Opioids

Question 1

What is opium?

Answer 1

Dried latex obtained from the poppy.

Question 2

What are opiates?

Answer 2

Any drug derived from opium.

Question 3

What are opioids?

Answer 3

Any drug that binds to an opioid receptor.

Question 4

What are narcotics?

Answer 4

Drugs that treat pain with sleep-inducing properties.

Question 5

What kind of receptors are opioid receptors?

Answer 5

Inhibitory G-protein coupled receptors.

Question 6

What does activation of opioid receptors cause?

Answer 6

Inhibition of calcium channels and activation of potassium channels, also inhibition of adenylyl cyclase.

Question 7

What are the four types of opioid receptors?

Answer 7

Mu, kappa, delta, and ORL1.

Question 8

Why do the opioid receptors produce differing effects when activated?

Answer 8

1. Receptor distribution throughout the brain is different for each receptor.
2. Ligands have different specificity for different receptors.

Question 9

Where are mu receptors most densely located?

Answer 9

In the brainstem and limbic system.

Question 10

Where are delta and kappa receptors most densely located?

Answer 10

In the cortex.

Question 11

Where are ORL1 receptors located?

Answer 11

Across the entire brain.

Question 12

What is ORL1 receptor activation thought to be involved in?

Answer 12

Fear processing.

Question 13

What does agonism at the mu receptor cause?

Answer 13

Analgesia, euphoria, antitussive effects, respiratory depression, constipation.

Question 14

What does antagonism at the mu receptor cause?

Answer 14

Aversive effects, prevent euphoria, block overdose.

Question 15

What does agonism at the delta receptor cause?

Answer 15

No euphoria, no analgesia (except in chronic pain), possibly seizure-inducing.

Question 16

What does antagonism at the delta receptor cause?

Answer 16

No obvious effects.

Question 17

What does agonism at the kappa receptor cause?

Answer 17

Aversive effects, hallucinations, produces anxiety.

Question 18

What does antagonism at the kappa receptor cause?

Answer 18

Potential antipsychotic and antidepressant effects.

Question 19

What are full mu opioid receptor agonists?

Answer 19

Morphine, methadone, fentanyl, heroin.

Question 20

What is the partial agonist at the mu opioid receptor used to treat substance use disorder?

Answer 20

Buprenorphine.

Question 21

What is buprenorphine?

Answer 21

Partial agonist at the mu receptor and antagonist at the delta and kappa opioid receptor. Common teatment for both pain and opioid addiction.

Question 22

What are beta-arrestins?

Answer 22

Family of intracellular proteins important for regulating signal transduction at GPCRs.

Question 23

What is the beta-arrestin signalling pathway?

Answer 23

1. Receptor is activated.
2. G-protein cleaves, GPCR is phosphorylated and signals beta-arrestin binding.
3. Beta-arrestin blocks further signalling and redirects signalling to alternative pathways and targets receptors for internalization.

Question 24

What are the symptoms of beta-arrestin recruitment?

Answer 24

Respiratory depression and constipation.

Question 25

What is receptor selectivity?

Answer 25

Selectivity of a drug for different receptor subtypes.

Question 26

What is functional selectivity?

Answer 26

Selectivity of a bound receptor for different signalling pathways.

Question 27

What mu agonist opioid must undergo intensive first-pass metabolism?

Answer 27

Morphine.

Question 28

What mu agonist opioid is not affected by first-pass metabolism?

Answer 28

Codeine.

Question 29

Where are opioids most highly concentrated?

Answer 29

In tissues like the brain, lungs, liver kidneys, and spleen because they are highly perfused.

Question 30

How is morphine metabolized?

Answer 30

Phase 2 glucuronidation in the liver by UGT2B7 into M3G and M6G.

Question 31

What is M6G?

Answer 31

Morphine-6-glucuronide, an active metabolite that cna prolong effects of morphine.

Question 32

How is codeine metabolized into morphine?

Answer 32

By CYP2D6.

Question 33

How are polar metabolites excreted?

Answer 33

Mainly in the urine.

Question 34

What are the three types of endogenous opioid peptides?

Answer 34

Beta endorphins, enkephalins, dynorphins

Question 35

What is the function of endogenous opioid peptides?

Answer 35

To mediate pain, reward, learning, and memory/cognition.

Question 36

What is the common protein precursor for opioid peptides?

Answer 36

Tyr-Gly-Gly-Phe.

Question 37

What is the precursor for enkephalin?

Answer 37

Pro-enkephalin.

Question 38

What is the precursor for beta-endorphin?

Answer 38

Pro-opioimelanocortin.

Question 39

What is the precursor for dynorphins?

Answer 39

Pro-dynorphin.

Question 40

What is the affinity for opioid receptors of enkephalins?

Answer 40

Delta, Mu, kappa.

Question 41

What is the affinity for opioid receptors of endorphins?

Answer 41

Mu equal to deta, kappa.

Question 42

What is the affinity for opioid receptors of dynorphins?

Answer 42

kappa, mu is equal to delta.

Question 43

Where in the brainstem are opioid receptors localized? What does agonism in this area cause?

Answer 43

Rostroventral medulla. Assist in increasing diffusion of noxious inhibitory control.

Question 44

What is the noxious inhibitory circuit comprised of? Function?

Answer 44

Comprised of the descending excitatory and inhibitory neurons in the medulla that inhibit or activate pain synapses in the spinal cord.

Question 45

What receptors are located on the ON cells in the medulla?

Answer 45

Mu, delta.

Question 46

If the mu and delta receptors on the ON cells in the medulla were activated, what would be the effect?

Answer 46

Inhibition of ON cells, reduction in nociceptive signalling.

Question 47

Where are dopamine neurons primarily located?

Answer 47

Ventral tegmental area.

Question 48

Where are mu receptors located in the VTA?

Answer 48

On inhibitory GABAergic interneurons.

Question 49

When the mu receptors in the VTA are activated, what would be the effect?

Answer 49

Inhibition of inhibitory GABAergic interneurons causing release of dopamine.

Question 50

What is TRV250?

Answer 50

A delta opioid receptor biased agonist that is biased to the G-protein pathway over the beta-arrestin pathway.

Question 51

What is CR845?

Answer 51

Potent analgesics that are peripherally restricted os that they do not cross the BBB. Agonist of kappa receptors.

Question 52

What is tolerance?

Answer 52

Decreased response to the effects of a drug, necessitating ever-larger doses to achieve the same effect.

Question 53

What is the mechanism of opioid tolerance?

Answer 53

Following agonist binding and G-protein signalling, beta-arrestin is recruited to shut off signalling and produce desensitization. Receptor is internalized for recycling.

Question 54

What is physical dependence?

Answer 54

Dependence on a drug such that withdrawal occurs when an individual stops administering.

Question 55

What are acute opioid withdrawal symptoms?

Answer 55

Runny nose, tearing eyes, chills, muscle aches, diarrhea, anxiety.

Question 56

What are the physical barriers of opioids used to prevent addiction?

Answer 56

Turning tablet into paste-like substance to prevent from snorting.

Question 57

How to chemical barriers help prevent opioid addiction?

Answer 57

Allow for the substance to resist extraction.

Question 58

What is agonist/antagonist combination?

Answer 58

Taking an opioid agonist with an antagonist to interfere with euphoria associated with abuse.

Question 59

What is agonist replacement therapy?

Answer 59

Replacing opioid agonists with opioids of lower efficacy/potency and with longer half-lifes to prevent adverse effects.

Question 60

What is methadone?

Answer 60

Full agonist at the mu-opioid receptor, long acting. Replacement therapy drug.

Question 61

What is naloxone?

Answer 61

non-selective competitive opioid receptor antagonist that treats acute intoxication via opioids.