Opioids
Classification
Classification by receptor affinity
- Opioid Agonists - Morphine, Codeine, Meperidine, Fentanyl, Sufentanil, Remifentanil, Methadone, Tramadol
- Opioid Agonist/Antagonists & Partial Agonists - Pentazocine, Nalbuphine, Butorphanol, Buprenorphine
- Opioid Antagonists - Nalorphine, Naloxone, Naltrexone, Naltrindole, Nalmefene
Classification by Exogenous Opioids Strength
According to the strength or potency based on the plasma concentrations at which they exert their effects. C50 or the plasma concentration causing a 50% effect.
- Strong Opioids include fentanyl, sufentanil, and remifentanil
- Weak opioids include codeine and tramadol
- Intermediate group includes morphine, methadone, oxycodone, and buprenorphine
Classification by synthetic process
- Naturally occurring compounds - Morphine, Codeine, Thebaine, Papaverine
- Semi-synthetic compounds - Diamorphine (heroin), Dihydromorphone, Buprenorphine, Oxycodone
- Synthetic compounds - Pethidine, Fentanyl, Methadone, Alfentanil, Remifentanil, Tapentadol
Pharmacology
Mu | Delta | Kappa | |
Mu1 - Analgesia
Mu2 - Sedation, vomiting, respiratory depression, pruritis, euphoria, anorexia, urinary retention, physical dependence. |
Analgesia, spinal analgesia | Analgesia, sedation, dyspnoea, psychomimetic effects, miosis, respiratory depression, euphoria, dysphoria, dyspnoea | |
Endogenous Peptides | |||
---|---|---|---|
Enkephalins | Agonist | Agonist | |
ฮฒ-Endorphin | Agonist | Agonist | |
Dynorphin A | Agonist | Agonist | |
Agonists | |||
Morphine | Agonist | Weak Agonist | |
Codeine | Weak Agonist | Weak Agonist | |
Fentanyl | Agonist | ||
Meperidine | Agonist | Agonist | |
Methadone | Agonist | ||
Antagonists | |||
Naloxone | Antagonist | Weak Antagonist | Antagonist |
Naltrexone | Antagonist | Weak Antagonist | Antagonist |
Receptor | Precursor | Peptide |
---|---|---|
DOP | Pro-enkephalin | [Met]-enkephalin
[Leu]-enkephalin |
KOP | Pro-dynorphin | Dynorphin-A
Dynorphin-B |
NOP | POMC
Unknown |
ฮฒ-Endorphin
Endomorphin-1 Endomorphin-2 |
MOP | Pre-pro-nociceptin | N/OFQ |
Mechanisms of Analgesia
Specific Opioids
Opioid Potency Comparison
Opioid Agonists | Potency | Half-life |
---|---|---|
Morphine | 1 | 2 - 3.5 |
Hydromorphone | 5 - 8 | 2 - 3 |
Oxycodone | 1.5 | 2 - 3 |
Methadone | 1 | 24 |
Fentanyl | 100 | 3 - 4 |
Codeine | 0.13 | 3 |
Tramadol | 0.2 | |
Sufentanil | 1000 | |
Alfentanil | 20 | |
Remifentanil | 100 |
Renal Failure
% Normal Dose | Dose (mg) | Dose Interval (hourly) | |
---|---|---|---|
Mild renal impairment (GFR 20-50) | 75% | 2.5-5 | 6 |
Moderate renal impairment (10-20) | 50% | 2.5-5 | 6-8 |
Severe renal impairment (<10) | Use small doses | 1.25-2.5 | 8-12 |
% Normal Dose | Dose (mg) | Dose Interval (hourly) | |
---|---|---|---|
Mild renal impairment (GFR 20-50) | 100% | 50-100 | 6 |
Moderate renal impairment (10-20) | 50% | 50-100 | 6-8 (modify as needed) |
Severe renal impairment (<10) | 50% | 50 | 6-8 (modify as needed) |
% Normal Dose | Dose (mg) | Dose Interval (hourly) | |
---|---|---|---|
Mild renal impairment (GFR 20-50) | 50% | 2.5-5 | 6 |
Moderate renal impairment (10-20) | 25-50% | 2.5-5 | 6-8 (modify as needed) |
Mild renal impairment (<10) | 25-50% | 2.5-5 | 8-12 (modify as needed |
Fentanyl in Renal Failure
Fentanyl is metabolised in the liver to inactive metabolites. It is a useful Strong opioid in renal failure with stable pain. Fentanyl is available in patches.
Liver Failure
There is variable time of onset and analgesic efficacy. They are reasonably well tolerated in adjusted dosing. Ramifentanyl has no hepatic metabolism. Fentanyl patches are a good choice.
Variation in Sensitivity
Polymorphism in human OPRM1 gene which encodes the mu opoid receptor might contribute to variation in sensitivity.
See Also
- โ Modified from Millers Anaesthesia