Analgesia: Opioids Flashcards
what are opioids most commonly used for?
perioperative analgesia
why are opioids less commonly used for chronic pain management?
poor oral bioavailability of opioids
in what pain states are opioids less effective?
neuropathic (e.g. brachial plexus avulsion where there is significant nerve damage)
what are the main pharmacological effects of opioids in mammals?
analgesia
sedation
excitation
bradycardia
respiratory depression
nausea and vomiting
decreased GI motility
varied urinary effects
antitussive
minimal effect on inotropy
effects on the pupil
when is excitation most often seen following opioid administration?
in pain free animals when giving as a premed
when does opioid induced bradycardia have most effect?
when the patient is anaesthetised
why do opioids cause respiratory depression?
depresses bodies response to rising CO2 so that respiratory drive now comes from lack of oxygen which is physiologically abnormal
when are nausea and vomiting most commonly seen following opioid administration?
when used as a premed in pain free animals
what are the main urinary effects seen with opioids?
increased or decreased micturition
reduced sensitivity to urge to urinate
what is inotropy?
heart contractility
what are the effects of opioids on the pupil in dogs?
miosis
what are the effects of opioids on the pupil in cats?
mydriasis
how do opioids have effect within the body?
mimic naturally occurring opioid peptides (neurotransmitters)
what are the endogenous naturally occurring opioid peptides?
beta-endorphin
leucine and methionine enkephalins
dynorphins
where are opioid receptors mostly found?
brain and spinal cord
what are the main opioid receptors found in the brain and spinal cord?
mu
kappa
delta
NOP
what does NOP stand for?
nociceptin opioid peptide
what is the endogenous ligand for the NOP receptor?
nociceptin
what are the subtypes of the delta opioid receptors?
delta 1
delta 2
where are delta opioid receptors located?
brain
peripheral sensory neurones
what is the function of delta opioid receptors?
analgesia
antidepressant
convulsant
physical dependence
what can be modulated by delta opioid receptors?
mu-opioid receptor-mediated respiratory depression
what types of kappa opioid receptor are there?
kappa 1
kappa 2
kappa 3
where are kappa opioid receptors located?
brain
spinal cord
peripheral sensory neurones
what is the function of kappa opioid receptors?
analgesia
anticonvulsant
depression
dissociation/hallucinogenic
diuresis
miosis
dysphoria
neuroprotection
sedation
stress
what opioid receptor provides the most effective analgesia?
mu
what types of mu receptor are there?
mu 1
mu 2
mu 3
where are mu opioid receptors found?
brain
spinal cord
peripheral sensory neurones
intestinal tract
what are the functions of mu 1 receptors?
analgesia
physical dependance
what are the functions of mu 2 receptors?
respiratory depression
miosis
euphoria
reduced GI motility
physical dependance
what are the functions of mu 3 receptors?
possible vasodilation
where can morphine be obtained from?
directly extracted from opium which is taken from the fried latex of poppy seed pods
how are opioids such as methadone and pethidine produced?
synthetically developed
where do all commercially available opioid drugs act?
opioid receptors
what information will suggest how an opioid drug will act?
receptors or receptor subtypes they act at
mechanism of action at these receptors
pharmacokinetics
species differences
what does the pharmacokinetics of a drug describe?
what the body does with the drug, how they are taken up by the body, transported and broken down
what are the main mechanisms of action at opioid receptors?
full agonist
partial agonist
mixed agonist-antagonist
antagonist
what mechanism of action at an opioid receptor provides the most effective analgesia?
full agonist
what type of opioids provide the most effective analgesia?
full mu agonist
what drugs are examples of full agonists?
methadone
fentanyl
what drugs are examples of partial opioid agonists?
buprenorphine
what drugs are examples of mixed agonist-antagonist?
butorphanol
what drug is an example of an opioid antagonist?
naloxone
what is the difference between full and partial agonists?
full agonists bind to and activate a receptor with the maximum response that an agonist can elicit at that receptor
partial agonists bind to and activate a receptor but only have partial efficacy even if they bind to all receptors
what does the potency of a drug describe?
how much of a drug is required to have an effect
what does the efficacy of a drug describe?
how much effect of the drug is seen at full receptor occupancy
why do the formulation concentrations of methadone and buprenorphine differ so much?
due to differences in potency - buprenorphine is more potent so requires less mg/kg to see effect
why is methadone better for severe pain than buprenorphine?
methadone is more effective than buprenorphine
describe the efficacy and potency of fentanyl
highly effective and potent making overdose likely
what are the routes of administration for opioids?
IM
SC
IV
OTM
transdermal
epidural/spinal
(not all by all routes)
what opioid cannot be administered by IV injection?
pethidine
why must pethidine not be administered IV?
risk of allergic reaction
what route of administration of opioids gives poor bioavailability?
oral
why does oral administration of opioids lead to poor bio-availability?
significant first pass metabolism of opioids by liver so are broken down before reaching site of action
what route of administration of buprenorphine may be less efficacious in cats?
SC
why does oral transmucosal administration of opioids provide better bioavailability than oral?
bypass of liver due to absorption across oral mucous membranes rather than swallowing
why are opioids limited in use for chronic pain?
not useful when administered orally due to poor bioavailablity
what are the advantages and disadvantages of IV administration of opioids?
rapid onset, reliable uptake, painless with no volume restriction
need IV access
what are the advantages and disadvantages of IM administration of opioids?
reliable uptake
painful, especially high volumes
what are the advantages and disadvantages of SC administration of opioids?
easy to perform
unreliable uptake
what are the advantages and disadvantages of OTM administration of opioids?
easy to perform
only certain opioids (buprenorphine in cats)
what are the advantages and disadvantages of transdermal administration of opioids?
good for chronic use
no licenced products
what are the advantages and disadvantages of epidural/spinal administration of opioids?
very effective analgesia for right cases (usually intraoperative analgesia)
no licenced opioids, technically difficult
what needs to be considered when planning what analgesic to use?
efficacy
duration of action
potential for adverse events
what must be balanced when deciding whether to use a more efficacious opioid?
need for severe pain management balanced against potential side effects