Opioids

Question 1

What exogenous opiods (aka narcotics) are used for

Answer 1

Can be used for instrumental and recreational use.
Instrumental: Pain medication (chronic and acute pain)
Recreational: Street drugs
Note: High abuse potential. Can be lethal (especially fentanyl), as it can shut down the ability to breathe.

Formerly called opiates if they were derived from the opium poppy, now typically all called opioids.

Question 2

Why are opioids legal if they have such high potential for abuse?

Answer 2

The instrumental value of opioids is too high for them to be prohibited

Question 3

Naturally occuring opiods

Opium from the opium poppy has these active ingredients:

Answer 3

Morphine, codeine, thebaine, narcotine

Narcotine is unpleasant, it causes vomiting.

Question 4

What are the five semi-synthetic opioids discussed in class?

Answer 4

• Diamorphine/diacetylmorphine (heroin) – from morphine
• Desomorphine (krokodil) – from codeine (people tried to make it by cooking codiene and harmed themselves)
• Buprenorphine (partial opiod receptor agonist, analgesic, weaker than morphine and has lower risk of causing breathing problems)
• Hydrocodone
• Oxycodone (aka oxycontin)

Your muscles can atrophy from the toxic byproducts in krokodil.

Question 5

Buprenorphine

Answer 5

Partial opiod receptor agonist, analgesic, weaker than morphine and has lower risk of causing breathing problems

Question 6

Desomorphine (krokodil)

Answer 6

Made from codeine (people tried to make it by cooking codiene and harmed themselves). Your muscles can atrophy from the toxic byproducts in krokodil.

Question 7

Three fully synthetic opioids

Answer 7

Fentanyl
Carfentanil
Methadone

Typically, synthetic drugs are most potent.

Dextromethorphan was considered a synthetic opioid but is not classified as one anymore.

Question 8

Methadone

Answer 8

Used in drug replacement therapy

• check for duplicate card

Question 9

Drug history placeholder

Answer 9

Out of class during this time, fill in later

Question 10

The three main forms of opioid administration

Answer 10

Oral - eg. methadone substitution
Inhalation - a.k.a. “chasing the dragon” (inhaling heated drug smoke through a straw)
Intravenous (IV) injection - a.k.a. “mainlining”

Question 11

With opioids, potency is determined by [answer], not pharmacodynamics

Answer 11

Lipid solubility - how bioavailable is the drug, how well can it pass through the
(acetyl groups improve the BBB permeability)

Question 12

Opioids are metabolized in the [answer]

Answer 12

Liver

Question 13

Heroin drug tests look for [answer].

Answer 13

Monoacetylmorphine (heroin specific metabolite)

Question 14

Endogenous neurotransmitters are large [blank] cleaved from very large [blank]

Answer 14

peptides, propeptides

Question 15

The four endogenous opioid propeptides

Answer 15

• Proopiomelanocortin (POMC)
• Proenkephalin
• Prodynorphin
• Pronociceptin (weird one)

Question 16

β-endorphins activate which receptors?

Answer 16

μ (mu) and δ (delta) receptors

Question 17

Dynorphin A & B and neoendorphins activate which receptors? What effect do the type of receptors activated have?

Answer 17

κ (kappa) receptors, which can cause occasional hallucinogenic effects.

Question 18

Robotripping

Answer 18

Using robitussin DM, which affects MDMA receptors, people get high. Robotussin DM is not an opioid, but is an agonist for opioid receptors and antagonist for NMDA receptors.

Question 19

Nociceptin activates which receptors? What effects does it have?

Answer 19

It activates ORL-1 receptors, which can cause pain.

Question 20

Activation of endogenous opioid receptors open [answer].

Answer 20

GIRKs

Question 21

What are GIRKs?

Answer 21

G-protein-coupled inward rectifying K+ channel
In other words, these are potassium ion channels.

GIRKs

Question 22

Opioid agonists: Examples and which receptors they effect

Answer 22

Heroin, morphine, fentanyl, etc.
Most effects are via delta and mu receptors

Question 23

Opioid antagonists: Examples and uses

Answer 23

Naloxone (narcan): For reversing opioid

Question 24

Effects of opioids

Answer 24

• Analgesia
• Constipation
• Decreased blood pressure
• Euphoria
• Hypothermia
• Relaxation
• Respiratory depression

Question 25

Nociception

Answer 25

The perception of pain

Question 26

Analgesia

Answer 26

Pain relief

Question 27

The brain produces endogenous opioids for [answer].

Answer 27

Pain relief

Question 28

Two notable regions for endogenous opioid neurons and what they do

Answer 28

Periacqueductal gray (PAG): Has opioid producing neurons that direct to the raphe nuclei and modulate pain.
Spinal cord interneurons: Release opiates/serotonin to prevent pain signals from reaching the brain.

Question 29

Opioids and stages of euphoria

Answer 29

Initial rush, then high, then nod (calm, sometimes unaware of surroundings, may fall asleep), then straight (period of normalcy between cravings and euphoria).

Tolerance builds for euphoric effects, thus people have to take higher doses to get the same effects.

Question 30

Opioid reward mechanisms

Answer 30

Opioid uses DA release from VTA to NAcc.
Seemes to increases DA release in VTA by inhibiting the inhibitory GABA neurons.

Question 31

Conditioned place preference (CPP)

Answer 31

Different solutions administered (vehicle vs opioid) in different chambers. A rat will prefer to stay in the chamber that an addictive drug has been administered in. A rat will avoid a chamber if an aversive drug has been administered in said chamber.

Question 32

Tolerance develops for which effects of opioids? How fast does tolerance build?

Answer 32

All effects. Tolerance builds to opioids very quickly.

Question 33

Long term use of opioids can lead to reduced activity at the [answer].

Answer 33

Sodium-potassium pump

Question 34

Opioid overdose symptoms

Answer 34

• Severe respiratory depression
• Weakness
• Inability to speak
• Bluish lips and skin
• Unconsciousness

Question 35

Name several

Symptoms of opioid withdrawal

Answer 35

Incredibly adverse effects:
- Pain
- Irritability
- Panting/yawning
- Dysphoria, depression
- Restlessness/insomnia
- Diarrhea
- Pupil dialation
- Hyperthermia
- Tearing, runny nose
- Spontaneous ejaculation
- Chilliness and “gooseflesh”

Question 36

What percent of heroin users started on prescription opioids?

Answer 36

75%