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Anti-inflammatory

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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 ... – PowerPoint PPT presentation

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Title: Anti-inflammatory


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

12
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
13
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
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 (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)

15
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

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 Addisons
  • Cats 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
  • 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

20
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

21
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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