P23: Anti-Inflammatory Drugs

What can inflammation arise from?

thermal, chemical, physical damage; ischaemia; infectious agents; antigen-antibody interactions

What subphases does the initial inflammation phase consist of?

acute, subacute, chronic

What is the acute phase of inflammation?

lasts 1-3 days; characterised by heat, redness, swelling, pain, loss of function

What is the subacute phase of inflammation?

2-4 days to 1 month; corresponds to cleaning phase before repair phase

What is the chronic phase of inflammation?

1 month to several months

What are the two types of anti-inflammatory drugs?

nonsteroidal (NSAIDs); steroidal (glucocorticoids)

What effects do NSAIDs have?

analgesic, anti-pyretic, anti-inflammatory

How do NSAIDs work?

inhibit the activity of cyclooxygenase-1 and cyclooxygenase-2 that catalyse conversion of arachidonic acid to prostaglandins, thromboxanes, prostacyclins (mediators of inflammation)

Describe COX-1

expressed in virtually all tissues;
catalyses the formation of constitutive prostaglandins, which mediate a variety of normal physiologic effects

What normal physiologic effects do the constitutive prostaglandins catalysed by COX-1 mediate?

haemostasis, GI mucosal protection, protection of the kidney from hypotensive insult

Describe COX-2

activated in damaged and inflamed tissues;
catalyses formation of inducible prostaglandin;
involved in thermoregulation and pain response to injury

Which inducible prostaglandin catalysed by COX-2 is associated with intensifying the inflammatory response?

PGE2

What is the inhibition of COX-2 by NSAIDs responsible for?

analgesic, antipyretic, anti-inflammatory (actions of NSAIDs)

What groups can NSAIDs be divided into according to their structure?

carboxylic acid derivatives; enolic acid derivatives; coxib class

What are the carboxylic acid subgroups of NSAIDs?

salicylates, propionic acids, fenemates, phenylacetic acids, aminonicotinic acids

What is an example of salicylate NSAIDs?

aspirin

What are examples of propionic acid NSAIDs?

ibuprofen, naproxen, carprofen, ketoprofen, vedaprofen

What are examples of fenemate NSAIDs?

tolfenamic acid, meclofenamic acid

What is an example of phenylacetic acid NSAIDs?

acetaminophen

What is an example of aminonicotinic acid NSAIDs?

flunixin

What are the subgroups of enolic acid NSAIDs?

pyrazolones, oxicams

What is an example of pyrazolone NSAIDs?

phenylbutazone

What are examples of oxicam NSAIDs?

meloxicam, piroxicam

What are examples of coxib class NSAIDs?

deracoxib, firocoxib, robenacoxib, mavacoxib

What group of NSAIDs does aspirin (acetylsalicylic acid) belong to?

salicylates (carboxylic acid)

What are the indications for aspirin?

relief of mild to moderate pain associated with musculoskeletal inflammation or osteoarthritis

What dosage forms are available for aspirin?

bolus, oral paste, oral solution, tablets

What are the indications for ketoprofen?

acute pain in dogs and cats;
in horse, used for pain and inflammation associated with osteoarthritis and visceral pain associated with colic

What are the indications for carprofen?

manage pain and inflammation associated with osteoarthritis and acute pain associated with soft-tissue and orthopaedic surgery in dogs

What are the indications for vedaprofen?

treatment of pain and inflammation associated with musculoskeletal disorders in dogs and horses;
for the treatment of pain associated with colic in horses

What group of NSAIDs do ketoprofen, carprofen, flubriprofen, and vedaprofen belong to?

propionic acid derivatives (carboxylic acid)

What are the indications for meclofenamic acid?

treatment of chronic laminitis; lower therapeutic index than other NSAIDs

What are the indications for tolfenamic acid?

fever, postoperative pain, acute and chronic inflammatory conditions in cats, dogs, cattle, and pigs

What group of NSAIDS do meclofenamic acid and tolfenamic acid belong to?

fenamates (carboxylic acids)

What is another name for acetaminophen?

paracetamol

What are the indications of acetaminophen?

pain, fever (analgesic, antipyretic)

Which species is acetaminophen contraindication for?

cats

How does acetaminophen compare to aspirin?

weaker anti-inflammatory effects; similar analgesic and antipyretic effects

What group of NSAIDs does acetaminophen belong to?

phenylacetic acids (carboxylic acids)

What are the indications of flunixin?

treatment of visceral pain associated with colic in horses;
reduce inflammatory-mediated haemodynamic response to endotoxin;
treat pain and inflammation associated with arthritis and other musculoskeletal disorders in dogs and cats

What group of NSAIDs does flunixin belong to?

aminonicotinic acids (carboxylic acids)

What are the indications for phenylbutazone?

treat acute laminitis in horses;
analgesic, antipyretic and anti-inflammatory in dogs, cattle, swine

What group of NSAIDs does phenylbutazone (PBZ) belong to?

pyrazolones (enolic acids)

What are the indications of meloxicam?

treatment of acute and chronic inflammation associated with musculoskeletal disease and management of postoperative pain in dogs, cats, cattle, horses

How does meloxicam work?

potent inhibitor of prostaglandin synthesis

What group of NSAIDs do meloxicam and piroxicam belong to?

oxicams (enolic acids)

What are the indication of piroxicam?

ankylosing spondylitis and osteoarthritis in dogs, cats, and horses

What are the indications of deracoxib?

postoperative pain and inflammation associated with orthopaedic surgery;
pain and inflammation associated with osteoarthritis is dogs

What are the indications of firocoxib?

postoperative pain and inflammation associated with orthopaedic and soft-tissue surgery;
pain and inflammation associated with osteoarthritis is dogs

What are the indications of robenacoxib?

postoperative pain and inflammation associated with osteoarthritis, orthopaedic and soft-tissue surgery in dogs;
pain and inflammation associated with musculoskeletal disorders and soft-tissue surgery in cats

What are the indications of mavacoxib?

pain and inflammation associated with degenerative joint disease in dogs

What group of NSAIDs do deracoxib, firocoxib, robenacoxib, and mavacoxib belong to?

coxib class

how does Tepoxalin work?

dual inhibitor of both COX-1 and COX-2, and 5-lipoxygenase (5-LOX)

What are glucocorticoids used for in veterinary medicine?

anti-inflammatory drugs;
antiallergic agents and immunosuppressants;
endocrine drugs;
anabolic and catabolic drugs

How do glucocorticoid drugs work?

(suppress virtually every component of the inflammatory process)
inhibit PLA2;
decrease synthesis of interleukins and other proinflammatory cytokines;
suppress cell-mediated immunity;
reduce complement synthesis;
decrease production and activity of leukocytes

Which group of drugs are the most efficacious anti-inflammatory drugs?

glucocorticoids

What are glucocorticoids normally used to treat?

allergy;
pruritic dermatoses, allergic lung and GI diseases;
acute cases of atopic or flea allergy dermatitis;
chronic allergic bronchitis, feline asthma;
acute respiratory distress syndrome (cattle);
chronic obstructive pulmonary disease (horses)

How should glucocorticoids be used?

in conjunction with therapies that target the underlying cause

What are examples of glucocorticoids?

hydrocortisone, prednisone, methylprednisone, flumethasone, dexmethasone, betamethasone