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Drugs and Behavior > Opioids > Flashcards

Opioids Flashcards

1
Q

Opiate definition

A

Refers to the “natural” opioids. Includes heroin, morphine, codeine

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2
Q

Opioid definition

A

Includes natural, semisynthetic, and synthetic opioids

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3
Q

Papaver somniferum

A

A species of poppy plant that opium is derived from. It is native to the middle east and is now cultivated throughout Asia and the Middle East. After the petals fall off, they leave a seed pod. The sap can be extracted and allowed to dry. This dried sap is opium, which can be consumed orally or by smoking.

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4
Q

Early history of papaver somniferum

A

There is evidence it was used by Sumerian and Assyrian civilizations (6 thousand years ago). In Egypt, medical uses were discovered 3500 years ago. The Greeks and Romans began to utilize opium for medical uses in 130 CE. It was also utilized in the middle east and China

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5
Q

Medical uses of opium by the Greek and Romans (3)

A
  1. Pain relief (analgesia)
  2. Cough suppressant
  3. Antidiarrheal properties
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6
Q

Use of opium in the Middle East

A

In the middle east, there are prohibitions against many drugs, like alcohol. However, there is no prohibition against opium, and use is widespread. This scenario demonstrates that cultural and societal values matter in terms of what drugs people decide to do

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7
Q

Use of opium in 19th century China

A

During this time, opium was not a big issue for Europe or the US yet. In China, opium was widely available in medicines (like laudanum). It was taken orally in a liquid form (“opium eating”). Soon, there was widespread recreational use of opium

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8
Q

When did opium use become prevalent in the west?

A

By the late 1800s, opium was widely used in the West- there was recognition of opium dependence as a western problem. Withdrawal effects were horrible and painful

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9
Q

F.W. Serturner

A

In 1803, he separated the morphine from opium- morphine is 10 times more potent, and was called “morphine” after the the Greek god of dreams, Morpheus. Morphine was widely available by the mid 1800s, the the invention of the hypodermic needle allowed the drug to reach your brain faster.

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10
Q

Soldier’s disease

A

Morphine was used widely during the Civil War. It was revolutionary for treating pain after surgery for injuries from war. However, many soldiers returned from the war dependent on morphine, so morphine dependence was termed “soldier’s disease”. People vulnerable to addiction also include people experiencing depression, sadness, or emotional distress, which is another reason why men in the military were so predisposed to addiction. Sometimes, recovery from morphine withdrawal was even worse than recovery from the initial injury.

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11
Q

How did the invention of the hypodermic needle increase the risk of addiction?

A

Once morphine was able to be injected through a hypodermic needle, effects occurred more quickly and were more intense, increased likelihood of addiction

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12
Q

Uses of morphine in the 19th century (2)

A
  1. Recreational use
  2. Used to recover from injuries, severe wounds, and surgery
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13
Q

How was heroin invented?

A

C.R. Adler Wright produced a new alteration of morphine called diacetylmorphine (what would later be called heroin). The compound went unnoticed until 1898, when Heinrich Dreser (German pharmacologist) rediscovered the compound and determined it was more potent than morphine. The drug had “heroic” properties, hence the name

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14
Q

How is heroin different from morphine?

A

Heroin (diacetylmorphine) is not really chemically different from morphine. However, heroin is lipid soluble and crosses the blood brain barrier more rapidly. It is therefore much more likely to produce dependence, and is twice as potent as morphine.

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15
Q

Initial uses of heroin

A

Used as a cough suppressant and pain reliever

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16
Q

1914 Harrison Narcotics Act

A

The law required opiate access to be controlled by physicians. Later laws placed further restrictions on who can be prescribed/how much/under what circumstances. The act created a market for illegal opioids and changed the demographics for addiction

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17
Q

How did the Harrison Narcotics Act change the demographics for addiction?

A

Prior to the act, people of all classes could purchase opioids at the drugstore and use the drug. After the act, opioids were generally used in large cities (where organized crime provided the supply). People developing addictions were more likely to be young, poorly educated, and men

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18
Q

Hser et al (2001) heroin addiction study

A

The study followed 581 heroin addicts over a 33 year period. Half of the participants died (50-100 times the death rate in the general population). Of the survivors, 20% were still using heroin (10% refused to be tested) and 14% were in prison. Addicts are also at higher risk of HIV/AIDs, hepatitis, and death by overdose

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19
Q

Medical use of opioids after the Harrison narcotics act

A

There are many medical uses, and the drugs are mainly used to treat severe and acute pain. They are generally only used after surgery or for traumatic injuries. People are usually only prescribed these drugs for a few days at a time

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20
Q

1970s synthetic opioids (2)

A
  1. Hydrocodone (Vicodin)
  2. Oxycodone (Percodan)
    These drugs were still used and prescribed cautiously at the time
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21
Q

During which time period did opioid prescriptions drastically increases?

A

Between 1999-2011, prescriptions quadrupled. Physicians began prescribing opioids for chronic pain, and were driven by a belief (based on a small study) suggesting that opiate drugs were not addictive. The pharmaceutical industry developed more opioids to treat

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22
Q

OxyContin

A

Developed in 1996, and was designed to treat severe and chronic pain. It was a higher dose of oxycodone in a time release form (over a period of 12 hours). People found that you could crush and snort- delivering a very large dose quickly. Doctors felt increasing pressure to prescribe opioid drugs during this time period

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23
Q

Opioid abuse prevalence by the mid 2000s

A

By the mid-2000s, the death rate due to opioid overdose was greater than the death rate from car accidents. Nearly 10% of US adolescents (age 12-17) reported use of illicit prescription opioids. There are no differences between African Americans, Hispanic, Asian, and Non-Hispanic white populations

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24
Q

Often, crack-down on one opioid will lead to

A

An uptick in the use of others. As prescriptions for opioids go down, heroin and fentanyl are being smuggled in at an alarming rate. Heroin deaths are now increasing substantially

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25
Q

What is the prevalence of opioid misuse/addiction among people who have been prescribed opioids?

A

More than 20% of people prescribed opioids for chronic pain misuse the drug, and 8-12% of people prescribed opioids develop a use disorder. 2014 data- more than 2 million people have a substance use disorder related to prescription opioid medication. 2021 data- almost 71,000 people died from overdose involving synthetic opioids

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26
Q

Fentanyl

A

A synthetic opioid that is the most powerful opioid drug ever developed. It is 100 times more powerful than morphine and has a shorter duration of action. This is not a new drug. It was available in the 1960s, and only recently started flooding the market from international suppliers

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27
Q

Medical uses of fentanyl

A

Fentanyl has legitimate medical uses, and is mainly used for surgical anesthesia

28
Q

Fentanyl overdoses

A

Overdose deaths start to spike when fentanyl shows up on the street, as fentanyl is sometimes combined with heroin and other illicit drugs. Combination with other drugs drastically increases the risk of overdose due to the synergistic effects of CNS depressants. Additionally, people aren’t necessarily aware when they are consuming a drug contaminated with something else, making it more dangerous

29
Q

Absorption of opioids

A

Opioids may be taken orally, injected intravenously, can also be absorbed through nasal mucosa and lungs through smoking and snorting. Pure opium and heroin are often smoked

30
Q

Absorption

A

The passage of a drug from the site of administration to the bloodstream. To do this, a drug must pass through different membranes, like the mucous membranes in the mouth or the walls of the intestines. The specific membrane the drug has to pass through depends on the drug’s route of administration

31
Q

Pharmacokinetics of opioids once in the bloodstream

A

The drug is distributed throughout the body and accumulates in the kidneys, lungs, liver, and muscles, as well as the brain. Some opioids penetrate the blood brain barrier better than others- heroin is more lipid soluble and enters the brain faster than morphine. Most drugs are rapidly metabolized and 90% is excreted within a day, but some traces can be found 2-4 days later

32
Q

Why does heroin penetrate the blood brain barrier faster than morphine?

A

Heroin is more lipid soluble and can therefore pass through the blood brain barrier faster than morphine

33
Q

Endorphins

A

Endorphins function as the body’s natural painkillers, or natural opioids. They function as neurotransmitters and bind to opioid receptors. Endorphins are released by the hypothalamus and pituitary gland in response to pain or stress, this group of peptide hormones both relieves pain and creates a general feeling of well-being.

34
Q

How do opioid drugs produce their effects?

A

Opioid drugs produce their effects by binding to opioid receptors and triggering activity in the endorphin system. They
also trigger a large release of dopamine in the nucleus accumbens- beyond the amount of dopamine that could be released naturally

35
Q

3 types of opioid receptors

A
  1. Mu
  2. Kappa
  3. Delta
36
Q

Functions of the opioid system

A

Opioid peptides and receptors are broadly expressed throughout peripheral and central nervous systems. The opioid system plays a central role in nociception (perception of painful stimuli) and analgesia (pain relief). The opioid system also regulates numerous physiological functions, including responses to stress, sensorimotor behavior, respiration, gastrointestinal transit, as well as endocrine and immune functions. This system also plays a key role in learning, modulating mood and well-being, as well as addictive behaviors.

37
Q

Where are opioid receptors most commonly expressed?

A

Opioid receptors are expressed primarily in the cortex, limbic system, and brain stem. Binding sites for the three opioid receptors overlap in most structures, but some structures exhibit higher expression of one receptor over the others. Mu is the most expressed opioid receptor in the amygdala, thalamus, mesencephalon, and some parts of the brain stem. Kappa is most represented in the anterior basal forebrain (hypothalamus, pituitary, nucleus accumbens). Mu and kappa coexist in most structures, whereas the distribution of delta is more restricted

38
Q

Influence of opioids in the midbrain

A

The mesolimbic dopaminergic system is the main area that mediates opioid reinforcement- the characterization of opioid-sensitive brain sites has focused mainly on the VTA and NA. Infusions of opioids to the VTA reduce GABA transmission- this is because opioid receptors are generally inhibitory. GABA itself shuts off the brain’s euphoria and pleasure networks. Opioids act as an “off switch to the off switch”, as GABA neurons shut off the release of dopamine. Once these neurons are shut off my opioids, the massive release of dopamine can occur in the NA. The mesolimbic areas of the brain likely mediates the rewarding and motivating aspects of these drugs

39
Q

Mu receptors

A

These receptors are the primary target of almost opioid drugs. These receptors have many functions, but are also responsible for opioid dependence and withdrawal. Stimulating this receptor with therapeutic drugs to help with opioid cessation seems to have a long term effect on cessation

40
Q

Mu receptors functions (5)

A
  1. Analgesic
  2. Sedating effects
  3. Rewarding effects when stimulated by the drug
  4. Respiratory depression
  5. Stomach problems
41
Q

Naloxone

A

An opioid antagonist that doesn’t produce any affects of opioid drugs. It has a high affinity for the opiate receptor site and blocks the affects of an opioid in the event of an overdose. All first responders are trained to administer naloxone.

42
Q

Effects of naloxone

A

If you take Naloxone before taking an opiate, the effects are blocked. However, if someone has overdosed on opiate drugs, naloxone can rapidly reverses the effect and can put people into withdrawal. People are switched from a pleasant stupor to an uncomfortable/painful situation- this can be dangerous for first responders. The drug has a short half life and doesn’t last very long. It can cause nausea and flu like symptoms

43
Q

Current medical uses of opioids (3)

A
  1. Obvious pain relieving effects-most potent and effective pain relievers known to medicine
  2. Make surgery possible
  3. More liberal uses of these drugs have contributed to the epidemic, but denying people the use of these drugs also has consequences. For some people with chronic pain conditions, opioids are the only things that help with the pain.
44
Q

Partial opiate agonists

A

Bind to the same receptors, but produce lower levels of activity- these drugs are less effective as well. They do produce analgesia, but have a much lower potential for abuse. There are currently 3 partial opiate agonists on the market that are approved for moderate to severe pain. They are thought to be safer, but can still result in dependence

45
Q

Psychological and physiological effects of opioids (5)

A
  1. Euphoria, drowsiness, heavy feeling in the limbs
  2. Relaxation- “like lying in warm salt water”
  3. Activates pleasure systems at a level that isn’t supposed to happen naturally
  4. Interference with other interests- reduced sex drive, impaired social interactions
  5. Pipe dreams
  6. Respiratory depression, constriction of pupils
46
Q

Pipe dreams

A

Vivid, dream like experiences that occur under the influence of opioids

47
Q

Opioid withdrawal

A

Dependence on opioids can occur very quickly, in as little as a week, and withdrawal symptoms can occur after 1-2 weeks of use. Because withdrawal is a compensatory response for when the body expects opioids, it is a physically painful process

48
Q

Which neurotransmitter is produced during withdrawal?

A

Noradrenaline is produced in excess during withdrawal

49
Q

When do withdrawal symptoms begin?

A

8-12 hours after the last use of the drug

50
Q

Withdrawal symptoms (5)

A
  1. Tremors
  2. Shaking
  3. Anxiety
  4. Muscle cramps
  5. Flu like symptoms
51
Q

Progression of withdrawal symptoms

A
  1. 8-12 hours after last use- flu like symptoms- runny nose, chills, tearing, sweating
  2. Over time, people experience more severe symptoms- anorexia, goosebumps
  3. 48-72 hours after the last dose, people can experience severe flu-like symptoms- nausea, diarrhea, sneezing, severe pain in the bones and joints- a compensatory mechanism to the analgesic effect
52
Q

Methadone

A

Was available as 1947 and is used to alleviate opioid withdrawal symptoms. It is administered by mouth as a liquid, pill, or sublingual tablet. Prevents withdrawal symptoms for 24 hours. Also, because it is an opioid receptor agonist, any other opioid would not be able to create a euphoric effect if administered. This creates fewer cravings and no positive reinforcers if relapse occurs

53
Q

Drawbacks of methadone

A

Due to Drug Addiction Treatment act, methadone is a controlled substance. It is still an opioid, and therefore it must be administered in a clinic to reduce the potential for abuse. However, methadone’s effects wear off after 24 hours, meaning that patients must travel to a clinic every 24 hours to get the medication. This can present a barrier to treatment for some people.

54
Q

Mechanism of methadone

A

Methadone acts as an agonist of mu receptors. It binds to and stimulates these receptors to reduce opioid cravings and prevent withdrawal symptoms. Also, methadone acts as an antagonist of NMDA glutamate receptors, blocking glutamate activity. This may contribute to methadone’s pain relieving effects

55
Q

How to opioids promote CNS depression at the synapse? (2)

A
  1. Opioids open potassium channels, so that the neuron is hyperpolarized and neurons are less likely to fire an action potential
  2. They also inhibit calcium activity, so neurons are less likely to release neurotransmitters
56
Q

How do opioids impact the ACC?

A

When opioids bind to receptors in the ACC, they reduce the emotional impact of pain

57
Q

Function of the nucleus accumbens

A

Releases a large and unnatural amount of dopamine when opioids bind to its receptors. This reinforces the idea that opioids are rewarding

58
Q

Function of the VTA

A

Activation of the VTA leads to activation of the mesolimbic and mesocortical pathways (these regions are connected to the VTA). This creates the rewarding feelings of drug administration

59
Q

Function of the amygdala in opioid administration

A

The amygdala is part of the limbic system and is involved in learning/conditioning. Opioids binding in this area relieves anxiety and stress, reinforcing the idea that opioids are rewarding

60
Q

Function of the prefrontal cortex in opioid administration

A

Opioids disrupt normal functioning and can cause compulsive drug seeking- administration is automatic, and habits and cravings overrule the PFC’s decision making abilities

61
Q

Buprenorphine

A

A semi-synthetic partial opioid receptor agonist. It is the first line treatment for opioid addiction. Buprenorphine is administered through sublingual tablet, or transdermally through a patch. It is not controlled and therefore does not have to administered at a clinic. It has a longer half life than methadone and has longer effects. It also causes less sedation than methadone, as methadone frequently causes drowsiness

62
Q

Drawbacks of buprenorphine

A

People tend to experience more withdrawal from buprenorphine than from methadone. Buprenorphine also suppresses stress related responses

63
Q

Buprenorphine mechanism

A

Buprenorphine is an opioid receptor agonist at mu receptors- it stimulates the opioid receptor so that the actual opioid can’t bind. It also acts as an antagonist to block both kappa and delta opioid receptors, preventing these receptors from being activated

64
Q

Recovery from opioid addiction

A

After detoxification procedures- 80-90% of people relapse within 2 years. Most relapses occur within 6 months. This is thought to be due to returning to the environment of use- CS leads to craving

65
Q

Robins et al (1975) soldiers returning from Vietnam study

A

This study looked at soldiers returning from Vietnam- 21% of these soldiers were addicted to heroin. After returning home, they went through detox procedures. Their relapse rate was only 15% of the study population, which is much lower than the 80-90% relapse rate of the general population. The patients in the study, upon returning home, drastically changed their environment. Most cues predicting the drug, as well as the general stress of war, had been removed. This evidence suggests that a change in environment is crucial to a person’s recovery from opioid addiction

Drugs and Behavior (8 decks)

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