Analgesia: NSAIDs Flashcards
what are the pros of initiating pharmacotherapy for chronic pain in dogs?
non-pharmacological methods to provide relief from discomfort rarely have rapid onset of action
welfare priority is to manage pain and provide relatively immediate relief
what drug class is useful in chronic pain management?
NSAIDs
what are the benefits of NSAIDs for chronic pain?
widely used
extensive evidence base for efficacy, doses and re-dosing interval
quick onset of action
licensed for use in dogs and cats in the short and long term
what are some of the non-pharmacological methods which can be used to provide pain relief?
supplements
weight loss
diet modification
prescription diets
hydrotherapy
acupuncture
what are some of the concerns associated with the use of NSAIDs for chronic pain management?
side effects
owner anxiety often high
what must be balanced when deciding to use NSAIDs for chronic pain?
management of pain
risk of organ damage
risks associated with different NSAID types
why must chronic pain be managed?
maladaptive
no benefit to the animal
welfare issue
is acute pain adaptive?
yes - provides protective function
what does the feeling of pain comprise?
sensory discriminative aspect being processed by the brain and then interpreted with both physical and emotional components
what are the 2 main ways to define pain?
nociceptive
neuropathic
what is nociceptive pain?
that which originates from tissues that are not part of the nervous system
what is neuropathic pain?
that which originates from the nervous system which is actively damaged
what types of pain are seen in most chronic pain conditions?
nociceptive
neuropathic
when is neuropathic pain alone often seen?
direct damage to the nervous system e.g. full limb amputation where nerves are directly cut
are opioid analgesics effective for neuropathic pain?
no
why are opioid analgesics less effective for patients with neuropathic pain?
when nerves are damaged cholycystokinin (CCK) is released which antagonises opioid mediated analgesia
what is the effect of cholycystokinin (CCK) on opioid analgesia?
antagonises opioid mediated analgesia
what is released when nerves are damaged?
cholycystokinin (CCK)
how do most NSAIDs act?
inhibition of prostaglandin production from arachidonic acid
how do NSAIDs inhibit prostaglandin production?
prevent prostaglandin production from arachidonic acid by inhibiting the cyclooxygenase (COX) enzyme
how do some other NSAIDs act if not on COX?
inhibition of leukotriene production by inhibiting lipoxygenase enzyme
how does grapiprant work?
non-COX inhibiting NSAID which acts as selective antagonist of EP4 receptor
what is an EP4 receptor?
key prostaglandin E2 receptor which predominantly mediates prostaglandin E2-elicited nociception
what enzyme is inhibited by most NSAIDs?
cyclooxygenase (COX)
where in the nervous system do most NSAIDs work?
periphery
where do some NSAIDs work if not in the periphery of the nervous system?
centrally through the dorsal horn
how do NSAIDs that work within the dorsal horns of the spinal cord work?
inhibition of COX but precise mechanism unknown
does evidence suggest that one NSAID is more effective than another?
no but owners may find one suits their pet more than others
what do the adverse effects of NSAIDs relate to?
protective functions of prostaglandins whos production is inhibited
how easily the NSAID can leave circulation and cross into the tissues
what are the types of prostaglandin?
constitutive / housekeeping
inducible
when are inducible prostaglandins produced?
induced by inflammation
what is the role of constitutive / housekeeping prostaglandins?
protective functions
what are the 2 main types of COX enzyme?
COX 1
COX 2
what causes the side effects of NSAIDs?
blockage of production of constitutive prostaglandins which perform protective functions
what type of prostaglandin does COX 1 produce ?
constitutive
what type of prostaglandin does COX 2 produce ?
inducible
what COX enzyme produces constitutive prostaglandins?
1
what COX enzyme produces inducible prostaglandins?
2
what COX selectivity is advantageous in NSAIDS?
COX 2
what is COX 2 selectivity in NSAIDs likely to do?
reduce the risk of renal side effects
reduce GI side effects
what selectivity is seen in all veterinary NSAIDs with perioperative licence?
COX 2
what selectivity does aspirin have?
non-selective
COX 1 and 2
what selectivity does meloxicam have?
COX 2 specific
what is the role of prostaglandins in the GI system?
maintenance of mucosal blood flow
bicarbonate and mucous secretion
epithelialisation
what GI side effects can be seen with NSAIDs?
GI ulceration
bleeding
what is the role of prostaglandins in the renal system?
regulation of glomerular filtration rate (GFR)
renin release
sodium excretion
why is NSAID use during times of hypotension and hypovolaemia dangerous?
vasodilatory prostaglandin may be blocked which could cause decreased GFR leading to kidney injury
when should NSAIDs be given with caution?
under GA especially if hypotensive
what effect on the renal system may NSAIDs have?
water retention and oedema
hypertension
impairment of glomerular filtration in patients with renal disease or hypotension
renal ischemia in patients with hypotension
what is the effect of NSAID therapy on the hepatic system?
induce liver enzymes in normal dogs
is the induction of liver enzymes by NSAIDs in normal dogs significant?
observed but significance unknown
may link to hepatopathy or reduced liver function
what is the effect of NSAID therapy on the central nervous system?
idiosyncratic dullness and lethargy in cats
what is the effect of NSAID therapy on the haemostasis?
older non-COX specific NSAIDs can affect clotting (e.g. asprin)
newer NSAIDs can prolong markers of blood clotting if given long term
are newer NSAIDs linked to clinical signs of bleeding?
no even though blood clotting markers may be prolonged if used long term
what does the risk of NSAID therapy depend on?
individual animal
COX 2 selectivity of NSAID used
when are NSAID adverse events most likely?
in initial doses
what can be done to reduce risk of NSAID side effects for chronic use?
do not exceed licensed dose
do not give 2 NSAIDs concurrently
do not give NSAIDs and corticosteroids concurrently
do not give NSAIDs to animals who are dehydrated / hypotensive
warn owners about side effects
what is essential when discussing NSAID therapy with owners?
warn about side effects
ensure they do not give human OTC formulations
when should NSAIDs be given?
with food only (unless specifically contraindicated - which is basically never)
when is GI ulceration following NSAID administration more likely?
if the pet has pre existing GI ulceration, liver disease and/or is geriatric
is there evidence that combining NSAIDs with gastroprotectents is positive?
very little
why should NSAIDs not be given to hypotensive animals?
action of prostaglandins inhibited by NSAIDs
prostaglandins important in maintaining renal blood flow and GFR during hypotension
what are the possible causes of hypotension that may be seen in patients on NSAIDs?
concurrent disease with V and D
trauma with blood loss or shock
anorexia / not drinking
what signs should owners be told to look out for if their pet is on NSAIDs?
V and D
signs of blood in faeces (smears of fresh or digested)
dullness
anorexia
what should owners be told to do if they are concerned about their pet who is on NSAIDs?
stop treatment and ring the practice
what is the gold standard screening for dogs and cats starting NSAID treatment?
clinical exam
history
haematology and biochem
urinalysis
blood pressure
what is often the only element of screening that is completed before animals begin NSAID treatment?
clinical exam as long as no abnormalities detected
when are side effects from NSAID treatment most likely to be seen?
within first 2 weeks of therapy
when should animals be rechecked following the start of NSAID therapy?
1-2 weeks depending on patient
what does the frequency of monitoring of animals on NSAIDs depend on?
risk of side effects in the individual animal
if patients are high side effect risk should NSAIDs be given?
no
how often should medium side effect risk patients on NSAIDs be monitored?
monthly
what should be involved in recheck of medium side effect risk patients on NSAIDs?
bloods
BP
urinalysis
how often should low side effect risk patients on NSAIDs be checked?
every 3-6 months
what can be used in order to check with owners that the patient is getting the best possible analgesia?
behaviour changes
absence of behaviours
life enjoyment
client specific outcome measures
QOL scoring
what can be done if one NSAID is not tolerated / efficacious enough?
swap to a different one (dogs only)
use adjunctive analgesic therapies (e.g. gabapentin)
use non-pharmacological therapies
what is an example of an adjunctive analgesic that can be used if NSAIDs are not appropriate?
gabapentin
what are non-pharmacological therapies which can aid pain management?
weigh management
diet
physio
accupuncture
