Download ANTI-INFLAMMATORIES

ANTI-INFLAMMATORY
DRUGS
Chapter 13
 Inflammation is a protective mechanism that occurs in response to
injury of the tissues.
 The goal of this process is to protect and stabilize the affected area
and improve the healing process.
 If inflammation interferes with the animal’s function or if it is
autoimmune in nature, it should be suppressed to avoid damaging
the healthy surrounding tissues.
 Two categories of drugs reduce inflammation: _______________ and
__________________anti-inflammatory drugs

Arachidonic Acid Cascade
(pg 297)
A pathway that generates inflammatory mediators called
______________________.
1st: The cell membrane’s PHOSPHOLIPID BILAYER is traumatized.
2nd: Phospholipase is activated and converts the phospholipids to
ARACHIDONIC ACID.
3rd: Either Cyclooxygenase and Lipoxygenase break down ARACHIDONIC
ACID.
4th : Cyclooxygenase produces PROSTAGLANDINS and THROMBOXANES.
Lipoxygenase produces LEUKOTRIENES.
PROSTAGLANDINS, THROMBOXANES, AND LEUKOTRIENES produce
the 5 signs of inflammation
Steroids block the action of Phospholipase and Cyclooxygenase,
NSAIDS block the action of Cyclooxygenase and Lipoxygenase.
CORTICOSTEROID REVIEW
 Group of hormones produced by the adrenal
cortex.
 Mineralocorticoids: affect the mineral
(electrolytes) and water balance of the body at
the kidney.
 Have little to no anti-inflammatory effect.
 __________________ is the main mineralocorticoid.
__ Na, __ K. Addison’s disease occurs when
Aldosterone is not adequately produced.
 Glucocorticoids: inhibit the arachidonic acid
cascade, suppress the immune system, and
influence metabolism.
 _______________ is the main naturally occurring
glucocorticoid. All body cells have glucocorticoid
receptors (which is why these drugs have so many
side effects).
GLUCOCORTICOID PRODUCTION
1.
Hypothalamus produces Corticotropin Releasing Hormone when
blood levels of glucocorticoids are low.
2.
This signals the pituitary to secrete Adrenocorticotropic Hormone.
3.
ACTH signals the adrenal glands to produce Cortisol.
4.
If Cortisol levels are high, NEGATIVE FEEDBACK will occur to inhibit
the production of CRH and ACTH until Cortisol levels fall below
normal.
SHORT ACTING – last less than 12 hours
 hydrocortisone
 Topical for skin inflammation
INTERMEDIATE ACTING - last 12-36 hours
 prednisone, prednisolone (______-______-_______), methylprednisolone
(______ ________), triamcinolone (_________,___________)
 oral or injectable
 can be given every other day and still be effective
LONG ACTING – last longer than 48 hours
 dexamethazone, betamethasone (________), flumethasone, isoflupredone
(___________)
 oral or injectable
Injectable glucocorticoids
• Glucocorticoids in aqueous solutions
 Drug is combined with a salt to make the drug
dissolvable in water (Ex: dexamethasone
sodium phosphate).
 Can be given in large amounts IV, so are often
used in emergency situations.
 Glucocorticoids in alcohol solutions
 Drug dissolves in alcohol without the addition of
any substances to the drug (Ex:
dexamethasone)
 Can also be given IV
Injectable Glucocorticoids
 Glucocorticoids in suspensions
 Drug is not dissolved in liquid and exists as large
crystals. Follow label instructions for storage info.
Extreme temps can cause the crystals to change
size/shape.
 Name has acetate, diacetate, pivalate, or valerate
added to it (Ex: triamcinolone acetonide)




Must be shaken
Opaque appearance
Do not give IV
Once injected, the crystals slowly dissolve over several
days, releasing small amounts of drug.
Effects of Glucocorticoids
Doses of glucocorticoids are low (_______________), medium
(______________________), and high (________________________).
Doses above physiologic can cause the following side effects:
1) Cause gluconeogenesis while simultaneously decreasing the
body’s response to insulin.
 Proteins go through catabolism during gluconeogenesis. The
sources of these proteins are skeletal muscle and collagen in
skin/wounds. Hence, gluconeogenesis also causes thin skin, pot
belly, and prolonged healing.
Effects of Glucocorticoids
 2) Decrease autoimmune response.
 Suppress T-lymphocytes which provide cell-mediated immunity
(encourages phagocytic cells to engulf foreign materials and/or
invaders). Cell-mediated immunity is the main defense against
fungal and bacterial agents so use in the presence of them is
contraindicated.
 Very high doses can also suppress humoral immunity (antibody
production by B-lymphocytes) which can effect vaccine efficacy.
• 3) Stress leukogram: neutrophilia, lymphopenia, eosinopenia
 4) Destroy malignant lymphocytes (often used with lymphoma
treatment).
Effects of Glucocorticoids
 5) Increase gastric acid secretion and decrease mucus production (ulcer
risk).
 6) Suppression of Antidiuretic Hormone, so PU/PD is noted.
 7) When used in the presence of a corneal ulcer, collagen that forms the
middle layers of the cornea can be degraded, which deepens the ulcer.
Decreased fibroblast activity will also prolong corneal ulcer healing.
(Note: horses on ophthalmic steroid medication are more prone to ocular
fungal infections due to their environment.)
 8) Myometrial contractions and cervical dilation.
Hyperadrenocorticism (Cushing’s) Review
 Iatrogenic Cushing’s is caused by glucocorticoid
administration to an animal.
 Clinical signs: poor hair coat, thin skin, muscle atrophy,
alopecia, pot-belly, polyuria, polyphagia, polydipsia
 Steroids should always be tapered to slowly stimulate the
atrophied adrenal glands and avoid an Addisonian crisis.
DVM Steroid Rules of Thumb:
• The animal should ideally have a diagnosis before the start of steroid
therapy as it is usually aimed at decreasing the signs of inflammation, not
the cause of the disease.
 If an NSAID or a glucocorticoid can be used to treat an animal, choose
the NSAID.
 If extended glucocorticoid use is required, choose an intermediate-acting
drug instead of long-acting to decrease adrenal atrophy.
 Use the smallest dose that provides a response and alternate day
therapy if possible.
 Taper an animal off of steroids by gradually reducing the dose and
frequency.
NON-STEROIDAL ANTIINFLAMMATORY DRUGS
(NSAIDS)
 Drugs that do not contain a _______________ ring structure
and have fewer side effects than glucocorticoids, while still
decreasing inflammation.
 Block cyclooxygenase in the Arachidonic Acid Cascade
(block the production of Prostaglandins and Thromboxanes),
but some also block lipoxygenase (blocks the production of
Leukotrienes).
 Because glucocorticoids work higher up in the pathway (by
blocking phospholipase), they are said to be more effective
anti-inflammatory medications than NSAIDS, however they
have more side effects.
A note about cyclooxygenase:
 -There is also Cyclooxygenase in the body that exists outside of
the arachidonic acid pathway!
 __________ (the good one), plays a major role in the
health of the stomach and kidneys by providing
prostaglandins that aid in their function.
 Prostaglandins in the stomach provide a balance between mucus
production and HCl secretion.
 Prostaglandins in the kidney counteract vasoconstriction to allow for
adequate blood supply to the kidney.
 __________ (will inflame you) is the cyclooxygenase that is
involved in the arachidonic acid pathway and causes
inflammation.
 Newer NSAIDS are more selective about inhibiting COX
2.
 Using NSAIDS that selectively inhibit COX 2 should be
able to decrease inflammation without damaging the
kidney or stomach.
 The catch is that research has shown that COX 2 has
been found to also play a role in gastric and renal health
and COX 1 can produce some prostaglandins that
encourage an inflammatory response. Also, when higher
doses of COX 2- selective NSAIDS are used, the
selectivity for COX 2 decreases.
 Still, COX 2 selective NSAIDS generally have fewer
gastric and renal side effects that non-selective
NSAIDS.
NSAID SIDE EFFECTS
 -All NSAIDS are highly protein-bound. Use with caution in
animals with __________________ or if giving with another
protein-bound drug as toxic levels can occur.
 Cox 1 inhibitors reduce the production of Prostaglandin E. This
can cause gastritis, ulcers, and GI upset. Animals on NSAIDS
long-term or that have received an overdose can be treated
with H2 antagonists, proton pump inhibitors, misoprostol,
and/or sucralfate.
NSAID SIDE EFFECTS
 The body naturally constricts blood flow to the kidney when
_________________ occurs. PGE is released by the kidney to
counteract this and maintain perfusion of the nephron. By
inhibiting COX 1, PGE cannot enhance renal blood flow
during times of hypotension and parts of the kidney can
become necrotic due to lack of oxygen.
 All NSAIDS (whether selective or not), have the potential to
produce __________toxicity. The cause is unknown and
occurrence is unpredictable.
NSAID SIDE EFFECTS
 By decreasing the activity of Thromboxane, NSAIDS may
cause the patient to bleed due to reduced platelet aggregation.
 Monitoring bloodwork is important for patients with NSAIDS.
Kidney and liver values should be assessed.
 DO NOT USE MULTIPLE NSAIDS OR AN NSAID +
CORTICOSTEROID SIMULTANEOUSLY!!!
NON SELECTIVE NSAIDS
 acetylsalicylic acid (_____________)
 Same family as salicylates
 Cats cannot metabolize salicylates rapidly due to low levels of the
liver enzyme needed for metabolism, so they are highly susceptible
to overdose. (NOTE: aspirin is used for saddle thrombus tx in cats
and uveitis tx in horses)
 Often used in people to “thin the blood” as these drugs effectively
inhibit thromboxanes from promoting platelet aggregation
 Other non selective common NSAIDS that humans use are ibuprofen
(__________ & __________) and naproxen (___________). These
should not be used in animals due to severe side effects!
NON-SELECTIVE NSAIDS
 phenylbutazone (aka __________)
 Commonly used in large animals. Approved,
but not commonly used in dogs
 Oral (tablet, bolus, paste, gel, powder) and
injectable
 Injectable should be given by IV only! IM or
SQ can cause tissue necrosis/sloughing
 Can cause bone marrow suppression with
long-term use
NON-SELECTIVE NSAIDS
 fluninxin meglumine (______________)
 Labeled for use in large animals
 Oral and injectable (ok to give IV or IM)
 fast acting- 15 minutes
NON-SELECTIVE NSAIDS
 diclofenac sodium (______________)
 Topical NSAID that treats lameness in horses
 Can have some systemic absorption so care must be taken to
not “over apply”.
 Wear gloves to avoid human absorption
 Ophthalmic formulation available
COX 2 SELECTIVE NSAIDS (aka Cox 1-sparing)
 carprofen (____________)
 1st veterinary-approved COX2
selective inhihibitor
 Approved for dogs (more species in
other countries)
 Oral and injectable
 deracoxib (_____________)
 Dogs, oral
 firocoxib (___________,
___________)
COX 2 SELECTIVE NSAIDS (aka Cox 1-sparing)
 meloxicam (_____________)
 Approved for use in dogs and single use in cats.
 Oral (liquid) and injectable
 robenacoxib (_______________)
 Approved for use in cats and now, dogs too
 Oral (tablet) and injectable
 Labeled for 3 day use
Onsior Pain Drug Approved for Dogs
Medication may be used to counter
postoperative pain and inflammation.
BY VETERINARY PRACTICE NEWS EDITORS
Published: 2016.12.08 09:22 AM
MISCELLANEOUS NSAIDS
 dimethyl sulfoxide (________)
 Compound derived from wood pulp
 Does not inhibit prostaglandins, but instead inactivates free
radicals that are produced by inflammation
 Can penetrate the skin and is used as a vehicle for dissolved
drugs.
 Clean the skin before applying!
 Label approval is for topical use in dogs and horses
 Smells like garlic and can cause the patient to taste garlic.
Apply in ventilated area.
 Wear gloves when applying
 Bandaging over DMSO can cause skin irritation
 Teratogenic
MISCELLANEOUS
 acetaminophen (________________)
 Technically not an NSAID, but it is often grouped with
NSAIDS. It decreases pain perception and decreases the
effects of pyrogens (fever-producing agents) in the body.
 Because it does not inhibit prostaglandins or
thromboxanes, it will not directly lead to ulcers or interfere
with platelet clumping.
 CATS SHOULD NEVER BE GIVEN ACETAMINOPHEN as
one dose can kill them.
MISCELLANEOUS
Metabolism of acetaminophen in cats forms a
toxic metabolite within RBCs that converts
hemoglobin to methemoglobin, which cannot
adequately carry oxygen. The metabolite also
accumulates in the liver, causing damage.
Hemolysis and Heinz bodies are seen on smears
Blood, urine, and mucous membranes are
“chocolate-colored”
acetylcysteine (Mucomyst), a mucolytic, converts
the toxic metabolite to a nontoxic form
OTHER METHODS OF PAIN/INFLAMMATION
REDUCTION:
 cyclosporine (_____________)
 Anti-inflammatory, anti-pruritic that is an immunosuppressant (Tlymphocytes)
 Used for skin conditions, cancer, and when other immunosuppression is
necessary
 oclacitinib (_____________)
 Newly released anti-inflammatory used to treat pruritis by inhibiting
cytokines
 Currently only approved for dogs over 1 year of age.
 NARCOTICS - OPIODS