Pain part two Dr. Baker

Question 1

1. When given an opioid classify it as: (full/partial) agonist/antagonist, phenanthrene/non-phenanthrene opioid, mixed kappa opioid, with/without NMDA activity.

Answer 1

Phenanthrenes – Morphine, codein, Thebaine
Non- phenanthrenes – Tramadol, Meperidine, Fentanyl
Benzylisoquinolines – Noscapine, papaverine
Partial agonist – buprenorphine
Naloxone – antagonist

Question 2

Describe the role of Mu opioid receptor type and link it with its respective endogenous opioid.

Answer 2

Mu – Endogenous opioid is endorphin
- Presynaptic: Work to inhibit calcium release
- Postsynaptic: activate GIRK to allow potassium to leave and making interior of neuron more negative making it harder to fire signaling
- Therapeutic use of Mu opioids: analgesia, Cancer pain, palliative care (end of life care), sedation, antitussive (suppress cough – codeine)

Question 3

3. Describe the role of Kappa opioid receptor type and link it with its respective endogenous opioid

Answer 3

Kappa- endogenous opioid is dynorphin
- Cause dysphoric feelings
- Potential use – mixed kappa Mu receptor drugs could be good to help with addiction potential
- Dynorphin release that activates kappa opioid receptors and these negativily affect dopamine release and cause lese dopamine release

Question 4

3. Describe the role of delta opioid receptor type and link it with its respective endogenous opioid

Answer 4

Delta – Endogenous opioid is enkephalin
- NO FDA approved delta opioids
- Role in hypoxia, ischemia, stroke
- May reduce anxiety, depression, treat alcoholism, relief hyperalgesia

Question 5

3. Describe the role of orphanin opioid receptor type and link it with its respective endogenous opioid

Answer 5

Nociceptin or Orphanin FQ receptor – endogenous opioid is nociceptin
These are Gi/o to reduces cAMP production, beta gamma subunit of the protein will open GIRK potassium channels which allows potassium to flow out of the cell and makes it harder for the neuron to fire pain signaling due to hyperpolarization

Question 6

5. Describe treatments of opioid dependence and overdose and explain the mechanism of action and limitations.

Answer 6

• Overuse can lead to constipation
  o Treatment of this with polyethylene glycol (miralax)
  o Dioctyl sodium sulfosuccinate/ docusate
• Opioid tolerance
  o Reduced effect over time even with higher dose
  o Tolerance to analgesic effect, nausea, urinary retention, respiratory depression, euphoria

Question 7

6. With regards to neonatal abstinence syndrome, describe the effect it can have on a fetus and how it can be treated.

Answer 7

• When a pregnant woman is using, causes baby to have withdrawal symptoms of the drugs
• Non-pharm treatment: swaddling, hypercaloric formula, frequent feeding, rehydration
• Pharmacological treatment: oral morphine, sublingual buprenorphine, clonidine (alpha 2 agonist)

Question 8

Morphine

Answer 8

Bioavailability 25%

CYP2D6, CYP3A4

Question 9

Pro drug opioids

Answer 9

Heroin, Codeine, Tramadol

Question 10

Fentanyl

Answer 10

comes in patch lollipop
agonist
good for pre/peri/post hospital procedures

Question 11

Tramadol (ultram)

Answer 11

Has SNRI properties

Question 12

Methadone

Answer 12

Slow acting
Used for opioid dependence
Prolonged QTc
NMDA antagonist
accumulates with repeated doses

Question 13

Buprenorphine

Answer 13

Works as a Mu and kappa agonist and a delta antagonist
used for opioid replacement therapy
Subutex - abuse potential

Question 14

Naltrexone

Answer 14

IM injection or daily oral dose
Decent oral bioacailability

Question 15

Treatment of neonatal abstinence syndrome

Answer 15

Morphine and buprenorphine
non pharm: swaddling, frequent feeding, rehydration