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Drugs, Brain and Behaviour > Opioids > Flashcards

Opioids Flashcards

1
Q

What is the main function of opioids?

A

analgesia

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2
Q

Where can you find naturally occurring opioids?

A

in alkaloids found in the opium poppy

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3
Q

What are opiates?

A

opiates are the naturally occurring opioid

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4
Q

What caused a surge in US opioid use?

A

end of the civil war; soldier’s disease

production of hypodermic syringe

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5
Q

What is heroin?

A

a semi-synthetic opioid

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6
Q

What is the potency of heroin?

A

5x more potent than morphine as it is more lipid soluble due to addition of 2 acetyl groups

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7
Q

What is the pharmacological effect of heroin?

A

identical to morphine as it is largely metabolised into morphine

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8
Q

How does administration affect the pharmacological effect?

A

oral; analgesia but no euphoria/rush

IV/smoking/snorting; analgesia and euphoria

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9
Q

What are the major clinical effects of opioids?

A 
analgesia
euphoria
conditioned place preference
reduced gastrointestinal motility
cough suppression
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10
Q

What are the major side effects of opioids?

A

reduced gastrointestinal motility
respiratory depression
nausea/vomiting

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11
Q

What are the effects of repeated opioid administration?

A

sensitisation
tolerance
withdrawal

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12
Q

What opioid effects can become sensitised?

A

stimulant effects; with VTA administration

rewarding effects

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13
Q

What opioid effects can become tolerated?

A

analgesia
euphoria
respiratory depression

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14
Q

What withdrawal effects are seen with opioid use?

A

symptoms are opposite to the acute effects

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15
Q

How can respiratory depression be reversed?

A

administration of naloxone

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16
Q

What is saturable binding?

A

the maximum effects observed in opioids suggests that there is a finite number of mechanisms on which opioids can act

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17
Q

How can we predict analgesic effects in humans from animal studies?

A

opioids causing contractions of the intestine in the guinea pig predicts human analgesia

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18
Q

What are the endogenous ligands/peptides that act on μ receptors?

A

endorphins

endomorphins

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19
Q

What propertied/precursor peptide is used to create μ peptides?

A

POMC

unknown

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20
Q

What are the endogenous ligands/peptides that act on δ receptors?

A

enkephalin

endorphin

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21
Q

What propertied/precursor peptide is used to create δ peptides?

A

proenkephalin

POMC

22
Q

What are the endogenous ligands/peptides that act on κ receptors?

A

dynorphins

23
Q

What propertied/precursor peptide is used to create κ peptides?

A

prodynorphin

24
Q

What is the structure of opioid receptors?

A

a chain of amino acids that span the cell membrane 7 times

25
How can the structure of opioid receptors affect there pharmacological effects?
alternative splicing can produce different receptor sequences, these SNP's cause individual variation such as; liability to alcoholism
26
Where are opioid receptors most frequently found?
in areas involved in emotion and pain; striatum, thalamus cortex
27
What method can be used to detect opioid receptors?
washing brain slices with a radioactive ligand and then PET scanning
28
What type of receptor are opioid receptors?
metabotropic g-protein coupled
29
What actions can the g-protein coupled receptors have?
postsynaptic; decreases firing by K+ release axoaxonic; decreases NT release by closing Ca2+ channels presynaptic autoreceptors; decreases NT release
30
How are neuropeptides released?
generally co-released with another transmitter | large vesicle with precursor peptides (pro peptides) is broken down by peptidases to liberate peptides
31
Where are the μ analgesic receptors found?
dorsal horn PAG limbic region
32
What mechanisms can relay pain information?
early; synapsing on interneurons in the spinal chord | late; direct projections up the spinal chord to the hindbrain, midbrain and thalamus
33
What is the spinal mechanism for pain sensation?
sensory neurons synapse with an interneuron/projection neuron to provide a basic reflexive response to avoid painful stimuli
34
How can spinal analgesia be induced by opioid drugs/endogenous opioids?
projection neurons have opioid receptors, opioids can inhibit the projection neurons
35
What is the supra-spinal pain modulation pathway?
PVG → PAG → raphe → dorsal horn → spinal chord
36
What evidence is there for a downward modulatory pathway?
stimulation of the PAG prevents neuronal firing in the dorsal horn lesions on the raphe blocks analgesic effects
37
How is pain information relayed by the supra-spinal pathway?
5-HT usually acts to inhibit projection neurons in the dorsal horn GABA is activated when pain is experienced and acts to inhibit 5-HT, disinhibiting projection neurons
38
How do opioids affect the supra-spinal pathway?
opioids inhibit GABA, releasing 5-HT from inhibition so it can returning to inhibiting projection neurons in the dorsal horn
39
Which brain regions are involved in sensory pain perception?
NAcc amygdala thalamus
40
Which brain regions are involved in affective pain perception?
NAcc thalamus ACC
41
Can the opioid system be influenced by cognitive factors?
a placebo experiment (Zubieta et al., 2005) found that when patients expected pain relief, the opioid system became more active, this effect was inhibitable by naloxone
42
Do morphine and heroin have different pharmacological actions?
evidence shows that they act on different receptors | Schuller et al. (1999); CXBK and MOR-1 knockout mice were insensitive to morphine but not heroin
43
Are kappa agonists abused?
no, they produce aversive, psychotomimetic effects in humans and are not self-administered by animals
44
How do the μ receptors influence DA release?
μ agonists release dopamine from inhibition by GABA and increases levels in the NAcc
45
What evidence is there for the role of DA in opioid mechanisms?
morphine is no longer self-administered following DA lesions or DA antagonism morphine place-preference abolished in D2 knockouts (Maldonado...Borrelli 1997)
46
Are all opioid effects mediated by DA?
no, subjective pleasure expressions not influenced by DA are influence by opioid administration
47
Where do the major reward and locomotion effects take place?
μ receptors in the VTA
48
Where do the major analgesic effects take place?
μ receptors in the dorsal horn, PAG and limbic system
49
Where do the major gastrointestinal motility effects take place?
μ and k receptors in the stomach and intestines
50
Where do the major respiratory depressive effects take place?
μ receptors in the medulla and nucleus of solitary tract

Drugs, Brain and Behaviour (6 decks)

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