Opioids (Exam V)

Question 1

What are the three endogenous ligands pertinent to pain signaling?

Answer 1

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

Question 2

What are hierarchical systems?

Answer 2

• Multiple Neurons linked to one another for signaling.

Question 3

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

Answer 3

Interneurons

Question 4

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

Answer 4

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

Question 5

Explain the mechanism of a feed-forward response.

Answer 5

Neuron A excites an interneuron which then inhibits Neuron B.

Question 6

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

Answer 6

They can be both.

Question 7

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

Answer 7

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

Question 8

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

Answer 8

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

Question 9

Where is serotonin produced?

Answer 9

Raphe Nuclei

Question 10

Where is dopamine produced?

Answer 10

Substantia Nigra & Ventral Tegmental Area

Question 11

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

Answer 11

Locus Coeruleus

Question 12

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

Answer 12

• Pontine Nuclei
• Serotonin/Melatonin

Question 13

What CNS effects does ACh have?

Answer 13

• Learning & Memory
• Sleep-wake cycles
• Arousal & sensory information

Question 14

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

Answer 14

Substance P; excitatory

Question 15

Is most pain signaling hierarchical or diffuse?

Answer 15

Hierarchical

Question 16

Most pain receptors are _____ ______ endings.

Answer 16

free nerve

Question 17

What fiber type can suppress fast pain?

Answer 17

Aβ through suppression of Aδ fast pain.

Question 18

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

Answer 18

• Bradykinin
• Prostaglandins
• Glutamate
• Substance P

Question 19

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

Answer 19

• Spinothalamic
• Spinoreticular
• Spinomesencephalic

Question 20

Which spinal tract is suppressive to painful stimuli?

Answer 20

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

Question 21

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

Answer 21

• μ(mu) opioid receptors
• Endorphins

Question 22

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

Answer 22

δ(delta) & κ(kappa) receptors.

Question 23

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

Answer 23

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

Question 24

What mediator is utilized with κ(kappa) receptors?

Answer 24

• Dynorphins

Question 25

What type of receptor are opioid receptors?

Answer 25

Gᵢ GPCRs

Question 26

Where are mu opioid receptors located on neurons?

Answer 26

- Pre-synaptic & post-synaptic neurons

Question 27

How do μ(mu) opioid receptors suppress pain?

Answer 27

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

Question 28

What opioid pathway leads to decreased effect & opioid tolerance?

Answer 28

G-protein independent pathway with ERK, JNK & β-arrestin. (ERK = E receptor Kinase, JNK = Janus Kinase)

Question 29

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

Answer 29

- Mu, delta, & kappa. - Mu

Question 30

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

Answer 30

Miosis (pupillary constriction)

Question 31

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

Answer 31

- Indirect CNS bradycardia - Meperidine (Demerol) has antimuscarinic traits = ↑HR.

Question 32

Is tolerance developed to the constipatory effects of opioids?

Answer 32

No

Question 33

What does Loperamide do? Why?

Answer 33

- Antidiarrheal opioid with no CNS effects due to GI ABCB1 clearance.

Question 34

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

Answer 34

- Quinidine - Blocks ABCB1 so loperamide accumulates and affects CNS.

Question 35

What is the treatment for Acute Coronary Syndrome?

Answer 35

- **M**orphine - **O**xygen - **N**itroglycerin - **A**spirin

Question 36

Why is morphine used in Acute Coronary syndrome?

Answer 36

- ↓ anxiety - ↓ HR (and thus metabolic demand) - ↓ pain

Question 37

What drug is indicated for post-operative shivering?

Answer 37

Demerol (meperidine)

Question 38

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

Answer 38

- Rapidly - β-arrestin pathway

Question 39

What mild symptoms might be seen from opioid withdrawal?

Answer 39

- Piloerection - Hyperventilation - Lacrimation - Rhinorrhea - Yawning

Question 40

What symptoms would be seen in severe opioid withdrawal?

Answer 40

- Mydriasis - Hyperthermia - N/V/D - Anxiety/Hostility

Question 41

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

Answer 41

- Increased pain response secondary to chronic use - 30% of chronic users develop this

Question 42

What is the mechanism for opioid induced hyperalgesia?

Answer 42

- Sensitization of MuOR-1K variant & ↑cAMP

Question 43

What is the treatment for opioid induced hyperalgesia?

Answer 43

- Wean opioid - GABA analogs

Question 44

Why are opioids partially contraindicated in head injuries?

Answer 44

↑ Resp depression

Question 45

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

Answer 45

- Fetal Dependence

Question 46

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

Answer 46

- Phenanthrene - Very strong (morphine, hydromorphone, heroine)

Question 47

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

Answer 47

- Phenyl**heptyl**amine - Very strong (Methadone)

Question 48

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

Answer 48

- Phenylpiperidine - Fentanyl & Meperidine

Question 49

What is heroin used for in the UK?

Answer 49

Palliative Care

Question 50

What is methadone's usefulness? Why is this?

Answer 50

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

Question 51

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

Answer 51

- **Post-op shivering** - neg inotrope, + chronotrope

Question 52

What is the most potent fentanyl derivative?

Answer 52

Carfentanil (10,000:1 morphine ratio)

Question 53

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

Answer 53

- 500% - ↑ kappa receptor agonism & serotonergic effects.

Question 54

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

Answer 54

- Oxycodone & codeine

Question 55

What is Dextromethorphan's use?

Answer 55

- Anti-tussive

Question 56

What is Buprenorphine used for?

Answer 56

- Opioid abuse (partial agonist)

Question 57

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

Answer 57

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