Opioids

This article is a stub.

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^[1]
Endogenous Peptides
	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
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

Mechanisms of Analgesia

Specific Opioids

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

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.