Test 3 (Chapters 7, 9, 12) Flashcards
(173 cards)
1
Q
What part of nervous system do sedatives and hypnotics effect
A
Central nervous system (CNS) depressants are a diverse group of drugs that slow physical and mental activities, relieve anxiety, diminish awareness, and increase sleep. Sedatives and hypnotics are two types of CNS-depressant drugs.
2
Q
What are sedatives and hypnotics and that are two popular classes
A
Sedatives are drugs that relieve anxiety, cause relaxation, and produce mild depression of the CNS. Hypnotics induce drowsiness and sleep (hypnos=Greek word for “sleep”). Two popular classes of sedative/hypnotics are barbiturates and benzodiazepines. Barbiturates are used mainly for an anesthesia and treatment of seizure disorders, while benzodiazepines (BZDs) are used mainly as muscle relaxants and to reduce anxiety.
3
Q
What is valerian used for
A
Valerian root has been used for thousands of years as a remedy for insomnia.
4
Q
First synthetic drug truly classified as hypnotic
A
Synthesized in 1832, chloral hydrate quickly induces a long, deep sleep. Today it is sometimes given to infants as a sedative prior to surgical or EEG procedures or to help people withdraw from opioid or alcohol addiction.
5
Q
That schedules are sedatives and hypnotics in
A
• barbiturates: Schedule IV
• BZD: Schedule IV
• Quaalude: Schedule III
• GHB: Schedule I
6
Q
Who synthesized barbiturates and how
A
In 1864, Adolf von Baeyer, a German scientist, synthesized barbituric acid by combining malonic acid from apples with urea, a waste product found in urine.
7
Q
Most frequently prescribed benzodiazepines and what they were originally marketed for
A
The most frequently prescribed benzodiazepines in Canada include Valium (diazepam), Ativan (lorazepam), and Xanax (alprazolam), totalling over 26 million prescriptions in Canada in 2017. During their early days, benzodiazepines were predominantly marketed to women to help them deal with the stress of daily life.
8
Q
How safe are benzodiazepines
A
At first, benzodiazepines were viewed as extremely safe and free from the problems of tolerance, dependence, and withdrawal. BZDs are relatively safe when used for short periods (and are much safer than barbiturates), but long-term use can cause tolerance, dependence, and withdrawal problems.
9
Q
Prevalence of Sedative and Hypnotic Use
A
In 2017 CTADS reported that 11.7 per cent of the population used sedatives. Sedative/hypnotic use is higher in females (14.3 per cent) than males (9.1 per cent), and increases with age: about 5.1 per cent of 15–19-year-olds, 7.5 per cent of 20–24-year-olds, and 12.6 per cent of those age 25 and older report past-year use.
10
Q
Different categories of barbiturates and what they are used for
A
Barbiturates are categorized as long-acting, intermediate-acting, short-acting, or ultra-short-acting, based on their duration and this decides their clinical use. Shorter-acting drugs are more lipid-soluble and take effect rapidly, because they quickly enter the bloodstream and easily cross the BBB and are cleared from system faster. These short-acting barbiturates are more likely to be abused.
Longer-acting drugs are best used as anticonvulsants in treatment of epilepsy or to reduce anxiety. Intermediate- and shorter-acting drugs are used to treat insomnia, for emergency management of seizures, and as a preanaesthetic sedative. Ultra-short-acting barbiturates can be used to rapidly anaesthetize a patient in emergency situations and to bring them out of anaesthesia quickly as well and they leave the patient with no memory of the experience.
11
Q
What are drugs that reduce anxiety called
A
Anxiolytics
12
Q
Routes of Administration of sedatives
A
Sedatives can be administered rectally or by injection, but they are most commonly administered orally. Some anaesthetic medications or drugs given to treat emergency seizures or status epilepticus (epileptic seizures following one another in which the sufferer remains unconscious) are administered intravenously.
13
Q
Sedative and hypnotic absorption + difference between BZD absorption and barbiturate
A
Sedative/hypnotics are absorbed into the bloodstream after oral administration. Barbiturates are absorbed in the stomach, while benzodiazepines are absorbed in the small intestine; this means that BZDs are absorbed into the bloodstream more slowly than are barbiturates.
14
Q
Distribution of sedatives in bloodstream is determined by what
A
Once in the blood, a sedative’s distribution is determined by its lipid solubility. Barbiturates are more fat-soluble than BZDs; as a result, barbiturates are better able to cross the blood brain barrier, leading to a faster onset of action. Shorter-acting barbiturates are especially lipid-soluble.
15
Q
Barbiturates and fatty tissues in body
A
Barbiturates stored in fatty tissues of the body. From these body fat deposits, the barbiturate is released slowly into the blood. The amount of body fat a person has can influence their response to barbiturates and BZDs. Although the initial effects of a short-acting barbiturate may recede quickly, the drug may be released from body fat deposits and then circulate at low levels in the blood for a significant period of time.
16
Q
How are sedatives metabolized + what happens when they enter bloodstream
A
Barbiturates and benzodiazepines are metabolized in the liver. When these drugs enter the bloodstream, some bind to plasma proteins. Only unbound molecules of the drug are free to bind to receptor sites and exert an action. As the unbound molecules of barbiturates are metabolized and excreted, the drug that was previously stored in fat or that was bound to plasma proteins becomes free and available for metabolism. The balance between the free and bound forms of the drug is responsible for the varying durations of action for different barbiturates.
17
Q
Benzodiazepines undergo two major pathways of metabolism:
A
Oxidation= such as diazepam (Valium), chlordiazepoxide (Librium), and flurazepam (Dalmane), produce active metabolites, prolonging their duration of action until they are further detoxified by metabolism and then excreted.
Conjugation= metabolized to pharmacologically inactive, water-soluble products that are excreted in urine.
18
Q
How does liver diseases/ weakness affect metabolism of sedatives
A
Metabolism is decreased. Half life becomes much longer, effects last very long
19
Q
Sedatives Mechanism of Action on receptors
A
Sedative/hypnotics exert their effects by binding to GABA receptors. Barbiturates and BZDs both work on the receptor, but by slightly different mechanisms.
20
Q
GABA receptors are _____ (what type)
A
ionotropic, meaning that the receptor itself is an ion channel
21
Q
Benzodiazepines Interaction with the GABA-A Receptor
A
GABA-A receptors in brain (limbic system and cortex) have binding sites for benzodiazepines, When a BZD binds to a GABA receptor, the shape of the receptor changes, increasing the frequency of chloride channel openings and enhancing GABA’s inhibitory effects. The GABA receptors that control respiration and other vegetative processes do not have many BZD sites, so BZDs do not suppress respiration as much as barbiturates do. There are also GABA receptors with BZD binding sites in the peripheral nervous system, which modulate the immune system and are involved in the body’s response to injury.
22
Q
Benzodiazepines effect on adenosine
A
BZDs slightly block the reuptake of the inhibitory neurotransmitter adenosine, which acts to increase adenosine’s activity at the synapse and is responsible for some of the anticonvulsant, anxiolytic, and muscle relaxant effects of BZDs.
23
Q
Barbiturates’ Interaction with the GABA-A Receptor
A
Unlike benzodiazepines, barbiturates don’t act at a specific single site on the GABA-A receptor, they bind to multiple cavities on the surface of the receptor. Barbiturates have a more general effect that enhances the inhibitory activity of GABA.
24
Q
Difference between effects of BZDs and barbiturates on chloride channels
A
Barbiturates increase duration of channel opening, even in the absence of GABA which is a reason why barbiturates are more dangerous than BZDs. BZDs can only open the chloride channel if GABA is present. Because barbiturates have a more general effect on GABA receptors, they have more widespread sedating effects than do the BZDs. Along with widespread CNS depression, barbiturates can suppress cognitive function, muscle activity, and respiration.
25
Physiological Effects of sedatives at Low and Moderate Doses
Barbiturates and BZDs are CNS depressants. They cause sedation, increase sleep, reduce anxiety, and relax muscles. Lower doses can lead to relaxation, decreased anxiety, and drowsiness. As the dose increases, the user may experience euphoria and disinhibition, as well as sedation, dizziness, staggering, and sleep.
26
Sedatives effect on sleep
Sedatives and hypnotics help people to fall asleep faster and increase a person’s total sleep time. But they decrease the time spent in REM sleep, as well as the time spent in deep sleep. Therefore, although most hypnotics increase total sleep time, the sleep they produce is not as restful and restorative as normal slumber.
27
Sedatives taken with alcohol
When taken with alcohol the drugs act synergistically, and a potentially fatal suppression of respiration can occur. (both are CNS depressants)
28
Behavioural and Psychological Effects of sedatives at Low and Moderate Doses
Sedatives and hypnotics produce mood changes that are similar to those caused by alcohol. They reduce anxiety and give a sense of relaxation and mellowness. People on sedatives may have difficulty thinking clearly and making rational judgments. Their learning and memory may be impaired. Disinhibition—the release of bizarre, uninhibited behaviours, or of hostility or rage—may occur, and users sometimes become emotionally unstable.
29
Sedative addiction and therapeutic index
Sedatives can be addictive. They bind to GABA receptors that modulate the firing of neurons in the addiction pathways of the brain. Abuse and dependence are more likely to occur with faster-acting agents than with those that have long-lasting effects.
Barbiturates have a narrow therapeutic index, a high potential for tolerance, dependence, and abuse and are lethal in overdose.
30
Side effects of barbiturates and bzd's
• drowsiness
• lethargy
• dizziness
• confusion
• reduced libido
• diminished concentration
• incoordination and impairment of driving skills
Barbiturates may also lead to
• gastrointestinal distress
• joint pain
• skin rash
• impotence and menstrual irregularities
• impaired thinking
• anterograde amnesia
31
Adverse Psychotic Reactions to Halcion (sedative)
Halcion was widely prescribed in 80s. Complaints from others began to accumulate, however, reporting that Halcion led to amnesia, confusion, paranoia, hostility, and adverse psychiatric reactions. The drug was banned in five countries, but the US Food and Drug Administration concluded that its benefits outweighed its risks, and Halcion is still available today in Canada
32
Sedatives and cancer/death
A recent study found that sedative/hypnotic drugs were associated with an elevated risk of death and cancer. The researchers followed 10,529 patients who received hypnotic prescriptions and 23,676 matched controls for an average of 2.5 years. They discovered that patients prescribed any hypnotic were more likely to die when compared to those prescribed no hypnotics.
33
Rohypnol
Rohypnol (sedative) is a colourless, odourless, tasteless drug that is 5–10 times stronger than Valium. When slipped into an unsuspecting victim’s drink (especially an alcohol-containing drink), Rohypnol can lead to blackouts, unconsciousness, and complete memory loss. Rohypnol is not approved for use in Canada (or in the United States), but it is available in many countries, including much of Europe.
34
Sedatives effect on fetus
About 2 per cent of pregnant women use benzodiazepines. BZD use during pregnancy is known to increase the risk of spontaneous abortion by almost 2x. Possible increased risk for cleft palate, no other malformations. May sensitize GABA receptors in infants. Baby may have withdrawal. Taking antiepileptic drugs during pregnancy is thought to increase the risk of congenital malformations.
35
Sedatives drug interactions
Barbiturates and benzodiazepines have a synergistic effect with other depressants, in which the combined result is greater than the sum of the effects of each drug alone. That means that when users take these sedatives with other CNS depressants such as alcohol, opioids, or general anaesthetics, there is a chance they may stop breathing. Both barbiturates and BZDs are metabolized by the cytochrome P450 (CYP450) enzymes of the liver and, therefore, may interact with other substances that use the same enzyme system.
36
Sedative overdose symptoms
One of the reasons barbiturates are so dangerous is that their lethal dose is not significantly higher than their effective dose. The exact lethal dosage depends on one’s tolerance, age, size, and other drugs that have been taken. Symptoms of a barbiturate overdose include sluggishness, incoordination, confusion, slurred and slowed speech, sleepiness, staggering, and shallow breathing, leading to coma and death.
37
Medical and Therapeutic Uses of Sedatives and Hypnotics
Benzodiazepines and barbiturates have been used as anaesthetics and preanaesthetic medications and to treat many conditions, including
• insomnia
• anxiety disorders
• seizure disorders
• withdrawal from chronic alcohol use
38
Why have bzd's replaced barbiturates
BZDs have for the most part replaced barbiturates because BZDs have more specific effects than barbiturates, fewer side effects, a much wider margin of safety, less potential for abuse or tolerance, less effect on REM sleep, and minimal effects on the respiratory centre of the brainstem.
39
Sleep stages
Sleep is divided into five stages—non-REM (NREM) stages 1, 2, 3, 4 and REM sleep—which are characterized by specific brain wave patterns and other physiological properties. One advances through these stages in cycles throughout the night. As one progresses from stage 1 to stage 4, sleep becomes progressively deeper and more restorative.
40
Different neurotransmitters and drugs affect our sleep/wake cycle:
Glutamate, norepinephrine, acetylcholine, and orexin all increase wakefulness. Non-REM sleep is increased by GABA, the main inhibitory neurotransmitter of the CNS. Adenosine also promotes sleep.
41
Insomnia can have widespread consequences:
Sleeplessness can increase the risk of memory and learning problems, inflammation, diabetes, weight gain, and mood disorders. Both depression and attention-deficit/hyperactivity disorder (ADHD) are associated with insufficient sleep (may not be causal).
42
Z drugs
Z drugs are not BZDs, but they bind to the same place on the GABA receptor, and their effects are primarily hypnotic rather than anxiolytic. Z drugs produce a sleep rhythm that more closely matches one’s natural sleep cycle.
43
Negatives of Z drugs
Z drugs are cross-tolerant (tolerance to one drug results in tolerance to another similar drug) with ethanol, overdose can occur if the Z drugs are combined with alcohol or other CNS depressants. Many ppl go to ER with z drug overdose
44
Chronic Effects of Sedatives and Hypnotics
Long-term use of sedatives, especially of barbiturates, is associated with daytime fatigue, accidents, and overall mortality. Use is especially problematic in the elderly, and is associated with increased risk of falls, traffic accidents, and cognitive decline. Except when they are used as anticonvulsants, barbiturates are typically recommended for only short-term use.
45
Tolerance to barbiturates
Tolerance to barbiturates develops at different rates. Those who take daily or near-daily barbiturates over a period of weeks or months will need ever-increasing doses to achieve the desired sedative or hypnotic effects. Tolerance does not develop for the anticonvulsant effects, even after years of use. Tolerance also fails to develop for respiratory depression, so the margin of safety decreases dangerously as the user becomes tolerant to the drugs’ sedative effects.
46
Cellular and metabolic tolerance to barbiturates
Cellular tolerance occurs when the neurons in the brain adapt to the presence of the drug and receptors downregulate. Metabolic tolerance occurs because barbiturates increase the activity of the liver’s CYP450 enzymes that metabolize barbiturates, the more drug used, the faster it is metabolized.
47
Bzd tolerance
Tolerance to BZDs is not as fast or complete. As with barbiturates, tolerance first develops to the sedative and hypnotic effects, tolerance to the anxiolytic effects develops slowly and to a limited extent. When the sedative effects wear off, the disinhibitory effects become more prominent. Unlike barbiturates, BZDs do not increase the activity of the liver enzymes that normally metabolize the drug, so they show no metabolic tolerance.
48
Sedative and Hypnotic Dependence and Addiction, when does it develop
When large quantities of barbiturates are taken for several weeks, physical dependence begins to develop. Benzodiazepines are not as strongly addictive. Most people who use BZDs as medically directed—even long term—do not become dependent. The risk of BZD dependence is higher in patients who are anxious or have sleep disorders, those who take large doses, individuals who abuse other drugs, and users who obtain the drug illegally simply to get high. Sedatives with a fast onset of action and a short half-life are typically more likely to be abused than slower-acting compounds.
49
Sedative and Hypnotic Withdrawal: when does it happen
Withdrawal from sedatives occurs when a person has a physical dependence to these drugs. Not all long-term users will experience withdrawal symptoms upon discontinuation, and when they do, the onset of symptoms may be delayed for days or even weeks.
50
Sedative withdrawal symptoms
• insomnia
• anxiety
• irritability
• tremor
They may also suffer from
• nausea and vomiting
• loss of appetite
• headache
• sweating
• muscle pain
• fever
• confusion
• memory problems
• difficulty concentrating
51
Sedative withdrawal treatment
Withdrawal should be medically supervised to monitor for fatal symptoms. Paper down drug use gradually. Therapy helps to deal with psychological symptoms underlying dependence.
52
_______ reduce anxiety and increase relaxation; _______ reduce anxiety and work as a muscle relaxant; _______ induce drowsiness and sleep; and _______ treat seizures and work as an anesthetic.
Sedatives; benzodiazepines; hypnotics; barbiturates
53
Why, given the sheer number of drugs in the sedative/hypnotic categories, is the search for CNS depressants that alleviate stress and anxiety still ongoing?
Drugs in these categories were all thought to be safe and non-addictive, however, they were later discovered to have significant dangers, and cause tolerance, dependence, and withdrawal.
54
What is the correct order in terms of best clinical uses of barbiturates from long-acting to intermediate/short-acting to ultra-short-acting?
epilepsy management → pre-anesthetic sedative → emergency (rapid) surgical anesthetic
55
Benzodiazepines can have a half-life ranging from
1–3 up to 200 hours
56
Barbiturates tend to work faster than benzodiazepines because
barbiturates are absorbed in the stomach, whereas benzodiazepines are absorbed in the small intestine
57
Sedatives: _______ work as GABA agonists, while _______ work at the GABA receptor but have a more specific mechanism of action involving GABAA
barbiturates and benzodiazepines
58
BZDs exert different primary effects depending on which subtype of GABA-A receptor they bind to. For instance, BZDs that bind to alpha1 subunits are effective _______, and those with a higher affinity for alpha2 or alpha3 subunits are better _______.
hypnotics; anxiolytics
59
One of the reasons that barbiturates are so dangerous is that
their lethal dose is not significantly higher than their effective dose.
60
BZDs are safer compounds than barbiturates, but they are not risk-free. In 2013, BZDs were involved in about ________ per cent of all fatal overdoses of prescription drugs in the United States.
30%
61
What is the link between the recent rise in BZD overdose mortality rates and opioids?
This rise occurred at the same time that opioid prescriptions were on the rise and opioids are involved in about three-quarters of the overdose deaths involving BZDs.
62
What is GHB and where does it naturally occur
Gamma-hydroxybutyric acid (GHB) is both a naturally occurring substance and a synthetic drug. GHB occurs naturally in beef, wine, and some fruits, and in the body from the breakdown of GABA; in fact, GHB is considered a neurotransmitter in its own right. GHB has both therapeutic and recreational uses.
63
History of GHB
Gamma-hydroxybutyric acid was first synthesized in 1960, when Dr Henri Laborit, a French researcher, investigated the drug’s properties as an anticonvulsant that could cross the blood brain barrier more easily than GABA. Later, GHB was used in a limited capacity as an anaesthetic. Although GHB does induce unconsciousness, it doesn’t prevent pain, which makes it less than ideal for surgical use. GHB gained popularity in the 1980s as a nutritional supplement for bodybuilders as it increases secretion of growth hormone
64
Pharmacokinetics of GHB
When given as a drug, GHB has effects similar to other CNS-depressant drugs. It is an odourless, colourless, salty-tasting liquid that is rapidly absorbed into the bloodstream and easily crosses the blood brain barrier. Effects are usually felt within 15 minutes and peak within 40 minutes.
65
Mechanism of action of GHB
GHB birds to excitatory GHB receptors and inhibitory GABA receptors which are metabotropic meaning it causes a cascade that open a separate ion channel, slower and more complex process than mechanism by which sedatives interact with GABA receptors.
66
Difference between low and high doses of GHB mechanism of action
At low doses, GHB binds almost exclusively to GHB receptors in brain. Binding to these receptors stimulates the release of excitatory glutamate. As the dose of GHB increases, more GHB binds to and activates GABAB receptors, producing sedation and sleepiness. GHB has a relatively low affinity for GABA receptors; a high dose is required for GHB to have an effect at these inhibitory receptors.
67
GHB also affects other neurotransmitters:
• GHB has a biphasic effect on dopamine—low doses of GHB inhibit the release of dopamine, while high levels of GHB increase it.
• GHB increases levels of acetylcholine and serotonin.
• GHB also mediates opioid effects in the brain. The opioid antagonist naloxone blocks some of GHB’s effects.
68
Acute effects of GHB for mild and higher dose
GHB can give the sensation of inebriation. A mild dose (1 gram or less) will cause relaxation, mild euphoria, a loss of inhibition, increased sociability, and short-term forgetfulness. The user may feel heightened sexual interest, although, like alcohol, GHB is actually associated with decreased sexual performance. A higher dose (2–3 grams) can cause lethargy, drowsiness, and sleep. Loss of muscle control, slurred speech, vomiting, dizziness, visual disturbances, and amnesia also may occur. Doses of 4–5 grams or more can lead to very deep sleep, depressed respiration, hypothermia, coma, and possibly death.
69
Medical and Therapeutic Uses of GHB
In Europe, GHB is approved for use as an anaesthetic, sleeping aid, and as a treatment for opioid addiction and alcohol withdrawal, because it has been found to help relieve withdrawal symptoms and to reduce cravings. In Canada, GHB’s only approved use is for the treatment of narcolepsy. Under the trade name Xyrem, GHB reduces the frequency of cataplexy and alleviates the excessive daytime sleepiness.
70
Quaaludes history, popularity
Originally introduced in India as antimalarial drug. Did not treat malaria but did have hypnotic properties. Quaalude was first marketed in America in 1965 and became quite popular in the late 1970s and early 1980s. Quaalude is a CNS depressant that works at GABA receptors to produce sedation and sleepiness.
71
Quaaludes effects
Quaalude is a CNS depressant that works at GABA receptors to produce sedation and sleepiness. Some reported positive effects include relaxation, calm, a sense of well-being, a loss of inhibition, and increased self-confidence. Fairly common unwanted side effects include stomach pain, nausea and vomiting, sweating, dry mouth, rapid heartbeat, dampened sexual response, dizziness, anxiety, restlessness, depersonalization, and paranoia. Quaalude can also be used as a date rape drug.
72
Methaqualone / Quaalude overdose
An overdose can cause convulsions, renal failure, coma, and death. Methaqualone overdose resembles barbiturate poisoning, but with increased motor difficulties and a lower incidence of respiratory depression. Methaqualone is categorized as Schedule III in the CDSA.
73
Propofol
Propofol (Diprivan) is a fast-acting anaesthetic that was first synthesized in 1986. Administered intravenously it is used for induction (the beginning process) of anaesthesia; for anaesthesia during short procedures, such as endoscopy; and to sedate individuals who are being put on mechanical ventilation. Propofol has a fast onset of action as well as a quick recovery time. Not only does propofol reduce awareness, it also leaves the patient with no memory of the experience; for this reason, propofol is sometimes called “milk of amnesia.” Propofol acts at GABA-A receptors, and also affects the endocannabinoid system. Recreational use of propofol has risen in recent years, especially among anaesthesiologists who have access to the drug.
74
GHB may take the form of a(n) _______ substance found in food, a(n) _______ drug used for therapeutic and recreational purposes, and a(n) _______.
natural; synthetic; neurotransmitter
75
At low doses, GHB binds almost exclusively to _______ receptors, which stimulates the release of excitatory _______. As the dose of GHB increases, more GHB binds to and activates _______ receptors.
GHB; glutamate; GABA-B
76
High doses of GHB can put the user into a(n) _______ state relatively quickly; however, it is not uncommon to _______ spontaneously and abruptly from this state. This is one example of how the effects of GHB appear as a(n) _______ mix of sedative and stimulatory properties.
inebriated; sober up; unpredictable
77
What are inhalants
Inhalants are a class of drugs that may be found in kitchen and bathroom products, as well as hardware stores and garages. Inhalants include a wide array of intoxicants and come in the form of volatile solvents. They are easily vaporized liquids or are gases at room temperature. High doses of inhalants can lead to effects similar to those of sedative/hypnotics
78
Temple of Apollo in Delphi and inhalants
The Temple of Apollo in Delphi was among the most sacred sites of ancient Greece, because it held the oracle. The oracle was a woman who went into a trance in order to allow the gods to speak through her. It has since been shown that there were hidden faults under the Delphic temple, and the oracle was probably inhaling ethylene gas, which, in lower doses, evokes a trance-like state leading to euphoria and mystical experiences.
79
Ether + what it was used for
Spanish alchemist Raymundus Lullius is credited with the discovery of ether in 1275. In 1540, German physician Valerius Cordus developed a method of synthesizing diethyl ether, and called it “sweet oil of vitriol.” Around the same time, Paracelsus (the Swiss physician who created laudanum) discovered ether’s analgesic properties. Ether was used as anaesthesia but today it is not used in Canada in surgical procedures because it triggers nausea and vomiting and is highly flammable.
80
Who discovered nitrous oxide and when and that is it used for today
The English scientist Joseph Priestley first discovered nitrous oxide in 1772. in 1845 dentist Horace wells gave a demonstration of using nitrous oxide during dental procedure. Wells did not fully understand the effective dosages of the drug, and his patient woke up and screamed in pain during the operation. Nitrous oxide is not a strong enough anaesthetic for use in major surgery, but today dentists sometimes may use the drug to relieve anxiety and pain during dental procedures.
81
Glue Sniffing history and popularity
The first known print reference to glue sniffing appeared in newspapers in 1959. The article warned readers about the dangers of sniffing glut but also informed that glue was a possible intoxicant. Ten months after the article appeared, there was a surge in the number of cases of glue sniffing. Glue sales rose as media coverage of the glue sniffing “epidemic” increased. In 1971, The New York Times began an anti-inhalant campaign, warning of the dangers of inhalants, complete with a description of how to get high on aerosols and which products were most popular.
82
Popularity of inhalants
Inhalants are one of the most commonly used drugs in grade 7 and 8 eschool children. Perhaps this popularity with young children is due to the fact that inhalants are readily available, inexpensive, legal to buy and possess, and easy to conceal. Also, their dangers are not as widely known as those for other drugs.
83
How many Canadians have used inhalants and what demographics is it more common in
Approximately 1.3 per cent of Canadians age 15 and older have reported inhalant use at least once in their lifetime. Inhalant use disproportionately afflicts the poor, mentally ill, and young. Indigenous communities in Canada have been particularly hard hit by inhalant abuse. Unlike nearly all other classes of drugs, inhalant use is most common among younger adolescents and declines as they get older.
84
More than ______ household products can be used as inhalants to get high. What do they have in common.
1,400. They have little in common in their chemical structure, pharmacology, or mechanism of action; what joins them is that they are all taken by inhalation. Inhalants often are categorized as volatile substances, anaesthetics, and nitrites.
85
Volatile Substances (what are they, their effects)
Volatile substances are chemicals that are liquid at room temperature and give off fumes that are inhaled. They were never intended for internal consumption, and they are among the most toxic substances used as recreational drugs. The fumes of these substances may cause mild euphoria, dizziness, loss of inhibition, impaired judgment, nausea, incoordination, disorientation, distorted perceptions, and hallucinations.
86
Some examples of volatile inhalants include:
• adhesives: glue and cement
• aerosols: hair spray, spray paint, air freshener, household cleaning spray, fabric protector spray, computer cleaner
• cleaning agents: dry-cleaning fluid, degreaser, spot remover
• fuels: butane, propane, kerosene, gasoline
• solvents: nail polish remover, paint remover, paint thinner, correction fluid
87
Three main functions of anaesthesia and which anaesthetics have been used recreationally
Anaesthesia has three main functions: pain relief, muscle relaxation, and loss of consciousness. Anaesthetics that have been used recreationally include ether and nitrous oxide.
88
What are nitrates and what are they used for
The nitrites are yellow, volatile, flammable liquids with a fruity odour. Amyl nitrite and butyl nitrite also are known as “poppers” have both medicinal and recreational purposes. Amyl nitrite is a vasodilator that is sometimes used to treat angina (chest pain), although its use has been mostly replaced by nitroglycerin. Amyl nitrite can be used to revive a person who has fainted and is also an antidote for cyanide poisoning. Amyl nitrite was used recreationally in1970-80, especially at dance clubs and gay bars. Part of amyl nitrite’s popularity was due to reports of enhanced sexual pleasure and prolonged orgasm. Health Canada prohibited the sale of “poppers” in 2013.
89
How users take inhalants
Users of inhalants will often sniff fumes out of a bag, from a rag saturated with the substance, or directly out of the original container in which the inhalants came. The process of sniffing fumes is known as huffing.
90
Pharmacokinetics of inhalants
The fumes of these substances often cause feelings similar to alcohol and anaesthetics. When they are inhaled, these lipid-soluble substances are easily absorbed into the bloodstream and rapidly enter the brain. After entering the brain, drug levels peak within a few minutes and usually last for 15–30 minutes; they then are absorbed by the body fat.
91
Mechanism of action of inhalants
Far less is known about the mechanism of action of inhalants than for other drugs. Inhalants are a diverse group of substances with diverse mechanisms. Due to some similarities in their acute effects, many volatile solvents are thought to have cellular actions in common with drugs such as barbiturates, benzodiazepines, and alcohol. Some inhalants probably do not exert their effects by binding to a specific receptor.
92
Glues, aerosols, and solvents are all types of _______ inhalants. Ether and nitrous oxide are _______ inhalants, and the _______ group includes amyl nitrite and butyl nitrite.
volatile; anesthetic; nitrite
93
Compared to the damage seen in cocaine abusers, long-term inhalant abusers
have more extensive brain damage, and have more memory, cognitive, and behavioural impairments. And do worse in memory, attention, and behaviour control but not neuroticism
94
Acute Effects of Inhalants
Resemble alcohol
• They may begin with euphoria, disinhibition, dizziness, and lightheadedness, followed by drowsiness, disorientation, and headache.
• As with alcohol, progressively heavier doses can cause slurred speech, poor coordination, lethargy, nausea and vomiting, double vision, ringing in the ears, delusions, and hallucinations.
• Very high doses can lead to unconsciousness, respiratory suppression, coma, and death.
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Dangers of inhalants
Dangers from inhalants include hazards from the high doses taken, the ways in which the drugs are administered, the risks associated with the behavioural effects that follow their use, and the toxic effects of the substances themselves. Hypoxia and asphyxiation can occur when a user inhales less oxygen than their body needs. Users may get frostbite or burns from gases erupting.
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Toxic effects of inhaled substances
vomiting (and the risk of choking on vomitus while unconscious), kidney damage, liver damage, anemia, seizures, cardiovascular problems, respiratory suppression, and death.
When it occurs, death is usually due to cardiac arrhythmia, hypoxia, accidents, or suicide.
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About ______ per cent of people who die from inhalants are first-time users.
20
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Sudden sniffing death syndrome
Inhalants make the heart more sensitive to the effects of adrenaline. If after using inhalants a person experiences sudden stress or vigorous activity, they may suffer a fatal cardiac arrhythmia.
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Acute Effects of Nitrous Oxide
Nitrous oxide (N2O) produces mild euphoria, giddiness, and drowsiness, and also reduces pain and inhibitions. Some may experience a brief loss of consciousness and a sensation of flying.
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4 dangers of nitrous oxide n2o
1. N2O itself is a non-toxic gas, but when a person inhales it without the addition of oxygen, severe hypoxia may occur, which can be fatal.
2. Administering nitrous oxide can cause physical damage to tissues due to the pressure of the expanding gas.
3. Nitrous oxide may be neurotoxic, especially if it is used in combination with other NMDA antagonists such as alcohol, dextromethorphan, or PCP.
4. Long-term use can cause vitamin B12 deficiency, which can damage the bone marrow and nervous system, and impair memory and mental functioning.
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Acute Effects of Amyl Nitrite
Amyl nitrite’s vasodilatory effects cause a sudden fall in blood pressure, along with a rise in heart rate, warmth, and flushing of the skin. Users may feel mildly euphoric or dizzy and often see a bright yellow spot with purple radiations. The anal sphincter dilates, and there is increased blood flow to the genitals. After inhaling amyl nitrite, users often feel nauseated, have short-term vision problems, and may experience a pounding headache. When inhaled, amyl nitrite has very low toxicity; when swallowed or injected, however, amyl nitrite can interfere with the ability of the blood to bind and transport oxygen.
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Chronic effects of inhalants
The long-term effects of inhalant abuse are not well documented, because inhalant abuse usually occurs only sporadically, and typically does not last more than a year or two. Tolerance may occur to the euphoric effects and long-term use may lead to withdrawal symptoms. Repeated use can cause rashes around the nose and mouth, nosebleeds, weight loss, depression, hostility, and paranoia, and may damage the liver, kidneys, lungs, bone marrow, and brain. Additionally, many of these substances are carcinogenic. Chronic inhalant abuse has been linked to brain damage and cognitive abnormalities that range from mild impairment to severe dementia.
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When scientists compared brain abnormalities and cognitive impairment among long-term inhalers of volatile solvents and cocaine abusers, they found:
inhalant abusers were more likely than cocaine users to have brain abnormalities, to have more extensive brain damage, and to have more memory, cognitive, and behavioural impairments. Brain areas that were especially affected include the basal ganglia, cerebellum, thalamus, and pons; inhalant users also had extensive loss of myelin in the brain
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Each year in Canada, alcohol abuse costs approximately ________, with about _______ emergency room visits, and causes approximately _______ deaths.
$ 17 billion, 700,000, 18,000
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Approximately ____ per cent of Canadians will abuse alcohol or have a dependence on alcohol at some point in their lives, and most go untreated.
18.1
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Early Historical Alcohol Use
Humans most likely discovered alcohol during the late Stone Age, when a jar of fruit or honey fermented. The development of agriculture around 8000 BCE enabled alcohol production to flourish. There wasn’t enough clean water for all inhabitants, so alcohol sustained life. Beer and wine helped distract people from the fatigue and boredom of life, alleviated pain, and were sources of pathogen-free liquid, which provided necessary vitamins, nutrients, and calories. It may be that people who drank fermented beverages lived longer and reproduced more, so the tendency to drink and the enzymes to metabolize alcohol were passed on.
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Early distillation of alcohol
In the 8th century, Arab alchemists developed a safe process of alcohol distillation, which increases the ethanol content of a beverage. Some suggest that early efforts at distillation were performed because it was easier to ship smaller amounts of liquid with higher alcohol content overseas. At the end of the voyage, the distilled beverage was meant to be diluted back to a lower alcohol concentration. But when the more potent beverage arrived, everyone liked it just fine as it was.
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Middle Ages alcohol use in Europe
Physicians investigated distilled alcohol as a treatment for many ailments. Alcohol was part of meals and medicines, given to children and invalids, and played a role in religious ceremonies. Men, women, and children had ale, the only safe or easily available drink. The widespread drinking of spirits surged after the Black Death of 1347–1351. Alcohol was completely ineffective as a cure for the plague, but it made the imbiber feel better. As a result, Europe emerged from the Middle Ages as a heavy-drinking culture. By the mid-18th century, every man, woman, and child in London drank an average of more than a half a litre of gin per week
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Colonial America alcohol use
During the Colonial period, men, women, and children drank alcohol on a daily basis. The tavern in the middle of town was the centre of social life, a place where one could find friends, food, drink, business, and local politics. Alcohol also played an important role in the economic development of the nation. The Atlantic provinces, for example, traded cod and other goods with rum-producing countries
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Temperance Movements in North America (19th Century)
The early 19th century was a time of the heaviest drinking in North America’s history, and alcohol was seen as a major cause of crime, violence, and immorality. Per capita consumption was about five drinks each day for each adult and a number of temperance movements appeared. Early temperance groups focused on moderation; their goal was to temper (moderate) the use of distilled spirits, not to eliminate them. Beer and wine were still largely considered acceptable and healthy beverages.
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View of abstinence in 1800's
Millions of Americans took either the “short pledge”—abstinence from spirits—or the “long pledge”—total abstinence. In this hard-drinking time, those who abstained from alcohol did so bravely, taking risks with their health, given that most public water supplies were contaminated. Abstainers were even forced to pay higher premiums for life insurance.
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Women’s Christian Temperance Union (WCTU)
The WCTU saw alcohol as both a cause and consequence of larger social problems. Members would march into saloons and stores that sold liquor and prevail upon customers to not buy alcohol. They visited elementary schools and warned students that if they started drinking, they would grow up to become a danger to themselves and others before dying young.
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Results of Canadian 1898 referendum on Prohibition
In 1898 a non-binding referendum on Prohibition found 51.3 per cent of Canadians were in favour of Prohibition, with a majority voting in favour in all provinces except Quebec. The prime minister at the time, Sir Wilfrid Laurier, felt Prohibition was not in the best interest of all Canadians, and decided to leave Prohibition up to local governments.
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Canadian prohibition
At the start of World War I, the Dominion Alliance convincingly argued that time and money spent on alcohol could be redirected toward the war effort, and in 1915 and 1916 all Canadian provinces entered Prohibition—except Quebec. During Prohibition so-called medicinal liquor was still permitted, so long as one had a note from their doctor. Prohibition saw the lowest alcohol consumption in history.
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Alcohol crimes during prohibition era
Prohibition laws did not forbid the use of alcohol; the crime was in supplying the alcohol. Bootleggers distilled and sold alcohol illegally, and rum-runners illegally smuggled liquor across borders. Speakeasies—illegal and clandestine nightclubs and drinking spots—began to sprout up in cities. Alcohol was illegal, but demand was high, and the illegal trade of alcohol encouraged the growth of organized crime.
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Societal differences in alcohol use
There are cultural differences regarding who may drink, how much, of what, and in what context, cross-cultural research has revealed some near-universal constants in the social norms of alcohol consumption. Most societies designate specific environments for communal drinking. In addition, most societies have rules of conduct concerning
* social control of intoxicated behaviour
* restrictions on female and underage alcohol consumption
* proscription of solitary drinking
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Alcohol Consumption in Canada
Alcohol is Canada’s most popular drug. With the exception of caffeine, more Canadians use alcohol than any other legal or illegal drug.
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Distribution of drinking in the US
30% doesn't drink at all, 50% drinks 20% of the alcohol. 10% drinks 20%. Final 10% drinks 60%
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Current alcohol use in Canada
Almost 80 per cent of Canadians age 15 and over consumed alcohol at least once in the past year, with more than 20 per cent of Canadian drinkers drinking above Canada’s Low-Risk Alcohol Drinking Guidelines
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Canada’s Chronic Low-Risk and acute low risk Alcohol Drinking Guidelines recommends:
Canada’s Chronic Low-Risk Alcohol Drinking Guidelines recommends “no more than 10 drinks a week for women, with no more than 2 drinks a day most days and 15 drinks a week for men, with no more than 3 drinks a day most days. Plan non-drinking days every week to avoid developing a habit” and the Acute Low-Risk Alcohol Drinking Guidelines recommend “drinking no more than 3 drinks (for women) or 4 drinks (for men) on any single occasion. Plan to drink in a safe environment. Stay within the weekly limits outlined.”
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Underage Drinking prevalence and issues
Alcohol is the most widely used drug by today’s teenagers. Underage drinking rates have declined significantly over the past few decades, but still, about 66 per cent of grade 12 students have used alcohol in the past year. Adolescents have a greater vulnerability to alcohol than do adults. A number of adverse effects result from underage drinking, especially binge drinking, including violence and illegal behaviour; risk-taking behaviour, impairment and drunk driving. Early drinking may also predispose someone to develop an alcohol dependency later in life.
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What percentage of Canadians aged 15 and over drank above Canada's Chronic Low-Risk Alcohol Drinking Guidelines in the past year?
20%
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Describe the process of fermentation
Alcohols produce from sugars, such as from fruits are dissolved in water, left to stand in a warm place and exposed to air yeast, then floats through air and lands on the fruit and consumes the sugar and converted into ethanol and carbon dioxide, the carbon dioxide, then bubbles out and the alcohol remains. Naturally fermented beverages do not exceed 15% alcohol because the yeast then dies.
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Distilled beverages
All hard liquors are distilled. In order to distill a fermented beverage and increase its potency, the fermented mixture is heated until it boils. the vapour has a higher alcohol content than what is left in the container. The condensed vapour is collected in a series of cooling tubes called a still. This condensate (the liquid formed by condensation) is known as hard liquor or distilled spirits.
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What does alcoholic proof mean?
Alcoholic proof is the measure of how much ethanol an alcoholic beverage contains. The “proof” typically equals twice the percentage of alcohol; a beverage that is 40 per cent alcohol is 80-proof. The strongest proof that any alcoholic beverage can be is 190. Above 95 per cent alcohol, the beverage draws moisture from the air and self-dilutes.
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blood alcohol content (BAC)
BAC is expressed as a percentage of alcohol in the blood. A BAC of 0.10 per cent means that one-tenth of 1 per cent of a person’s blood is ethanol.
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Absorption of alcohol and what affects absorption.
After oral ingestion, alcohol enters the stomach and small intestine where it is easily absorbed into the bloodstream. Many things affect ethanol’s absorption into the bloodstream, including the type of alcohol, the rate of consumption, and the presence of food in the stomach. Distilled liquors are absorbed the fastest, followed by sparkling wine, and then by wine. Beer is absorbed more slowly.
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Effects of food in stomach on alcohol absorption
If a person’s stomach is full, the alcohol mixes with the stomach contents, which are released a little bit at a time into the small intestine, where most absorption occurs. If there is no food in the stomach, contents pass directly into the small intestine for rapid absorption into the bloodstream. The type of food also can influence the rate of alcohol absorption. Fats are emptied from the stomach more slowly than are carbohydrates or proteins, so high-fat foods slow ethanol’s absorption more so than high-carb or high-protein foods.
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Distribution of alcohol
Once absorbed, alcohol is freely distributed throughout all the body fluids and tissues, including the placenta, if a woman is pregnant. Alcohol easily crosses the blood brain barrier and distributes to the cerebral cortex, limbic system, cerebellum, hypothalamus, pituitary gland, and lastly, the medulla.
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Metabolism of alcohol
After being absorbed into the bloodstream, ethanol travels to the liver, where it undergoes oxidation. The rate of metabolism varies in each person. Unlike most other drugs, in which the rate of metabolism increases with a higher plasma concentration of the drug, the rate of alcohol metabolism remains constant over time (a phenomenon known as zero-order kinetics). Typically, the liver can metabolize about 10 ml of pure ethanol per hour; any unmetabolized alcohol circulates throughout the blood and BAC rises.
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2 prominent enzymes responsible for metabolizing ethanol
Alcohol dehydrogenase (ADH) breaks ethanol down into acetaldehyde, which is toxic and causes reddening of the skin, rapid heart rate, and nausea. But acetaldehyde also stimulates the reward areas of the brain, which is why a person may continue to drink despite negative consequences.
Aldehyde dehydrogenase (ALDH) converts acetaldehyde to acetyl-CoA, which is broken down into CO2 and water.
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Elimination of alcohol
The liver metabolizes 95 per cent of the alcohol that reaches the general circulation, which is then eliminated in urine. The remaining 5 per cent is eliminated unchanged in the breath, where it can be detected by a Breathalyzer
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Combining Alcohol and Caffeine
Although caffeine may speed one’s reaction time, it does not reduce impairment. Caffeinated alcoholic beverages (CABs) have become increasingly popular, especially among adolescents. Makes people drink more and not want to stop drinking. those who drink CABs report more alcohol-related risk behaviours
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Alcohol easily crosses the _______, absorbs better in _______ than _______, and disperses more easily the more _______ a person has.
blood–brain barrier; muscle; fat; body fluid
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What is full name of LSD
Lysergic acid diethylamide
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Ethanol’s reinforcing properties are due to an interaction of dopamine, GABA, opioids, and glutamate where:
1. Release of dopamine in the VTA leads to reward.
2. GABA normally inhibits dopamine release in the VTA.
3. In the VTA, GABA’s effects are activated by glutamate and inhibited by opioids.
4. Ethanol increases the inhibitory actions of opioids and blocks the activating effects of glutamate, both of which lead to reduced activity in GABAergic neurons, thereby freeing dopaminergic cells from their inhibition and leading to increased dopamine release in the VTA, which produces rewarding sensations.
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By increasing GABA's inhibitory actions in the brain, ethanol _______ GABA's release which results in increased _______, decreased _______, and _______.
increases; sedation; anxiety; incoordination
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Alcohol effects on brain
Even moderate alcohol consumption can shrink the brain and cause cognitive decline. Those who drink more than 14 drinks per week lose approximately 1.6 per cent of brain size compared to non-drinkers. Parts of the brain that are particularly affected by alcohol include
* the ventral tegmentum and nucleus accumbens
* the prefrontal cortex
* the hippocampus
* the amygdala
Higher doses interfere with
* the cerebellum (balance and coordination)
* the inner ear (sense of one’s location and movement).
* the medulla. Very high doses of alcohol suppress the respiratory centres of the brainstem.
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Alcohol overdose
Ethanol’s therapeutic index is 5–10, which is similar to heroin’s. Ethanol’s average lethal dose corresponds to a BAC of 0.45%, which is five to six times the BAC that produces intoxication (0.08%). Death from alcohol overdose usually occurs from a suppression of the respiratory centres of the brainstem, or from inhaled vomit blocking one’s airway.
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Health benefit of alcohol
Moderate alcohol consumption is correlated with a reduced risk of death by cardiovascular disease, cancer, and diabetes.
More than 100 studies have shown that moderate drinkers have a lower risk of heart attack, stroke, and heart disease. Alcohol may reduce one’s risk of myocardial infarction by reducing the blood’s clotting tendency, by raising HDL levels, or because it improves insulin sensitivity, which lowers one’s risk of cardiovascular disease. These cardiovascular health benefits also may be due to the stress reduction or vasodilation caused by alcohol. Not general to every race and age. May be confounded.
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Alcohol with drawl symptoms
Mild to moderate alcohol withdrawal is characterized by a craving for alcohol, anxiety, irritability, difficulty sleeping, vivid dreams, and decreased appetite. Tremors, sweating, headache, nausea and vomiting, and irregular and elevated heart rate may occur. These effects usually peak 24–36 hours after the cessation of drinking, and are generally over within 48 hours.
Less common, but more dangerous, delirium tremens (DTs) may occur in 5–10 per cent of those withdrawing from chronic alcohol use. DTs are characterized by severe agitation; confusion; delusions; elevated heart rate, blood pressure, and body temperature; and seizures. Frightening visual, auditory, or tactile hallucinations can occur.
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Wernickes encephalopathy
Alcohol interferes with the body’s ability to absorb thiamine, a B vitamin that helps brain cells produce energy. Wernicke’s encephalopathy is an acute reaction to severe thiamine deficiency. When levels get too low, neurons cannot generate enough energy to function properly. Wernicke’s encephalopathy is due to damage in the thalamus and hypothalamus and is characterized by confusion, abnormal gait, loss of muscle coordination, abnormal voluntary eye movements, and vision problems.
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Korsakoff's syndrome
Korsakoff’s syndrome often follows Wernicke’s encephalopathy, as thiamine deficiency leads to frontal lobe and hippocampal damage. This can cause hallucinations and vision problems, and make it difficult to remember recent events or to form new memories. Sufferers will confabulate—replace gaps in their memory with imaginary remembered experiences that they believe to be true. People with Wernicke-Korsakoff syndrome may seem drunk even when they are not.
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Alcoholic hepatitis
Up to one-third of heavy drinkers may eventually develop alcoholic hepatitis, which is characterized by the inflammation and death of liver cells. Mild cases can be reversed with abstinence, but severe cases are potentially lethal.
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Alcoholic cirrhosis
develops gradually over time. Inflammation leads to irreversible scar tissue, which replaces healthy liver cells and blocks the blood vessels that supply that liver with oxygen, leading to further cell death. With increased loss of liver function, nutrients are not processed, toxins and fluids accumulate, and immune function is compromised.
Cirrhosis occurs with long-term heavy drinking—at least 10 drinks a day for at least 10 years, and the liver damage is permanent.
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FAS is defined by four criteria:
confirmed maternal exposure to alcohol; certain craniofacial anomalies in the child; pre- and postnatal growth retardation; and neurological abnormalities, which often are manifested as intellectual difficulties or behavioural problems.
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Define hallucinogen
Drugs that change ones perceptions of reality at relatively low doses. They show incredible diversity in chemistry, mechanism of action, and use.
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Difference between hallucination and illusion
A hallucination is a sense perception for which there is no external stimulus—the perception occurs in the absence of environmental stimulation, as might occur in a dream or psychotic state. Illusions alter and distort perceptions, thoughts and feelings
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Hallucinogen use in Indigenous communities
In Indigenous communities of North and South America, shamans—specially trained individuals who act as liaisons between the human and spirit worlds—largely control the use of hallucinogens in their communities. They use psychedelic drugs to facilitate healing, communicate with spirits, locate missing objects or people, and guide rites of passage.
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History of hallucinogens: Salem witch trials
Ergotism may explain the events that took place in Salem. Many of the conditions exhibited by the “possessed” girls were symptoms of ergotism: burning and tingling of the skin, sensory disturbances, and hallucinations. Additionally, the spring and summer of 1691 were warm and rainy, conditions that favour the growth of the ergot fungus, and 72 per cent of the households in Salem with an afflicted member were located close to a riverbank or swamp.
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Ergot
Ergot is a group of fungi that grow on grains such as rye and barley and produce alkaloids. Ergot contains lysergic acid, a chemical precursor of LSD, and produces hallucinatory convulsive effects.
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Albert Hofmann discovering LSD
Albert Hofmann worked as a chemist for Sandoz, a large pharmaceutical company in Switzerland. In 1938, he was studying an ergot derivative—lysergic acid—as a way to treat problems associated with childbirth. LSD-25 was the 25th compound synthesized, and he tested it on animals but saw no interesting properties, so LSD remained on the shelf until 1943, when Hofmann accidentally spilled a tiny amount on his hand. He then tripped hard for 3 days.
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The CIA and LSD
In the US during World War II, the Office of Strategic Services (OSS; the precursor to the CIA) began a top-secret research program to develop a truth serum. They thought LSD might be useful “for eliciting true and accurate statements from subjects under its influence during interrogation,”. Did not work as planned. In 1953 the CIA began project mk-ultra where they gave people LSD without their knowledge or consent. The CIA’s experiments with LSD eventually ended when the drug was deemed too unpredictable.
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Timothy Leary and the 1960s Counterculture
One of the reasons for the change in society’s awareness of and attitudes about LSD stemmed from the actions of Dr Timothy Leary. Was fired from Harvard for testing psilocybin on graduate students, even in non lab settings. He encouraged young people to “turn on, tune in, and drop out,” a phrase that became the philosophy of the youth movement of the 1960s. Throughout the decade, LSD became associated with cultural and political rebellion. Leary was #I most wanted for opposing governments ideologies.
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What is MAPS
MAPS—the Multidisciplinary Association for Psychedelic Studies—promotes research that shows potential clinical applications for hallucinogenic drugs.
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How to distinguish between a true hallucinogen and a drug which may cause hallucinations
True hallucinogens distort a user's perception of reality at a relatively low dose while other drugs require a higher than normal dose to have hallucinatory effects.
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Prevalence of Hallucinogen Use
In 2017, about 1.5 per cent of the Canadian population age 15 and older used a hallucinogen. Almost 15 per cent of Canadians have used a hallucinogen at some point in their lives.
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Difference between psychedelics, deliriants, dissociatives
Hallucinogens may be classified as: Psychedelics produce a vivid sensory experience and altered perceptions (LSD, peyote).
Deliriants result in mental confusion and the inability to differentiate reality from fantasy (deadly nightshade).
Dissociatives cause analgesia, amnesia, catalepsy, and a sense of detachment from the environment (salvia, pcp, ketamine)
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What is DMT and where is it found
Dimethyltryptamine (DMT) is a short-acting psychedelic found in the bark, leaves, and seeds of several varieties of trees native to Central America, South America, and the Caribbean (small amounts of DMT also occur naturally in mammalian blood, brain, and cerebrospinal fluid). DMT is ineffective when taken orally because the enzyme monoamine oxidase (MAO) breaks down DMT in the stomach before it can enter the bloodstream. When smoked, snorted, or injected, DMT’s effects begin within seconds, producing colourful and visually intense hallucinations that typically last less than one hour.
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Ayahuasca
The Incans called ayahuasca “the vine of the soul” or “the vine of the spirits.” Ayahuasca is an herbal tea made from two plants that grow in the jungles of South America, one of which contains DMT. Ayahuasca produces powerful visions, emotional reactions, and profound personal, spiritual, and mystical insights. The Indigenous Quechuan Peoples would drink ayahuasca during initiation rites, before a hunting expedition, or before making any major community decisions. Ingestion of ayahuasca often causes vomiting or diarrhea, which led South American shamans to believe this represented the elimination of negative energy and emotions built up over years. In fact, ingestion of these substances might have helped users purge their bodies of worms and parasites.
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Ibogaine
Ibogaine is a serotonergic hallucinogen that comes from a rain forest shrub that grows in Central Africa. The roots of the plant are psychoactive. Ibogaine may help treat addiction to cocaine, alcohol, and heroin by blocking receptors in the addiction pathway of the brain. Unfortunately, not enough is known about the risks of using the drug. There is some evidence that ibogaine may damage the cerebellum, cause severe motor tremors, and increase the risk of heart attack and seizures, so ibogaine has not been approved for treatment of addiction.
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While ________ psychedelics have a structure similar to serotonin, _________ are structurally similar to dopamine and norepinephrine.
Indoleaminic, phenylethylamines
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All of the drugs discussed in the deliriant category have these three factors in common. They are all
plants, muscarinic acetylcholine antagonists, and uncontrolled (nightshade, mandrake)
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This category is the most heterogeneous in terms of the drug source, the mechanism of action, the acute effects, and the legal status of these drugs.
Dissociatives ( salvia, Amanita muscaria, PCP, ketamine)
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________ name means "saviour of the seers," and the Indigenous Mazatec Peoples in Mexico used it for centuries for healing and spiritual practices.
Salvia
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Absorption, Distribution, Metabolism and excretion of hallucinogens
When taken orally, hallucinogenic drugs typically take effect in 20 to 60 minutes; onset of action is faster when drugs are snorted, smoked, or given intravenously. A drug’s duration of action depends on many factors, including the dosage, purity, and drug taken. DMT lasts only 30min, LSD can last 11 hours or more. Hallucinogens are metabolized by the liver and mostly excreted in the urine.
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How psychedelic hallucinogens (psilocybin, LSD, and mescaline) affect brain
work by affecting serotonergic receptors (especially 5-HT2A receptors) in the thalamus, locus coeruleus, and cortex. In general, there is more communication among all areas of the brain, and the greater this increased global connectivity, the more users feel a sense of connection with people and things around them.
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Difference between MDMA and psilocybin and LSD on seratonin
Unlike psilocybin and LSD, MDMA seems to markedly deplete the amount of serotonin in the presynaptic cell and inactivate the enzyme necessary to synthesize new serotonin. As a result, cells cannot replenish their serotonin levels for 24 hours.
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Salvinorin-A, found in the dissociative hallucinogen salvia, binds to _______ receptors that regulate perception.
Kappa opioid
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Synaesthesia
Overlap of senses. Someone experiencing synaesthesia may taste music, or hear colours. Synaesthesia may occur because the thalamus does not route sensory information to its proper destination.
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Therapeutic index of MDMA
14-16
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Hyponatremia
MDMA increases secretion of antidiuretic hormone, which causes the user to retain fluid and have overall lower plasma levels of sodium. Hyponatremia can lead to headache, nausea and vomiting, muscle cramps, weakness, fatigue, confusion, seizures, and cerebral edema. Often, those with MDMA-induced hyponatremia will lose their ability to speak, even before they lose consciousness. Estrogen exaggerates MDMA’s effect on antidiuretic hormone, so women are more likely to be affected by hyponatremia. Hyponatremia can occur with just a single dose of ecstasy. Nearly 20 per cent of those who report this complication die. Others experience permanent brain damage.
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Seratonin syndrome
MDMA triggers an excessive release of serotonin, serotonin syndrome sometimes results. Serotonin syndrome is characterized by cognitive symptoms, such as headache, agitation, confusion, and hallucinations; autonomic indications, including elevated blood pressure and heart rate, diarrhea, shivering, sweating, and hyperthermia; and somatic signs, such as muscle rigidity and twitching, heightened reflexes, and tremor. In severe cases, heart rate, blood pressure, and body temperature may elevate enough to cause seizures, muscle breakdown, renal failure, and death. Serotonin syndrome is fatal 10–15 per cent of the time. The condition is more severe in patients who have taken other drugs such as antidepressants that increase synaptic serotonin.
