Anti-inflammatory

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Anti-inflammatory Pain-reducing drugs

• Chapter 13 -1

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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

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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

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MOA - Inflammation
EICOSANOIDS
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ARACHIDONIC PATHWAY
Phospholipids cell membrane

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

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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)

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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/ Addisons
• hyperkalemia, hyponatremia because of a lack of
  aldosterone production
• TX desoxycorticosterone pivalate (Percorten-V
• glucocorticoids

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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

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

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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
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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 gt deepening
  ulcer, Desmetocele poor prognosis
• /- induce abortion cattle and mares , bitches
• Stress leukogram lymphopenia, monocytopenia,
  eosinopenia, neutrophilia sequestered - lungs,
  spleen

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Cushings Disease (hyperadrenocorticism)

• Corticosteroids catabolic breakdown of protein
  gt 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 DONT GIVE TOO MUCH EOD
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Addisons Disease (hypoadrenocorticism)

• extended use of glucocorticoid lack of CRF and
  ACTH
• adrenal cortex begins to atrophy gt natural
  cortisol is diminished.

weakness, lethargy, vomiting, and/or diarrhea
Taper off slowly
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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 (Addisons) OR iatrogenic
  cushions 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 (Dont use in pregnant
  animals)

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CORTICOSTEROIDS (ADRENOCORTICOSTEROIDS)
GLUCOCORTICOIDS
Topical steroids almost always effect
systematically so dont give to
immunocompromised/ pregnant animals

• Short-acting lt 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

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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

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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 Addisons
• Cats not really affected

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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

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Non-Steroidal Anti-inflammatory Drugs
IDEAL DRUG COX 2 INHIBITOR Newer NSAID
Deramaxx, Rimadyl, etogesic

• NSAIDs work by blocking the activity of
  cyclooxygenase gt inhibit prostaglandins.
• Few NSAIDs such as ketoprofen, ibuprofen, and
  tepoxalin (Zubrin) gt 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

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NSAID - CON
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 gt 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

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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.