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AU15 - Pharmacology Test 2 > Opioids > Flashcards

Opioids Flashcards

1
Q

What is the pathway of orofacial pain

A

Nociceptors on trigeminal nerve endings –> A-d fibers and C fiber –> Trigeminal ganglion –> Trigeminal nuclei on the brainstem –> Thalamus –> Limbic Systema and Cerebral cortex

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2
Q

T/F - Orofacial pain follows a path different than other pain pathways throughout the body

A

False - it’s the same

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3
Q

Where are nociceptors located?

A

Throughout the skin, oral mucosa, and tooth pulp

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4
Q

A-delta fibers

A

Faster, myelinated axons response first to noxious mechanical stimuli
Produce the initial sensation of sharp pain

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5
Q

C fibers

A

Slower, unmyelinated axons that respond to thermal, mechanical, and chemical assaults
Dull, aching, or burning pain

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6
Q

Are there more C or A-delta fibers in the body?

A

There are 5x more C fibers than A-delta

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7
Q

Nociceptor signaling

A

Nociceptors are molecular sensors
Different nociceptors respond to various noxious stimuli such as heat, cold, mechanical perburbations, or protons
Their activation leads to local depolarization which in turn initiates action potentials

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8
Q

How does inflammation cause pain?

A

Mediators such as prostaglandins, substance P, TNF-a, Il-16, and Il-6 interact with nociceptors and facilitate the transmission of pain signals

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9
Q

T/F - Tissue injury can lead to sensitization of the pain response

A

True

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10
Q

Where can pharmacologic intervention occur to diminish pain?

A

At the periphery
Periphery signaling to the CNS
CNS activity

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11
Q

Where do NSAIDs and SAIDs act to diminish pain?

A

Inhibition at the periphery

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12
Q

Where do local anesthetics act to diminish pain?

A

Inhibition of signaling to the CNS

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13
Q

Where do opioids act to diminish pain?

A

Inhibition at the periphery and

Inhibition of CNS activity

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14
Q

What are the four families of endogenous opioids?

A

Pro-opiomelanocortin peptides
Pro-enkephalin peptides
Prodynorphin peptides
Endomorphins

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15
Q

What are the three important opioids receptors?

A

Mu (u)
Kappa (k)
Delta (d)

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16
Q

Opioids receptors

A

GCPRs
Widely distributed in the CNS
They activate Gai

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17
Q

B-endorphin

A

31 amino acid peptide

Natural agonist of the u-opioid receptor

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18
Q

Where is B-endorphin made, and what is it made from?

A

Formed from processing of pro-opiomelanocortin (POMC)

Made in the pituitary and hypothalamus

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19
Q

Met-enkephalin

A

5 amino acid peptide (pentapeptide)
Derived from pro-enkephalin precursor
Found in the adrenal medulla and throughout the CNS
Natural agonist of the d receptor

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20
Q

Leu-enkephalin

A

5 amino acid peptide (pentapeptide)
Derived from pro-enkephalin and pro-dynorphin
Found throughout the CNS
Natural agonist of the d receptor

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21
Q

Dynorphin A

A

13 aa peptide
Derived from Pro-dynorphin precursor
Found throughout the CNS
Natural agonist of the k receptor

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22
Q

Dynorphin B

A

13 aa peptide
Derived from Pro-dynorphin precursor
Found throughout the CNS
Natural agonist of the k receptor

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23
Q

a/B neo-endorphin

A 
10 aa peptide (a)
9 aa peptide (B)
Derived from Pro-dynorphin precursor
Found throughout the CNS
Natural agonist of the k receptor
24
Q

What do opioid receptors activate?

A

Gai and GBGy

25
Q

What does opioid activation of Gi do?

A

Inhibits adenyl cyclase activity, which reduces PKA, which reduces Ca entry
Reduction in Ca entry prevents the synapse from working

26
Q

What does opioid activation of GBGy do?

A

Activates a Cl channel, hyperpolarizing the postsynaptic terminal, inhibiting an AP on the synaptic membrane

27
Q

T/F - Opioids can inhibit synaptic transmission pre and postsynaptically

A

True

28
Q

What are the different forms of u receptors, and which are the most physiologically important?

A

u1, u2, u3

29
Q

Where are u receptors found?

A

PAG
Superficial dorsal horn of the spinal cord
Nucleus ambiguous
Amygdala
Cerebral cortex
GI tract (inhibit peristaltic action, causing constipation)

30
Q

What is the natural agonist of the u-opioid receptor?

A

B-endorphin

31
Q

What receptor do the majority of analgesic drugs act upon?

A

U receptors

32
Q

What is the site of Analgesic action?

A

Inhibits the ascending pathway of pain

  • can inhibit the transmission of an impulse
  • can inhibit excitatory neurotransmitter release
33
Q

How can analgesics inhibit the descending pathway of pain inhibition?

A

Opioids inhibit GABA release on the PAG

-by inhibiting the inhibitor, opioids activate the pathway that produces CNS mediated inhibition of pain

34
Q

What is the clinical effects of opioids?

A

All opioids produce analgesia, respiratory depression, constipation, GI spasm, and physical dependence

35
Q

What receptor does morphine target?

A

It is the prototypical full agonist for the u receptor (weak agonist for k)

36
Q

What do patients report after taking morphine?

A

They report that the pain is still present, but it is no longer unpleasant

37
Q

What is the most serious acute adverse effect of all opioids (especially morphine)

A

Respiratory depression

38
Q

What is tolerance?

A

A state in which an organism no longer responds to a given dosage of a drug
A higher dose is required to achieve the same effect

39
Q

T/F - tolerance develops to all effects uniformly

A

False - tolerance firsts manifests as shortened or diminished analgesia

40
Q

What does the rate of tolerance depend on?

A

Dose and the frequency of administration

Generally seen 5-7 days after treatment

41
Q

T/F - If tolerance is developed, the toxic effects of a drug are also diminished

A

False - toxic effects remain even if tolerance develops

42
Q

T/F - Dependece and tolerance are the same thing

A

False

43
Q

What enzyme metabolizes morphine, and where is it?

A

UGT2B7

In the liver as well as the brain

44
Q

What is the primary product of morphine metabolism? The secondary?

A 
1' = Morphine-3-glucuronide (M-3-G)
2' = Morphine-6-glucuronide (M-6-G)
45
Q

Which product of morphine can cross the BBB?

A

M-6-G

46
Q

Which morphine product (along with morphine) can act on u receptors?

A

M-6-G

47
Q

How does Codeine compare to morphine?

A

It is more effective orally than morphine

Codeine binds poorly to u receptors

48
Q

What are the products of codeine metabolism?

A

Codeine-6-glucuronide (80%)

Morphine (5%)

49
Q

What dosage of codeine is recommended? Why?

A

30-60mg daily

Side effects are minimal at this dose, and we usually don’t see dependence at this dose either

50
Q

T/F - Pain with an inflammatory component can be treated without an anti-inflammatory

A

False - pain with an inflammatory component should NOT be treated without an anti-inflammatory drug (we want to beat down the inflammation as well)

51
Q

What do Dihydrocodeine, Oxycodone, and Hydrocodone have in common with morphine? What makes them different?

A

They’re all methylated in the 3’ position

These can be taken orally

52
Q

Naloxone, naltrexone, and nalmefene are all what?

A

Opioid antagonists

53
Q

What are opioid antagonists used for?

A

Used to treat opioid toxicity

54
Q

Which opioid antagonists is injected and works rapidly?

A

Naloxone

55
Q

Which opioid antagonists is effective orally and lasts a long time?

A

Naltrexone

But, Nalmefene can last even longer

56
Q

Which opioids are used most commonly in dentistry?

A

Codeine, Hydrocodone, oxycodone, pentazocine

AU15 - Pharmacology Test 2 (10 decks)

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