NSAIDs and Paracetamol

what is the mechanism of action of NSAIDs?

block COX1 or COX2, which are the enzymes that convert arachidonic acid into prostaglandins (inflammatory molecules)

what important NSAID is a salicylate?

Acetylsalicylic acid/Aspirin

Salicylates (Acetylsalicylic acid, Aspirin) have what effects on the animal?

analgesic

antipyretic

anti-inflammatory

antiplatelet aggregation (blood thinning effect)

what adverse effects might a patient present when using Salicylates (Acetylsalicylic acid, Aspirin)?

dogs- mucosal erosion and ulceration

vomiting and melena at high doses

what NSAID is sometimes given chronically at low doses in order to prevent cardiovascular effects due to thrombus?

Acetylsalicylic acid/Aspirin

which biotransformation reaction (I or II) do Salicylates (Acetylsalicylic acid, Aspirin) go through?

both

how are Salicylates (Acetylsalicylic acid, Aspirin) excreted?

urine

which species is more susceptible to the toxic effects of Salicylates (Acetylsalicylic acid, Aspirin)? what adjustment must be made in this case?

cats, because they cannot metabolize it rapidly. therefore, we must increase the dosing interval to 2+ days

clinically, what do we use Salicylates (Acetylsalicylic acid, Aspirin) for?

-minor pain and inflammation in chronic conditions, such as arthritis

-antipyretic in large animals

-antiplatelet effects in thromboembolic disease

what must we be aware of when using Salicylates (Acetylsalicylic acid, Aspirin) as an antiplatelet drug?

there is the possibility of interaction with oral anticoagulants, which can cause bleeding

which NSAIDs can be used as an antipyretic in large animals?

Salicylates (Acetylsalicylic acid, Aspirin)

which, COX1 or COX2 is constitutive? what does this mean?

COX1

this means that it is always active (constantly secreted in the body)

which, COX1 or COX2 is inducive? what does this mean?

COX2

this means that there must be a trigger for its release (it is only released when there is an inflammatory stimulus)

what is COX1?

an constitutive enzyme, constantly released in the blood vessels, stomach, and kidney, as a "housekeeping enzyme"- it is essential for the organism. it regulates renal blood flow, and is

in charge of platelet aggregation and mucosa protection of the GI.

it works by synthesizing prostaglandins.

what is COX2?

an inducible enzyme, that is released in response to inflammatory stimuli into the site of inflammation.

it converts arachidonic acid into prostaglandins, and causes inflammation, pain, fever, ischemia (CNS), Alzheimer Morbus, and even cancer.

where are Salicylates (Acetylsalicylic acid, Aspirin) absorbed in the body?

stomach and duodenum

(they have a marked first-pass effect)

does aspirin have GI side effects?

yes, it can cause mucosal erosion and ulceration in dogs.

which COX do Salicylates (Acetylsalicylic acid, Aspirin) act against?

COX1

is aspirin COX1 or COX2 specific?

COX1

which NSAID is a pyrazolone derivative?

phenylbutazone

what are the effects of phenylbutazone?

anti-inflammatory

antiplatelet

does aspirin have analgesic action?

yes

also has antithrombic, anti-inflammatory, and anti-pyretic effects

does phenylbutazone have antiplatelet action?

yes

also has anti-inflammatory effect

where is phenylbutazone absorbed in the body?

digestive tract

does phenylbutazone have a high or low affinity for plasma proteins?

high (99%)

so is more likely to have reactions with other drugs, especially warfarin

phenylbutazone is used in ______ (species) to relieve pain related with ______

horses; arthritis

which NSAID is contraindicated in food-production species because of its immunosuppressive effects?

phenylbutazone

why is phenylbutazone contraindicated in food producing species?

because it has immunosuppressive effects

how is phenylbutazone excreted?

urine

what are the possible side effects of phenylbutazone?

diarrhea

anorexia

ulcers

colitis

perivascular admin- swelling, necrosis, sloughing at injection site

is it recommended to administer phenylbutazone parenterally?

no, because this can cause necrosis, swelling, and sloughing at the injection site

which is the most commonly used NSAID in horses due to its effectiveness and affordability?

phenylbutazone

what is the main clinical use of phenylbutazone in vet med?

relieve pain related with arthritis in horses

do we use phenylbutazone in dogs?

it is not recommended, because it can cause bone marrow suppression and anemia

which NSAIDs are anthranilic acid derivatives?

tolfenamic acid

flunixin meglumine

what is tolfenamic acid used for in veterinary medicine?

to reduce inflammatory processes related to locomotion and postoperative treatments.

most commonly used in small animals, especially cats.

tolfenamic acid has a higher specificity against _______ (COX1 or COX2)

COX1

which NSAID is good for treating inflammatory processes related to locomotion in small animals?

tolfenamic acid

what adverse reactions can tolfenamic acid produce?

GI irritation- vomiting, diarrhea, decreased appetite

what effects does tolfenamic acid have on the body?

antiinflammatory

antiplatelet

does tolfenamic acid have antiplatelet effects?

yes

+ antiinflammatory

which is more potent- flunixin or phenylbutazone?

flunixin

what is the main effect of flunixin on the body?

analgesic

how can we administer flunixin?

orally or parenterally

flunixin is eliminated from the body by ____

feces

what adverse reactions are possibly produced by flunixin?

mild gastric intolerance

hypoprothrombinemia

what are the clinical applications of flunixin in veterinary medicine?

-treat visceral pain associated with colic in horses

-treat musculoskeletal inflammation

-decrease the inflammatory mediated hemodynamic response to endotoxins

which NSAIDs are the most effect in treating endotoxemia?

flunixin

phenylbutazone

meloxicam

which NSAID is commonly used in horses to treat visceral pain associated with colic?

flunixin

what NSAIDs are belonging to the group of arylpropionic acid derivative?

carprofen

ibuprofen

ketoprofen

noproxen

which arylpropianic acid derivative NSAID is used in animals?

carprofen

carprofen has greater selectivity for _______ (COX1 or COX2)

COX2

carprofen is used in what species?

small animals, especially dogs

what are the effects of carprofen in the organism?

anti-inflammatory

analgesic

how is carprofen administered?

orally

what are the adverse reactions that can be produced by carprofen?

vomiting, diarrhea, anorexia

rare risk of renal or hepatic adverse reactions

what do we use carprofen for in veterinary medicine?

in small animals, especially dogs

long term management of arthritis

acute pain associated with soft tissue and orthopedic surgery

which NSAID is commonly used in dogs to treat acute pain that is associated with soft tissue and orthopedic surgery?

carprofen

what NSAID is commonly used in dogs for the long term management of arthritis?

carprofen

why are ibuprofen, ketoprofen, and naproxen contraindicated in animals?

because they cause severe GI problems- vomiting and possibly death due to GI bleeding from ulcers

which common human NSAIDs are contraindicated in animals due to their severe GI effects (vomiting, death due to GI bleeding by ulceration)?

ibuprofen

ketoprofen

naproxen

does meloxicam target COX 1 or COX2?

COX2

what are the effects of meloxicam?

analgesic

antiinflammatory

which NSAID is considered to be a good analgesic in comparison to other NSAIDs of their class, but occasionally needs analgesia supplementation to achieve desired levels of post surgical analgesia?

meloxicam

why might we sometimes use analgesia supplementation with meloxicam?

to achieve desired levels of postsurgical analgesia

what are the adverse reactions produced by meloxicam?

GI toxicity and perforation (but not much)

NSAIDs that target COX__ (1 or 2) have more GI effects

COX1

how can we administer meloxicam?

oral

SC

IM

IV

what is meloxicam commonly used for?

to treat acute and chronic inflammation associated with musculoskeletal disease and postoperative pain

it can be used in dogs, cats, horses, cattle, pigs

meloxicam is approved for use in what species?

dogs, cats, cattle, pigs, horses

in cats, what NSAID is well tolerated and safe for chronic administration?

meloxicam

which NSAID can be used for its antiexudative action in respiratory conditions, such as pneumonia or endotoxemia?

meloxicam

what are coxibs?

the group of NSAIDs with the highest effect against COX2. this includes firocoxib, deracoxib, and robenacoxib

which NSAIDs have the most effect against COX2?

coxibs- firocoxib, deracoxib, and robenacoxib

which coxib is the most commonly used in vet med?

robenacoxib

(given 1x daily)

is Robenacoxib effective against COX1 or COX2?

VERY effective against COX2

what are the effects of coxibs (firocoxib, deracoxib, and robenacoxib)

analgesic

anti-inflammatory

what are the adverse reactions an animal might have to coxibs (firocoxib, deracoxib, and robenacoxib)?

possible vomiting and anorexia, but rare

NOT gastrolesive

Cardiovascular effects

which, COX1 or COX2 inhibitors are more safe for the GI tract?

COX2 inhibitors

what are the common clinical applications of coxibs (firocoxib, deracoxib, and robenacoxib)?

treatment of postoperative pain and inflammation associated with osteoarthritis, orthopedic and soft-tissue surgery in dogs; musculoskeletal disorders and soft-tissue surgeries in cats

which NSAID is commonly used for the treatment of postoperative pain and inflammation associated with osteoarthritis, orthopedic and soft-tissue surgery in dogs?

coxibs (firocoxib, deracoxib, and robenacoxib)

which NSAID is preferred for the treatment of musculoskeletal disorders and soft-tissue surgeries in cats?

coxibs (firocoxib, deracoxib, and robenacoxib)

what is grapiprant?

not an NSAID, but a new molecule that is a selective antagonist for the EP4 receptor (this is the PGE2 receptor that is responsible for pain and inflammation associated with arthritis)

what is the MOA of grapiprant?

selective antagonist for the EP4 receptor (this is the PGE2 receptor that is responsible for pain and inflammation associated with arthritis)

which drug is a selective antagonist for the EP4 receptor (this is the PGE2 receptor that is responsible for pain and inflammation associated with arthritis)?

grapiprant

what are the effects of grapiprant?

antiinflammatory

how do we administer grapiprant?

orally

what are the possible adverse reactions that can come with grapiprant?

vomiting and inappetance

not gastrolesive

what are the clinical uses for grapiprant?

treatment of osteoarthritis in dogs (they are a good, safer alternative for OA, but are not as effective in treating acute pain)

which is the safest option for the treatment of osteoarthritis in dogs?

grapiprant

which is more effective- traditional NSAIDs or grapiprant?

traditional NSAIDs

which is the new molecule that was approved by the FDA for vet med in 2016, and is used as an osteoarthritis treatment in dogs?

grapiprant

what are Eicosanoids?

signalling molecules made by the oxidation of fatty acids. by action of phospholipase2 (released by inflam. cells), they are converted into arachidonic acid, which is converted by COX 1 and COX 2 into prostaglandins

what are prostanoids?

signalling molecules including prostaglandins, prostacyclin, thromboxane.

synthesized from arachidonic acid by COX1 and COX2.

promote inflammation (pain, fever, and all other inflam. signs)

which- COX1 or COX2- induces the pathological production of prostaglandins?

COX2

which- COX1 or COX2- induces the physiological production of prostaglandins?

COX1

COX2 can be dangerous to the body.. what adaptations have animals acquired for protection?

-renin secretion

-wound/ulcer healing

-female reproductive functions

-bone metabolism

-vascular protection

what triggers the production of COX2?

inflammation (cytokines, growth factors, ILs, TNF)

how are NSAIDs classified into categories?

according to their chemical structure

NSAIDs are ____soluble, so are well absorbed after ______ administration

lipid; oral