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Pharmacology fall 2024 > Opioids (Exam V) > Flashcards

Opioids (Exam V) Flashcards

1
Q

What are the three endogenous ligands pertinent to pain signaling?

A
  1. Endorphins (1°)
  2. Enkephalins (pain signaling)
  3. Dynorphins (pain signaling)
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2
Q

What are hierarchical systems?

A
  • Multiple Neurons linked to one another for signaling.
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3
Q

What specific type of neuron is pertinent to feed-forward & feed-back responses in relay systems?

A

Interneurons

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4
Q

Explain the mechanism of a feed-back response.
What is the purpose of this system?

A
  • Excitatory neuron depolarizes an inhibitory interneuron which suppresses the initial excitatory neuron.
  • Seizure prevention from constant excitatory stimulation.
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5
Q

Explain the mechanism of a feed-forward response.

A

Neuron A excites an interneuron which then inhibits Neuron B.

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6
Q

Are feed-forward & feed-back systems inhibitory or excitatory?

A

They can be both.

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7
Q

How does an axoaxonic interaction differ from a feedback or feed-forward neuron interaction?

A
  • Inhibition/excitation occurs at the axon rather than the neuron body.
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8
Q

How do non-specific, diffuse systems differ from relay systems?

A
  • Monoamine Transmitters used (NE, Dop, 5-HT)
  • Slower
  • Diffuse throughout the CNS. (en-passant synapses used)
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9
Q

Where is serotonin produced?

A

Raphe Nuclei

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10
Q

Where is dopamine produced?

A

Substantia Nigra & Ventral Tegmental Area

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11
Q

Which diffuse system area of the brain is associated with NE?

A

Locus Coeruleus

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12
Q

Which area of the brain is associated with ACh diffusion?
What neurotransmitter does ACh have a similarity to in the CNS?

A
  • Pontine Nuclei
  • Serotonin/Melatonin
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13
Q

What CNS effects does ACh have?

A
  • Learning & Memory
  • Sleep-wake cycles
  • Arousal & sensory information
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14
Q

Tachykinins use _________ __ receptors and have a __________ effect on pain signaling.

A

Substance P; excitatory

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15
Q

Is most pain signaling hierarchical or diffuse?

A

Hierarchical

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16
Q

Most pain receptors are _____ ______ endings.

A

free nerve

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17
Q

What fiber type can suppress fast pain?

A

Aβ through suppression of Aδ fast pain.

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18
Q

What mediators of pain (discussed in lecture) are released in response to tissue damage?

A
  • Bradykinin
  • Prostaglandins
  • Glutamate
  • Substance P
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19
Q

What are the three pain tracts of the CNS (discussed in lecture)?

A
  • Spinothalamic
  • Spinoreticular
  • Spinomesencephalic
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20
Q

Which spinal tract is suppressive to painful stimuli?

A
  • Spinomesencephalic through μ(mu) opioid receptors in the periaqueductal gray matter.
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21
Q

What is the primary opioid and endogenous ligand receptor?
What endogenous ligands are used by this receptor?

A
  • μ(mu) opioid receptors
  • Endorphins
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22
Q

What are the other opioid receptors aside from μ(mu) opioid receptors?

A

δ(delta) & κ(kappa) receptors.

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23
Q

Differentiate full agonist, partial agonists, & antagonists of the opioid receptors. Give examples for each.

A
  • Full Agonists (strong to moderate effect) morphine, fentanyl, etc.
  • Partial Agonists (moderate to mild effect) codeine, oxycodone, etc.
  • Antagonists (Reversal) Naloxone
24
Q

What mediator is utilized with κ(kappa) receptors?

A
  • Dynorphins
25
Q

What type of receptor are opioid receptors?

A

Gᵢ GPCRs

26
Q

Where are mu opioid receptors located on neurons?

A
  • Pre-synaptic & post-synaptic neurons
27
Q

How do μ(mu) opioid receptors suppress pain?

A

Gᵢ = ↓AC → ↓cAMP = ↑pK⁺, ↓pCa⁺⁺ = Hyperpolarized neuron.

28
Q

What opioid pathway leads to decreased effect & opioid tolerance?

A

G-protein independent pathway with ERK, JNK & β-arrestin.

(ERK = E receptor Kinase, JNK = Janus Kinase)

29
Q

Which opioid receptors are responsible for analgesia?
Which opioid receptor is responsible for CNS respiratory depression & dependence/addiction?

A
  • Mu, delta, & kappa.
  • Mu
30
Q

What symptom of opioid organ system effects is always present with opioid use & no tolerance develops to it?

A

Miosis (pupillary constriction)

31
Q

What effects may opioids have on the cardiovascular system?
What is the exception?

A
  • Indirect CNS bradycardia
  • Meperidine (Demerol) has antimuscarinic traits = ↑HR.
32
Q

Is tolerance developed to the constipatory effects of opioids?

A

No

33
Q

What does Loperamide do? Why?

A
  • Antidiarrheal opioid with no CNS effects due to GI ABCB1 clearance.
34
Q

What drug can cause respiratory depression when given with loperamide?
Why?

A
  • Quinidine
  • Blocks ABCB1 so loperamide accumulates and affects CNS.
35
Q

What is the treatment for Acute Coronary Syndrome?

A
  • Morphine
  • Oxygen
  • Nitroglycerin
  • Aspirin
36
Q

Why is morphine used in Acute Coronary syndrome?

A
  • ↓ anxiety
  • ↓ HR (and thus metabolic demand)
  • ↓ pain
37
Q

What drug is indicated for post-operative shivering?

A

Demerol (meperidine)

38
Q

How quickly does opioid tolerance build?
What is the probable mechanism for this?

A
  • Rapidly
  • β-arrestin pathway
39
Q

What mild symptoms might be seen from opioid withdrawal?

A
  • Piloerection
  • Hyperventilation
  • Lacrimation
  • Rhinorrhea
  • Yawning
40
Q

What symptoms would be seen in severe opioid withdrawal?

A
  • Mydriasis
  • Hyperthermia
  • N/V/D
  • Anxiety/Hostility
41
Q

What is opioid induced hyperalgesia?
How many patients will experience this?

A
  • Increased pain response secondary to chronic use
  • 30% of chronic users develop this
42
Q

What is the mechanism for opioid induced hyperalgesia?

A
  • Sensitization of MuOR-1K variant & ↑cAMP
43
Q

What is the treatment for opioid induced hyperalgesia?

A
  • Wean opioid
  • GABA analogs
44
Q

Why are opioids partially contraindicated in head injuries?

A

↑ Resp depression

45
Q

What can occur when opioids are given to a pregnant mother?

A
  • Fetal Dependence
46
Q

What structure is indicated in the figure below?
What strength is typically seen with these opioids?

A
  • Phenanthrene
  • Very strong (morphine, hydromorphone, heroine)
47
Q

What structure is indicated in the figure below?
What opioids are seen with this structure?

A
  • Phenylheptylamine
  • Very strong (Methadone)
48
Q

What structure is indicated in the figure below?
What types of opioids are associated with this structure?

A
  • Phenylpiperidine
  • Fentanyl & Meperidine
49
Q

What is heroin used for in the UK?

A

Palliative Care

50
Q

What is methadone’s usefulness?
Why is this?

A
  • Suppression of opioid withdrawal symptoms (and chronic pain)
  • Long Half-Life = 25-50 hours
51
Q

What is the primary use of Meperidine?
What cardiac effects are seen with it?

A
  • Post-op shivering
  • neg inotrope, + chronotrope
52
Q

What is the most potent fentanyl derivative?

A

Carfentanil (10,000:1 morphine ratio)

53
Q

How much can shivering increase O₂ consumption?
By what mechanism does meperidine treat shivering?

A
  • 500%
  • ↑ kappa receptor agonism & serotonergic effects.
54
Q

Which phenanthrenes are moderate agonists & more useful with acetaminophen or aspirin?

A
  • Oxycodone & codeine
55
Q

What is Dextromethorphan’s use?

A
  • Anti-tussive
56
Q

What is Buprenorphine used for?

A
  • Opioid abuse (partial agonist)
57
Q

What are the two opioid antagonists? What are their uses?

A
  • Naloxone - Overdose antidote (short duration, supportive therapy still needed)
  • Naltrexone - EtOH abuse.

Pharmacology fall 2024 (23 decks)

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