Opioid Agonist-antagonists

Question 0

How do non competitive antagonists work?

Answer 0

Irreversibly bind to receptor at a separate site from agonist

• exerts action from other biding site
• does not compete with agonist
• prevents conformational changes in receptor which are required for activation (disables)
• inhibits full agonist response
• no amount of agonist can completely overcome inhibition

Question 1

How do competitive antagonists work?

Answer 1

Reversibly binds to receptor at same site as agonist but does not activate receptor

• prevents agonist from binding to and activating receptor
• clinical response depends on concentration of agonist that is competing for binding at receptor

Question 2

How do partial agonists work?

Answer 2

Has a high affinity for the receptor but not so much intrinsic activity

-occupies receptor but produces decrease in response

Question 3

What is a superagonist?

Answer 3

Has greater effects at the receptor than the defining receptor agonist
*fentanyl is 100x more potent at the Mu receptor than morphine

Question 4

What are opioid agonists/antagonists?

Answer 4

• “mixed” agonist and antagonist
• synthetic or semi synthetic analgesics
• structurally related to morphine
• produce a degree of competitive antagonism to morphine and pure agonists

Question 5

What are some benefits of agonist-antagonists use?

Answer 5

• opioid addiction (less addictive)
• acute and chronic pain
• beneficial when unable to tolerate pure opioid agonist
• maintain analgesic effect (k) while simultaneously reversing respiratory depression (Mu) or opioid od
• ceiling effect limits toxicity of drug (respiratory depression)
• no significant elevation of biliary pressure (useful with biliary colic; less constipation)

Question 6

What are some disadvantages of agonist-antagonist use?

Answer 6

• subsequent dose of agonists after these may not provide adequate analgesia
• dysphoria
• confusion, esp with elderly
• depression
• undesirable CV effects
• mu receptor antagonist can lead to withdrawal
• ceiling effect (weak ability to decrease anesthetic required)

Question 7

What are the negatives of mu receptors that may be prevented with agonist-antagonists?

Answer 7

• slowed gastric emptying
• skeletal muscle rigidity
• decreased pulmonary compliance
• respiratory depression

Question 8

Describe pentazocine (Talwin)

Answer 8

-weak antagonist of Mu receptors, partial kappa agonist

• *does not antagonize respiratory depression
• *can be antagonized by narcan
• *antagonist effects cause withdrawal in patients chronically receiving opioids

*cause sedation, analgesia, mild respiratory depression

Question 9

What are some indications of pentazocine use?

Answer 9

• Relief of moderate pain

* Chronic pain and increase risk of physical dependence

Question 10

What are the side effects of pentazocine?

Answer 10

• sedation, dizziness
• dysphoria
• diaphoresis
• dissociation
• “weird” feelings, hallucinations
• crosses placenta, potential fetal depression
• *increased HR and cardiac workload (catecholamine release) increase SBP, pulm artery pressure, and myocardial O2 consumption
• *caution with ischemic heart dx, CHF, MI

Question 11

Describe butorphanol (Stadol)

Answer 11

• more potent than Talwin (agonist 20x and antagonizes 10-30x greater)
• analgesia more potent than morphine
• nasal spray available
• more kappa effect then Mu or delta
• withdrawal after dc’d

*effect: analgesia and respiratory depression (equal to 10 mg morphine or 80-100 mg Demerol)

Question 12

What are some indications for butorphanol use?

Answer 12

• post op pain
• migraibe headaches
• post op shivering (if Demerol contraindicated)

Question 13

What are the side effects of butorphanol?

Answer 13

• sedation
• respiratory depression
• nausea, diaphoresis
• dissociation
• *CV effects: increased CO and workload, increased SBP and PAP (caution with CHF and MI)
• *dysphoria rare

Question 14

Describe nalbuphine (Nubain)

Answer 14

• potency comparable to morphine
• Mu receptor antagonist, kappa agonist
• subsequent morphine dosing less effective

*can be antagonized by narcan

Withdrawal can occur after dc’d

**effects: adequate analgesia with less respiratory depression

Question 15

What are some benefits of nalbuphine?

Answer 15

• useful in reversing lingering fentanyl-induced respiratory depressant effect while providing satisfactory analgesia
• antagonizes pruritus induced by epidural morphine caused by histamine release
• can give to patients with cardiac history

Question 16

What are some side effects of nalbuphine?

Answer 16

Sedation (33%) 
Respiratory depression (ceiling effect) 
Dissociation 
Diaphoresis 
Headache 

**no CV effects

Question 17

Describe buprenorphine (Buprenex)

Answer 17

• Mu receptor affinity 50% > morphine
• prolonged duration of up to 8 hrs
• partial Mu agonist and antagonizes Mu
• withdrawal after dc’d
• resistant to narcan

Question 18

What are some indications of buprenorphine?

Answer 18

• effective on moderate to severe cancer pain
• opioid dependence (d/t partial Mu agonist)
• *antagonizes fentanyl-induced respiratory depression w/o antagonizing pain relief

Question 19

What are some side effects of buprenorphine?

Answer 19

Sedation
N/V
Diaphoresis 
Headache
Dizziness