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Fundamentals of Pharmacology for Veterinary TechniciansChapter 16 Anti-inflammatory and Pain-Reducing Drugs Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Basic Physiology Inflammation is a useful and normal process that consists of a series of events, including vascular changes and release of chemicals that help destroy harmful agents at the injury site and repair damaged tissue Vasodilation increases permeability of blood vessels in the early phase Accumulation of leukocytes, reduced blood flow, chemical release (histamine, prostaglandin, and bradykinin) and tissue damage in cellular phase Severe inflammation must be reduced to avoid additional damage to the body See Table 16-1 Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Anti-inflammatory DrugsTwo main groups of anti-inflammatory drugs Steroidal anti-inflammatory drugs block the action of phospholipase Nonsteroidal anti-inflammatory drugs block the action of cyclooxygenase Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Steroidal Anti-inflammatoriesCorticosteroids are hormones produced by the adrenal cortex Two groups of corticosteroids used in veterinary medicine are the glucocorticoids and the mineralocorticoids Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Glucocorticoids Have anti-inflammatory effects due to their inhibition of phospholipase Raise the concentration of liver glycogen and increase blood glucose levels Affect carbohydrate, protein, and fat metabolism Are regulated by negative feedback Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Glucocorticoids May be categorized asShort-acting (duration of action < 12 hours) Cortisone and hydrocortisone Intermediate-acting (duration of action 12–36 hours) Prednisone, prednisolone, prednisolone sodium succinate, methylprednisolone, methylprednisolone acetate, and triamcinolone Long-acting (duration of action > 36 hours) Dexamethasone, betamethasone, and fluocinolone May be given orally, parenterally, or topically Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Glucocorticoid Use Benefits: Drawbacks: Reduce inflammation and painRelieve pruritus Reduce scarring by delaying wound healing Reduce tissue damage Drawbacks: Delay wound healing Increase risk of infection May cause GI ulceration and bleeding Increase the risk of corneal ulceration if corneal damage exists May induce abortion in some species Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Key Points About Glucocorticoid TreatmentGlucocorticoids do not cure disease They may help disseminate infectious microorganisms Use caution when giving high dosages of glucocorticoids to pregnant animals Whenever possible, use the topical form to avoid systemic imbalances Use alternate-day dosing at the lowest possible doses to prevent iatrogenic Cushing’s disease Taper animals off glucocorticoids to prevent iatrogenic Addison’s disease Do not use glucocorticoids in animals that have corneal ulcers Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Nonsteroidal Anti-inflammatory DrugsNSAIDs work by inhibiting cyclooxygenase, which has two forms Cox-1 is involved with the stomach Cox-2 is involved with inflammation NSAIDs are also referred to as prostaglandin inhibitors NSAIDs have fewer side effects than glucocorticoid drugs Side effects of NSAIDs include GI ulceration and bleeding and bone marrow suppression Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Types of NSAIDs Salicylates Pyrazolone derivativesPotent inhibitors of prostaglandin synthesis; include drugs such as aspirin Aspirin is an analgesic, antipyretic, and anti-inflammatory Side effects include gastrointestinal problems Pyrazolone derivatives Inhibit prostaglandin synthesis Phenylbutazone is an analgesic, antipyretic, and anti-inflammatory Used in equine medicine for musculoskeletal pain Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Types of NSAIDs Propionic acid derivatives Flunixin meglumineBlock both cyclooxygenase and lipoxygenase Examples include ibuprofen, ketoprofen, carprofen, and naproxen (the –fen drugs) Side effects include gastrointestinal problems and possible liver toxicities Flunixin meglumine Inhibits cyclooxygenase Used in cattle and horses for musculoskeletal and colic pain Is a potent analgesic, antipyretic, and anti-inflammatory Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Types of NSAIDs Dimethyl sulfoxide (DMSO)Inactivates superoxide radicals produced by inflammation Is also able to penetrate skin and serve as a carrier of other drugs (may cause burning) Must use caution when applying Indol acetic acid derivatives Inhibit cyclooxygenase (more selective for Cox-2) Is an analgesic and anti-inflammatory An example is etodolac, which has the benefit of once-a-day dosing Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Types of NSAIDs Fenamates Cox-2 inhibitors Inhibit cyclooxygenaseAre analgesics and anti-inflammatories An example is meclofenamic acid Cox-2 inhibitors Inhibit cyclooxygenase-2 without interfering with the protective cyclooxygenase-1 Examples include deracoxib and meloxicam Side effect include anorexia, vomiting, and lethargy Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Types of NSAIDs Dual-pathway NSAIDsBlock arachidonic acid cycle (both cyclooxygenase and lipoxygenase pathways) Are analgesics and anti-inflammatories An example is tepoxalin, which is a rapidly disintegrating tablet used for osteoarthritis in dogs Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Other Osteoarthritis TreatmentsGlycosaminoglycans: proteoglycans form part of the extracellular matrix of cartilage. Polysaccharide groups in proteoglycans are called glycosaminoglycans (GAGs). GAGs include: Hyaluronic acid: part of joint fluid; given intra-articularly, helps cushion degenerating joints Polysulfated glycosaminoglycans: semisynthetic mix of GAGs from bovine cartilage. Helps promote production of joint fluid and has anti-inflammatory effects Glucosamine and chondroitin sulfate: believed to play a role in the maintenance of cartilage Orgotein: a superoxide dismutase drug that inactivates superoxide radicals (such as DMSO) Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Antihistamines Antihistamines counteract the effect of histamine (histamine cause bronchoconstriction and inflammatory changes) Antihistamines compete with histamine for receptor sites (H1 receptors constrict smooth muscles and H2 receptors increase gastric secretions) H1 blockers are used to treat pruritus, laminitis, motion sickness, anaphylactic shock, and some upper respiratory conditions Examples include diphenhydramine, dimenhydrinate, chlorpheniramine, pyrilamine maleate, triplelennamine, terfenadine, hydroxyzine, and meclizine Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
Analgesics Analgesics are drugs that relieve pain without causing loss of consciousness Analgesics fall into two categories: Narcotics (covered in Chapter 7) Non-narcotics: (covered previously in this chapter) Aspirin Pyrazolone derivatives Propionic acid derivatives Flunixin meglumin Indol acetic acid derivatives Meclofenamic acid Copyright © 2004 by Delmar Learning, a division of Thomson Learning, Inc.
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