Opioids Flashcards
What does the word ‘narcotic’ mean?
- stupor (state of near unconscious) including painkiller
What does the word ‘analgesic’ mean?
- painkiller, drug used to relieve pain
What does the word ‘opiate’ mean?
- DRUGS derived from the juice of the opium poppy
What does the word ‘opioid’ mean?
- drugs (includes opiates) that act at the opioid receptors
- it usually means synthetic whereas opiate refers to natural substances
How is pain transmitted from receptors to higher centres?
- via spinothalamic tract
- first order neurones receptors for noxious stimuli cell bodies are found in dorsal root ganglion
- fibres= A delta myelinated and faster conducting; C fibres is unmyelinated
- terminates in the dorsal horn of spinal cord
- second order neurones: ascends in contralateral Spinothalamic tract and terminates in the thalamus
- third order neurones: terminate in the post-central gyrus of the cerebral cortex
How is pain being modulated in the descending pathway?
- Descending fibres from the higher centres eg. periaqueductal grey matter can inhibit transmission in substantia gelatinosa
- there are different types of fibres involved: enkephalinergic fibres, noradrenergic fibres, serotonergic fibres and local release of dynorphin
->this descending pain modulation is activated by opioids
What are the three families of endogenous opioid peptides?
- dynorphins, enkephalins and endorphins
Morphine
- first alkaline to be extracted from opium
- name after the Greek god of dreams because it causes tendency to sleep
Opioid Receptors
- there are different subclasses: mu opioid receptor (MOP); kappa opioid receptor (KOP); delta opioid receptor (DOP)
- they can all be antagonised by naloxone
- another type is Nocieptin receptor (NOP)
- cannot be antagonised by naloxone
Mu opioid receptor (MOP)
- it is a G-protein coupled receptor which has 7 transmembrane domains
- this is a crucial receptor in order to respond to morphine
- mechanism: morphine binds and causes voltage sensitive calcium channels to close; increased potassium efflux and hyperpolarisation; inhibit adenylate cyclase and reduce cAMP
What are the full mu opioid receptor agonists?
- morphine, diamorphine(heroine), codeine, fentanyl(fentanil), methadone
- heroine could be used for acute left ventricular failure-> reduces preload and anxiety
What are the examples of partial agonists for MOP?
- buprenorphine
- has agonist activity (partially) but will antagonise full agonists and cause withdrawal in opioid dependence
What are the examples for MOP antagonists?
- Naloxone, important use for opioid overdose
What are the routes of opioid administration? (6)
- intranasal-> for dimorphine, usually for children
- intramuscular
- transdermal
- orally
- intravenous
- epidural space
What are the main problems with administrating opioids orally?
- poorly absorbed and high first pass metabolism by gut wall and liver
- oral bioavailiablity 20%
- oromorph is used for cancer pain and it contains morphine sulphate