Opiods Flashcards
What are the components of pain
Psychological: perception of pain affected by mood
Physiological: perception of pain affected by nociceptors
How do opioids affect pain
Produce euphoria thus increase pain tolerance
Act on opioid receptors thus reduce pain transmission
What is the process of pain pathway
Pain detected by nociceptor
Signal transmission down C fibres
C fibres synapse with secondary neurones in dorsal horn (substantia gelatinosa)
Release of neurotransmitter Substance P
Pain transmitted to Thalamus + PMC and perceived
What are the types of gate control of pain
By A fibres via Inhibitory interneurones
Descending inhibition via inhibitory interneurones
Inhibitory interneurones release enkephalins that inhibit pain transmission bw C fibres and secondary neurones
What are the types of endogenous opioids
Enkephalins
Endorphins
Dynorhin
What are the types of opioid receptors
Where are they found
Mu - supraspinal (brain)
Kappa - spinal
Delta - widespread
What is the mechanism of action of opioids
Opioids bind to opioid receptors
Opioid receptors are GPCRs
Expressed pre-synaptic and post-synaptic membranes of pain neurones
1. +very coupled to K channels - hyperpolarisation, inhibit Ca influx
2. Negatively coupled to AC - reduced cAMP, inhibit Ca influx
3. Directly inhibit Ca channels - inhibit Ca influx
Reduced intracellular[Ca] - reduce Substance P release
What are the different pharmacodynamics of opioids
Agonist - morphine
Partial agonist - buprenorphine
Agonist/antagonist - Nalbuphine
Antagonist - Naloxone
What is mechanism of action of Partial agonists
Have lower efficacy - produce partial response on binding
But has higher affinity than agonists - Acts as an antagonist of agonists
What is mechanism of action of Nalbuphine
Agonist at delta receptor
Partial agonist at kappa receptor
Antagonist at mu receptor
Thus produce analgesia without euphoric effects
What is route of admin of opioids
Oral
SC
Slow IV
What are PK properties of morphine
25% oral bioavailability - oral admin not effective
T0.5 - 4 hours
Phase II metabolism (glucuronidation)
MGG is active metabolite
Metabolites have long T0.5 - metabolites in urine to screen for opioid misuse
What are PK properties of diamorphine
90% oral bioavailability
Lipid soluble
Cross BBB
T1/2 - 5mins
Metabolism -
ester bond hydrolysed rapidly
Convert to active metabolite - morphine
Thus allows high dose of morphine to enter CNS rapidly
What are PK properties of methadone
T1/2 - 20hrs
Thus used for chronic pain and maintenance therapy for opioid dependence
What are PK properties of codeine
T1/2 - 2hrs
CYP 206 metabolism - polymorphic thus efficacy varies in population
What are clinical indications of opioids
Analgesia:
Moderate - severe pain
Especially Chronic or visceral pain
What are indications of morphine
Analgesia - palliative for Terminal illness
Diarrhoea
What are indications of diamorphine
Analgesia - terminal illness, epidural
What are indications for methadone
Analgesia
Maintenance therapy for opioid dependence (longer acting but less euphoric opioid)
What are indications of Tramadol
Analgesia
Serotonergic and NA-ergic activity
Thus analgesia with euphoric effects
What are indications of Tapentadol
Analgesia:
Mu receptor specific
NA reuptake inhibitor
Thus analgesia with euphoric effects
What are artificial opioids
Fentanyl
Pethidine
What are indications of Fentanyl
Anaesthesia
1000x more potent
What are indications of Pethidine
What caution do you need to take
Analgesia in labour
Do not give frequent repeat dosing - risk of convulsions
What are indications of naloxone
Opioid overdose
Respiratory depression
How do you administer naloxone
IV
Repeat dosing every 2 mins until response
What receptor is the side effects mediate by
Mu
What are the side effects of opioids
N+V Constipation Miosis Hyperalgesia Drowsiness Hypotension Respiratory depression Tolerance Dependence
What medications do you prescribe with opioids to minimise side effects
Anti emetics
Laxatives
Why do you get respiratory depression with opioid overdose
Reduced sensitivity to pCO2
Thus reduced signalling in response to change in pH/pCO2
Occurs in dependence + overdose
What are the types of new endogenous opioid receptors
Opioid receptor like 1:
GPCR -vely coupled to AC
What are the types of new endogenous opioid peptides
What do they bind to
Nociceptin - ORL1
Endomorphine 1
Endomorphine 2
Mu receptors with higher affinity + efficacy
What are medico-legal implications of opioids
Some opiates are Controlled drugs
Schedule 5: diamorphine, morphine, pethidine
Schedule 2: codeine
There are prescribing requirements
What are prescribing requirements of opioids
Must write down: Dose If preparations - form + strength If liquids - volume, dosing units In words and figures
