lecture 22: opioids Flashcards
potency def
the amount of drug needed to produce a given effect
examples of affinity, potency and efficacy in opioids
- Naloxone = high affinity for the u-opioid receptor but no efficacy
- buprenorphine = lower affinity than naltrexone and low efficacy
- morphine = lower affinity than naltrexone and high efficacy
- fentanyl = lower affinity than naltrexone and high efficacy
what are the three main opioid receptors
- u-opioid receptor
- target for analgesic drugs
- Gi-coupled GPCR - S-opioid receptor
- k-opioid receptor
- causes dysphoric (opposite of euphoria) hallucinations
what is a analgesic drug
drug that relieves pain without impairing other senses
what is a anaesthetic
drug that relieves pain and impairs other senses
two main types of analgesics
- NSAID
non-steroidal anti-inflammatory drug - opioids
- drugs with similar effects as morphine, which comes from opium
- natural and synthetic forms
what are the two main types of pain
- nociceptive
- neuropathic
nociceptive pain
- from direct stimulation of “pain receptors” - nociceptors
- transmission along normal/healthy nerves
- sharp, aching, throbbing pain
- tissue injury apparent
- treated with opioids and other analegesics such as NSAIDs
neuropathic pain
- from injured peripheral or central nerves
- can result from trauma eg: trigeminal nerve pain can result from facial trauma
- pain can occur without observable injury eg: burning, tingling, shooting, stabbing, electrical pain
- management is different than for nociceptive pain
what is acute pain
- identified event = injury or infection
- resolves in days or weeks
- usually nociceptive
what is chronic pain
- cause not always easily identified
- often involves multiple factors
- indeterminate duration
- nociceptive and/or neuropathic
treatment for acute pain
- short term treatment with an analgesic with the required strength to relieve pain
- usually an NSAID or opioid
- opioids are better because you only need to take them for a short period of time, reduces risk of dependence
treatment for chronic pain
- treatment requires minimization of the adverse effects of long term use of analgesics
- neuropathic pain may not be reduced with NSAIDs
how is opioid analgesia used for different types of pain
- used for both acute and chronic pain
- may be more effective for nociceptive than neuropathic pain
opioid receptors mechanisms
- u receptors (MOP)
- Gi coupled inhibitory GPCRs
- responsible for most of the analgesic effects, as well as the important adverse effects
- opioid analgesics are MOP agonists
- can cause hyperpolarisation of neuron membrane potential
–> decreases neurotransmission - k-opioid (KOP)
- k-opioid agonists can cause psychedelic effects
- Gi coupled inhibitory GPCRs
- salvinorum A
- ibogaine - S - opioid receptor
- Gi coupled inhibitory GPCRs
examples of agonists selectivity for opioid analgesics
- morphine
u = +++
k = +
S = + - methadone
u = +++
k = —
S = ___ - fentanyl
u = +++
k = —
S = +
how do opioids cause analgesia
–> opioid receptors are the natural targets for endogenous opioids
- endorphins are the primary u-opioid receptor endogenous agonists
- activated by nociceptive and other inputs
–> act in the brain and the spinal cord as a pain inhibitory system
- block the transmission and perception of pain
- Gi coupled inhibitory GPCRs stop neurons from sending pain signals
what is the role of the thalamus
acts as a relay service in the brain, all senses get sent here first, filters out different types of sensory stimuli, goes from thalamus to cortex where sensory signals are processed and perception of senses occurs
how is pain perceived in the brain
- pain signals travel up the spinal cord into the thalamus
- thalamus sends pain signals to the somatosensory cortex
- this is where pain perception occurs
opioid receptors in the brain
- opioid receptors are highly concentrated in the thalamus
–> thalamus is a relay station for sensation in the brain –> blocks transmission of pai n - opioid receptors in the VTA/nucleus accumbens
–> responsible for opioid euphoria
–> also play a role in social connection - opioid receptors in the brainstem suppress breathing response
–> decrease CO2 sensitivity
opioid tolerance
- tolerance to morphine can occur within 12-24 hrs of treatment
- with high dose treatment, ED50 can increase 5-fold over 3-4 days
- tolerance to euphoria, analgesia, respiratory depression but not constipation
- addicts can take very high doses (50-100x therapeutic) with no respiratory depression
opioid dependence
- abstinence produces a withdrawal syndrome (fever, sweating, nausea, diarrhea, insomnia)
- dependence is most severe with short acting, potent opioids
eg: diamorphine (heroin) - risk is lower with weak opioids (codeine)
- mediated through u-receptor
tramadol
= an opioid with a complex mechanism of action
- u-opioid receptor agonist prodrug
(metabolised by CYP2D6)
- serotonin and norepinephrine reuptake inhibitor (causes a lot of different physiological effects)
- prescribed for moderate-severe pain
- exhibits a dependence rate of 10% for people that abuse tramadol
abuse = people who do not take it as prescribed
dependence of prescription opioids
- meta-analysis have found the dependence risk of prescription opioids to be 3.3-4.7% (not very high, need to factor in how many people are prescribed opioids)
–> strong opioids were associated with a lower incidence of dependence (0.7%) than weak opioids (5.5%) or a mix (6.1%)
–> opioids prescribed for >3months were associated with a significantly lower incidence of dependence (2.3%)
