Lecture 9/10- Opioids

Question 1

What is the definition of Analgesics?

Answer 1

Reduction of pain

Question 2

What is the definition of anaesthesia?

Answer 2

Loss of sensation

Question 3

What are narcotic analgesics?

Answer 3

Reduction of pain without loss of sensation but promotes sense of relaxation/sleep

Overdoses lead to comas/death

Question 4

What are opiates?

Answer 4

Extract of opium poppy plant, and substances are directly derived from opium

Question 5

What is produced after altering natural narcotics?

Answer 5

Related semisynthetic and synthetic compounds

Question 6

What is the last stage of opium alteration?

Answer 6

Endogenous peptides acting on same receptors (opioid)

Question 7

What are acute actions of opioids?

Answer 7

Analgesia
Respiratory depression
Euphoria
Decreased blood pressure
Reduced sex drive

Question 8

What are some withdrawal symptoms of opioids?

Answer 8

Pain/ irritability
Dysphoria/ depression
Insomnia
Increased blood pressure
Hyperthermia

Question 9

What are the 3 aspects of the molecular structure of opioids?

Answer 9

Heroin
Codeine
Naloxone

Question 10

What is the molecular structure of heroin?

Answer 10

Added acetyl group to morphine structure w/ more lipophil.
Crosses blood-brain barrier more quickly and has strong high/euphoria.
In the brain, heroin is converted to morphine.

Question 11

What is the molecular structure of Codeine?

Answer 11

Less analgesic, but also less die effects and less addictive
but still a very potent cough suppression.

Question 12

What does Naloxone do?

Answer 12

Opioid receptor antagnist?

Question 13

What is the history of opioids?

Answer 13

Medical use eg pain/coughing
Recreational use eg euphoria

Question 14

What is the current opinion of Opioids?

Answer 14

Medical use is restricted and recreational is illegal

Question 15

What is the opioid epidemic?

Answer 15

-High levels of opioid use esp. in USA -Opioids are main cause of overdose deaths in both US and UK, in UK 51% of all drug poisoning deaths were from opioids.

Question 16

What are symptoms of opioid overdose?

Answer 16

Respiratory depression, hypothermia, Stupor (unresponsiveness)

Question 17

How can opioid overdose be treated?

Answer 17

Opioid antagonist naloxone

Question 18

What the 4 types of opioid receptor endogenous ligand?

Answer 18

Endomorphins
Enkephalins
Dynorphins
Nociceptin/orphanin

Question 19

What is the endogenous ligand endomorphin?

Answer 19

Most commonly acted upon by opioid receptors.
-Widely distributed in brain eg thalamus, striatum, brain stem, hippocampus
-Has variety of effects eg analgesia, cardiovascular/respiratory depression.

Question 20

What is the endogenous ligand Dynorphins?

Answer 20

Selectively act on kappa opioid receptor which mediates effects opposite to opioid receptor
Found in pituitary gland, hypothalamus
-Neuroendocrine function, water balance, temperature control

Question 21

What protein are opioid receptors coupled up to?

Answer 21

Opioid receptors are G-protein coupled receptors

Question 22

What does activation of opioid receptors do?

Answer 22

Inhibit neural activity/ neurotransmitter release of neurons carrying opioid receptor

Question 23

What are the 3 ways opioid receptors inhibit neural activity?

Answer 23

Postsynaptic inhibition
Axoaxonic inhibition
Presynaptic auto receptors

Question 24

What is postsynaptic inhibition?

Answer 24

Opioid receptors on post synaptic neuron leads to g-protein activation which opens potassium channel which inhibits neuron.

Question 25

What is Axoaxonic inhibition?

Answer 25

Closes calcium channels which reduces neurotransmitter release as calcium influx into presynaptic terminal triggers neurotransmitter release

Question 26

What is pain?

Answer 26

An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage

Question 26

What is presynaptic auto receptors?

Answer 26

Inhibition of neurotransmitters release from presynaptic terminal.

Question 26

What is chronic pain?

Answer 26

Pain that lasts or recurs for longer than 3 months; can be symptom or disease in itself

Question 27

What are the 2 types of pain pathways?

Answer 27

Ascending Descending

Question 27

What is Nociception?

Answer 27

The neural process of encoding noxious stimuli eg stimuli causing tissue damage.

Question 27

What happens in the Ascending pain pathway?

Answer 27

Dorsal horn of Spinal cord, Primary sensory neurons (PSN) in dorsal root ganglion (DRG). Deals with first/fast and late/slow pain

Question 27

What is First/fast pain in the ascending pain pathway?

Answer 27

PSNs with Adelta fibres -> Somatosensory cortex

Question 27

What are the 2 ways opioid inhibit pain processing and what does it only apply to?

Answer 27

1. Opioids disinhibit a descending pain pathway that inhibits pain. 2. Opioids inhibit signal transmission in the ascending pain pathway. Only applies to acute pain

Question 27

What is late/slow pain in ascending pain pathways?

Answer 27

PSNs with C fibres -> Other cortical/sub cortical areas

Question 27

What happens in the Descending pain pathway?

Answer 27

Originate in midbrain regions incl periaqueductal grey and inhibit pain processing. Modulates experience with pain

Question 28

What method can we use to measure levels?

Answer 28

Microdialysis can be used to measure if opioid administration increases dopamine release in nucleus accumbens

Question 28

How do rewards affect dopamine transmission?

Answer 28

Rewards activate meso-corticolimbic dopamine transmission.

Question 28

How do opioids increase dopamine release in nucleus accumbens?

Answer 28

Disinhibition of dopaminergic neurons in the VTA: opioids stimulate opioid receptors of GABA neurons, inhibiting GABA release by these neurons, thereby allowing an increase of dopaminergic VTA neurons.

Question 28

What is Opioid modulation of meso-corticolimbic dopamine system?

Answer 28

Opioids can increase NAC dopamine release via mu-opioid receptors in the VTA. -Opioids with preferential action on kappa-receptors can act presynaptically on dopamine terminals in NAC to reduce dopamine release.

Question 28

What is the difference between reward and pleasure

Answer 28

Reward= something you want/desire Pleasure= feeling of liking

Question 28

What is the Nucleus accumbens shell?

Answer 28

Stimulation of opioid receptors increases ‘liking’, whereas stimulation of dopamine receptors reduces ‘liking’

Question 29

What 2 adaptations created by repeated opioid use affect dependence?

Answer 29

Tolerance Lt compensatory changes

Question 31

What are the tolerance changes due to repeated opioid use?

Answer 31

Repeated use leads to acute effects which can lead to higher doses or stronger opioids

Question 32

What are the LT compensatory changes due to repeated opioid use?

Answer 32

In the neural mechanisms, the response to repeated opioid use can lead to withdrawal symptoms w/o continued use.

Question 33

What are the changes over time for prescription opioids?

Answer 33

-Since the late 90s early 2000s, heroin dependent patients in the US have mainly initiated opioid abuse with a prescription opioid. -More recently, with reduction in supply of prescription opioids, heroin again gains in importance as initiating drug

Question 34

What is detoxification?

Answer 34

Usually assisted by substitution with a long-acting opioid drug (methadone or buprenorphine) which has lower highs and less pronounced withdrawal symptoms Reduces mortality from overdoses

Question 35

What is the negative effect of detoxification?

Answer 35

Substitution drugs can have adverse effects and can interfere with normal life

Question 36

What does treatment for full abstinence do?

Answer 36

Treatment for full abstinence w/ opioid antagonist (naloxone) will make opioid administration ineffective but requires highly motivated patients.