Analgesia: NSAIDs

Question 1

what are the pros of initiating pharmacotherapy for chronic pain in dogs?

Answer 1

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

Question 2

what drug class is useful in chronic pain management?

Answer 2

NSAIDs

Question 3

what are the benefits of NSAIDs for chronic pain?

Answer 3

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

Question 4

what are some of the non-pharmacological methods which can be used to provide pain relief?

Answer 4

supplements
weight loss
diet modification
prescription diets
hydrotherapy
acupuncture

Question 5

what are some of the concerns associated with the use of NSAIDs for chronic pain management?

Answer 5

side effects
owner anxiety often high

Question 6

what must be balanced when deciding to use NSAIDs for chronic pain?

Answer 6

management of pain
risk of organ damage
risks associated with different NSAID types

Question 7

why must chronic pain be managed?

Answer 7

maladaptive
no benefit to the animal
welfare issue

Question 8

is acute pain adaptive?

Answer 8

yes - provides protective function

Question 9

what does the feeling of pain comprise?

Answer 9

sensory discriminative aspect being processed by the brain and then interpreted with both physical and emotional components

Question 10

what are the 2 main ways to define pain?

Answer 10

nociceptive
neuropathic

Question 11

what is nociceptive pain?

Answer 11

that which originates from tissues that are not part of the nervous system

Question 12

what is neuropathic pain?

Answer 12

that which originates from the nervous system which is actively damaged

Question 13

what types of pain are seen in most chronic pain conditions?

Answer 13

nociceptive
neuropathic

Question 14

when is neuropathic pain alone often seen?

Answer 14

direct damage to the nervous system e.g. full limb amputation where nerves are directly cut

Question 15

are opioid analgesics effective for neuropathic pain?

Answer 15

no

Question 16

why are opioid analgesics less effective for patients with neuropathic pain?

Answer 16

when nerves are damaged cholycystokinin (CCK) is released which antagonises opioid mediated analgesia

Question 17

what is the effect of cholycystokinin (CCK) on opioid analgesia?

Answer 17

antagonises opioid mediated analgesia

Question 18

what is released when nerves are damaged?

Answer 18

cholycystokinin (CCK)

Question 19

how do most NSAIDs act?

Answer 19

inhibition of prostaglandin production from arachidonic acid

Question 20

how do NSAIDs inhibit prostaglandin production?

Answer 20

prevent prostaglandin production from arachidonic acid by inhibiting the cyclooxygenase (COX) enzyme

Question 21

how do some other NSAIDs act if not on COX?

Answer 21

inhibition of leukotriene production by inhibiting lipoxygenase enzyme

Question 22

how does grapiprant work?

Answer 22

non-COX inhibiting NSAID which acts as selective antagonist of EP4 receptor

Question 23

what is an EP4 receptor?

Answer 23

key prostaglandin E2 receptor which predominantly mediates prostaglandin E2-elicited nociception

Question 24

what enzyme is inhibited by most NSAIDs?

Answer 24

cyclooxygenase (COX)

Question 25

where in the nervous system do most NSAIDs work?

Answer 25

periphery

Question 26

where do some NSAIDs work if not in the periphery of the nervous system?

Answer 26

centrally through the dorsal horn

Question 27

how do NSAIDs that work within the dorsal horns of the spinal cord work?

Answer 27

inhibition of COX but precise mechanism unknown

Question 28

does evidence suggest that one NSAID is more effective than another?

Answer 28

no but owners may find one suits their pet more than others

Question 29

what do the adverse effects of NSAIDs relate to?

Answer 29

protective functions of prostaglandins whos production is inhibited how easily the NSAID can leave circulation and cross into the tissues

Question 30

what are the types of prostaglandin?

Answer 30

constitutive / housekeeping inducible

Question 31

when are inducible prostaglandins produced?

Answer 31

induced by inflammation

Question 32

what is the role of constitutive / housekeeping prostaglandins?

Answer 32

protective functions

Question 33

what are the 2 main types of COX enzyme?

Answer 33

COX 1 COX 2

Question 34

what causes the side effects of NSAIDs?

Answer 34

blockage of production of constitutive prostaglandins which perform protective functions

Question 35

what type of prostaglandin does COX 1 produce ?

Answer 35

constitutive

Question 36

what type of prostaglandin does COX 2 produce ?

Answer 36

inducible

Question 37

what COX enzyme produces constitutive prostaglandins?

Answer 37

1

Question 38

what COX enzyme produces inducible prostaglandins?

Answer 38

2

Question 39

what COX selectivity is advantageous in NSAIDS?

Answer 39

COX 2

Question 40

what is COX 2 selectivity in NSAIDs likely to do?

Answer 40

reduce the risk of renal side effects reduce GI side effects

Question 41

what selectivity is seen in all veterinary NSAIDs with perioperative licence?

Answer 41

COX 2

Question 42

what selectivity does aspirin have?

Answer 42

non-selective COX 1 and 2

Question 43

what selectivity does meloxicam have?

Answer 43

COX 2 specific

Question 44

what is the role of prostaglandins in the GI system?

Answer 44

maintenance of mucosal blood flow bicarbonate and mucous secretion epithelialisation

Question 45

what GI side effects can be seen with NSAIDs?

Answer 45

GI ulceration bleeding

Question 46

what is the role of prostaglandins in the renal system?

Answer 46

regulation of glomerular filtration rate (GFR) renin release sodium excretion

Question 47

why is NSAID use during times of hypotension and hypovolaemia dangerous?

Answer 47

vasodilatory prostaglandin may be blocked which could cause decreased GFR leading to kidney injury

Question 48

when should NSAIDs be given with caution?

Answer 48

under GA especially if hypotensive

Question 49

what effect on the renal system may NSAIDs have?

Answer 49

water retention and oedema hypertension impairment of glomerular filtration in patients with renal disease or hypotension renal ischemia in patients with hypotension

Question 50

what is the effect of NSAID therapy on the hepatic system?

Answer 50

induce liver enzymes in normal dogs

Question 51

is the induction of liver enzymes by NSAIDs in normal dogs significant?

Answer 51

observed but significance unknown may link to hepatopathy or reduced liver function

Question 52

what is the effect of NSAID therapy on the central nervous system?

Answer 52

idiosyncratic dullness and lethargy in cats

Question 53

what is the effect of NSAID therapy on the haemostasis?

Answer 53

older non-COX specific NSAIDs can affect clotting (e.g. asprin) newer NSAIDs can prolong markers of blood clotting if given long term

Question 54

are newer NSAIDs linked to clinical signs of bleeding?

Answer 54

no even though blood clotting markers may be prolonged if used long term

Question 55

what does the risk of NSAID therapy depend on?

Answer 55

individual animal COX 2 selectivity of NSAID used

Question 56

when are NSAID adverse events most likely?

Answer 56

in initial doses

Question 57

what can be done to reduce risk of NSAID side effects for chronic use?

Answer 57

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

Question 58

what is essential when discussing NSAID therapy with owners?

Answer 58

warn about side effects ensure they do not give human OTC formulations

Question 59

when should NSAIDs be given?

Answer 59

with food only (unless specifically contraindicated - which is basically never)

Question 60

when is GI ulceration following NSAID administration more likely?

Answer 60

if the pet has pre existing GI ulceration, liver disease and/or is geriatric

Question 61

is there evidence that combining NSAIDs with gastroprotectents is positive?

Answer 61

very little

Question 62

why should NSAIDs not be given to hypotensive animals?

Answer 62

action of prostaglandins inhibited by NSAIDs prostaglandins important in maintaining renal blood flow and GFR during hypotension

Question 63

what are the possible causes of hypotension that may be seen in patients on NSAIDs?

Answer 63

concurrent disease with V and D trauma with blood loss or shock anorexia / not drinking

Question 64

what signs should owners be told to look out for if their pet is on NSAIDs?

Answer 64

V and D signs of blood in faeces (smears of fresh or digested) dullness anorexia

Question 65

what should owners be told to do if they are concerned about their pet who is on NSAIDs?

Answer 65

stop treatment and ring the practice

Question 66

what is the gold standard screening for dogs and cats starting NSAID treatment?

Answer 66

clinical exam history haematology and biochem urinalysis blood pressure

Question 67

what is often the only element of screening that is completed before animals begin NSAID treatment?

Answer 67

clinical exam as long as no abnormalities detected

Question 68

when are side effects from NSAID treatment most likely to be seen?

Answer 68

within first 2 weeks of therapy

Question 69

when should animals be rechecked following the start of NSAID therapy?

Answer 69

1-2 weeks depending on patient

Question 70

what does the frequency of monitoring of animals on NSAIDs depend on?

Answer 70

risk of side effects in the individual animal

Question 71

if patients are high side effect risk should NSAIDs be given?

Answer 71

no

Question 72

how often should medium side effect risk patients on NSAIDs be monitored?

Answer 72

monthly

Question 73

what should be involved in recheck of medium side effect risk patients on NSAIDs?

Answer 73

bloods BP urinalysis

Question 74

how often should low side effect risk patients on NSAIDs be checked?

Answer 74

every 3-6 months

Question 75

what can be used in order to check with owners that the patient is getting the best possible analgesia?

Answer 75

behaviour changes absence of behaviours life enjoyment client specific outcome measures QOL scoring

Question 76

what can be done if one NSAID is not tolerated / efficacious enough?

Answer 76

swap to a different one (dogs only) use adjunctive analgesic therapies (e.g. gabapentin) use non-pharmacological therapies

Question 77

what is an example of an adjunctive analgesic that can be used if NSAIDs are not appropriate?

Answer 77

gabapentin

Question 78

what are non-pharmacological therapies which can aid pain management?

Answer 78

weigh management diet physio accupuncture