Transcript ANTI-INFLAMMATORIES - Claire Simms, DVM VTI

ANTI-INFLAMMATORY
DRUGS
Chapter 13
 Inflammation is a bodily process that occurs in response to
injury of the tissues caused by trauma.
 The goal of this process is to remove/isolate the cause of
the injury and to repair/replace the damaged tissue.
 Blood supply is increased to the affected area, leukocytes
migrate, and phagocytic cells become more active.
Arachidonic Acid Pathway
(pg 345)
Cell membrane
With
phospholipids
phospholipase
Arachadonic acid
cyclooxygenase
Prostaglandins
Thromboxanes
lipoxygenase
Leukotrienes
INFLAMMATION cont’d
 Signs that an animal is in pain: increased heart/respiratory
rates, mydriasis, salivation, vocalization, facial expression,
aggressiveness, guarding painful area, restlessness,
unresponsiveness, failure to groom, abnormal gait/stance.
 CORTICOSTEROID DRUGS:
-block phospholipase
 NON-STEROIDAL ANTI-INFLAMMATORY DRUGS:
-block cyclooxygenase
CORTICOSTEROID REVIEW
 Group of hormones produced by the cortex
of the adrenal glands.
 Mineralocorticoids: affect the mineral
(electrolytes) and water balance of the body
 Have little to no anti-inflammatory effect.
Aldosterone is the main mineralocorticoid.
 Glucocorticoids: inhibit phospholipase in the
arachidonic acid pathway, suppress the immune
system, and influence metabolism.
 Cortisol is the main naturally occurring
glucocorticoid.
GLUCOCORTICOID PRODUCTION
1.
Hypothalamus produces Corticotropin Releasing Hormone
when blood levels of glucocorticoids are low.
2.
This signals the pituitary to secrete ACTH.
3.
ACTH signals the adrenals to produce glucocorticoids
(Cortisol).
4.
If Cortisol levels are high, Negative Feedback will occur to inhibit
the production of CRH and ACTH until Cortisol levels fall
Effects of Glucocorticoids
 Cause gluconeogenesis, decrease the ability of glucose to
leave the blood and enter the cells, and glycogenesis.
 Increase gastric acid secretion and decrease mucus
production.
 Stress leukogram: Neutrophilia, Lymphopenia (possible
Eosinopenia and Monocytosis)
 Inhibition of fibroblasts, whose role is to help close wounds
and form scar tissue.
Effects of Glucocorticoids
 Destroy malignant lymphocytes.
 Cause catabolism of protein during gluconeogenesis.
 When used in the presence of a corneal ulcer, the protein
that forms the middle layers of the cornea can be catabolized
which deepens the ulcer. Decreased fibroblast activity will
also prolong corneal ulcer healing.
Effects of Glucocorticoids
 Myometrial contractions and cervical dilation.
 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 agents so use in the presence of a fungal infection is
contraindicated.
 High doses can also suppress humoral immunity (antibody
production by B-lymphocytes) which can effect vaccine efficacy.
SHORT ACTING – less than 12 hours
 Cortisone, Hydrocortisone
 topical
INTERMEDIATE ACTING - last 12-36 hours
 Prednisone, Prednisolone (Solu-Delta-Cortef), Methylprednisolone (Depo
Medrol), Triamcinolone (Vetalog, Panalog)
 oral or injectable
 can be given every other day and still be effective
LONG ACTING – last longer than 48 hours
 Dexamethazone, Betamethasone (Azium)
 oral or injectable
Injectable glucocorticoids
 Glucocorticoids in alcohol solutions
 Drug dissolves in alcohol without the addition of any substances to
the drug (Ex: Dexamethasone)
 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.
Injectable Glucocorticoids
 Glucocorticoids in suspensions
 Drug is not dissolved in liquid and exists as large
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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: Dexamethasone acetate)
Must be shaken
Opaque appearance
Do not give IV
Once injected, the crystals slowly dissolve over several
days, releasing small amounts of drug.
DVM Steroid Rules of
Thumb:
 If an NSAID or a glucocorticoid can be used to treat an animal,
choose the NSAID.
 If extended glucocorticoid use is required, choose an intermediateacting 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 cholesterol ring structure and have
fewer side effects than glucocorticoids, while still decreasing
inflammation.
 Most block cyclooxygenase in the arachidonic acid pathway
(block the production of Prostaglandins and Thromboxanes),
but some also block lipoxygenase (which 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!
 COX 1 (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.
 COX 2 is the cyclooxygenase that is involved in the
arachidonic acid pathway and causes inflammation.
 Using NSAIDS that selectively inhibit COX 2 should be able to
decrease inflammation without affecting kidney or stomach
health.
 Newer NSAIDS are more COX 2 selective.
 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 2selective 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 hypoproteinemia or if giving with another proteinbound drug as toxic levels can occur.
 Blocking Prostaglandins E and I (Cox 1 inhibitors) can cause
gastritis, ulcers, and signs of 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
hypotension 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 hepatotoxicity. 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!!!
COX 2 SELECTIVE NSAIDS (aka Cox 1-sparing)
 Meloxicam (METACAM)
 Approved for use in dogs and cats, however the manufacturer
cautions using it often in cats.
 Oral (liquid) and injectable
 Robenacoxib (ONSIOR)
 Approved for use in cats, dog product exists for other countries
 Oral (tablet) and injectable
COX 2 SELECTIVE NSAIDS (aka Cox 1-sparing)
 Carprofen (RIMADYL)
 Approved for dogs
 Oral and injectable
 Deracoxib (DERAMAXX)
 Dogs, oral
 Firocoxib (PREVICOX)
 Dogs, oral
NON-SELECTIVE NSAIDS
 Phenylbutazone (aka BUTE)
 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 (BANAMINE)
 Labeled for use in large animals
 Oral and injectable (ok to give IV or IM)
 fast acting- 15 minutes
MISCELLANEOUS NSAIDS
 Dimethyl Sulfoxide (DMSO)
 Does not inhibit prostaglandins, but instead
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inactivates free radicals that are produced by
inflammation
Label approval is for topical use in dogs and
horses
Smells like garlic and can cause the patient to
taste garlic
Wear gloves when applying as it can
penetrate intact skin
Bandaging over DMSO can cause skin
irritation
Teratogenic
MISCELLANEOUS NSAIDS
 Acetylsalicylic acid (ASPIRIN)
 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
 Often used in people to “thin the blood” as these drugs effectively
inhibit thromboxanes from promoting platelet aggregation
MISCELLANEOUS
 Acetaminophen (TYLENOL)
 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
 Acetaminophen (TYLENOL)
 Metabolism of Acetaminophen in cats forms a
toxic metabolite within RBCs that converts
hemoglobin to methemoglobin within, which
cannot adequately carry oxygen.
 Hemolysis and Heinz bodies are seen on smears
 Blood, urine, and mucous membrane are
“chocolate-colored”
 Acetylcysteine (Mucomyst), a mucolytic, converts
the toxic metabolite to a nontoxic form
OTHER METHODS OF
PAIN/INFLAMMATION REDUCTION:
 Cyclosporine – ATOPICA
 Anti-inflammatory, anti-pruriticthat is an immunosuppressant
(T- lymphocytes)
 Used for skin conditions, cancer, and when other
immunosuppression is necessary
 Oclacitinib- APOQUEL
 Newly released anti-inflammatory used to treat pruritis by
inhibiting cytokines
 Currently only approved for dogs over 1 year of age.
 NARCOTICS - OPIODS