ANTI-INFLAMMATORY & PAIN-REDUCING DRUGS

Chapter 13 -1

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

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

MOA - Inflammation

EICOSANOIDS

ARACHIDONIC PATHWAY

EICOSANOIDS•GOOD PG: PgE and PgI2. normally decrease the volume, acidity, and pepsin content of gastric secretions released during normal digestion

Phospholipids: cell membrane

Anti-inflammatory Drugs

Two main groups of anti-inflammatory drugs SteroidalSteroidal anti-

inflammatory drugs block the action of phospholipase phospholipase (lipoxygenase)(lipoxygenase)

NonsteroidalNonsteroidal anti-inflammatory drugs block the action of cyclooxygenase cyclooxygenase (thromboxane)(thromboxane)

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

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

• Glucocorticoids are natural hormones

• adrenocorticotropic hormone (ACTH)

• corticotropin-releasing factor (CRF)

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

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

Cushing’s Disease (hyperadrenocorticism)

iatrogenic Cushing's : DON’T GIVE TOO MUCH: EOD

• 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

Addison’s Disease (hypoadrenocorticism)

Taper off slowly

• extended use of glucocorticoid: lack of CRF and ACTH

• adrenal cortex begins to atrophy > natural cortisol is diminished.

weakness, lethargy, vomiting, and/or diarrhea

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)

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

Topical steroids almost always effect systematically so don’t give to immunocompromised/ pregnant animals

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

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

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

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

IDEAL DRUG: COX 2 INHIBITOR: Newer NSAID: Deramaxx, Rimadyl, etogesic

NSAID - CON 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

Cox -2 inhibitors: Flavorful hence put away from animals to avoid toxicities

References

Bill, R.L. Clinical Pharmacology and Therapeutics for the Veterinary Technician, 3rd edition. 2006.

Romich, J.A. Pharmacology for Veterinary Technicians, 2nd edition. 2010.