Opioids Flashcards
MOA for opioid analgesia
- Inhibition of pain signaling
2. Reduce CNS response to pain signal (pro-analgesic)
One of the natural active constituents of opium, prototype
Morphine
IM, SC, IV, oral
Readily absorbed, effect in 5-15 minutes, 4-5 hr duration
Morphine (12 H DOA with sustained release)
Morphine: main metabolic pathway, active metabolites?
Glucuronidation (liver), morphine-6-B-glucuronide (long half-life) and morphine-3-B-glucuronide (seizures)
Are there dosing considerations for morphine with impaired liver or kidney function?
Yes
3 therapeutic effects of morphine:
Analgesia, sedation, euphoria
T/F: Sedation arising from morphine will lessen with use (tolerance).
True
MOA morphine analgesia (2)
Acts at peripheral and spinal levels to block pain transmission and acts at higher brain levels to block response to pain
5 major side effects of morphine
Respiratory depression, nausea/vomiting, constipation, pupillary constriction, itching
MOA of respiratory depression associated with morphine
Decreased sensitivity of chemoreceptor centers to plasma CO2 levels (hypoxic response still present)
T/F: Tolerance does NOT develop against respiratory depression.
False (tolerance develops)
CVD side effects of morphine
Mild, orthostatic hypotension due to histamine release (that also causes the itching)
Immune system side effects of morphine
Inhibition, minor unless someone is already immune compromised
Hormonal side effects of morphine
Altered effects, usually minor
Biliary & urinary tract side effects of morphine
Increased pressure, may worsen biliary colic and urinary tract obstruction
6 contraindications/limitations of morphine
- Patients with decreased respiratory reserve (asthma, emphysema, cor pulmonale)
- Head injuries
- CNS tumors
- Pregnancy
- Neonates & elderly (much more sensitive)
- Potential for dependence and misuse
DDIs for all opioid analgesics
Other CNS depressants (sedatives, ethanol, antidepressants, etc.)
Given orally, onset in 30-60 minutes, DOA 4-6 hours
Codeine
Potency of codeine (fraction)
1/10 (used for milder pain)
Metabolism of codeine (reaction, enzyme, product)
Demethylated by CYP2D6 to morphine
Clinical uses of codeine (3ish)
- Mild-moderate pain 2. With aspirin or APAP (additive effects)
- Cough suppression (lower doses)
Codeine vs. morphine: important differences (2)
More likely to cause constipation and less likely to cause addiction
Oral, IV, IM, transdermal, intranasal, sublingual
Onset times differ depending on route, but generally rapid onset and short DOA (ex: few minute onset for oral)
Fentanyl
Clinical uses of fentanyl (what type of pain?)
Chronic and breakthrough pain
Fentanyl vs. morphine: differences
Fentanyl does not promote histamine release (itching), affects the cardiovascular system less than morphine, more likely to produce truncal rigidity, VERY HIGH addiction potential (rapid onset, short duration)
More potent and lipid soluble than morphine, allowing for rapid CNS entry
Heroin
Synthetic opioid with very effective oral administration, but also given IV at low doses
Methadone
Metabolism enzymes and duration of methadone
CYP3A4 and CYP2B6, slowly
Onset ~15-30 minutes, half-life 15 H when acute, but 22 H when chronic
Longer DOA than morphine when used chronically
Methadone
ADEs: serious cardiovascular events, like QT prolongation and torsades de pointes
Parenterally, causes euphoria and dependence, but NOT orally
Methadone (CV events when dose is too high)
Effects of partial agonists/mixed agonists compared to full
Less analgesic action, but less respiratory depression
T/F: Partial agonists act as antagonists when in the presence of full agonists.
True, can precipitate withdrawal
What are mixed agonists-antagonists?
Drugs that are primarily agonists are ONE RECEPTOR subtype, but primarily antagonists at ANOTHER RECEPTOR subtype
Kappa agonist, mu antagonist
Nalbuphine (kappa analgesia with ceiling on mu respiratory depression)
Not given orally, similar potency as morphine, CIII
Onset 15 minutes, DOA 4-6 hours
Nalbuphine
Partial agonist at mu receptors, antagonist at kappa receptors
Buprenorphine (mu analgesia & respiratory depression ceiling without kappa side effects)
Not given orally, 30X more potent than morphine, CIII
Buprenorphine
Major use for buprenorphine= opioid dependence and cocaine abuse, much like methadone. How does its use differ from methadone?
Its partial mu agonist (antagonist!) properties precipitates withdrawal in addicts using morphine, heroin, or other full agonists
ADEs: QT prolongation and torsades de pointes
Available IV, IM, buccal film, or subdermal implant
Buprenorphine
Anti-diarrheal agent that uses opioids unwanted constipating effects for therapy!
Loperamide (Imodium)
Can be taken orally, as action is limited to GI tract
Onset 2-4 hours, DOA 10-15 hr
Loperamide
Diphenoxylate difference from loperamide
CV, limited abuse potential (loperamide available OTC, no CNS actions, no abuse)
Antitussive effects, like codeine
NOT analgesic, but can still be abused
Dextromethorphan (Robitussin)
Dextromethorphan MOA (suspected)
CNS NMDA receptor antagonist for antitussive effect
Opioid antagonist for treating opioid-induced constipation
Methylnaltrexone
MOA of methylnaltrexone
Administration
Blocks GI opioid receptors that mediate constipation, SC injection daily
T/F: Methylnaltrexone crosses the blood-brain barrier, but does not significantly contribute to CNS effects.
False, does not cross the BBB
Naloxone MOA
Competitive antagonist at opioid receptors
T/F: naloxone works with the same efficacy for full and partial agonists.
False, works better with full agonists (partial agonists are highly potent and slowly dissociate from receptors)
Opioid antagonist:
Poor oral absorption, IV
Rapid onset 2-5 minutes, DOA 30 minutes- 2 hours
Naloxone (Narcan)
Used to counteract effects of opioids, particularly in life-threatening events of respiratory depression 1. After surgery 2. After overdose
Naloxone (Narcan)
T/F: Naloxone is NOT effective in treating respiratory depression due to non-opioid CNS depressants, like benzodiazepines.
True
Opioid antagonist:
Very effective orally
Long DOA ~ 24 H
Naltrexone
Used for treating opioid dependence…PREVENTING effects of opioids, so requires a strong patient commitment
Naltrexone
Added to opioid products to prevent abuse. When taken orally, no effect. When taken parenterally, blocks opioid receptor (precipitates withdrawal and/or prevents opioid effect)
Naloxone
