1. Anti-inflammatory & Pain-reducing drugs
Chapter 13 -1

2. OBJECTIVES Terminology used to describe anti-inflammatory drugs
MOA by which inflammation occurs
MOA which glucocorticoids and NSAIDs work
Comparisons of glucocorticoids and NSAIDs in their effects and side effects
Precautions that apply to glucocorticoids, nonsteroidal anti-inflammatory drugs, and cyclooxygenase-2 inhibitor drugs

3. Terminology
Anti-inflammatories: Drugs that relieve pain or discomfort by blocking or reducing the inflammatory process
Steroidal anti-inflammatory drugs (corticosteroids)
Nonsteroidal anti-inflammatory drugs (NSAIDs)
not considered to be true analgesics
Opoids work on CNS and reduce perception of pain

4. MOA - Inflammation
EICOSANOIDS

5. ARACHIDONIC PATHWAY EICOSANOIDS Phospholipids: cell membrane
GOOD PG: PgE and PgI2. normally decrease the volume, acidity, and pepsin content of gastric secretions released during normal digestion

6. Anti-inflammatory Drugs
Two main groups of anti- inflammatory drugs
Steroidal anti- inflammatory drugs block the action of phospholipase (lipoxygenase)
Nonsteroidal anti- inflammatory drugs block the action of cyclooxygenase (thromboxane)

7. Steroidal Anti-inflammatories
Corticosteroids /adrenocorticosteroids
hormones produced by the cortex (the outer layer) of the adrenal gland.
mineralocorticoids
water and electrolyte balance (sodium, potassium, and other electrolytes), aldosterone
Hypoadrenocorticism/ Addison’s:
hyperkalemia, hyponatremia because of a lack of aldosterone production
TX: desoxycorticosterone pivalate (Percorten- V
glucocorticoids

8. Glucocorticoids-Antiinflammatories
Inhibit phospholipase, and to a lesser degree cyclooxygenase
Decreasing the production of prostaglandins and leukotrienes
Every corticosteroid drug has both mineralocorticoid (sodium retention) and glucocorticoid (anti-inflammatory effects to some degree
Are regulated by negative feedback

9. Glucocorticoids are natural hormones
adrenocorticotropic hormone (ACTH)
corticotropin-releasing factor (CRF)

10. Glucocorticoid - Pros decrease inflammation
relieve pruritus
help maintain the integrity of the capillaries - decreases swelling
inhibit fibroblasts: reduce scarring by delaying wound healing
normal therapeutic doses of glucocorticoid does not affect humoral immunity so ok to vaccinate animals on these drugs

11. Glucocorticoid - Cons Dec. fibroblast activity delay wound healing
Suppress T-lymphocytes (normal therapy dose):
Protects fungal agents (e.g., histoplasmosis…)
Horses: fungal eye infections
Inc. gastric acid secretion and decrease mucus production: hyperacidity and GI ulceration
catabolize protein in the cornea > deepening ulcer, Desmetocele: poor prognosis
+/- induce abortion: cattle and mares , bitches
Stress leukogram: lymphopenia, monocytopenia, eosinopenia, neutrophilia: sequestered - lungs, spleen

12. Cushing’s Disease (hyperadrenocorticism)
Corticosteroids: catabolic – breakdown of protein > provide amino acids for gluconeogenesis
hyperglycemia
muscle wasting atrophy, alopecia, and decreased bone density.
“pot-bellied” appearance of dogs after long term glucocorticoid treatment
PU/PD/PP, risk to infections
iatrogenic Cushing's : DON’T GIVE TOO MUCH: EOD

13. Addison’s Disease (hypoadrenocorticism)
extended use of glucocorticoid: lack of CRF and ACTH
adrenal cortex begins to atrophy > natural cortisol is diminished.
weakness, lethargy, vomiting, and/or diarrhea
Taper off slowly

14. Uses for Glucocorticoid Drugs
Overreaction of the immune system: Autoimmune reactions such as lupus, Autoimmune hemolytic anemia, Hypersensitivity reactions such as allergic reactions
Shock
Systemic disease (Addison’s) OR iatrogenic cushion’s disease 
Cancer: Lymphosarcoma: lymphocytosis
glucocorticoids are part of the treatment protocol for this cancer
Inflammatory conditions: Ocular inflammation, MSK inflammation, IVD
Lameness (horses)
Pregnancy termination (Don’t use in pregnant animals)

15. CORTICOSTEROIDS (ADRENOCORTICOSTEROIDS) GLUCOCORTICOIDS
Topical steroids almost always effect systematically so don’t give to immunocompromised/ pregnant animals
CORTICOSTEROIDS (ADRENOCORTICOSTEROIDS) GLUCOCORTICOIDS
Short-acting: < 12 hrs
Hydrocortisone: topical
Cortisone
Intermediate-acting: 12 to 36 hrs; EOD; allergies/ inflammation
Prednisone
Prednisolone
Triamcinolone
Methylprednisolone (depomedrol)
Isoflupredone
Long-acting: 12 to 36 hours
Dexamethasone
Betamethasone
Flumethasone

16. Glucocorticoids - Formulations
Aqueous solutions
combined with a salt: Na-phosphate or Na-succinate to make them soluble (dissolvable) in water.
E.g. dexamethasone sodium phosphate and prednisolone sodium succinate (Solu-Delta-Cortef)
Adv: can be given in large doses intravenously with less risk of an adverse reaction; shock or CNS trauma
DA: pain, irritation, or inflammation at the site of injection
in hot/cold climate
Alcohol solutions
Suspensions: acetate-glucocorticoid lipid soluble: topical
ophthalmic medications
acetate, diacetate, pivalate, acetonide, or valerate appended to the glucocorticoid drug name
Opaque

17. Safe Use of Glucocorticioid
•Use NSAID rather than a glucocorticoid (as long as no contraindications exist for NSAID use).
•Avoid continuous use of glucocorticoids: it is preferable to use an intermediate-acting glucocorticoid such as prednisolone rather LA- glucocorticoids: systemic administration (versus topical administration
•Use the smallest dose of glucocorticoids that provides a clinical response. EOD
Tapering: to avoid Addison’s
Cat’s not really affected

18. NSAID
COX-2 inhibitors: Carprofen (Rimadyl), Etodolac (EtoGesic), Deracoxib (Deramaxx), Meloxicam (Metacam), Firocoxib (Previcox)
Tepoxalin (Zubrin)
Phenylbutazone
Aspirin (salicylates)
Propionic acid derivatives: Ibuprofen (Advil, Motrin), Ketoprofen (Ketofen), Naproxen (Aleve)
Flunixin meglumine (Banamine)
Meclofenamic acid (Arquel)
Dimethyl sulfoxide (DMSO)
Chondroprotective agents Polysulfated glycosaminoglycans
Hyaluronic acid
Glucosamine
Chondroitin sulfate (Cosequin)
Acetaminophen
Orgotein (superoxide dismutase)
Gold salts
Piroxicam

19. Non-Steroidal Anti-inflammatory Drugs
IDEAL DRUG: COX 2 INHIBITOR: Newer NSAID: Deramaxx, Rimadyl, etogesic
Non-Steroidal Anti-inflammatory Drugs
NSAIDs work by blocking the activity of cyclooxygenase > inhibit prostaglandins.
Few NSAIDs such as ketoprofen, ibuprofen, and tepoxalin (Zubrin) > inhibit lipoxygenase
Cyclooxygenase has two forms
Cox-1: in stomach: secretion of stomach-protective mucus, decrease acid; kidney: vasodilation of the renal blood supply and other organs
Cox-2: prostaglandins – inflammation
They can be used for analgesia
Post operative analgesia

20. NSAID - CON Hepatotoxicity
Cox -2 inhibitors: Flavorful hence put away from animals to avoid toxicities
NSAID overdose/ nonselective NSAIDs extended period : anorexia, diarrhea, ulcerations of the stomach or duodenum
sucralfate, histamine 2 (H2) blockers (e.g., cimetidine or ranitidine), and omeprazole are used to treat the open ulcer and reduce the acidity of the stomach, misoprostol: like PG-E
Protein bound hence toxic in hypoalbuminemia
Block good PG (PgE and PgI2):
Hypotension > prostaglandin E2 is released by the kidney to dilate vessels
renal papillary necrosis
Seen also in cox -2!!
Hepatotoxicity
GI SE is reported much more frequently in dogs than horses
E.g phenylbutazone (old NSAID) toxic in dogs: gastritis/ melena
Cats: poorly tolerant of NSAIDs
Low dose aspirin every 2 days can be tolerable

21. References
Bill, R.L. Clinical Pharmacology and Therapeutics for the Veterinary Technician, 3rd edition
Romich, J.A. Pharmacology for Veterinary Technicians, 2nd edition