NSAIDs Flashcards
What drugs can be used to treat inflammatory disorders?
Non-steroidal anti-inflammatories Glucocorticoids Anticytokines Immunosuppressants Antihistamines
What are prostanoids?
Prostoglandins and thromboxanes
Explain the mechanism of action of NSAIDs
Prostanoids are synthesised via the metabolism of arachidonic acid.
This involves the enzyme cyclo-oxegenase (COX)
NSAIDs are COX inhibitors which suppress prostanoid synthesis
What is the full name of COX enzyme?
Cyclo-oxygenase
Where are Cox 1 and 2 found and what is their action?
Cox 1- present in most cells, produces prostanoids that act as homeostatic regulators (gastric acid secretion)
Cox 2- not normally present (CNS and renal exempt) but is strongly induced by inflammatory stimuli (IL-1)
Name 5 NSAIDs?
Asprin Ibuprofen Phenylbutazone Paracetamol Meloxicam Over 50 used in vet med
How can NSAIDs be administered?
Oral, injectable and transdermal gels
In what species should paracetamol not be used?
Cats- toxic
How is NSAIDs absorbed, distributed and eliminated?
Absorbed- weak acids, readily absorbed in GI tract, injectable usually alkaline (painful)
Distribution- Bound by albumin
Elimination- Hepatic phase I and II metabolism, conjugate metabolites are excreted in urine/faeces
What NSAID can be used in companion animals but not food producing animals and why?
Phenylbutazone- can cause aplastic anaemia in humans and has very long half life
What are the main examples of use of NSAIDs?
Anti-inflammatory action- decrease prostaglandin E2 and prostacyclin reduces vasodilation and indirectly oedema
Analgesia- decreased prostaglandin means less sensitisation of nociceptive nerve endings
Antipyretic- Pyrexi is caused by the release of prostaglandins in the CNS where they elevate the hypothalamic set point and cause fever- NSAIDs prevent the release of prostaglandins in the CNS
What are the adverse effects of NSAIDs?
GI ulceration and erosion
Renal damage- don’t use on hypotensive and hypovolaemic animals
Hepatotoxicity
Circulatory disturbances
What are the contra-indications of NSAIDs?
Pregnancy
Use with other NSAIDs or glucocorticoids
Underlying renal, liver and cardiac impairment
What species is phenylbutazone used for?
Dogs and Horses - very long half life, 99% bound
What is meloxicam used for and what are its features?
Preferential COX 2 inhibitor
97% bound to albumin
Used in acute/chronic pain and inflammation
Species variation in half life- long in cats, short in horses
What are the effects of paracetamol and what species is it licensed in?
Antipyretic and analgesic action
Only acts in CNS- less adverse effects
Oral absorption
Licensed in pigs and dogs
What is aspirin used for?
Anti-clotting agent- inhibits platelet aggregation
Significant adverse effects- vomiting, GI ulceration, anorexia
Inhibits COX 1
What are exogenous glucocorticoids used for?
Reversing all types of inflammatory reaction
In high doses as immunosuppressive drugs
What are the anti-inflammatory effects of glucocorticoids on cells?
Decreases extravasation of neutrophils
Decreased activation of neutrophils, macrophages, mast cells
Decreased fibroblast function
Decreased production of collagen and glycosaminoglycans which can lead to decreased wound healing
What are the anti-inflammatory effects of glucocorticoids on chemical mediators?
Decreased production of prostanoids (COX2)
Decreased generation of cytokines
Decreased complement components of plasma
Decreased IgG production
Decreased synthesis of nitric oxide
Decreased histamine release from basophils and mast cells
Increased synthesis of anti-inflammatory mediators
How are glucocorticoids administered?
Orally, systemically, intra-articular, drops in eye, ointment and creams
What are the main uses of glucocorticoids?
Replacement therapy for dogs with Addisons disease
Anti-inflammatory and immunosuppressive therapy
What are the adverse effects of glucocorticoids?
Suppression of the response to infection/injury Wound healing impaired Cushing's syndrome Latrogenic hypoadrenocorticism Osteoperosis Hyperglycaemia Muscle wasting Fluids and electrolyte imbalances Oedema Reduced milk yield in dairy cows GI ulceration Abortion in late pregnancy Laminitis
What are the contra-indications of glucocorticoids?
Diabetes mellitus Infections Corneal ulceration Cardiac disease Laminitis Pregnancy
