Opioids

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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

Analgesia Effect of Opioid Receptors

	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
β-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

Opioid receptors and their endogenous ligands and precursors

Receptor	Precursor	Peptide
DOP	Pro-enkephalin	[Met]-enkephalin [Leu]-enkephalin
KOP	Pro-dynorphin	Dynorphin-A Dynorphin-B
NOP	POMC Unknown	β-Endorphin Endomorphin-1 Endomorphin-2
MOP	Pre-pro-nociceptin	N/OFQ

Opioid Potency Comparison

Opioid Potency and Half-life

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

Conversion Ratios and Examples

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

Morphine in 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

Tramadol in Renal Failure

	% 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)

Oxycodone in Renal Failure

	% 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

Opioid Deprescribing