Exam 3 Flashcards
Explain Centrally Acting Opiates/ Opioids
Introduction
- Opiates a large group of naturally occurring compounds from opium, the latex from the opium poppy
- Main psychoactive opiates in opium are: Morphine, Codeine, Thebaine
- Afghanistan largest illegal producer of opium
- India, Turkey, and Australia largest legal producers
- Lethbridge Opium production (Same conditions to grow opium)
- Opium used as far back as 5,000 BCE
- Used in ancient Asia, Egypt, Arabia, Greece, Rome
- Introduced to western medicine 1500s
- Morphine isolated from opium in 1805 and codeine isolated in 1832
- Opium often combined with alcohol to laudanum
- 1/400 North Americans addicted in early 1900s (women and children)
The latex from the opium poppy is what?
Papaver Somniferum
Opium was historically used for…
- Pain relief, surgical analgesia, insomia, depression, and diarrhea
- Religious and ritualistic context
- Suicide and executions (combined with hemlock)
- Recreational use
Women and children were
addicted to opiates and opium
Opiates/ Opioids used for executions was combined with…
Hemlock
Mrs. Winslow’s Soothing Syrup AKA
Baby Killer (1tsp fatal)
1895-1915 state provincial laws
eliminated the over-the-counter availabilty of opiates and opioids
Recreational use of opioids in Canada was made illegal in
1908
Recreational use of opium was made illegal in the U.S. in
1914
Why was recreational use of opium made illegal?
Addiction concerns and widespread use amongst immigrant chinese labourers and increasing recreational use in non-chinese
Opioids are…
Synthetic
Opiates are…
Natural (Codeine, Morphine, Thebine)
First Synthetic Opioid
Heroin
Heroin
- Made form morphine 1874
- Reaches brain faster, 2-3 times more potent than morphine
- Introduced as a substitute for codeine and morphine to suppress coughing from tuberculosis and pneumonia
- Mistakenly believed to have fewer side effects
Oxycodone
- OcyContin, Percocet
- Thebaine
- 1916
Hydromorphone
- Dilaudid
- From Morphine (Kadrian)
- 1922
Methadone
- Synthetic Opioid
- 1939
Pethidine
- Demerol
- Synthetic opioid
- 1939
Pentazocine
- Talwin
- 1959
Fentanyl
- Sublimaze
- 1959
Naloxone
- Narcan
- 1961
Naltrexone
- Trexan
- ReVia
- 1965
Loperamide
- Imodium
- 1969
Buprenorphine
- Suboxone
- 1969
Carfentanil
- 1974
Modern Uses of Opiates and Opioids
- Pain relief
- Coughing
- Diarrhea
- Anesthesia
- Opiate/ Opioid addiction (drug substitute)
- Opiate/ Opioid O.D.
- Alcohol, Gambling addiction (anti-craving-)
- Executions (U.S.)
- Chemical Weapons
- Euphoria (Recreational use and abuse)
What is used for U.S. executions (Modern)
Fentanyl combined with potassium chloride to stop heart
Opiates/ Opiods are taken
Orally, Intravenously (Mainlined), intramuscular, subcutaneous, smoked, snorted
True or False: More absortion when taken orally because it is lipid soluble
False
Less complete absorption when taken orally because tends to be lipid ins
What is the Neuromechanism of Opiates?
Mimics endogenous and natural opioids. Endogenous opioids are distributed throughout the Central Nervous System, particularly in areas that involve pain like spinal chord and midbrain, and mood (limbic system), also found in stomach and intestines
What endogenous/ natural opioids are mimicked?
fins
endorphins, dysnorphins, and enkephalins
Natural Opioids function as…
Neuro
Neurotransmitters, neurohormones, and neuroegulators
True or False: Overall role of opioids/ opiates are complex and not well understood
True
Body releases…
Exercise and Stress
Cortisol toincrease glucose in blood to aid muscles
Brain releases…
Exercise and Stress
BNDF to protect neurons from cortisol and stimulate neuronal growth for learning, memory, and thinking
Endorphins and endocannabinoids to block pain
What happens after exercise ends?
- Cortisol returns to normal levels
- Endorphins, endocannbainoids, and BDNF still elevated
- Produces a sense of well-being
12 hours of mood elevation can be achieved by
a 20 minute work-out
Name the 4 types of opioid receptors
- Mu (euphoria
- Kappa
- Delta
- NOP
What is the primary effect of the opioid receptor?
activation is reduction or inhibition of neurotransmission, particularly neurotransmitter release
Spinal chord
Inhibit substance P release
Ventral Tegmental Area
Inhibits GABA neurons thus disinhibiting dopaminergic neurons and increasing dopamine input in nucleus accumbens
Main Effects of Opioids and Opiates
Physical
- Analgesia
- Relief of anxiety, euphoria, lose all concerns
- Decreased respiration (including coughing)
- Constipation
- Reduced Sex Drive
- Decreased pupil size
- Mental clouding, drowsiness
What is a less effective non-opiate alternative?
Dextromethorphan
Thousands of Overdose Deaths/ Year
- Respiratory suppression
- 80% associated with other drugs (stimulants and alcohol)
- Increasing since 2000, peak during pandemic (2020-2021)
Highest Opioid Death Rates in Canada
- Fentanyl and Carfentanil users
- Yukon, British Columbia, Alberta
- Young and Middle-Aged males
- Indigenous
- Stimulant users (cocaine and meth)
True or False: Lethbridge does not have the highest death rate per capita in North America
False they have the highest
What is the fatal dose of fentanyl
2mg or 2000mcg
fatal dose of carfentanil
0.02mg or 20mcg
Opiates/ opioids differ in ____ degree pass through blood-brain barier, which opioid receptor they act on, whether they are agonists or antagonists, and duration
Potency
Opioids are mostly metabolized by…
The liver and excreted by kidneys
Opioids and Opiates for pain, sedation, and coughing
- Codeine
- Morphine
- Pentazocine
- Oxycodone
- Hydromorphone
- Heroin/ Diamorphine
- Fentanyl
- Carfentanil
Opiates and Opioids for Addiction
- Buprenorphine
- Naltrexone
- Naloxone
Opiates and Opioids for Diarrhea
Loperamide
Long-Term Effects of Occasional Opioid Use
- Not associated with long-term effects
Long-Term Effects of Reccurent Opioid Use
- Profound tolerance and strong physical and psychological dependence
- Crime
- Severe withdrawal symptoms (excitation, nausea, insomnia, hypersensitivity to pain, rarely fatal)
- Constipation, indigestion, nausea
- Increased risk of sexual dysfunction, fatigue, depression, sleep apnea, neuropsychological deficits, increased sensitivity to pain due to neuroadaptation
- Use of needles can lead to vein collapse, hepatitis, blood poisoning, AIDS (unclean needles)
Harm Minimization for Opioid/ Opiate Use
- Supervised injection sites
- ARCHES
Periferally Acting Analgesics
- Often subclassified into NSAIDs and atipyretics
- Most common are aspirin, acetaminophen, ibuprofen, naproxen, and voltarin
- Most widely used medications in the world
- All but acetaminophen work primarily on the body and peripheral nervous system
- For pain, inflammation, fever, differences between them in efficacy profile
- More effective for pain when combined with caffeine
- Increased risk for gastrointestinal bleedin, stroke, and heart attack, adverse effects on kidneys and liver
- Fatal in large doses
- Inhibit enzymes related to prostaglandins
- Minimal tolerance and dependence
- Most available over the counter
What are prostaglandins
Lipids having hormone-like effects to mediate pain, inflammation and fever
Aspirin
- Found in willobark and spiraea
- Used for pain and fever for thousands of years
- Most commonly used peripherally acting analgesic
- No cardiovascular risk other than PAA, daily low dose helps to stop blood clots and prevent heart attacks
- Useful in preventing certain cancers (colorectal)
- Increases risk of gastrointestinal bleeding and kidney problems
- Shouldn’t be given to children and teens. Associated with Reye Syndrome
What is Reye Syndrome?
A brain disease associate with aspirin in children and teens
Acetaminophen
- Tylenol
- 1955
- Less risk of gastrointestinal bleeding
- Higher risk of liver damage and fatal OD due to liver failure (500 deaths/ year U.S.)
- Not effective for inflammation, less effective for pain relief
- Increase cardiovascular problems and kidney damage
- Unlike other analgesics effects mostly in Central Nervous System
Ibuprofen
- 1974 (relatively new)
- Gastrointestinal irritation (less than aspirin), increased cardiovascular risk, increased risk of kidney damage
- May help prevent Parkinson’s
Naproxen
- 1976 (relatively new)
- Longer duration than other peripherally acting analgesics
- Low risk of cardiovascular problems
- Increased risk of gastrointestinal bleeding and kindey problems
What are Psychotherapeutic Drugs?
- Exotic compounds also prescribed in historical times for mental disorders
- Most operated via placebo effect
- Exception; Opium, Alcohol, Cannabis, Willow bark
morphine
1804
Pain, depression, and insomnia
Chloroform & Ether
1840s
Pain
Aspirin
1899
Pain
Phenobarbital
1912
Seizures
Amphetamines
1935
Narcolepsy, Depression
Lithium
1949
Mania
Chlorpromazine
1953
Schizophrenia
MAOI
1957
Depression
Tricyclic Antidepressants
1957
OCD, Anxiety, Depression
I-Dopa
1961
Parkinson’s Disease
Diazepam
1968
Anxiety
Naltrexone
1894
1980s
- New Antidepressants
- Antianxiety
- Antipsychotics
1987
Prozac/ Fluoxetine
2006
Varenicline (Champix)
Current Prevalence of Mental Health Medication
- Significant increase in rx psychotropics in past 30 years
- Primarily due to increased use of antidepressants
- Signficant increase in children and adolescents as well (mostly due to stimulant medication for ADHD), although this has leveled off recently
- Billions currently spent on antidepressants, antianxiety, antipsychotics, and stimulant drugs
In 2019, adults…
- 14% rx opiate/ opioid
- 11% rx sedative
- 10% antidepressant
- 2% rx stimulant
Increase of Psychotropic use due to…
- Family physicians being main mental health practitioners
- Quick fix
- Short-term effectiveness
- Wide range of mental health conditions that can be treated
- Mild to short-term side effects
6% of U.S. adults were prescribed psychotropic medication in…
1990
What is an issue with the increase of psychiatric drugs?
- Increasing the chronicity of mental health problems
- Very difficult to withdraw from the drug
Demographic Correlates of Mental Health Medication Usage
- Higher in Western countries
- Higher in North America compared the Europe
- Higher in females
- Higher in whites
Psychotropics are the first line treatment for…
- Bipolar types I and II
- Schizophrenia
- Severe depression
Psychotropics also effective in short-term for other mental heath problems. However…
Long-term mental health tends to be worse compared to people who have went to psychotherapy or received no medication at all
Psychotherapeutic drugs should always be…
The last resort
Physicians refer to…
Compendium of Pharmaceuticals and Specialties (CPS)
ADHD medications
- Methylphenidate (Ritalin, Concerta)
- Amphetamines (Dexedrine, Vyvanse)
Both medications have 1/day administration
How does ADHD medication work?
- Increases on-task behaviour and decreases disruptive behaviour
- Equivocal impacts of academic achievement
Side Effects of ADHD Medication
- Appetite suppression
- Insomnia
- Small growth retardation
- Motor and vocal tics, may produce permanent tics
- 1.5% risk of psychosis
- Abuse potential
New formulation of Vyvanse
Converted to dextroamphetamine after enzymatic break-down in red blood cells
