Therapeutics for the MSK System

Question 1

What are benzodiazepams used for?

Answer 1

Used as part of the pre-anaesthetic or sedation protocol as muscle relaxants

Question 2

What are NMBA’S Used for?

Answer 2

Used to induce paralysis – small rapid moving muscles
(eyes, larynx) relax before limbs and trunk

Question 3

What are non-depolarising agents?

Answer 3

• ACh antagonists which produce motor paralysis
• Can be reversed using anticholinesterases e.g.
  neostigmine, pyridostigmine

Question 4

What are depolarising agents?

Answer 4

ACh receptor agonists – not metabolized by
acetylcholinesterase –> end plate cannot
repolarize
* Cannot be reversed

Question 5

What is a ryanodine receptor antagonist?

Answer 5

dantrolene - blocks
release of Ca2+ ions from sarcoplasmic reticulum in striated
muscle preventing muscle contraction

Question 6

What is a ryanodine receptor used to treat

Answer 6

Used to treat recurrent exertional rhabdomyolysis in horses
* Historically used to treat malignant hyperthermia (a
runaway contraction of muscle which was a complication
with older volatile anaesthetics e.g. halothane).

Question 7

What are intra articular glucocorticoids used for?

Answer 7

Intra-articular glucocorticoids (e.g. methylprednisolone,
triamcinolone) used to treat inflammatory musculoskeletal
conditions (esp. horses)

Question 8

What is the benefit of COX 2?

Answer 8

Selective NSAIDs mainly reduce GI side effects. The
frequency of other AEs such as emesis, lethargy and death is
not significantly different

Question 9

What are the adverse effects of NSAIDS?

Answer 9

GI (nausea and vomiting, gastric & intestinal damage
with risk of bleeding and ulceration)
* Reversible renal insufficiency – avoid in dehydrated
patients and in patients on potentially nephrotoxic
drugs – monitor renal function
* Small risk NSAIDs may precipitate cardiac failure in
animals with cardiovascular disease

Question 10

What is grapipant?

Answer 10

Non-steroidal, non-cyclooxygenase inhibiting antiinflammatory drug
* Selective antagonist of the EP4 receptor
* The EP4 receptor is important in mediating pain and
inflammation as it is the primary mediator of the
prostaglandin E2-elicited sensitization of sensory neurons
and prostaglandin E2-elicited inflammation

Question 11

What is the side effect of grapipant?

Answer 11

soft faeces/diarrhoea, vomiting) are generally
transient

Question 12

What is the function of pentosan polysulfate?

Answer 12

is indicated for treatment of lameness and pain of degenerative joint disease/OA in dogs

Question 13

What is pentosan polysulfate?

Answer 13

Semi-synthetic polymer with anti-inflammatory properties –
reduces metalloproteinases thereby preserving proteoglycan
content and protecting cartilage matrix from degradation

Question 14

What is a neutraceutical?

Answer 14

Nutritional supplements for normal body structure and
function with the intent of improving health and well-being

Question 15

What is Bedinvetmab?

Answer 15

Nerve growth factor (NGF) increases inflammatory mediators
and stimulates nociceptors

Question 16

What is paracetamol?

Answer 16

First line pharmaceutical treatment for OA in humans
* NSAID with analgesic and antipyretic but weak antiinflammatory
* MoA not clear - seems to have specific activity for the CNS COX
enzyme, COX3 (few GI effects). It may also reduce conduction
in pain sensory neurons (action through TRPA1 ion channel).
* Careful with the dose in dogs – no veterinary product licenced
for dogs. DO NOT USE in cats.

Question 17

What is tramadol?

Answer 17

Centrally acting analgesic with complex mechanism of action
involving opioid, norepinephrine, and serotonin receptors
* Unlike morphine, tramadol does not have depressing
effects on respiration or gastrointestinal motility

Question 18

What is gabapentin?

Answer 18

Analogue of the neurotransmitter GABA. Initially used as an
antiepileptic, now used in the treatment of neuropathic pain
* MoA of its analgesic effect is unknown
* Start with a low dose and increase slowly. May cause
mild sedation and ataxia
* Withdraw therapy slowly too (potential for rebound pain
shown in humans)

Question 19

What does tissue injury provoke?

Answer 19

Provokes a response that involves the release of inflammatory mediators

Question 20

What do inflammatory mediators trigger?

Answer 20

• they trigger nociceptors
• pain signal is then transmitted along different axons
• blocking of transmission
• pain is perceived in the CNS

Question 21

What do glucocorticoids inhibit in the arachidonic acid cascade?

Answer 21

• Phospholipase A
• therefore the production of arachidonic acid

Question 22

What do NSAIDS inhibit in the arachidonic acid cascade?

Answer 22

• Cyclo-Oxygenase
• therefore no prostaglandins produced

Question 23

What does COX-1 produce?

Answer 23

Arachidonic acid with homeostatic functions

Question 24

What does COX-2 produce?

Answer 24

Arachidonic acid with inflammation functions
(expressed in inflammatory cells)

Question 25

What does Grapipant inhibit?

Answer 25

PGE 2 (prostaglandins 2)

Question 26

What are the GI side effects of grapiprant?

Answer 26

GI side effects (soft faeces/diarrhoea, vomiting) are generally transient

Question 27

What is NaPPS indicated for?

Answer 27

for treatment of lameness and pain of degenerative joint disease/OA in dogs

Question 28

What is NApps/ Pentosan polysulphate given as?

Answer 28

Given as a course of 4 weekly sc injections
* Response variable
* Duration of effect variable – max 3 courses of 4 injections
in 12 months
* Concurrent use with steroids and NSAIDs
contraindicated (risk of bleeding due to
combined effects on platelet aggregation)

Question 29

What nutraceuticals are used for normal body structure?

Answer 29

Multiple substances commonly used in arthritis, all have
variable and incomplete evidence for efficacy
* Chondroitin sulfate – component of cartilage
* Glucosamine – component of cartilage
* Antioxidants – counter potentially damaging oxidants
* EFAs – weak anti-inflammatory properties

Question 30

What is bedinvetmab?

Answer 30

a canine monoclonal antibody (mAb) and
frunevetmab is a felinised mAb targeting NGF

Question 31

What is bedinvetmab used for?

Answer 31

Long term management of OA pain
do not use in young animals under 12 months- critical role in development
there is also limited long term data

Question 32

What is the MoA for paracetamol?

Answer 32

• Unclear
• may reduce conduction in pain sensory neurons
• should not be used in cats

Question 33

What is the function of tramadol?

Answer 33

Centrally acting analgesic with complex mechanism of action
involving opioid, norepinephrine, and serotonin receptors
* Unlike morphine, tramadol does not have depressing
effects on respiration or gastrointestinal motility

Question 34

What is tramadol used to manage?

Answer 34

Management of mild to moderate acute pain, but also as
adjunctive analgesic in management of chronic arthritic pain
* Effects may be variable
* Sedation at high doses, dysphoria more likely in cats
* Can be combined with other classes of analgesic

Question 35

Why might you need to withdraw gabapentin slowly?

Answer 35

Potential for rebound pain

Question 36

What is amantadine commonly used for?

Answer 36

multimodal treatment for progressive moderate to severe OA pain and for pain relief in osteosarcomas