Opioids

Question 0

What does the word ‘narcotic’ mean?

Answer 0

• stupor (state of near unconscious) including painkiller

Question 1

What does the word ‘analgesic’ mean?

Answer 1

• painkiller, drug used to relieve pain

Question 2

What does the word ‘opiate’ mean?

Answer 2

• DRUGS derived from the juice of the opium poppy

Question 3

What does the word ‘opioid’ mean?

Answer 3

• drugs (includes opiates) that act at the opioid receptors

- it usually means synthetic whereas opiate refers to natural substances

Question 4

How is pain transmitted from receptors to higher centres?

Answer 4

• 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

Question 5

How is pain being modulated in the descending pathway?

Answer 5

• 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

Question 6

What are the three families of endogenous opioid peptides?

Answer 6

• dynorphins, enkephalins and endorphins

Question 7

Morphine

Answer 7

• first alkaline to be extracted from opium

- name after the Greek god of dreams because it causes tendency to sleep

Question 8

Opioid Receptors

Answer 8

• 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

Question 9

Mu opioid receptor (MOP)

Answer 9

• 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

Question 10

What are the full mu opioid receptor agonists?

Answer 10

• morphine, diamorphine(heroine), codeine, fentanyl(fentanil), methadone
• heroine could be used for acute left ventricular failure-> reduces preload and anxiety

Question 11

What are the examples of partial agonists for MOP?

Answer 11

• buprenorphine

- has agonist activity (partially) but will antagonise full agonists and cause withdrawal in opioid dependence

Question 12

What are the examples for MOP antagonists?

Answer 12

• Naloxone, important use for opioid overdose

Question 13

What are the routes of opioid administration? (6)

Answer 13

• intranasal-> for dimorphine, usually for children
• intramuscular
• transdermal
• orally
• intravenous
• epidural space

Question 14

What are the main problems with administrating opioids orally?

Answer 14

• 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

Question 15

What are the actions of morphine?

Answer 15

• 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

Question 16

What are the problems with long term morphine use?

Answer 16

• 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

Question 17

How is morphine being eliminated?

Answer 17

• 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

Question 18

Coedine

Answer 18

• 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

Question 19

Fentanyl (Fentanil)

Answer 19

• 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

Question 20

Methadone

Answer 20

• slow metabolism and fat soluble= long acting
• maintenance therapy for patients with opioid addictions
• can block the euphoria effect if IV heroin is used

Question 21

Naloxone (Narcan)

Answer 21

• 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