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
Q

How can the structure of opioid receptors affect there pharmacological effects?

A

alternative splicing can produce different receptor sequences, these SNP’s cause individual variation such as; liability to alcoholism

26
Q

Where are opioid receptors most frequently found?

A

in areas involved in emotion and pain; striatum, thalamus cortex

27
Q

What method can be used to detect opioid receptors?

A

washing brain slices with a radioactive ligand and then PET scanning

28
Q

What type of receptor are opioid receptors?

A

metabotropic g-protein coupled

29
Q

What actions can the g-protein coupled receptors have?

A

postsynaptic; decreases firing by K+ release
axoaxonic; decreases NT release by closing Ca2+ channels
presynaptic autoreceptors; decreases NT release

30
Q

How are neuropeptides released?

A

generally co-released with another transmitter

large vesicle with precursor peptides (pro peptides) is broken down by peptidases to liberate peptides

31
Q

Where are the μ analgesic receptors found?

A

dorsal horn
PAG
limbic region

32
Q

What mechanisms can relay pain information?

A

early; synapsing on interneurons in the spinal chord

late; direct projections up the spinal chord to the hindbrain, midbrain and thalamus

33
Q

What is the spinal mechanism for pain sensation?

A

sensory neurons synapse with an interneuron/projection neuron to provide a basic reflexive response to avoid painful stimuli

34
Q

How can spinal analgesia be induced by opioid drugs/endogenous opioids?

A

projection neurons have opioid receptors, opioids can inhibit the projection neurons

35
Q

What is the supra-spinal pain modulation pathway?

A

PVG → PAG → raphe → dorsal horn → spinal chord

36
Q

What evidence is there for a downward modulatory pathway?

A

stimulation of the PAG prevents neuronal firing in the dorsal horn
lesions on the raphe blocks analgesic effects

37
Q

How is pain information relayed by the supra-spinal pathway?

A

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
Q

How do opioids affect the supra-spinal pathway?

A

opioids inhibit GABA, releasing 5-HT from inhibition so it can returning to inhibiting projection neurons in the dorsal horn

39
Q

Which brain regions are involved in sensory pain perception?

A

NAcc
amygdala
thalamus

40
Q

Which brain regions are involved in affective pain perception?

A

NAcc
thalamus
ACC

41
Q

Can the opioid system be influenced by cognitive factors?

A

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
Q

Do morphine and heroin have different pharmacological actions?

A

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
Q

Are kappa agonists abused?

A

no, they produce aversive, psychotomimetic effects in humans and are not self-administered by animals

44
Q

How do the μ receptors influence DA release?

A

μ agonists release dopamine from inhibition by GABA and increases levels in the NAcc

45
Q

What evidence is there for the role of DA in opioid mechanisms?

A

morphine is no longer self-administered following DA lesions or DA antagonism
morphine place-preference abolished in D2 knockouts (Maldonado…Borrelli 1997)

46
Q

Are all opioid effects mediated by DA?

A

no, subjective pleasure expressions not influenced by DA are influence by opioid administration

47
Q

Where do the major reward and locomotion effects take place?

A

μ receptors in the VTA

48
Q

Where do the major analgesic effects take place?

A

μ receptors in the dorsal horn, PAG and limbic system

49
Q

Where do the major gastrointestinal motility effects take place?

A

μ and k receptors in the stomach and intestines

50
Q

Where do the major respiratory depressive effects take place?

A

μ receptors in the medulla and nucleus of solitary tract