Week 6: Opiates

Question 1

What are opioids also called

Answer 1

Narcotics : as they can cause sleep and produce analgesia

Question 2

Problem with the term narcotic

Answer 2

-Has become synonymous with drug addiction and law enforcement i.e. has become an umbrella term for all drugs (narcotics anonymous isn’t just referring to Opioids)

-Therefore Opiate or opioid is the preferred term.

Question 3

What is the natural source of opium

Answer 3

-The popypy: papaver somniferum

-Originally from Asia, but now cultivated in similar climates all over the world

Question 4

Active ingredients in opium

Answer 4

-Morphine
-Codeine
-Thebaine (present in much lower quantities)

Question 5

How is opium harvested?

Answer 5

-For 10 days in its life cycle, the plant manufactures opium

-Opium is the sao that seeps out of the seedpod after the petals fall off

-Pods are scored, the sap is allowed to dry and is gathered and formed into cakes.

Question 6

Thebaine is used to make other opioids…

Answer 6

-Thebaine was one of the active ingredients in opium present in much lower quantities.

-It can be used to make other opioids…
e.g. Oxycodone – Percocet, Percodan. OxyContin – slow release formulation, but can be crushed and injected
e.g. Buprenorphine
e.g. Nalorphine
e.g. Naloxone
e.g. Hydrocordone - Vicodin

Question 7

Synthetic opioids

Answer 7

-Drugs that do not resemble morphine but have similar pharmacological and behavioural profiles

e.g. Meperidine (Demerol)
e.g. Methadone – used as a heroin maintenance drug
e.g. Fentanyl (Designer drugs “china white” synthesized based on fentanyl)

Question 8

Routes of administration

Answer 8

-Opioids are given orally as analgesics, but this route is not used when they are taken for their euphoric effects

-Usually injected

-Heroin can be snuffed or vaporized and inhaled “chasing the dragon”

Question 9

Morphine heroin relationship in terms of route of administration

Answer 9

-morphine is not lipid soluble (cannot pass the BBB)

-undergoes significant first-pass metabolism

-heroin is lipid soluble and becomes morphine in the brain. So heroin is a way to get morphine into the brain quicker.

Question 10

Neurophysiology

Answer 10

-Brain has receptors for opioids: Identified in 1973 by Candice Pert and Solomon Snyder

-Brains of most vertebrates have opioid receptors: Used with endogenous opioids (endorphins, enkephalins)

Question 11

Opioid receptors: three types? What one is response for the most effects of opioids?

Answer 11

-Mu : responsible or most effects of opioids
-Kappa
-Delta

Question 12

What type of receptors are opioid receptors

Answer 12

G-protein coupled receptors (produce an internal cascade of events).

Question 13

Will excitatory and inhibitory receptors always have the same effects

Answer 13

-No depends on what type of neuron the opioid receptor is on.

Question 14

Why do different opioids have different effects?

Answer 14

-All opioids have the same effects on cells, but the overall effect depends on:
—> The affinity for each receptor type
—>The cell type and regional distribution of the receptors
—-> All receptor subtypes have distinct expression profiles

Question 15

True or false: the opioids with the most affinity produce the strongest effects?

Answer 15

False, In general, the opioids with less affinity produce the strongest effects

-Seems counterintuitive!

Question 16

Sites of action in CNS i.e. what parts of CNS have opoid receptors?

Answer 16

-Brain
-Brainstem
-Spinal cord
-Peripheral neurons
- Intestine : why when take a lot of opioids can become constipated.

Note: last two are not part of the CNS?

Question 17

Opioids and dopamine

Answer 17

-Morphine activates the opioid receptors on GABAergic interneurons in the nucleus accumbens in the brain

-This reigns in the release of GABA

-This drop in GABA causes a neighbouring cell to expel dopamine (i.e. GABA was acting as a break and now the inhibition on the neighbouring cell has been lifted –> double inhibition effect)

-This in turn elicits the europhia associated with opioids

Note: any time a drug produces a high/ europhoria it is having a positive effect on the dopamine system.

Question 18

Effects of opioids on the body

Answer 18

Good effects:
-They are effective painkillers
Morphine was referred to as ‘gods own medicine’ . Useful during the civil war

Bad effects:
-Drowsiness, confusion, memory loss, fatigue, hallucinations,
-Convulsions
-Respiratory depression –> causes overdose
-Nausea, vomiting, weight loss
-Sexual dysfunction
-Constipation

Question 19

Effects of opoids on sleep

Answer 19

-Person to person variation but in general makes it harder to sleep

Question 20

Effects of opioids on human behaviour: subjective reports

Answer 20

-Many literary figures were known to be opium users and would write about their subjective experiences e.g. Thomas De Quincey wrote about his opium use in his book Confessions of an English Opium Eater

• Helped focused him
  -Dreams

Question 21

In general: Why do intellectuals often use opium?

Answer 21

• In general, opium users are convinced that using the drug enhances the creative process: not substantiated yet by science.

Question 22

Difference in administration route and feeling produced by opium

Answer 22

• Taking the drug orally produces intense feelings of euphoria, but only injecting the drug produces the immediate intense “rush”

Question 23

Systematic effects on mood

Answer 23

Although authors write about the euphoric effects, systematic studies show that positive feelings don’t last and are replaced by mood changes and negative feelings

Question 24

What does the mood effects of opium depend on?

Answer 24

Effects also depend on whether users are new or experienced:

Lasagana et al. (1955)

• 17 out of 30 former addicts wanted to use morphine again
• 2 out of 20 nonusers wanted to use again

-Suggests that for non-users taking the drugs is not a pleasant experience for the most part

Question 25

Opium: performance

Answer 25

Not many effects on performance:
-Psychomotor performance may be slowed
-Cognitive performance mostly intact

-Tolerance also develops to performance effects

-Detrimental effects on performance are diminished when opioids are given to people experiencing pain

Question 26

Tolerance to opium

Answer 26

-Within 3 to 4 months, consumption increases 10 fold: Doses much higher than can be handled by a nonuser

-Tolerance to different effects occurs along different timelines

-Changes in opioid receptors and metabolism contribute to tolerance

Question 27

Cross tolerance

Answer 27

-Tolerance extends to all mu opioid agonists

-Does not extend to depressants, stimulants, or hallucinogens

-Some cross tolerance to alcohol (alcohol is a ‘dirty drug’ that effects many different systems.

Question 28

What is the one of the most misunderstood aspects of drug use?

Answer 28

-Withdrawal

-Usually portrayed as much more extreme than in real life.

Question 29

When might heroin withdrawal been more extreme?

Answer 29

-May have been more severe in 1920s and 1930s: Addicts had access to much more and cheaper heroin – took it in much greater quantities than users take today

Question 30

How does heroin withdrawal compare to alcohol withdrawal?

Answer 30

-Even in its most severe form, heroin withdrawal is not as severe as barbiturate or alcohol withdrawal

-Alcohol withdrawal can be fatal – heroin withdrawal never is

Question 31

Timeline and symptoms of heroin withdrawal in an addict

Answer 31

Begins 6 to 12 hrs after last drug use, peaks at 26 to 72 hrs, and is over within a week:

-Restlessness, agitation
-Violent yawning
-Pacing, stooped head and shoulders
-Chills, hot flashes, quick, jerky breathing
-Goose bumps (“going cold turkey”)
-Sleep which may last for 8 to 12 hrs
-Vomiting, diarrhea, cramps, twitching in the hands and legs (“kicking the habit”)
Sweating

Question 32

What does severity of heroin withdrawal depend on? How severe is it typically?

Answer 32

-Severity of withdrawal depends on the daily dose

-For most people, it resembles a bad case of the flu i.e. not life threatening but extremely uncomfortable

Question 33

Withdrawal to mu opioids agonists e.g. heroin can be immediately stopped by….

Withdrawal to mu opioids agonists e.g. heroin can immediately be generated by…

Answer 33

-An agonist (taking the drug)

-An antagonist

Question 34

Are more people who use heroin addicts?

Answer 34

-Nope: they use heroin occasionally – maintain a normal lifestyle and seldom require treatment

Question 35

Typical heroin addict looks like…

Answer 35

-Uses at least once a day,
-Preoccupied with obtaining drug
-Physically dependent (goes through withdrawal without the drug)
-Has little time or money for other activities
-Has friends who are also users

Question 36

What is first exposure to heroin usually like?

Answer 36

-First exposure usually via a friend

-Almost always unpleasant

-Persistent use required for dependence to develop

-In this way the common perception that people take a drug have this insane amount of pleasure from the experienced and then simply must use again is false.

Question 37

Many people mature out of use… While others…

Answer 37

-Mature out: Spontaneously discontinue use after a period of around 5 – 10 years in their 30s or 40s

-Others are never able to leave the addiction behind survive into old age still using

Question 38

In lab studies do opioids act as reinforcers?

Answer 38

-Opioids act as reinforcers (in terms of subjective effects and enhanced mood) in users, but not in nonusers.

-Lasagna et al., 1955 found that 17 out of 30 former users would repeat morphine administration, but only 2 out of 20 non users

-Opioids typically are only reinforcers in non-users in the presence of pain

Question 39

Why are there few studies of self-administration in non-users?

Answer 39

-Ethical reasons: can’t ask people who don’t use to use for the purpose of the study!

-Makes it hard to truly assess whether they are reinforcing or not for non-users

Question 40

Extent of use by country for opioids

Answer 40

-NZ is fairly high in our use (greater than 1%)

Question 41

Acute harmful effects of opioid use + reasons for overdose…

Answer 41

-Severe depression of respiration (due to there being lots of opioid receptors on the parts of the brain that control respiration) —> results in death

-Overdose is the leading cause of death among heroin users. Severe potential reasons:

e.g. Quinine - something that drug dealers might cut their drugs with. If put with heroin this can be deadly –> why organisations like know your stuff/ drug checking is so important and is a huge argument for legalisation. If the drug market is regulated people would know what they were getting.

e.g. lose of tolerance for example if take a drug in a new environment you don’t have the same contextual cues and so the body does not prepare in the same way and don’t have the same level of tolerance.

-e.g. Drug mixes: often people are polydrug users but some mixes are extremely dangerous as both depress the respiratory system.

Question 42

Why is the word overdose misleading?

Answer 42

-It’s not just people taking too much of a drug

-Overdose is complicated and there are many things that come into it.

Question 43

Where does heroin sit on the active/ lethal dose ratio and dependence potential of psychoactive drugs?

Answer 43

-Very high

Question 44

Chronic effects of Heroin?

Answer 44

Chronic effects:
- Health: very few chronic health effects (except death)
- Constipation
- Cancer promoter: heroin inhibits the body’s ability to repair DNA

CNS effects:
- some abnormal brain activity patterns
- Does not alter the structure of the brain
- Reduced activation in cortical areas during cognitive tasks

Question 45

CNS effects of Heroin?

Answer 45

• some abnormal brain activity patterns
• Does not alter the structure of the brain
• Reduced activation in cortical areas during cognitive tasks

Question 46

Effects on reproduction: males

Answer 46

decreased testosterone; decreased fertility; changes in secondary sex characteristics

Question 47

Effects on reproduction: females

Answer 47

-Changes in menstrual cycle; decreased fertility

-During pregnancy, harm may come to the fetus from withdrawal or other problems associated with the addicts lifestyle

-Anemia, cardiac disease, swelling, liver disease, hypertension, pneumonia, tuberculosis, bladder infections

Question 48

Effects on babies born to mothers addicted to heroin?

Answer 48

-Babies born to addicted mothers have lower birth weights; experience illness and complications after birth. Have to go through withdrawal

-There is a steady amount of addicted babies been born: every 15 minutes a baby is born suffering from opioid withdrawal.

Question 49

Lifestyle effects of heroin use?

Answer 49

-Costs a lot of money: Health, housing, nutrition all take second place

Question 50

Clean needles?

Answer 50

-Clean needles are not common

-Exposure to hepatitis and HIV/AIDS greatly increases

-Organisations that provide needles/ a safe space to administer drugs with advice.

Question 51

Death rate of heroin users versus general population

Answer 51

Rate of death is 50 to 100x the rate in the general population

Question 52

Status of heroin addicts after a 33 year period study

Answer 52

of 581 heroin addicts admitted to compulsory drug treamtent between 1962 to 1964, nearly half had died by 1997

-Of the surviving 242 addicts who were interviewed in 1996-1997 1 in 5 were currently using heroin. 14% were incarcerated, 9.5% refused to be tested. 55.8% were abstinent.

Question 53

Years of potential life lost: what + how does this measure compare for addicts and normal US population?

Answer 53

-Pick a reference age (65) and subtract the age at death from it. Yields a metric of the years of life lost per 1,000 people

-Refer to table. A range of causes of death looked at e.g. unintentional injuries, liver disease, heart disease, homicide, suicide, stroke. Addicts were higher in YPLL for all. In total addicts estimated 229.14 conditions compared to 39.17 of normal US population.

Question 54

Prescription opiate addiction

Answer 54

-Since the 1990s, prescription opiates (oxycodone) have skyrocketed in popularity. So much so that as of 2011 were equal with morphine.

• Over prescribed: Drug company marketing and kickbacks for doctors. Addictive nature purposefully downplayed.

Question 55

PurduePharma

Answer 55

• PurduePharma guilty of criminal misbranding and fined $634 million (makes $3 billion a year on oxycontin alone)

Side note: there is a netflix show on this painkiller if you wanna do some ‘study’

Question 56

Drugs invovled in US overdose deaths 2000- 2016

Answer 56

-Synthetic opioids other than methadone have skyrocketed and now the leading cause

Question 57

Opiates in New Zealand’s

Answer 57

-Produces the highest number of overdose casualties despite more prevalent use of meth and other drugs
429 deaths between 2004 and 2010 – half due to overdoses

-Prescription opiate use on the rise

Question 58

Percent of people dispensed a strong opioid in the months before death in 2017

Answer 58

-Upwards curve : i.e. the closer you get to death the more likelihood you were prescribed an opioid.

-People who are going to die much more likely to be prescribed opioid

• Not necessarily that the opioid is causing death

-But there is an interesting statistic to consider