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
What are the actions of morphine?
- CNS: analgesia, euphoria (increase sense of well-being), sedation/ drowsiness/coma, cough suppression, nausea and vomiting, miosis(stimulation of Edinger-westphal nucleus of CN 3)
- CVS: depression of vasomotor centre at higher doses and mast cell degranulation so results in hypotension
- Respiratory: respiratory depression and alveolar hypoventilation = respiratory acidosis
- GI: reduced motility and secretions so result in constipation, spasm of sphincter of Oddi
- GU: urinary retention
What are the problems with long term morphine use?
- tolerance ( ie reduce responsiveness to the drug and requiring higher doses to achieve the same effect) and dependence ( sudden termination of drug can induce a withdrawal effect) can develop.
- DOP seems to be responsible in causing the withdrawal effect
How is morphine being eliminated?
- conjugated with glucoronic acid to morphine-3-glucoronide that is excreted in urine
- need to adjust dosage with patients with hepatic or renal impairment.
- liver usually makes the drugs which are more water soluble for kidneys to excrete
Coedine
- a prodrug which can be metabolised to the active form (morphine and other metabolites)
- 1 in 10 people lack CY2D6 enzyme in liver so cannot metabolite coedine into morphine. This means there’s a less analgesic effect
- often used in combination with other analgesic eg. co-codamol
- loperamide (related drug) is used in the treatment of severe diarrhoea
Fentanyl (Fentanil)
- synthetic
- 80-100 times more potent than morphine
- given IV so can have a rapid onset of analgesic effect but short duration
- used for intra and post operative pain treatment
- dose in micrograms
Methadone
- slow metabolism and fat soluble= long acting
- maintenance therapy for patients with opioid addictions
- can block the euphoria effect if IV heroin is used
Naloxone (Narcan)
- usually for IV or intramuscular
- can reverse opioid overdose within 1-2 mins
- last for 20-30 mins, while half life of morphine is 2-3 hours so continuous infusion of naloxone is required until morphine wears off
