Opioids Flashcards
What is an opiate?
An alkaloid derived from the poppy - papaver somniferum
What are examples of opiates?
Morphine, codeine, papaverine, thebaine
What is the structure-activity relationship of morphine?
The tertiary form of nitrogen appears to be crucial to he analgesic effect, making nitrogen quaternary appears to decrease the analgesic effect greatly (it can’t pass into the CNS)
- the tertiary nitrogen permits receptor anchoring
- extending the side chain generates antagonists
Changes to the methyl group also decrease analgesic effect, creating antagonists
What is the structure-activity relationship of Codeine and Heroin compared to Morphine
The hydroxyl group at poisiton 3 is required for binding. Unlike Morphine, Codeine and Heroin don’t have these therefore must undergo some metabolism to become activated and reveal it’s hydroxyl group
-> also the hydroxyl group at position 6 increases the lipophilicity of the drug 10 fold when oxidised form but heroin doesn’t have this
What is different in methadone and fentanyl compared to morphine?
Methadone has a tertiary nitrogen and fentanyl has 2
What are routes of administration of opiods?
Oral and IV
List the lipid solubility of the following in order of most soluble to least: Heroin, Morphine, Methadone/Fentanyl. What is the link between lipid solubility and potency?
Methadone/Fentanyl»_space; Heroin > Morphine
More lipid soluble, more potent
How is morphine metabolised in the body
Via morphine-6-glucuronide, u-receptor agonist (potent analgesic activity)
Morphine has a greater affinity for u2 receptors than M6G which is related to adverse effects
What kind of metabolism do better tolerated opiods often undergo?
CYP mediated metabolism
How is codeine metabolised in the body
5-10% of codeine is metabolised into morphine, there are also activating and inactivating enzymes in the liver:
- activation (slow) via CYP-2D6 (O-dealkylation) can have polymorphism so doesn’t respond to codeine
- deactivation via CYP-3A4
What enzymes metabolise most opioids in the liver?
CYP-2D6 and CYP-3A4
Give examples of opioid peptides
endorphins
enkephalins
dynorphins
neoendorphins
What opiate receptor do endorphins act on and what effect do they have?
Mu/Delta receptors in the thalamus, amygdala, nucleus accumbens, PAG
Affecting pain, mood, CVS
What opiate receptor do enkephalins act on and what effect do they have?
Delta in nucleus accumbens, cerebral cortex and amygdala
Affecting pain, mood, CVS
What opiate receptor do dynorphins act on and what effect do they have?
Kappa in hypothalamus
Affecting appetite