrous oxide “laughing gas” has been used since 1800s, still used for light anesthesia and in combination with more effective inhaled anesthetics. Also found in whipping cream containers. Nitrites: rapid dilation of arteries, reduce blood pressure to brain faintness or even unconsciousness. Ch 13 Opioids -activate presynaptic receptors for inhibiting the release of GABA, extra dopamine. Enkephalins act like morphine released by adrenal gland, endorphins found in brain tissue and have potent opioid and released in times of stress Reduce the awareness of the pain stimulus. Patient is readily awakened if sleeping and dreams during the sleep period are frequent (“on the nod”) -they can be used to treat dysentery and dehydration, decreases number of peristaltic contractions that move food through intestines and considereable water is absorbed through intestines -codeine used for antitussive, decreases activity in cough control centre in the medulla. They make shallow cuts into unripe seedpods and during the night a white substance oozes from cuts, oxidizes to red-brown, scraped and collected in small balls. Originated in Middle East. Used as a cure-all in Greek medicine, Arabic world forbade alcohol so opium mixed with hashish became choice drug. Opium wars: 1729 China creates law against opium, smuggling opium becomes a profitable business. India has monopoly of opium where it is legal, almost everyone knew it was going on. Soon Chinese government discovers and captures a large amount of supplies, the British bargain for the return of the opium. Drunken American and British sailors kill a Chinese man and starts the opium wars in 1839. The British win the war but not until 1906 did they pass a bill ending the opium trade Morphine: Serturner synthesizes active opium ingredient ten times as potent in 1806. 1832 codeine is also isolated. Hypodermic syringe in 1853. Originally thought would not produce as much craving as opium. Civil war it was used as relief for soldiers and many came home with addiction. Attaches to morphine receptors in the brain, stimulate the receptor culminating in the discovery of endorphins. Mu agonist morphine, Kappa, Delta, Sigma Heroin: 1874 two acetyl groups attatched to morphine called under brand name Heroin. It is three times as potent as morphine, the acetyl groups increase the lipid solubility of the molecule. Synthesized using acetyl chloride or acetic anhydride that compose a significant portion of the cost of manufacture. Common way of smuggling is hollowed out objects. In US majority of opium used to come from Turkey but in 1970’s US pays Turkey to ban cultivation of opium. In Mexico the opium is processed differently creating brown or black heroin, called black tar. 1990’s reduce in price and increase in potency injection: mixed with water, heated to evaporate the water, filtered through a cotton ball and injected. Dode: grinding dried seed pod and taken with tea or hot water for a sense of well-being Oxycodone: long acting dose OxyContin, Prescription Opiods ranked third among emergency room mentions and first among drug-associated deaths. Fentanyl: approximately a hundred times more potent than morphine, used in conjunction with surgical amnesia Opioid antagonists: drugs that block the action of morphine, heroin Naxalone (Targin): reverses depressed respiration resulting from an opioid overdose, precipitate immediate withdrawl syndrome, prevents user from feeling high if they use heroin. Afghanistan, Pakistan, Iran, India and Turkey and less often Myanmar, Thailand and Laos. Opium powder can be bought for $1 a gram. Generally smuggled via transit countries, supplied by organized crime groups. Heroin is $10 per small plastic bag. Vietnam: US soldiers were there they obtained significantly stronger cheaper heroin Tolerance: cross-tolerance exists with all the opioids- reduces the effectiveness of the others. Physical dependence: nausea, vomiting, diarrhea, aches, pains, general sense of misery, rarely life threatening but very unpleasant. Withdrawal signs might begin about four hours later but usually begin 6 to 8 hours so most heroin users 3-4 injections daily. Clonidine used to treat high blood pressure but can diminish severity of symptoms. Regular use seems more im
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