Opioid Analgesics Flashcards
Three MoA of opioids
- Inhibit the transmission of nociceptive input from the periphery to the spinal cord
- Activate descending inhibitory pathways that modulate transmission in the spinal cord
- Later limbic system activity (pain perception)
What is each Mu receptor primarily responsible for?
Mu1 = analgesia
Mu2 = respiratory depression, Meiosis, reduced gastric motility, sedation, euphoria, pruritus, urinary retention, physical dependence
Which opioid is the most hydrophilic and which is the most lipophilic?
Morphine is the most hydrophilic, Fentanyl is the most lipophilic
Does tolerance develop equally to all opioid effects?
No, GI and Resp continue to be effected long after tolerance to the analgesic effect develops
What is the most serious AE w/opioid therapy?
Respiratory depression
Which opioid is associated with the greatest histamine release?
Morphine (oxycodone and fentanyl cause fewer)
What is the treatment for opioid toxicity?
Naloxone- pure opioid antagonist
Full agonists
Effectiveness is not limited by dose increases…pure agonist: do not antagonize the effects of other full agonists
Partial agonists
Medications have a ceiling analgesic effect whereas the pure agonists do not…meaning greater doses won’t increase analgesic effectiveness, only greater SEs
Partial/mixed agonist
Agonist for some receptors and antagonist for others
Antagonist
No analgesic effect, used to block the effect of opioids
Anti-tussive opioids work by inhibition of the coughing center in the medulla, but don’t cure the irritation, what are the three opioids used for this?
Codeine (MC)
Hydrocodone
Dextromethorphan
Phenanthrene opioids to remember
Morphine Hydromorphone (Dilaudid) Hydrocodone ER Hydrocodone/APAP (Vicodin, Lortab) Levorphanol Oxycodone (OxyContin) Oxycodone/APAP (Percocet) Oxymorphone (Opana) Codeine Codeine/APAP (Tylenol #3) Mixed agonist/antagonist - Buprenorphine - Butorphanol - Nalbuphine Heroin
Strong agonist, slow and erratic oral absorption, enters all body tissues, least lipophilic, crosses placenta…used for pain
Morphine
Two opioids that are metabolized to morphine
Heroin and codeine (so morphine in urine could mean exposure to morphine, heroin, or codeine)
AEs for this opioid: Increase in ICP, so significant caution in severe head injury…N/V, itching, hypotension
Morphine
Metabolite of morphine with better oral absorption, more fat soluble than morphine for moderate to severe pain…ER form is a Risk Evaluation and Mitigation Strategy (REMS) drug that requires provider training every 2 years
Hydromorphone (dilaudid)
Opioid that’s a moderate agonist, metabolized to hydromorphone for moderate to severe pain…there are two combination forms
Hydrocodone ER
Opioid metabolized to noroxycodone and oxymorphone (active metabolites)…several formulations: CR, IR (contact w/water turns it gummy for abuse protection), and Percocet/combined tabs
Oxycodone
Synthetic Mu agonist w/greater analgesic profile than morphine for moderate/severe pain. The ER brand has an abuse-deterrent and the IR brand does not
Oxymorphone (Opana)
Prodrug with no analgesic activity that gets metabolized to morphine, usually used as an antitussive unless combined w/another drug
Codeine
BB warning: death related to ultra-rapid metabolism of this drug to morphine especially in the young
Codeine
Codeine on its own
Codeine w/APAP
Codeine w/Guaifenesin
What class is each?
C-II
C-III
C-V
AEs: This group of opioids precipitate opioid withdrawal in opioid-dependent patients, they have a ceiling effect on respiratory depression and analgesia, and a lower abuse potential
Mixed agonist/antagonists
This mixed agonist/antagonist is a partial Mu receptor agonist and kappa receptor antagonist that’s used for opioid detoxification (as effective as methadone)
Buprenorphine (resistant to naloxone reversal due to long duration of action, limited access to physicians, caution in pregnancy)
This opioid is a partial mu and kappa receptor agonist used for pain especially during labor if epidural is not possible
Butorphanol
This non-controlled mixed agonist/antagonist is a partial mu antagonist and strong kappa agonist used for sedation w/ minimal respiratory depression and to reverse ventilator depression in opioid overdose while maintaining some analgesia
Nalbuphine (may be resistant to naloxone reversal)
Phenylpiperidines to know
Meperidine (Demerol)
Fentanyl
Fentanyl derivatives (alfentanil, sufentanil, remifentanil)
Mu and delta strong agonist with anticholinergic effects used to treat SHIVERING AND RIGORS, but shouldn’t be a first choice for pain
Meperidine (Demerol) - extensive hepatic metabolism, turns to normeperidine which is really cleared and have negative inotropic actions on the heart
Meperidine (Demerol) is CI specifically in pts taking these types of meds (as are pretty much all opioids)
MAOIs
Meperidine should be avoided in renal insufficiency and causes some strange AEs including?
Tachycardia, mydriasis, more frequent and profound hypotension than morphine, delirium and seizures, severe withdrawal syndrome
Very potent synthetic opioid, lipophilic, rapid onset, short duration of action, available in transdermal product for chronic pain, IV, and Buccal for breakthrough pain and in the field/combat
Fentanyl
Three fentanyl derivatives
Alfentanil (rapid onset, shorter doa)
Sufentanil (slower onset than fentanyl, same doa)
Remifentanil (rapid onset, shortest doa)
Antagonist at NMDA receptor, inhibits serotonin/NE used for Chronic pain syndrome and detox of opioid addiction
Methadone (arrhythmias prolong QT interval)
Partial mu agonist, full kappa agonist used, when IV only, for labor pain when epidural is not possible
Pentazocine
Adjunct therapy to treat diarrhea symptoms ONLY
Diphenoxylate with atropine (lomotil)
Serotonin and NE reputable inhibitor for moderate/severe pain associated with increased risk of serotonin syndrome and seizures
Tramadol (ultra-rapid metabolizers could lead to significant respiratory depression)
ONLY OPIOID WITH INDICATION FOR DIABETIC PERIPHERAL NEUROPATHY
Tapentadol
Opioid antagonist with no systemic effect when given orally
Naloxone
Opioid antagonist used in opioid and alcohol addiction, 100% absorbed and active orally
Naltrexone (competes but does not displace opioids) - precipitates withdrawal
Opioid antagonist that competes and displaces opioids, shorter duration of action
Naloxone (Narcan)
How often can naloxone be given?
Every 2 to 5 minutes
When tapering opioids, the goal is to taper by how much per week?
20-50%
Dose at which two opioid agents are expected to produce similar analgesic effects
Equianalgesic opioid dosing
Greater than expected potency in a new opioid, even in the same class of analgesic…risk is respiratory depression
Incomplete cross tolerance
