Test 2 (Chapters 6, 8, 10) Flashcards
History of cocaine in South America
Indigenous people used chew coca leaves, then Spanish colonizers tried to ban it but decided to unban when they realized it makes People more productive
Why was cocaine considered a medical miracle?
Was used as local anaesthetic, used to perform the first nerve block. Also used to treat morphine addiction, exhaustion, depression, tuberculosis and allergies
Neurotransmitters effected by cocaine and amphetamine
Dopamine, norepinephrine, serotonin
How did Sigmund Freud popularize cocaine?
Was a big advocate for cocaine use, authored paper called “Uber coca” that promoted cocaine, said it was treatment for many diseases. Gave his friend cocaine to help him with opiate addiction but friend died of cocaine poisoning, then Freud stopped being big fan of cocaine
Why did USA impose much harsher sentences for crack compared to powder cocaine?
Unfair discrepancy based largely on race. Powder cocaine associated with rich while folk, crack associated with poor minorities. Average drug sentence 49% higher for black Americans than white ones.
How much of the global adult population uses cocaine?
About 0.4%. Canada one of world’s largest consumers of cocaine.
How many Canadians use cocaine?
More than 13% used at least once. 2.5% used in last month. (Ctads). Men more likely to use. Cocaine use increasing over past few years. Use by high schoolers goes through cycles.
What is Erythroxylum coca
Native shrub to Andes mountains. 1% of weight of the leaf is cocaine but higher altitude = more cocaine. Contain iron and calcium and may have helped indigenous people survive.
3 main steps to isolating cocaine from coca leaves
- Crude coca paste is extracted from the leaf
- Coca paste purified to Coke base
- Coke base is converted into cocaine HCI
Drug mules
People who carry cocaine across the border
Forms of cocaine
- Coca leaves, only have a small amount of cocaine, gives a coffee like lift, very little abuse
- Powder cocaine, water soluble, can’t be smoked because breaks down at high temperatures, higher percentage than leaves.
- Freebase, when cocaine is separated from acid it’s lipid solubility increases. Can be smoked.
- Crack, safer than freebase in terms of flammability and quicker and more intense than powder.
Cocaine routes of administration
Topical, oral (not common as first pass effect metabolizes 70-80% of it before it reaches brain), snorting (insufflation), smoking (fastest way), injection (takes longer bc needs to travel to heart to go into lung to then go into brain)
Distribution, metabolism and elimination of cocaine
Distributed through body tissues by cytochrome P450 system of liver, liver and blood enzymes degrade cocaine.
Mechanism of action of cocaine and affects on neurotransmitters
Blocks sodium channels which interferes with action potentials in pain pathways. Blocks reuptake of dopamine, norepinephrines and serotonin. Cocaine increases dopamine in basal ganglia, ventral tegmental area and nucleus accumbens. Affects functions controlled by seratonin like mood and sleep and appetite. Affects norepinephrine which controls sympathetic nervous system.
Acute effects of cocaine
Euphoria, arousal, energy, dry mouth, headache, sweating, decreased appetite
Cocaine is sympathomimetic meaning:
It mimics the effects of the sympathetic nervous system and increases heart rate, increases blood clots, constricts blood vessels. Decreases appetite and causes headache.
Adverse side effects of cocaine
Psychological effects like fear, hostility, anxiety and irritability. Can cause heart attacks. Overstimulation of CNS, perforation of nasal septum. Formication: delusion that insects are crawling under skin.
Cocaine taken with alcohol
Forms a new compound called cocaethylene, gives greater euphoria, enhances stimulation and is more toxic. Increases risk of death by 18-25x
Adverse effects from chronic use of cocaine
Speed up aging of the brain, higher rates of brain shrinkage, sexual dysfunction, can develop autoimmune disease. Death and scarring of heart tissue. Premature death.’ hallucinations and delusions.
Effects of cocaine when taken during pregnancy
Higher rates of miscarriage and stillbirths. Constricts blood flow to placenta. Low birth rate and smaller heads. Babies more jittery and overly sensitive to sensory stimuli.
Cocaine tests on monkeys
Monkey pressed bar to get cocaine 12,800 times. They would self administer cocaine until they die and do nothing but consume cocaine.
Delay discounting
Delay discounting measures self control. Cocaine use associated with significant impairments in this, and ppl world rather get small rewards than wait for big ones. More likely to have unprotected sex.
Cocaine is in which schedule and approved for which type of surgeries?
Schedule I, oral and eye
According to CTADS, what % of Canadians over 15 have used cocaine or crack?
13%
One of the major drawbacks of using cocaine in this form is that it is usually cut with another substance before being sold to consumers, and this additive may be more harmful than the drug.
Powder
One easy way to recall many of the physiological effects of cocaine is to remember that it is a sympathomimetic, which means that
cocaine mimics the effects of the sympathetic nervous system, which turns on the fight-flight response.
Chronic users of cocaine may develop _______ to certain effects of the drug, including euphoria and some stimulant effects, more quickly than other less desirable effects.
Tolerance
It is difficult to study the _______ effects of prenatal cocaine use due to confounding factors such as access to healthcare and use of other drugs during pregnancy; however, it is clear that unborn infants of women who use cocaine during pregnancy have higher rates of ________.
long-term; miscarriage and stillbirths
Compared to other common drugs of abuse, cocaine withdrawal is more dangerous than withdrawal from _______, and less dangerous than withdrawal from _______.
marijuana and nicotine; opioids and alcohol
All of the following pharmacological interventions may be helpful in treating cocaine addiction EXCEPT:
-Antabuse, which is used to treat cravings in alcohol addiction.
-Nicoderm, which is used in smoking cessation.
-Modafinil, which is used to treat narcolepsy.
-Propranolol, which is used to lower blood pressure.
Nicoderm, which is used in smoking cessation.
What is more popular, amphetamines or cocaine?
Amphetamines are currently more popular than cocaine, in part because their effects are more potent and sustained, they can be administered by several routes, and they can be easily and inexpensively synthesized. As many as 27 million people around the world used amphetamines, including prescription stimulants, in the past year.
What is ma Huang and what is its active ingredient?
For more than 5,000 years, ma huang has been used to treat asthma and other breathing problems. Ma huang is the Chinese name for the leafless Ephedra sinica shrub, which grows throughout the desert regions of Asia and North America. Ephedrine, an active ingredient of ma huang, was isolated in 1885. Ephedrine is less fat-soluble than amphetamine and cocaine, so it has fewer psychostimulating effects, although it does increase heart rate and blood pressure.
What was amphetamine originally made for?
Developed to treat asthma. In 1930’s it was marketed to treat congestion, narcolepsy and depression. The drug also became popular in the 1930s with college and university students cramming for exams, dieters, long-distance drivers, and factory workers, who found that amphetamine decreased their appetite and their need for sleep. Amphetamine was considered a miracle drug. By the 1940s, there were 39 clinical conditions for which amphetamine could be used.
When did methamphetamine become popular?
Eventually, the medical community became aware of the dangers of amphetamine use. The phrase “speed kills” became popular, and amphetamines began to fall out of favour until the 1990s, when methamphetamine, a more potent form of the drug, increased in popularity. Went up 3x in use in 90s but now on decline.
Prevalence of amphetamine use
Around 27 million people around the globe use amphetamine-type stimulants each year. Stimulant drugs containing amphetamines are used to treat attention-deficit/hyperactivity disorder (ADHD)
Methamphetamine legality in US and Canada
Methamphetamine is not legally available under any circumstance in Canada, but it is legally available by prescription (under the brand name Desoxyn) in the US to treat ADHD and obesity.
Amphetamine chemical forms (right and left handed amphetamine molecules)
Amphetamine (Benzedrine) is a mixture of both right- and left-handed amphetamine molecules. The left-handed derivative (levoamphetamine) raises blood pressure, opens nasal passages, and causes headaches, but does not have significant mood-elevating effects. The right-handed isomer—dextroamphetamine (Dexedrine)—has stronger effects in the brain, elevates mood, and enhances energy. Replacing a hydrogen atom on dextroamphetamine with a methyl group (thus producing methamphetamine) increases its lipid solubility and potency and leads to even stronger effects in the brain.
Therapeutic doses for amphetamines
Therapeutic doses typically range from 2.5 to 40 mg per day for ADHD and from 5 to 60 mg per day for narcolepsy. Common abused doses are 100 to 1,000 mg per day, but binge users may take as much as 5,000 mg per day.
ROA for amphetamine and methamphetamine
Amphetamine and methamphetamine can be ingested, injected, snorted, and smoked. Just as with cocaine, smoking has the fastest onset of action, followed by injection, then snorting, and finally, oral administration.
Cocaine vs amphetamine pharmacokinetics
The time it takes for effects to first occur is slightly slower compared with cocaine, but the peak effects and duration of action is longer with amphetamines than with cocaine. Methamphetamine is more lipid-soluble than amphetamine, and it is, therefore, better able to penetrate the BBB.
Ice (meth)
Ice is the freebase concentrated, smokable form of methamphetamine. Ice is to methamphetamine as crack is to cocaine. Unlike crack, ice has a very long half-life (about 12 hours), resulting in an intense, persistent high.
Amphetamine absorption (from where, and what is fastest) and distribution (to where)
Amphetamine is well absorbed from the nasal cavity, lungs, and GI tract. It is absorbed fastest when smoked or injected, but unlike cocaine, amphetamine also is effective when swallowed. Once absorbed, amphetamine is distributed to the brain, kidneys, and spleen.
Amphetamine/meth metabolization
Methamphetamine is metabolized into amphetamine in the liver via N-demethylation and the cytochrome P450 enzyme system. The liver metabolizes amphetamine more slowly than it does cocaine, which increases amphetamine’s duration of action, as well as its toxicity.
Meth/amphetamine excretion
These drugs are excreted by the kidneys, as well as in the sweat and saliva. Amphetamine is alkaline, so when urine is more acidic, the drug is leached out of the blood into the urine and excreted more rapidly. Consumption of large amounts of vitamin C, vinegar, or acidic fruit juices can speed up the elimination of amphetamines.
Mechanism of Action of Amphetamines: neurotransmitters
Amphetamine and methamphetamine increase postsynaptic levels of dopamine, norepinephrine, and serotonin (more than cocaine). They do this via a number of mechanisms: increasing release; blocking reuptake; and at high concentrations by inhibiting MAO, the enzyme that breaks down monoamine neurotransmitters such as dopamine, norepinephrine, and serotonin. It causes dopamine to be released from inside the vesicles into the cytoplasm of the nerve terminal. Amphetamines also increase release of serotonin and norepinephrine.
Acute and Adverse Effects of Amphetamines + withdrawal
The physiological and psychological effects of amphetamine resemble those of cocaine, although there is a slower onset of effects and a longer duration. Amphetamines reduce appetite, food intake, and body weight, but tolerance quickly develops and these beneficial effects are lost. The side effects and withdrawal seen with amphetamines are similar to those of cocaine. Upon withdrawal, users may experience craving, depression, lethargy, muscle pain, and abnormal sleep patterns.
Amphetamine tolerance
With high doses of amphetamines, rapid tolerance can occur. Because amphetamines work, in part, by displacing dopamine, norepinephrine, and serotonin from their presynaptic storage sites, a dose of amphetamine can deplete neurotransmitter levels enough such that another dose might produce a reduced effect. This tolerance can last for days or longer.
Adverse Effects from Chronic Use of Amphetamines
• weight loss
• skin sores that do not heal
• poor oral hygiene, including tooth deterioration
• liver disease
• hypertensive disorders
• cerebral hemorrhage
• cardiac arrhythmias
• myocardial infarction
• kidney damage
• seizures
Psychological effects of amphetamine use
Repeated use of amphetamines over days or weeks can lead to a psychotic state of hallucinations, hostility, panic, and paranoia that resembles schizophrenia. Amphetamine psychosis can persist for weeks or even months after the drug has been withdrawn. These psychological deficits can be much more severe than the psychosis associated with cocaine use, due to amphetamines’ higher potency and longer half-life.
Amphetamine neurological effects
Sustained administration of high doses of amphetamines (especially meth) can produce persistent—and possibly irreversible—damage to dopaminergic and serotonergic nerve endings, an effect that does not seem to occur with cocaine use. The duration of damage is not yet known. This dopamine loss is especially significant in brain areas responsible for movement, memory, and decision-making. Hyperthermia, another effect of amphetamine use, enhances this neurotoxicity
Amphetamine Dependence and Addiction (what percent of ppl have problematic use)
Not all users become addicted, and many users of methamphetamine stop abusing the drug without formal substance abuse treatment. 2017 CTADS survey notes that about 0.3 per cent of the Canadian population over age 15 self-reported problematic use of prescription stimulants. Notably, of those who have ever used prescription stimulants to get high, almost 20 per cent of these individuals self-report eventual problematic use.
This substance, historically used to treat breathing problems, has fewer psychostimulating effects compared to cocaine or amphetamine and was the impetus for creating synthesized amphetamine in the search for a more efficient treatment.
Ephedrine
Amphetamine was initially touted as a miracle drug and was thought to be safe and effective. In fact, _______ considered giving amphetamines to his employees to keep his workers focused and working longer hours.
Henry Ford
Approximately _______ of the Canadian population age 15 and older report using prescription stimulants such as Adderall, Vyvanse, or Ritalin in the past year.
2%
List forms of amphetamine from weakest to strongest
Levo-amphetamine → dextro-amphetamine → methamphetamine
For both cocaine and amphetamine, what is the correct order from fastest to slowest onset of action based on route of administration?
Smoking → injection → snorting → oral administration
Compared to cocaine, amphetamine has a _______ onset, a _______ period of peak effects, and a _______ duration of action.
slower; longer; longer
Sustained administration of high doses of amphetamines may produce which effect that is not seen in cocaine users?
Damage to dopaminergic and serotonergic nerve endings that is probably irreversible
Khat/Cathinone (bath salts)
Catha edulis is a leafy shrub native to East Africa and the southern part of the Arabian Peninsula. Khat is one of the most popular stimulants worldwide; up to 10 million people use it daily. The fresh leaves of the shrub contain the active ingredient cathinone, which is structurally similar to amphetamine. Methcathinone (sometimes called “cat”) is a synthetic variant that is more potent than cathinone.
Khat ROA effects
When taken orally and in moderation, khat is a mild stimulant, much like strong coffee. When it is snorted, smoked, or injected, khat’s effects are more similar to those of amphetamines. Exhilaration, euphoria, elevated energy, hyperactivity, talkativeness, thirst, and appetite suppression are all effects associated with khat.
Bath salts
Synthetic derivatives of cathinone, such as mephedrone, methylone, and MDPV (3,4-methylenedioxypyrovalerone) are psychoactive substances similar to khat.
Bath salts side effects
Desired effects reported by users include euphoria, increased energy, wakefulness, enhanced motivation, empathy, mental stimulation, sociability, and increased libido. The more common effects include rapid heart rate, high blood pressure, insomnia, nausea, GI distress, teeth grinding, hyperthermia, headache, dizziness, and ringing in the ears. People may feel agitated, confused, paranoid, and experience delusions, violent behaviour, and suicidal thoughts. Kidney failure, liver failure, seizures, heart attacks, and death have occurred due to the use of bath salts, which are now classified as Schedule III compounds.
Khat comes from _______, a leafy shrub that contains the stimulant substance _______; _______ was developed as a synthetic version but never marketed due to the side effects.
catha edulis; cathinone; methcathione
Mephedrone, methylone, and MDPV are all synthetic derivatives of _______ and therefore have psychoactive properties similar to _______.
cathinone; khat
History of tobacco-early uses
- Indigenous people used for thousands of years
- Columbus brought back to Europe and its use spread
History of tobacco: 17th - early 20th century
- English colony of Virginia cultivated tobacco
- in Canada, began in Ontario in 1800
- development of cigarette rolling machines boosted production and lowered costs
- smoking became very popular global habit
- marketing to women
- 1908 tobacco restraint act prohibited sales to people under 16, never endorsed
History of tobacco- 20th century
- Early 1950s, scientific studies showed link between smoking and lung cancer
- 1964 U.S. surgeon general report said cigarette use related to many serious illnesses
- tobacco industry response: industry research committee launched public relations campaign to encourage sneaking, attack scientific findings
1988 tobacco sales to young persons act
Prohibited sales to under age 18, non smokers health act banned smoking in federal workspaces, planes, trains, ships except some areas. Hazardous products act amended to ban advertising of tobacco, warnings or packages became stronger
1997 tobacco act
Comprehensive regulations and standards. Tobacco companies may not associated with youth or attempt to convince youth to use their product
2000 tobacco damages and health care costs recovery act
To recoup some health care costs associated with tobacco related diseases. Upheld by Supreme Court, allowing provinces to sue tobacco companies for damages
Prevalence of tobacco + is it increasing
- Smoking declining in Canada and most western nations but on rise in developing world, especially Asia
- Canadian tobacco and nicotine survey (2019) of ages 15+: 12% of Canadians current cigarette smokers, 9% daily smokers who half of term have attempted to quit, 5% use vapes
Tobacco use - gender and race
Men more likely than women, men 4 x more likely to smoke cigars. Indigenous people much more likely to use tobacco than other groups
Tobacco use-education, employment, use of other drugs and mental health
- The more educated a person, less likely to smoke
- smoking rates highest for those who are poor even though cigarettes very expensive
- use of other drugs and mental illness makes individual significantly more likely to smoke
Tobacco use - age
- most addicted smokers started as teens
- cigarette use among teens declining due to: higher disapproval and awareness of danger, less advertising, better control on sales and increased popularity of e-cigs
- teens more vulnerable to becoming addicted because frontal lobe not developed, and if they are exposed to it
Governmental Economic and social issues related to tobacco
Canadian government receives less tax revenue from tobacco companies than costs of health care and other issues.
Efforts to reduce tobacco use: packaging
2000 - products must have warning messages covering 50% of display space
2011- 75% of display space must be warnings
2019 - plain packaging regulations, standardize size and appearance of cigarettes and their packaging
How tobacco companies advertise to specific groups
Would have specific cigarettes for children and teens (joe camel) and women (Virginia slims). Increase in # of smokers in targeted groups. Deaths from lung cancer increased in women after intro of Virginia slims
Sources and forms of tobacco
Tobacco plant: nicotiana tabacum, native to North America. Natural source of nicotine, highly addictive and toxic stimulant. Different method of curing the leaves with different pH and nicotine levels
3 Most important toxic compounds in tobacco smoke
Carbon monoxide: invisible toxic gas, attaches to hemoglobin better than oxygen, slow asphyxiation of body, cause of cardiovascular diseases
Tar: sticky, adheres to cells in lungs and airways, impairs ciliary escalator ( self clearing mechanism of airways), permits carcinogenic compounds to settle on pulmonary tissue, origin of metastatic cancers
Nicotine: widely used as insecticide, toxic, dependence producing psychoactive drug found exclusively in tobacco. Passes blood brain and blood placental barrier in 5-8 seconds
What is most toxic way of consuming tobacco
Smoking cigarettes. Manufactures add as many as 600 different chemicals, including hydrogen cyanide (used in lethal execution by gas), chlorofluorocarbons (refrigerants) ammonia (toilet cleaners), industrial solvent, car batteries, many carcinogens. Manufactures control amount of nicotine to make cigarettes more addictive. Tar clogs up Cilia in lung airways and contaminants can’t be cleared.
Electronic cigarettes/vaping difference from cigs
Deliver nicotine as a vapor, no tobacco is consumed. Contain flavouring and propylene glycol. Reduces exposure to tar but long-term effects of propane, glycol or unknown some studies fine health risks. Quality control standards may be lacking, and there is risk of exploding batteries and exposure to concentrated nicotine and severe pulmonary illness.
Risks associated with vaping
Vapes purchase from online retailers have been linked to thousands of hospital and missions and deaths. Contain diacetyl, formaldehyde and acene, which is a weed killer. Risk of popcorn lung with no treatments and vaping related lipoid pneumonia. symptoms of chronic cough, shortness of breath, chest pain, and coughing up blood.
Is vaping more or less addictive than regular tobacco smoking?
Preteen and teens who use vapes are 7X more likely to become cigarette smokers. Nicotine concentration can be much higher in vapes compared to cigarettes. The Fagerstorm test for nicotine dependence reveals that vape users may have double dependence for nicotine compared to tobacco smokers, although studies inconclusive. Although other health effects are significantly less for vapes compared to tobacco smoking.
Hookahs
Large water pipes imported from Arab countries. Tobacco is placed in the head where it is burned the outage cool contributes to a number of added toxins to tobacco sessions tend to last up to 25 minutes with people puffing between 5200 times. A single water pipe session results in same carbon monoxide and tart intake as smoking 100 cigarettes.
Smokeless tobacco
Allows, nicotine fix in situations where smoking is prohibited, false perception that smokeless tobacco is safe as users are still exposed to many carcinogens and other health risks, examples, chewing tobacco and snuff, which is snorted.
Absorption of nicotine
Nicotine is rapidly absorbed through the skin, mucous membranes, lungs, and G.I. tract depends on root of administration, composition, quantity, and volume and pH of tobacco. Smoking is quickest way to get nicotine to brain, absorbed nicotine concentrated in the brain, liver, kidneys, salivary, glands, and stomach.
Metabolism of nicotine
Primarily in liver, also kidneys and lungs. Half-life about two hours. Most is transformed by one of the cytochrome P450 system enzymes into two active metabolites. metabolism can be slowed by menthol, grapefruit, SSRIs. Women metabolize, nicotine, faster than men.
Nicotine drug interactions
Nicotine feeds metabolism of some drugs, such as Valium. Increases cocaine addictiveness. Increases alcohol use, and makes smokers more likely to be addicted to alcohol.
Mechanism of action of nicotine
Has biphasic effect on ACH receptors. Find two nicotine colonic receptors and excites them and has high affinity-stays bound, which prevents nerve firing until removed. Find two receptors in the ANS. CNS receptors are in the cortex hippocampus and midbrain, has reinforcing an addictive effects mediated by midbrain specifically ventral tegmentum, and nucleus accumbens
Acute effects of tobacco and nicotine
Overdose is rare but possible, therapeutic index 21. Nicotine calms and relaxes smokers probably due to alleviation of withdrawal symptoms associated with depression. Smoking may be self medicated and inhibits MAO. May enhance memory and cognitive function.
Acute toxic effects of nicotine
60 mg is lethal to an adult. Approximately 8 mg per cigarette. 2.5 dead adults per pack of cigarettes if 100% nicotine absorbed. Death is by acute and severe convulsions/epilepsy, legitimate risk for children, tobacco workers and laboratories use.
Chronic effects of tobacco and nicotine
Tolerance to develop rapidly for some effects, but little to no tolerance to increasing heart rate, tremor. Withdrawal occurs fairly rapidly, including craving mood changes, physiological, and cognitive symptoms
Tobacco addiction and death
Tobacco addiction is the single greatest cause of premature death in the world. Also kills 45,000 Canadians each year more than alcohol, illegal drugs, fires, motor vehicle injuries, homicide and suicide combined. Top four causes of death in North America: heart disease, cancer, stroke, and lung problems can all be traced to tobacco
Adverse effects of tobacco usage
Life-threatening conditions like cardiovascular disease, cancer, and chronic obstructive pulmonary disease. Also causally associated with diabetes, tuberculosis, hearing and vision problems inflammation and cancer. Prematurely, aged and wrinkled skin.
Prenatal and postnatal effects of tobacco
Harmful to fetus, nicotine other chemicals can pass the placenta. Prenatal exposure to nicotine may result in long-term, intellectual and physical deficiencies high risk of miscarriage, stillbirth, premature birth, depression, ADHD.
Secondhand smoke
Combination of smoke exhaled from the silver plus smoke that rises off the end. Associated with her incident of heart, disease and lung cancer causes 800 deaths every year. Concern over second month has led to bands on public smoking.
Why is nicotine so addictive?
Rapid delivery of nicotine to brain 5 to 8 seconds, short interval between behavior, reward pairings. High frequency of smoking behavior. Environment/social context in which nicotine is used causing complex environment reward pairings. Nicotine receptors are widely expressed in brain and widespread effects on neurobiological learning mechanisms. Six months relapse rate is 80%.
Quitting tobacco and nicotine
Most people could smoke water to quit and have tried quitting once in the past year, but it is very hard. Combining pharmaceutical aids and cessation programs increase odds of successfully quitting. Nicotine replacement therapy like nicotine, gum, and skin patches or drugs that don’t replace nicotine like antidepressants. Counselling stress management and behaviour modification.
Canada’s federal tobacco control strategy
Services to help young Canadians quit, funds for research and public health groups. Protect youth and non-tobacco uses from nicotine addiction with educational programs etc. Work with Indigenous groups to create specific plans. Strengthen science, surveillance and partnerships.
Why are opioids sometimes referred to as narcotics
Nacro-means sleep. Opioids make you sleepy, dulls senses and relieves pain.
Opiates vs opioids
Opiates are drugs—including opium, morphine, and codeine—that occur naturally in the opium poppy. Opioids is a comprehensive term that refers to any natural, synthetic (manufactured), or endogenous (produced by the body) substance that binds to the opioid receptor.
Early opioid use
The first known written reference to the plant is in an ancient Sumerian text from around 4,000 BCE that refers to the opium poppy as hal gil, or “joy plant.” Opium use spread throughout the Middle East, North Africa, and Greece. Alexander the Great gave his army opium to help them march longer and sleep more restfully, and the Greek physician Hippocrates wrote of opium’s sleep-inducing properties.
Laudanum
In 1524, the Swiss physician Paracelsus created laudanum (from the Latin meaning “to praise”), a medicinal drink that combined opium, wine, musk, crushed pearls, and spices. Physician Thomas Sydenham introduced his own formulation in 1680, which skyrocketed in popularity over the next two centuries.
Opium den
Opium smoking was typically a social/communal event rather than a private event. Many opium dens had couches or beds on which users could recline as the drug took effect. Opium dans became social meeting places
Opium in 1700 - 1800
Sailors and traders introduced China to opium smoking. Widespread opium addiction followed. In 1750, Britain assumed control of opium growing districts in India, and for the next several decades, England held a monopoly on the sale of opium. England’s desire to maintain their lucrative opium trade to China would eventually lead to not one, but two wars.
Opium wars
By the 1830s, the opium habit was associated with so much crime that the Chinese government banned it. In 1839, the emperor of China sent Commissioner Lin Tse-Hsu to the port of Canton, where he seized and destroyed over 20,000 chests of opium. In retaliation, the first Opium War started (Britain called it “The War for Free Trade”). 25,000 Chinese solids died, Shanghai fell to Britain. The second Opium War began in 1856, and this time French and American forces joined British soldiers to once again defeat China. Among other conditions, the terms of the Convention of Peking, which ended the war, legalized the opium trade. By 1900, half of the adult male population of China was addicted to opium.
Opiate addiction in the Western world skyrocketed during the 19th century. This was due to a number of factors, including the following:
Isolation of morphine, invention of the hypodermic syringe (by Dr Alexander Wood in 1853) , influx of Chinese immigrants to build railroads and had opium dens to help them cope, war and war injuries (400,000 veterans addicted), patent medicine (opium found in many medicines as treatements)
Social factors influencing opiate laws
In 1868, the British Parliament passed the Pharmacy Act, which restricted the sale of opiates to pharmacists and doctors. This meant that the wealthy could go to a doctor to obtain their morphine, but it was more difficult for the poorer people to obtain their less addictive and less potent opium. In reality, administration of morphine by a physician was more likely to lead to addiction than consumption of opium in a patent medicine. The first drug law in Canada—the Opium Act of 1908—was in large part aimed at outlawing opium smoking by Chinese immigrants.
Synthesis of heroin
Heroin was first synthesized in 1874 by British chemist Charles Adler Wright. After initial tests, Wright shelved the drug, and heroin went unnoticed for 23 years, until chemist Felix Hoffman, working at the Bayer Company, resynthesized it. He added two acetyl groups to morphine and created diacetylmorphine, eventually to be named heroin. Later that year, Hoffman added an acetyl group to salicylic acid, thus creating Aspirin. Hoffman’s supervisor, thought Aspirin was a worthless product, but he had confidence in heroin’s commercial potential and marketed the drug as a remedy for tuberculosis, laryngitis, and cough.
Opioids in 20th century
By the beginning of the 20th century, opium and its derivatives were found in more than 50,000 medicines, causing widespread addiction. The Canadian government began to introduce measures to crack down on drug use. As they did in England years earlier, in Canada drug laws reflected a racial and class bias.
Behind Canada’s 1908 opium act
In Canada in 1907, White residents rioted in Vancouver’s Chinatown, opposed to the rumoured arrival of more cheap labourers. The deputy minister of labour (and future prime minister), William King, was dispatched to Vancouver to assess the damage. He identified that there was an increased popularity in opium smoking among White people, Profits from the sale of opium were going to the Chinese, not to Canadians and Opium smoking was contrary to Christian beliefs.
1908 proprietary and patent medicine act
Required manufacturers to disclose if opium, heroin, morphine, or cocaine was included in the formulation of a medicine
How many people used heroin in Canada 1980-2000
In the early 1980s, there were perhaps 20,000 heroin users in Canada, based on RCMP estimates—about 60% of whom lived in Vancouver, with most of the remainder living in Toronto and Montreal. By the early 1990s this estimate increased into the 30,000s, and by the 2000s, perhaps 50,000 daily users in Canada
What is worlds largest heroin supplies
In the 1990s, Afghanistan increased its poppy cultivation and became the major source of opium around the world. In 2000, the ruling Taliban banned poppy cultivation, which cut Afghanistan’s production by 94 per cent. But in 2001, American and British troops removed the Taliban from power, and heroin production increased once again.Today, Afghanistan is the world’s largest supplier of heroin (and is a major supplier to Canada), producing more than 90 per cent of the world’s opium and earning $3 billion in revenue for local farmers.
How much does non-medical use of opioids cost Canada
costs Canada about $3.5 billion each year in health care, lost productivity, and criminal justice costs.
Worlds biggest opioid consumers
individuals in the United States consume more narcotic medication than any other nation worldwide. Americans consume about 80 per cent of the global opioid supply.27,28 Canadians, per capita, are the world’s second-biggest consumers of prescription opioids. Canada was also the second-biggest consumer of oxycodone. Whereas the use of these drugs has increased sharply over the past few decades in the United States, use in Canada has been declining. Prescriptions also declining.
The rates of prescription opioid use and abuse may be due to
• an increased number of prescriptions being written by primary care physicians instead of pain management experts
• unethical pain clinics and “pill mills” that dispense prescription pain medications outside of the scope of legitimate medical practices
• increased internet access to prescription drugs
• insufficient oversight to control inappropriate prescribing
• greater social acceptability when it comes to using these medications
• aggressive marketing by the pharmaceutical industry in direct-to-consumer ads
Prescription opioids abuse routes
The non-medical use of prescription painkillers to get high in Canadians age 15 and over is low—in many CTADS and CADUMS surveys the number is suppressed and when reported is much less than 1 per cent. Of the 12 per cent of Canadians who reported prescription opioid use in 2017, about 3 per cent of these individuals reported problematic use. The situation is much different in the United States, where non-medical use of opioids has more than quadrupled since 1987. In 2015, almost 1 in 20 Americans (12 million people) reported using prescription opioid pain relievers for non-medical purposes, in the past year.
Heroin usage in Canada
According to the 2017 Canadian Tobacco, Alcohol, and Drug Use Survey, about 0.7 per cent of Canadians age 15 and older have tried heroin at least once in their lives, up from 0.4 per cent in 2015, 0.5 per cent in 2013. The 2016–17 Canadian Student Tobacco, Alcohol, and Drugs Survey reported about 0.6 per cent of students in grades 7–12 had used heroin in the past year, similar to the 0.6 per cent past-year use reported in 2014–15. The most recent CTADS data suggest that lifetime heroin use may be on the rise
Why heroin use may be on rise+change in demographic
Use of prescription pain medications-80 per cent of new heroin users started out misusing prescription pain medications. Some people who abuse prescription opioids may find that heroin is easier to obtain, more potent, and less expensive. Today, heroin is purer than in the past, and users can snort or smoke the drug, which brings in more users who might otherwise be dissuaded by the prospect of injecting.
The demographic composition of heroin users also has changed. In the past, heroin use was largely seen in inner-city minority populations, but use has spread to the suburbs and rural towns, where it is primarily used by young White men and women in their late twenties.
Natural, semi-synthetic and synthetic opioids
Natural: morphine, codeine
Semi-synthetics: made by chemically modifying natural opiates. heroin, hydrocodone, oxycodone
Synthetic: Synthetic opioids do not occur naturally and are not all chemically related to natural opiates. Methadone, fentanyl, tramadol, meperidine
Primary source of naturally occurring opioids
The poppy flower, Papaver somniferum (“the poppy that brings sleep”). Native to southern Europe and western Asia, the poppy flower is now cultivated all over the world. The plant, which grows to a height of a little more than one metre, produces red, white, or purple flowers. Nearly 100 different kinds of poppies exist, but only Papaver somniferum produces a sufficient quantity of opium.
pharmacologically active alkaloids in natural opioids
3 most common: morphine (10x more potent than opium, soluble), codeine (1/12 effective as morphine, given in combo with NSAIDS, produces less sedation and better orally), thebaine (no psychoactive effectives, not abused).
OxyContin (semisynthetic)
Oxycodone’s delayed-release form is OxyContin. Used to treat chronic and severe pain, OxyContin was formulated to be delivered over a longer period of time than Percocet or Percodan. Resourceful users discovered that if they crushed the pills and snorted them, or dissolved the powder in water to inject, then all 12 hours of opioid was delivered at once, making OxyContin as potent as heroin.
Purdue Pharma, OxyContin’s manufacturer, admits that scores of people have died from the drug. In 2007, they agreed to pay US$634.5 million for understating OxyContin’s problems. Three years later, they reformulated the drug to decrease its abuse potential, and abuse has decreased significantly.
Hydrocodone (Vicodin) semi-synthetic
often formulated in combination with acetaminophen, and is about 1.5 times as potent as morphine. Although hydrocodone is prescribed in Canada, it does not have near the popularity that it does in the United States
buprenorphine (Subutex, Butrans) -semi - synthetic
Low doses of buprenorphine (Subutex, Butrans) relieve mild to moderate pain, but higher doses are used to treat opioid addiction. Buprenorphine relieves opioid cravings but does not tend to cause dependence itself and can be given alone or combined with naloxone.
Etorphine (semisynthetic)
Etorphine is an extremely potent opioid discovered in 1960 in an Edinburgh lab when some scientists accidentally stirred their morning tea with a glass rod used in an experiment. The unsuspecting scientists were knocked into a coma. Once they recovered, they analyzed the compound and found it 10,000 times as strong as morphine. Other studies have shown etorphine to be as much as 80,000 times as potent as morphine. Etorphine is not used medically for humans. Instead, it is the key ingredient in dart guns used to stun elephants and rhinos.
Meperidine (Demerol) - synthetic
Meperidine (Demerol) is about as strong as codeine. Shorter-acting and less potent than morphine, meperidine is used for relief of moderate to severe pain, particularly in obstetrics and after surgery.
methadone (Dolophine)- synthetic
German scientists invented methadone (Dolophine) as a substitute for morphine during World War II when natural opium could not be obtained from the Far East. Methadone is chemically different than morphine, is better absorbed orally, longer lasting, and provides pain relief with little to no euphoria. Tolerance, dependence, and withdrawal do develop to methadone, but at a slower rate than with morphine. Methadone not only blocks the effects of heroin, but its gradual and mild onset of action also staves off withdrawal without the intense highs and lows of heroin. Today, methadone is used for relief of chronic pain, but it is most commonly used as a maintenance drug for opioid addicts.
Fentanyl
Fentanyl (Sublimaze, Actiq) is highly lipid-soluble (passes through BBB), and so it has a rapid onset and short duration of action. Fentanyl can be administered intravenously for general anaesthesia, and in the form of patches and lollipops to treat chronic pain. Easy and cheap to produce and similar in form and colour to heroin, fentanyl is sometimes added to batches of heroin and other illicitly created versions of drugs. Because it is up to 50 times more potent than heroin, fatal overdose is possible, and fentanyl-related deaths are on the rise. When taken intravenously, fentanyl can paralyze the muscles of the chest wall, which prevents breathing, and can kill within minutes.
Onset of Opioid Effects Based on Route of Administration
smoking 7–10 seconds
intravenous injection 10–20 seconds (heroin enters bloodstream fastest like this but dangerous for some drugs like OxyContin because some components of pills are insoluble and damage blood vessels)
intramuscular injection 5–8 minutes
snort or sublingual 5–15 minutes
oral ingestion 30–45 minutes, go through significant first pass effect
transdermal patch up to 16 hours
Absorption and metabolization of opioids
After absorption into the bloodstream, opioids accumulate in the liver, lungs, spleen, muscles, and GI tract. Because most opioids are not very lipid-soluble, they do not easily cross the blood brain barrier. In fact, less than 0.1% of an opioid typically reaches its active site in the central nervous system. Drugs like heroin and fentanyl are more fat-soluble, so they reach the brain faster. Once heroin reaches the brain, it is converted back into morphine—heroin is essentially just a more effective delivery system for morphine. Opioids are metabolized in the liver, and some metabolites are more potent analgesics than morphine. Once metabolized, most opioids are eliminated in the urine and feces.
Naloxone
In the 1960s, chemists slightly altered the morphine molecule and produced a substance called naloxone, which reversed the effects of morphine. Scientists assumed that naloxone and morphine must act at a common brain receptor site. Prevent overdose
What opioids do when binding to pre/post synaptic receptors
Opioid receptors are located both presynaptically and postsynaptically. When opioids bind to presynaptic opioid receptors, they act as neuromodulators and affect the release of neurotransmitters such as dopamine, norepinephrine, GABA, histamine, and acetylcholine. When opioids bind to postsynaptic receptors, they act as neurotransmitters and directly alter membrane potential. The body’s response to an opioid depends on which receptor it binds to, its affinity for the receptor, and whether the opioid is an agonist (initiating a physiologic response) or antagonist (blocking a physiologic response).
four principal classes of opioid receptors
- Mu, ventral tegmentum, reward and addiction
- delta, changes in sensory and perception, anti depressant and addiction
- kappa, pituitary gland, hormone release, sedation and disorientation
- ORL -I, lambic system, anxiety, depression, pain modulation
Endogenous opioids
If our brains have receptors for specific compounds, it must mean that our bodies produce a similar chemical that binds to those receptors. In 1974, two different laboratories identified a naturally occurring peptide that mimicked opioid action and bound to opioid receptors and was found in high concentrations in brain areas similar to those in which opioid receptors are found. As a group, these endogenous opioids are called endorphins
Opioids Physiological Effects at Low and Moderate Doses
Opioids cause muscles to relax and limbs to feel heavy. Body temperature generally falls, and skin may flush. Opioids also release histamine, which can cause itching over the entire body. In addition to these acute effects, opioids may affect pain, mood, breathing, digestion, urination, sleep, and reproduction
Opioids and Central nervous system
Opioids bind to many areas of the brain and spinal cord, including regions that control pain, mood, cognition, reward, and addiction. They bind to nuclei in the midbrain that cause the pupils to constrict. When first administered, opioids also stimulate the area postrema, which is the vomiting centre of the brain. Tolerance happens quickly to vomiting.
Other acute symptoms of opioids
Opioids also dilate the blood vessels, decrease blood pressure, and cause flushing of the skin. Constipation + difficult to pee. Sedation and drowsiness.
Opioid effects on Reproduction and Newborn
Lowers reproductive hormones. Neonatal abstinence syndrome. Some newborns who are exposed to opioids in utero will experience withdrawal symptoms and have lower birth weight.
Opioid Behavioural and Psychological Effects at Low and Moderate Doses
Sense of euphoria with dopamine increase. Relaxation. Mental clouding and impaired judgement.
Opioid drug interactions
Most opioid deaths are due not to the ingestion of morphine or heroin alone, but rather to the combination of opioids with alcohol, benzodiazepines, or other drugs that amplify their lethal effects. Opioids are particularly dangerous when taken with other respiratory suppressants such as alcohol or Xanax.
Opioid overdose
Opioid-related overdoses are one of the leading causes of preventable death in Canada, killing more than 4,500 Canadians in 2019 (one Canadian every two hours); the majority (more than 90 per cent) were deemed accidental. Most in BC and least in eastern Canada. Deaths increasing.
Several factors underlie the increased death rate from opioids:
• Increased number of users, many of whom began with prescription opioids
• Inconsistencies in the purity of illegally obtained opioids, which can lead to accidental overdose
• Dangerous impurities found in opioids, including the presence of fentanyl
• The concurrent use of alcohol or other sedatives
• Opioid use that occurs after a chronic user has gone weeks or months without opioids and then injects the same amount they used before, not realizing tolerance has worn off
Opioid triad
The opioid triad of coma, depressed respiration, and pinpoint pupils is the classic sign of opioid poisoning. (Also skin turning blue but larder to tell that). Naloxone is administered intravenously or via a nasal spray, and immediately reverses the life-threatening respiratory suppression of breathing. Narcan - nasal spray naloxone in Canada
the Good Samaritan Drug Overdose Act.
For those who experience an overdose, or those who are at the scene seeking emergency support during an overdose, the Act gives some legal protection from charges concerning possession of a controlled substance or breach of conditions (e.g., probation, parole, etc.) regarding simple possession. Production, trafficking, and other crimes are not protected under the Act.
Pain/nociceptors
Several types of stimuli—touch, pressure, temperature, light, sound, or even smell—that stimulate nociceptors can produce pain. Pain is also highly subjective and dependent on many other factors, including expectations, emotions, environmental stimuli, and stress.
Analgesic
Pain relieving drug
Chronic pain in Canada
About one in five Canadians have long-term pain that persists for weeks, months, or years. The financial cost to treat pain, and costs associated with lost productivity, is estimated at $56 billion to $60 billion per year in Canada.
Other medicinal uses of opicias
Cough suppressant, diarrhea treatment (causes constipation)
Opioid tolerance: 3 types
Three different types of tolerance to opioids may develop: metabolic, cellular, or behavioural. With chronic use, the liver becomes able to metabolize opioids faster. On a cellular level, downregulation (loss) of opioid receptors occurs with habitual opioid administration, meaning a user will have to use ever-increasing doses to achieve the same effect. Most interesting is behavioural tolerance. Long-time opioid users show increased tolerance to the drug if they take it in locations other than where they have previously repeatedly taken the drug.
Adverse Effects of Chronic opioid use
Unlike other drugs, which are harmful to the body with long-term use, heavy use of (safely administered) opioids, including heroin, even after a lifetime of addiction, does not damage or destroy the organs of the body. Except for constipation. Long-term opioid use may lead to difficulties in problem-solving and decision-making. Opioids’ analgesic properties may conceal early symptoms of illnesses such as pneumonia. Opioids may interfere with the body’s ability to repair damaged DNA and may even stimulate the growth and spread of cancer cells and may make a person more sensitive to pain over time. Opioid lifestyle dangerous as well (sharing needles, not taking care of yourself). Poisoning or overdose and life of crime
Opioid dependence and behaviour
Opioids are highly addictive. Not only do they produce feelings of euphoria, but they also boost dopamine’s effects in the reward and addiction pathway of the brain.
Factors that make a opioid addiction more likely
• Frequent use
• Higher dosage
• A family history of substance abuse problems
• A history of alcohol and other drug use beginning in adolescence and the young adult years
• A dependence on nicotine, alcohol, or sleeping pills
• A past history of depression or other mental illness
• Opioid use as a means of dealing with life’s difficulties—to alleviate feelings of anxiety, depression, or boredom
• environmental and social factors
Treatment for Opioid Dependence and Addiction
- medications to treat addiction, typically antagonists that block opioid receptors interfering with opioids rewarding effects
- self-help therapies like NA
- needle exchange programs show success in form reduction
- vaccines being developed
Withdrawal of opioids
Withdrawal from opioids is miserable, but unlike withdrawal from alcohol or sedative/hypnotics, it is not life-threatening. Longer drugs taken worse the withdrawal. Withdrawal begins 6–12 hours after the last dose, peaks in 48–72 hours, and is usually over within 5–10 days. Withdrawal symptoms are typically opposite those of the direct effects of the drug
Withdrawal from opioids generally follows these stages:
Craving and anxiety, yawning, sweating, dilated pupils, fever, nausea, diarrhea, weakness, depression
The Differences between Naloxone, Naltrexone, and Buprenorphine
naloxone- A short-acting opioid antagonist used to reverse opioid overdose in emergency situations. Naloxone has a higher affinity for the opioid receptor than morphine or heroin, so when administered it replaces the drug bound to the receptor.
naltrexone- longer acting opioid antagonist used to treat alcohol and opioid addiction.
buprenorphine-A partial agonist. When bound to an opioid receptor, it will not cause an opioid response, but because it is occupying the receptor, other opioids are prevented from binding.
Ultra-Rapid Opioid Detoxification
In ultra-rapid opioid detoxification (UROD), a person who is addicted to opioids is put under general anaesthesia or heavy sedation and then given clonidine, as well as enough naloxone to completely block the opioid receptors. When they awaken a few hours later, withdrawal and detoxification are complete. General anaesthesia or heavy sedation are used because the more rapid the withdrawal, the more severe the symptoms. All patients who undergo UROD will successfully detox. Risks associated: anaesthesia dangers, loss of tolerance making future overdose more likely
Substitution opioids
opioid substitution therapy replaces a heroin (or other injectable or smoked opioid) habit for another opioid dependency, the addict has a chance at a much-improved lifestyle.
Methadone
Long acting opioid. Methadone is medically safe even with long-term use, and it does not interfere with one’s daily activities. methadone substitution therapy is cost-effective.
