opioids

Question 1

what are narcotic analgesics?

Answer 1

drugs that produce analgesia (reduction of pain) without anaesthesia (loss of all sensation)

Question 2

what are opiates?

Answer 2

opium (extract of opium poppy plant)

substances directly derived from opium

Question 3

what are opioids?

Answer 3

related semisynthetic and synthetic compounds

endogenous peptides acting on same receptors (opioid receptors)

Question 4

what are acute effects of opioids?

Answer 4

analgesia

respiratory depression

euphoria

relaxation and sleep

tranquilisation

decreased blood pressure

constipation

pupil construction

hypothermia

drying of secretions

reduced sex drive

flushed and warm skin

Question 5

what is the molecular structure of heroin?

Answer 5

two hydroxyl groups of morphine are replaced by acetyl groups

this chemical difference makes heroin more lipophil and is responsible for heroin crossing the blood-brain barrier better and causing stronger highs than morphine

Question 6

what is the molecular structure of codeine?

Answer 6

less analgesic

less side effects

less addictive

still very potent cough suppression

Question 7

what is naloxene?

Answer 7

opioid receptor antagonist

Question 8

how are opioids used and misused?

Answer 8

long history of medical use (against pain, coughing, diarrhoea) and recreational use (for euphoria and relaxation)

nowadays, medical use is strictly regulated and recreational use is illegal

opioids are highly addictive - high euphoria

main cause of overdose deaths

Question 9

how can opioid overdose be treated?

Answer 9

by injection with opioid antagonist naloxene

Question 10

what are the symptoms of opioid overdose?

Answer 10

respiratory depression

miosis (pupil constriction)

stupor (unresponsiveness)

hepatic injury from acetaminophen or hypoxemia

myoglobinuric renal failure

rhabdomyolysis

absent or hypoactive bowel sounds

compartment syndrome

hypothermia

possible presence of one of more fentanyl patches

Question 11

what are peripheral opioid receptors?

Answer 11

on peripheral nerve endings

in gastrointestinal tract

Question 12

what does it mean that opioid receptors are G-protein coupled receptors?

Answer 12

receptors that after activation interact with “G-protein” and have knock-on effects that mediate neuronal responses

interactions with ion channels, another enzyme in neuron

Question 13

what is opioid-receptor mediated neural inhibition?

Answer 13

activation of opioid receptors tends to inhibit neural activity or neurotransmitter release of the neurons carrying the opioid receptor

Question 14

what is post-synaptic inhibition?

Answer 14

sit on post-synaptic neuron

open K+ channels

Question 15

what is axoaxonic inhibition?

Answer 15

close Ca2+ channels

Question 16

what are presynaptic autoreceptors?

Answer 16

reduce transmitter release

Question 17

what is pain?

Answer 17

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

Question 18

what is nociception?

Answer 18

the neural process of encoding noxious stimuli (e.g. stimuli causing tissue damage)

Question 19

what is chronic pain?

Answer 19

pain that lasts or recurs for longer than 3 months

can be symptom or disease in itself (i.e. with no clear relation to tissue damage)

affects about 20% of people worldwide

Question 20

what is the leading cause of disability in the UK?

Answer 20

pain

low-back and neck pain

Question 21

what are ascending pain pathways?

Answer 21

PSN (primary sensory neuron) receive information from periphery and detect mechanical stimuli tissue damage

active cortical areas leading to conscious perception of pain

PSN in DRG (dorsal root ganglion) -> neuron in dorsal horn of spinal cord -> thalamus -> cortex

“first/fast” pain PSNs with Adelta fibres -> somatosensory cortex

“second/low/late” pain PSNs with C fibres -> other cortical and subcortical fibres

Question 22

what are descending pain pathways?

Answer 22

goes out from CNS to PNS = modulate experience of pain

originate in midbrain regions, including periaqueductal gray

inhibit pain processing

Question 23

how do opioids inhibit pain processing?

Answer 23

disinhibit descending pain pathway that inhibits pain (make it more active)

inhibit ascending pain pathway

mechanisms only apply to acute pain (not chronic)

Question 24

what is the mesocorticolimbic dopamine system?

Answer 24

rewards activate mesocorticolimbic dopamine transmission

Question 25

how do opioids increase dopamine release within nucleus accumbens?

Answer 25

disinhibition of dopaminergic neurons in VTA stimulate opioid receptors of GABA neurons inhibiting GABA release by these neurons allowing increase of dopaminergic VTA neurons use microdialysis to measure if opioid administration increases dopamine release in nucleus accumbens

Question 26

what is opioid modulation?

Answer 26

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

Question 27

how do you measure rewarding properties of a drug?

Answer 27

operational definition of a reward = something we and other animals work for drug self-administration procedure how hard work to get drug = press lever? if press lever = find it rewarding rats self-administer a wide range of opioids intravenously and intracranially, including into VTA

Question 28

what is the distinction between reward and pleasure/liking?

Answer 28

just because something is rewarding doesn't mean it gives us pleasure how much a subject works for a reward may not directly reflect the "liking" or "pleasure" induced by the reward, but rather "wanting" or "desire" for the reward

Question 29

how was "liking" measured?

Answer 29

facial expressions to sweet or bitter tastes as measures of "liking" nucleus accumbens shell stimulation of opioid receptors increases "liking" = morphine stimulation of dopamine receptors reduces "liking" = amphetamine

Question 30

what contributes to dependence?

Answer 30

neuropharmacological adaptions to repeated opioid use

Question 31

what is tolerance?

Answer 31

reduced acute effects may lead user to increase dose or take stronger opioid

Question 32

what do long-term compensatory changes in neural mechanisms lead to?

Answer 32

withdrawal symptoms compensatory changes are opposed to acute opioid effects

Question 33

what effect may prescription opioids have?

Answer 33

may initiate users to heroin abuse and dependence since late 90s, early 2000s, heroin dependent patients in 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

how can opioid dependence be treated?

Answer 34

detoxification maintenance with methadone or buprenorphine treatment for full abstinence with opioid agonist (e.g. with naloxone)

Question 35

what is detoxification?

Answer 35

usually assisted by substitution with long-acting opioid drug (methadone or buprenorphine) has lower highs less pronounced withdrawal symptoms

Question 36

what is maintenance with methadone or buprenorphine?

Answer 36

reduces mortality from overdoses and other causes substitution drugs have adverse effects and interfere with normal life partial agonist buprenorphine may have reduced adverse effects compared to methadone high-equality evidence that significantly improves patients' life is lacking

Question 37

what is treatment for full abstinence with opioid agonist (e.g. with naloxene)?

Answer 37

antagonist will make opioid administration ineffective typically very low adherence requires highly motivated patients