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Psychopharmacology > Opiates > Flashcards

Opiates Flashcards

1
Q

General info about opiates?

A

POTENT analgesics (primary medicinal use)

Very reinforcing

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2
Q

When did opiates start getting used?

A

May predate history of man

7000 years +

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3
Q

What are the main effects of opiates?

A

Analgesic

Antitussive (cough-supressant)

Sedative

Gastro-intestinal muscle relaxant (you poop)

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4
Q

Where were opiates derived from historically?

A

Poppy plant

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5
Q

What (ecologically) is opium?

A

The resin that oozes out of poppy plants

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6
Q

Where do you get morphine / codeine from?

A

Extracted from opium

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7
Q

What are the endogenous opioids?

A

Enkephalins
Endorphins
Dynorphins

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8
Q

What are synthetic opiates like compared to naturally-occuring?

A

e.g. fentanyl

100x as powerful as morphine

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9
Q

What pharmacological factor varies administration of opiates?

A

Fat solubility

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10
Q

How is morphine generally administered?

A

Orally, by inhalation, or by injection (injection fastest, it’s slow-absorbing)

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11
Q

How is heroin generally administered?

What is its fat solubility compared to morphine?

A

Smoked or injected.

Increased lipid solubility

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12
Q

What happens to heroin once it’s in the CNS?

A

Converted to morphine

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13
Q

What do naloxone/naltrexone do?

A

Direct opiate antagonists
Synthetically developed

Used in EMT cocktail

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14
Q

What happens to codeine in the CNS?

Where are its effects?

A

Converted to morphine (like heroin)

Little effect on its own, only cough centers in brainstem

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15
Q

Where are all the opiates metabolized?

A

Liver; excreted by kidney in urine

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16
Q

What do the half-lives of morphine / heroin look like?

A

~4 hr

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17
Q

What do the half lives of opiates in general look like?

A

Widely variable

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18
Q

What is the basic pharmacodynamic effect of opiates?

A

Direct agonists

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19
Q

Which receptors do opiates work on?

A

Opiate receptors (three main kinds)

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20
Q

Are opiate receptors metabotropic or ionitropic?

A

Metabotropic

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21
Q

What happens to changes in ion conductances with opiates?

A

Inhibition

Decrease excitability (K+)

Synaptic transmission (Ca2+)

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22
Q

How do opiates affect K+ channels?

A

Increase opening for leak channels

As an EPSP comes along, driving force for K+ gets changed

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23
Q

What happens with opiates and postsynaptic inhibition?

A

Open K+ channels

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24
Q

What happens with opiates and axoaxonic inhibition?

A

Close Ca2+ channels

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25
Q

What happens with opiates and presynaptic autoreceptors?

A

Reduce neutrotransmitter release

Colocalization with neurotransmitter / opioid

26
Q

Who first discovered opiate receptors?

A

Snyder and Pert, 1972

27
Q

What is the Mu receptor?

A

Opiate receptor

Most sensitive to morphine / heroin / codeine. It’s the one that binds these.

28
Q

How / where do opiates alter pain sensitivity? What is the first place possible?

A

Dorsal horns are the first place, chock full of opiate receptors

29
Q

(And where is the first place touch can get modulated?)

A

Medulla, somatosensory axons just project directly there (pain axons stop at dorsal horns)

30
Q

Why does rubbing help with pain?

A

Somatosensory neurons have inputs to pain-modulating inhibitory interneurons

These interneurons get excited by the somatosensory neurons

Interneurons project to pain neurons, inhibiting them

31
Q

What physiological responses to Mu receptors modulate?

A

Euphoric, brain and spinal analgesic, sedative, GI motility effects

32
Q

What do opiates do to peristaltic contraction in the GI tract?

A

Inhibit it (lots of opiate receptors in GI tract!)

33
Q

What are Delta opiate receptors? What is the difference between them and Mu?

A

More sensitive to endogenous opiates (e..g enkephalins)

Involved in spinal mechanisms of analgesia

34
Q

What are Kappa opiate receptors?

A

Most sensitive to dynorphin

Not involved in rewarding properties of opiates

Mostly in spinal cord, brainstem

35
Q

What is nociceptin/orphanin (NOP-R)?

A

No clue, but it’s new

learning, motor function, neuroendocrine? regulates hormonal pathways / stress response…

36
Q

Who discovered the endogenous opiates?

A

Both Kosterlitz and Hughes, 1975. Discovered them independently

37
Q

What did both kosterlitz and Hughes isolate?

A

Enkephalins - changes to endorphins (‘naturally occurring substance that acts like DA’)

38
Q

How do the endogenous opiates begin prior to synthesis?

A

Begin as large molecules made by neurons

proopiomelanocortin, etc

39
Q

How are the endogenous opiates synthesized?

A

Large molecules cleaved into different types of chemical messengers

40
Q

What is the potency of large molecule opiate precursors?

A

Much more potent than most endogenous opiates

41
Q

When are endogenous opiates released?

A

Stress response, times of pain, strenuous exercise (childbirth, fight, long-distance running)

42
Q

What (generally) are the behavioral effects of the opiates?

A

Sedative-hypnotic like

But not considered sedative hypnotics b/c they have other effects

43
Q

What opiate receptor subtype is most involved in analgesic effects?

A

Mu

44
Q

What opiate receptor subtype is most involved in euphoric effects?

A

Mu

45
Q

Which opiate receptor subtype is most involved generally?

A

‘Mu leads the way’

46
Q

What brain areas are involved in pain sensation?

A

NAcc
Amygdala
Thalamus

47
Q

What brain areas are affective during pain?

A

NAcc
ACC
Thal

48
Q

What is the first place pain is modulated at?

A

Dorsal horn, right when it enters spinal cord

49
Q

Where does pain sensation go after?

A

Medulla > through pons > reticular formation/periaquaductal grey in midbrain > up to somatosensory cortex

50
Q

Where does supraspinal control of pain begin?

A

Frontal lobes / hypothalamus

51
Q

Where is the periaquaductal grey?

A

Encircles cerebral aquaduct
FULL of receptors involved in control of pain

Activates during anxiety / stress, mutes perception of pain

52
Q

What is the locus coereleus and when does it activate?

A

It’s the brain’s equivalent of adrenal gland - release EP, NE (adrenaline) when you’re stressed

53
Q

Where is the LC?

A

Junction of mesencephalon and pons

54
Q

How do opiates reduce pain in the spinal cord?

A

A) Inhibit projection neurons

B) Inhibit interneurons that activate projection neurons

C) Exciting interneurons that inhibit projection neurons

55
Q

How quickly does opiate tolerance develop?

A

Incredibly fast, and LOTS of tolerance - way more than anything else

56
Q

What protein kinase do opiate second messengers modulate?

Why is this important?

A

PKC

Modulates NMDA receptors; opiate tolerance can be reduced by concurrent administration of NDMA antagonists

57
Q

What is the difference between conditioned and contingent tolerance?

A

Conditioned = pavlovian - environmental. Environment becomes stimulus for the response. “Where am I taking drug”

Contingent = tolerance dependent on the activity of a specific neural circuit when an analgesic is present. “What am I doing while taking drug”

58
Q

How do you reduce opiate tolerance with a drug?

A

Apply an NMDA antagonist

Because opiate receptors activate PKC, which agonizes NMDA receptors

59
Q

How bad is opiate withdrawal?

A

Real bad, but not as bad as the press makes out

Bad case of the flu in worst case scenario

60
Q

What are the physical effects of opiate withdrawal?

A

Anxiety, runny nose, nausea, fever, etc

61
Q

What are the psychological effects of opiate withdrawal?

A

Fueled by negative reinforcement (avoidance of withdrawal) and positive (seeking rewarding effects)

Psychopharmacology (12 decks)

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