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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

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objectives
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
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
arachidonic pathway
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
anti inflammatory drugs
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)
steroidal anti inflammatories
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
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
slide9

Glucocorticoids are natural hormones

  • adrenocorticotropic hormone (ACTH)
  • corticotropin-releasing factor (CRF)
glucocorticoid pros
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
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
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

addison s disease hypoadrenocorticism
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

uses for glucocorticoid drugs
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

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
glucocorticoids formulations
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
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
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

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
nsaid con
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 > 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
references
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.
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