7.2.2 Anti-inflammatory drugs: NSAIDs, glucocorticoids, immunosuppressants

Question 1

What are the clinical uses of NSAIDs (4)?

Answer 1

• pain control in acute and chronic inflammatory conditions
• decrease swelling post injury/surgery
• reduce fever
• inhibit platelet activation in thromboembolic disease

Question 2

What does cox inhibition lead to?

Answer 2

• decreases vasodilation
• decreases swelling
• analgesia
• decreased inflammatory associated fever

Question 3

How do NSAIDs work?

Answer 3

Competitive reversible COX inhibitors…
Inhibiting prostaglandin release.

Question 4

Give 3 harmful effects of NSAIDs

Answer 4

Inhibits gastric acid secretion
Contract the uterus
Increase renal blood flow

Question 5

What are the two types of COX? Which type is targetted by NSAIDs?

Answer 5

COX-1: Constitutive = active type, dries physiological effects

COX-2: Inducible = drives inflammatory response

NSAIDs target COX2, they block inflammatory pathways without having systemic effects

Question 6

What NSAIDs can be used in large and small animals?

Answer 6

Carprofen
Ketoprofen
Meloxicam (Metacam)

Question 7

What NSAIDs can be used in horse and farm animals only?

Answer 7

Fluixin
Phenylbutazone (Equipalazone)
Sodium salicylate

Question 8

What NSAIDs can only be used in small animals?

Answer 8

Tepoxalin
Robenacoxib
Mavaboxib

Question 9

What are the pharmacokinetic considerations of NSAID use?

Answer 9

• Oral and parenteral routes of admin
• Dose requirements vary between species
• Do not use different NSAIDs within 24hr of each other
• Do not use NSAIDs if dehydrated/hypovolaemic/hypotensive

Question 10

What are the side effects of NSAIDs?

Answer 10

• Damage to GIT
• Nephrotoxicity when dehydrated
• Hepatotoxicity
• Bone marrow disturbances

Question 11

What is a glucocorticoid? Give two examples

Answer 11

Anti-inflammatory drug
- Inhibits formation and action of pro-inflammatory mediators - Induces the formation of anti-inflammatory mediators

Dexamethasone
Prednisolone

Question 12

What are the four mechanisms of anti-inflammatory action of glucocorticoids?

Answer 12

1 - Effects on protein synthesis
2 - Decreases release of some inflammatory mediators
3 - Decreases production of inflammatory cells by BM
4 - Decreases circulating complement components

Question 13

What is the anti-inflammatory activity of glucocorticoids?

Answer 13

↓ vasodilation
↓ vascular permeability
↓ leukocyte accumulation
↓ leukocyte activation

Question 14

Pharmacokinetic considerations of corticosteroid use

Answer 14

• Oral, topical, inhalation, intra-articular routes of admin
• Short and long acting
• Duration of effect is longer than predicted plasma clearance

Question 15

Clinical uses of corticosteroids

Answer 15

• Allergic dieases, anaphylaxis
• Topical - inflammation of skin, eye, ear
• Chronic inflammation
• Shock - high doses via IV (contraversial)

Question 16

Side effects of corticosteroids

Answer 16

• Suppression of wound healing and response to infection
• Inhibition of osteoblast and increased osteoclast activity
• Can predispose lami in horses
• Induce iatrogenic Cushings syndrome
• Suppression of endogenous steroid production
• Rapid withdrawal = addisonian crisis

Question 17

Describe the mechanism of action for cyclosporine and its analogues.

Answer 17

• Inhibits enzyme calcineurin to prevent transcription factor, nuclear factor of activated T cells
• T lymphocyte activation decreased
• Histamine release from mast cells and basophils decreased