Title: Anti-inflammatory
1Anti-inflammatory Pain-reducing drugs
2OBJECTIVES
- 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
3Terminology
- 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
4MOA - Inflammation
EICOSANOIDS
5ARACHIDONIC 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
6Anti-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)
7Steroidal 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
8Glucocorticoids-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)
10Glucocorticoid - 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
11Glucocorticoid - 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
12Cushings 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
13Addisons 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
14Uses 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)
15CORTICOSTEROIDS (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
16Glucocorticoids - 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
17Safe 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
18NSAID
- 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
19Non-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
20NSAID - 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
21References
- Bill, R.L. Clinical Pharmacology and Therapeutics
for the Veterinary Technician, 3rd edition. 2006. - Romich, J.A. Pharmacology for Veterinary
Technicians, 2nd edition. 2010.