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
Morphine
- Low lipid solubility
- Slow onset action (slow BBB penetration)
- High 1st pass metabolism (LIVER)
- Metabolism CYP450 / glucuronidation
- 40-60% reach systemic circulation
- Renal excretion
Methadone
- Longer duration action
- Limited first pass metabolism
- High bioavailability
- ANTAGONIST NMDA receptor โ Neuropathic pain
- Inhibits re-uptake NA/Serotonin
- Metabolised in Liver / excretes feaces (mostly)
Tramadol
- Phenylpiperidine analogue (Codeine)
- Modulation Serotonin and NA reuptake
- Less Respiratory depression
- Less GIT S/E (for comparable analgesic effect)
Tapentadol
- MOP receptor agonist
- NA reuptake inhibition
- Comparable opioid potency to Oxycodone
Ramifentanyl
- High Lipid solubility
- Rapid extra-hepatic metabolism
Codeine
- โPro-drugโ
- Converted to morphine for effect
- 5-10% population unable to convert / ineffective
Pethidine (Meperidine)
- Relative weak opioid (10% morphine)
- ++ anticholinergic effects
- Neurotoxic S/E (Particularly in renal disease)
- Delerium
- Excitation
- Seizures
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 |
Converting | Ratio | Example | ||
---|---|---|---|---|
from | to | |||
Codeine oral | morphine oral | 10:1 | Codeine 60mg oral | -> morphine 6mg oral |
Tramadol oral | morphine oral | 10:1 | Tramadol 100mg oral | -> morphine 10mg oral |
Dihydrocodeine oral | Morphine oral | 10:1 | Dihydrocodeine 100mg oral | -> Morphine 10mg oral |
Oxycodone oral | Morphine oral | 1:1.5 | Oxycodone 10mg oral | -> Morphine 15mg oral |
Morphine oral | Oxycodone oral | 2:1 | Morphine 20mg oral | -> Oxycodone 10mg oral |
Morphine oral | Morphine subcut | 2 to 3:1 | Morphine 30mg oral | -> Morphine 10-15mg subcut |
Oxycodone oral | Oxycodone subcut | 2:1 | Oxycodone 20mg oral | -> Oxycodone 10mg subcut |
Oxycodone subcut | Morphine subcut | 1:1 | Oxycodone 10mg subcut | -> Morphine 10mg subcut |
Morphine oral | Fentanyl subcut | 100:1 | Morphine 30mg oral | -> Fentanyl 0.3mg subcut |
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