Flashcards in Opioid Agonist-antagonists Deck (20)
How do competitive antagonists work?
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
How do non competitive antagonists work?
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
How do partial agonists work?
Has a high affinity for the receptor but not so much intrinsic activity
-occupies receptor but produces decrease in response
What is a superagonist?
Has greater effects at the receptor than the defining receptor agonist
*fentanyl is 100x more potent at the Mu receptor than morphine
What are opioid agonists/antagonists?
-"mixed" agonist and antagonist
-synthetic or semi synthetic analgesics
-structurally related to morphine
-produce a degree of competitive antagonism to morphine and pure agonists
What are some benefits of agonist-antagonists use?
*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)
What are some disadvantages of agonist-antagonist use?
-subsequent dose of agonists after these may not provide adequate analgesia
-confusion, esp with elderly
*undesirable CV effects
*mu receptor antagonist can lead to withdrawal
-ceiling effect (weak ability to decrease anesthetic required)
What are the negatives of mu receptors that may be prevented with agonist-antagonists?
-slowed gastric emptying
-skeletal muscle rigidity
*decreased pulmonary compliance
Describe pentazocine (Talwin)
-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
What are some indications of pentazocine use?
-Relief of moderate pain
*Chronic pain and increase risk of physical dependence
What are the side effects of pentazocine?
-"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
Describe butorphanol (Stadol)
-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)
What are some indications for butorphanol use?
-post op pain
*post op shivering (if Demerol contraindicated)
What are the side effects of butorphanol?
**CV effects: increased CO and workload, increased SBP and PAP (caution with CHF and MI)
Describe nalbuphine (Nubain)
-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
What are some benefits of nalbuphine?
*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
What are some side effects of nalbuphine?
Respiratory depression (ceiling effect)
**no CV effects
Describe buprenorphine (Buprenex)
-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
What are some indications of buprenorphine?
-effective on moderate to severe cancer pain
-opioid dependence (d/t partial Mu agonist)
**antagonizes fentanyl-induced respiratory depression w/o antagonizing pain relief