Opioids Flashcards
Name the opioid agonists (not including agonist/antagonists)
Morphine Codeine Meperidine Fentanyl Sufentanil Alfentanil Remifentanil Methadone Hydromorphone
What is the mechanism of action of opioid agonists?
Opioid agonist binds GPCR –> inhibits adenylyl cyclase –> 2 signaling effects:
1) Decrease conductance of voltage-gated Ca channels –> decreased transmitter release
2) Increase K outflow post-synaptically –> hyperpolarization
Both of these effects result in prevention of excitation and propagation of action potential –> analgesia (mostly mu receptor) and other side effects
What are side effects of Mu receptor activation?
Constipation (due to decreased ACh release –> slower gastroparesis and peristalsis –> more water absorption)
Euphoria
Physical dependence
Respiratory depression (depressant effect on brainstem ventilation centers - loss of CO2 responsiveness, but retain hypoxic drive)
Sedation
What are side effects of Delta receptor activation?
None, just involved in analgesia
What are side effects of Kappa receptor activation?
Constipation (due to decreased ACh release –> slower gastroparesis and perstalsis –> more water absorption)
Miosis (can be antagonized with atropine)
Psychotomimesis
Sedation?
Which opioid agonists are anti-tussive?
D-methorphan
Codeine
When do opioid agonists cause muscle rigidity?
Large doses, rapid injection
Interacts with opioid receptors in striatum and substantia nigra and inhibit DA release
What effect do opioid agonists have on the cardiovascular system?
No direct effect on myocardium, but can cause hypotension due to the following:
- Bradycardia due to decreased central sympathetic tone
- Increased activity over vagal nerve
- Direct depressant effect on SA node
- Histamine release (morphine and meperidine)
Do opioid agonists cause urinary retention or incontinence?
Urinary retention
Causes increased tone and peristalsis of ureter, which would normally cause incontinence
But also increases tone of sphincter, which outweighs ureter tone and peristalsis
Why does morphine have delayed penetrance of BBB?
Poor lipid solubility
Highly ionized
Binds protein
Rapidly conjugated in liver
What are the metabolites of morphine and which are active?
M3G - inactive
M6G - active - can cause increased ventilatory depressant effects in renal failure patients
What is unique about the structure of meperidine and why is it significant?
Structurally similar to atropine - can cause atropine-like side effects at high doses (tachycardia, mydriasis)
What is the metabolite of meperidine and what are its effects?
Normeperidine
Causes myoclonus and seizures in renal failure patients
What are the two drugs that cause histamine release?
Morphine
Meperidine
What is the main clinical use of meperidine?
Post-operative shivering
Is meperidine more or less potent than morphine?
Less - 1/10 as potent
Is fentanyl more or less potent than morphine?
More - 75-125x as potent
Compare the onset and duration of fentanyl (and its derivatives) to that of morphine (and its derivatives)
Fentanyl - more rapid onset, but shorter duration than morphine
(rapid onset due to better lipid solubility)
(shorter duration due to rapid redistribution to inactive sites)
What are the metabolites of fentanyl and what are their effects?
No metabolites! Trick question!
What cardiovascular effects does meperidine have?
Large doses decrease myocardial contractility
Is sufentanil more or less potent than fentanyl?
More - 5-10x as potent
Is alfentanil more or less potent than fentanyl?
Less - 1/5-1/10 less potent
How is alfentanil cleared?
Hepatic clearance - CYP3A
Is remifentanil more or less potent than fentanyl?
About the same
What is unique about remifentanil?
Unique ester linkage
Allows it to be metabolized by tissue plasma esterases
So metabolism will be unaffected by hepatic or renal failure - ideal in these patients
What receptor (in addition to Mu) does Methadone act at?
NMDA antagonist
Why can methadone be difficult to dose?
Has prolonged action after repeated doses
Accumulates in tissues, causing prolonged and unpredictable half-life and negative side effects
(Analgesia half-life different from half-life of side effects)
Is hydromorphone more or less potent than morphine?
More - 5x as potent
In what patients will hydromorphone be a much better choice than morphine?
Patients with renal failure
Hydromorphone does not have the buildup of M6G active metabolite
What drugs are opioid agonists/antagonists?
Buprenorphine
Butorphanol
Nalbuphine
When is an agonist/antagonist a better choice than a pure agonist?
When patient cannot tolerate a pure agonist
i.e. cannot tolerate ventilatory depression, has a high potential for physical dependence
What is the mechanism of opioid agonists/antagonist?
Act as agonist at one receptor (usually mu)
Act as antagonist at another receptor (delta or kappa)
What drugs are opioid antagonists?
Naloxone
Naltrexone
What is the mechanism of opioid antagonists?
Binds opioid receptors with high affinity and can displace the agonist –> reverses effect of agonist (ventilatory depression AND pain suppression)
When are opioid antagonists used?
To treat opiate induced ventilatory depression or opioid overdose (rescue situations)
What are potential problems to monitor for when using an opioid antagonist in a rescue situation?
CV stimulation due to increased sympathetic activity
Re-narcotize (antagonists have short duration and half-life, so excess opioid agonist may be hanging around once the antagonist has been metabolized, potentially re-causing opioid agonist effects)
