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Psychopharmacology > Lecture 17: Opioid Analgesics > Flashcards

Lecture 17: Opioid Analgesics Flashcards

1
Q

two types of chronic pain

A
  1. nociceptive

2. neuropathic

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2
Q

nociceptive pain

A

caused by tissue damage

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3
Q

processes that increase or decrease nociception are __ or ___

A

pronociceptive or antinociceptive

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4
Q

neuropathic pain

A

caused by a lesion or dysfunction of NS; characterized by increased sensitivity (hyperalgesia) to pain-producing or innocuous stimuli

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5
Q

laudanum

A

opium + alcohol; used to relieve diarrhea, cough, pain, produce sleep

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6
Q

rate of abusing prescription pain drugs is ___

A

second only to marijuana abuse

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7
Q

opium

A

dried exudate of opium poppy

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8
Q

opiate

A

drug extracted from opium, mainly morphine and codeine (+thebaine)

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9
Q

opioid

A

any exogenous drug that binds to an opiate receptor, produces agonistic morphine-like effects, and is blocked by opiate antagonists

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10
Q

semisynthetic opioids

A

come from opiates (e.g. heroin from morphine)

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11
Q

synthetic opioids

A

come from precursor compounds (e.g. methadone)

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12
Q

4 naturally occuring alkaloids from poppy

A
  1. morphine
  2. codeine
  3. thebaine
  4. papaverine
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13
Q

3 main opiate receptors

A
  1. mu
  2. kappa
  3. delta
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14
Q

what activates mu?

A

endorphin

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15
Q

what activates delta?

A

enkephalin

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16
Q

what activates kappa?

A

dynorphin

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17
Q

three endogenous opiates

A
  1. endorphin
  2. enkephalin
  3. dynorphin
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18
Q

how many membrane spanning regions and amino acids in a GPCR?

A
  1. 7

2. 400

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19
Q

what channel does cAMP activate? what is the effect?

A

HCN channel (non selective cation channel, opened by hyperpolarization)

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20
Q

what do opioids do to adenylyl cyclase? what is the effect?

A

inhibit it; causes the cell to hyperpolarize. net inhibition

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21
Q

what is the main location of mu receptors?

A

periaqueductal gray

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22
Q

7 areas mu receptors are

A
  1. periaqueductal gray
  2. spinal trigeminal nucleus
  3. caudate
  4. thalamus
  5. dorsal horn of spinal cord
  6. brain stem nuclei that control respiration
  7. nucleus accumbens
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23
Q

prototypical mu receptor agonist

A

morphine

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24
Q

what receptors does morphine act on?

A

agonizes mu, kappa, and delta

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25
Q

what receptors does naloxone act on?

A

antagonist at mu, kappa, and delta

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26
Q

what receptors does fentanyl act on?

A

agonist at mu, kappa, and delta

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27
Q

7 areas kappa receptors are in

A
  1. basal ganglia
  2. nucleus accumbens
  3. VTA
  4. cerebral cortex
  5. hypothalamus
  6. periaqueductal gray
  7. dorsal horn of spinal cord
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28
Q

5 effects of kappa receptors

A
  1. modest analgesia
  2. respiratory depression
  3. dysphoria
  4. disorientation
  5. depersonalization
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29
Q

kappa receptors may antagonize ___

A

mu receptor activity

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30
Q

bremazocine

A

kappa receptor agonist; more analgesic than morphine w/o euphoria, dependence, and respiratory depression. limited by perceptual side fx

31
Q

2 effects of delta receptor stimulation; why?

A
  1. antidepressant
  2. anxiolytic
    increase levels of brain-derived neurotrophic factor (BDNF) which are reduced during high stress or depression
32
Q

3 synthetic opioids

A
  1. methadone
  2. meperdine
  3. fentanyl
33
Q

morphine is __ more potent than codeine

34
Q

heroin is ___ as potent as morphine

35
Q

codeine is converted to ___

36
Q

when is endorphin released? (5)

A
  1. exercise
  2. excitement
  3. pain
  4. sex
  5. spicy food
37
Q

where are nociceptors located?

A

dorsal root ganglia of spinal cord

38
Q

nociceptors have ___ axons

A

bidirectional

39
Q

where do bidirectional nociceptors relay pain impulses?

A

to synapse in dorsal horn of spinal cord, and then to brain

40
Q

activation of opioid receptors causes ___ of neurotransmission due to ___

A
  1. reduction/inhibition

2. presynaptic inhibition of NT release

41
Q

what NT is inhibited in spinal cord?

A

substance P

42
Q

what NT is inhibited in VTA?

A

GABA (disinhibits DA release)

43
Q

4 methods of mediation of analgesic effects

A
  1. activation of inhibitory endorphine-secreting or GABA-secreting neurons in dorsal horn of spinal cord
  2. activation of descending inhibitory neurons from brain to spinal cord
  3. modulation of central processing of pain stimuli (reduces sensory and affective aspects of pain)
  4. presynaptic inhibition of nociceptive afferent sensory neurons (inhib release of subst P in dorsal horn)
44
Q

mixed agonist-antagonist

A

binds to opioid receptors esp kappa; causes analgesia in non-opioid-dependent people, but may precipitate withdrawal in opioid-dependent persons

45
Q

4 pure agonists

A

morphine
heroin
demerol (meperidine)
methadone (dolophine)

46
Q

2 pure antagonists

A

naloxone (narcan)

naltrexone (vivitrol)

47
Q

3 partial agonists

A
  1. buprenorphene (suboxone)
  2. tramadol (ultram)
  3. tapentadol (nucynta)
48
Q

3 medical uses of opiates

A
  1. analgesia
  2. suppression of cough
  3. GI symptoms
49
Q

6 other effects of opiates

A
  1. euphoria
  2. resp depression
  3. nausea
  4. sedation/anxiolysis
  5. pupillary constriction
  6. endocrine effects
50
Q

how is morphine put into spinal fluid?

A

delivered directly via implanted subcutaneous pump and intrathecal catheter

51
Q

cause of morphine euphoria

A

activation of NAc

52
Q

cause of drive to resume morphine use

A

cannabinoid system

53
Q

___ can block compulsion for drug use

A

cannabinoid receptor antagonist

54
Q

how does morphine suppress cough?

A

suppression of cough center in brain system

55
Q

why does morphine cause nausea?

A

stimulation of medulla’s chemoreceptor trigger zone

56
Q

how does morphine reduce GI symptoms?

A

acts directly on intestine

57
Q

endocrine effects of morphine

A

reduce sex hormone releasing agents from hypothalamus

58
Q

what pathway is necessary for initiation of opioid psychological dependence?

A

mesolimbic dopaminergic pathway (VTA to NAc)

59
Q

the way morphine increases dopamine to NAc

A

binds to mu in VTA, inhibiting GABA

disinhibits DA neurons in VTA

60
Q

codeine is usually combined with ___

A

aspirin or acetaminophen

61
Q

codeine duration of action

A

three-four hours

62
Q

___ or 6 SSRI antidepressants can block ___. why?

A

4
pain relief of codeine
block conversion of codeine to morphine

63
Q

why does heroin have more psychoactive effects than morphine?

A

more lipid soluble; quickly passes BBB

64
Q

3 metabolites of heroin

A
  1. monoacetylmorphine
  2. morphine
  3. codeine
65
Q

what is heroin derived from?

66
Q

demerol

A

synthetic opioid structurally different from morphine, prescribed as subst drug for heroin addicts

67
Q

demerol potency

A

1/10 of morphine

68
Q

4 excitatory side effects of demerol. why?

A
  1. tremors
  2. delirium
  3. hyperreflexia
  4. convulsions
    metabolite of meperdine causes CNS excitation
69
Q

2 benefits of methadone

A
  1. oral absorption

2. long half life

70
Q

two uses of methadone

A
  1. prevention of w/d in opioid dependent persons

2. long acting analgesic for chronic pain

71
Q

5 uses of naloxone

A
  1. opioid reversal
  2. treatment of alcoholism to reduce craving
  3. may reduce opioid craving
  4. treatment of autism, self-injurious behaviors, BPD
  5. chronically block opioid euphoria
72
Q

tolerance to opioids dont have cross tolerance to ___

A

sedative-hypnotics

73
Q

2 reasons withdrawal occurs

A
  1. reduced DA in nucleus accumbens

2. increased NE release from locus coeruleus

74
Q

4 treatments for opioid dependence

A
  1. agonist maintenance therapy (methadone)
  2. agonist-antagonist therapy (suboxone)
  3. antagonist therapy (naltrexone)
  4. treatment of comorbid disorders

Psychopharmacology (22 decks)

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