anti-inflammatory agents Flashcards
acute inflammation
initial response to injury, release of pro-inflammatory mediators, precedes immune response
pro-inflammatory mediators examples
histamine, seratonin, bradykinin, prostaglandin, leukotrienes
chronic inflammation
different mediators than acute inflammation, causes pain, destruction of tissue and disability
what do non-steroidal drugs block?
they do not allow cyclooxygenase to have effect, preventing prostaglandin formation
what to steroidal drugs inhibit?
steriods inhibit phospholipase production
Arachidonic acid
first precursor to all inflammatory mediators
COX 1 functions
present in stomach cells and aid in mucous production in the stomach. when it is inhibited, ulcers may occur
effect of eicosanoids on muscle
vascular: vasoconstriction or vasodilation, GI:contraction or colic Uterus:contraction (may cause abortion in mares) pulmonary:constriction
Non-steroidal anti-inflammatory drugs (NSAIDS) mode of action
activity of the drug is mediated by inhibition of prostaglandin, during treatment inflammation is reduced by decreasing the release of mediators from granulocytes, basophils and mast cells.
NSAID characteristics
analgesic, anti-inflammatory, antipyretic and inhibit platelet aggregation (aspirin is irreversible). they are gastric irritants (cuts mucous production) and can cause kidney problems (by prolonged use or too long of a dose)
analgesic
treat pain
antipyretic
treats fever
common NSAIDs used in horses
flunixin meglumine (banamine), phenylbutazone,ketoprofen, naproxen,firocoxib (like prevacox, used for arthritis), aspirin, dypirone
uses for NSAIDs
relieving pain, reducing fever, counteracting endotoxemia, reducing excessive blood clotting
how do NSAIDs relieve pain?
prostaglandins produce pain, by reducing prostaglandins, pain is reduced
how do NSAIDs reduce fever?
prostaglandins produced during both infection and inflammation cause fever, while high fever is a way to fight infection, high fever can denature proteins and cause irreversible brain damage
how do NSAIDs counteract endotoxemia?
endotoxemia is when bacteria toxins reach the bloodstream. these toxins can be life threatening. generally flunixin melglumine (ban amine) is the preferred NSAID for endotoxic effects
how do NSAIDs reduce excessive blood clotting?
by blocking thromboxane production, NSAIDs help maintain blood flow in situations where excessive blood clotting causes problems ex. thromboembolic colic
thromboembolic colic
clots in the blood vessels that supply GI tract can lead to necrosis of portions of the intestine
phenylbutazone
potent pain reliever, antipyretic and anti-inflammatory, commonly used for lameness, resulting from soft tissue injury, muscle soreness, bone and joint problems and laminitis, may be given IV or orally, pain relief and fever reduction usually within 1-2 hours. if a horse needs bute for more than a few days,use drugs that protect the GI tract
fluxinin Meglumine
used for pain relief in the treatment of colic, used for protection from the septic/endotoxic shock due to any gastrointestinal insult, used as an anti-inflammatory in the treatment of painful conditions of the eye (corneal ulcers, uveitis,conjunctivitis,and before/after eye surgery), may be used to reduce or control fevers due to viral or bacterial infection, may be given IV, IM or PO. can cause GI Ulcers
cortisol production
stress hormone, produced by the adrenal cortex and synthesized from cholesterol
actions of cortisol
aids in proper glucose metabolism, regulation of blood pressure, insulin release for blood sugar maintenance, immune function (decreases immune activity), inflammatory response (impedes immediate pain with huge surges)
when are there higher levels of cortisol in the body
in the morning, stressed horses have higher level of cortisol
functions of cortisol in a fight or flight situation
gives quick burst of energy for survival reasons, heightened memory functions (remember tiny details of an event), burst of increased immunity (then immunity decreases afterwards), lowers sensitivity to pain, helps maintain homeostasis in the body
effects of prolonged levels of cortisol in the bloodstream
impaired cognitive performance, suppressed thyroid function (makes people tired), blood sugar imbalances such as hyperglycemia, decreased bone density, higher blood pressure, lowered immunity and inflammatory responses in the body, slowed wound healing and other health consequences
what type of feedback does cortisol have
negative feedback, when levels of cortisol are high, cortisol is not produced, dexamethasone and prednazone cause the body to think there is increased levels of cortisol in the body so CRH and ACTH are not produced
Metabolic effects of Glucocorticoids
carbohydrate protein and fat metabolism. increase serum glucose, stimulate insulin release and lipogenesis (production of fat tissue)
catabolic effect of glucocorticoids
supra physiologic amounts o steroids lead to decreased muscle mass and weakness..catabolic effect on bones is osteoperosis
anti-inflammatory effects of glucocorticoids
effects on concentration, distribution and function of peripheral leukocytes. reduces leukotrienes, prostaglandin etc.
immunosuppressive effects of glucocorticoids
inhibit functions of macrophages and antigen presenting cells, inhibits the ability of macrophages to phagocytise and kill microorganisms, antibody production is reduced by large doses on steroids
side effects of glucocorticoids
chronic administration suppresses the pituitary release of ACTH, growth hormone, thyroid suppressing hormone and leutenizing hormone, increases body fat(visceral, facial nuchal and supraclavicular), antagonizes effects of vitamin D on calcium absorption (bones become frail)
use of synthetic corticosteroids
used in treatment of inflammatory, allergic and other disorders, great for allergies, tendon injuries, heaves etc
types of synthetic corticosteroids
short and medium acting (works 1-12 hours):cortisone, hydrocortisone, prednisone,prednusolone,meprednisone long acting (lasts 24 hours): dexamethasone, betamethasone
uses of corticosteroids
used to diagnose cushings syndrome, given for allergies (hives, heaves->give lowest possible dose), recurrent uvitis, dex may be used in joint injections to reduce swelling, may be given PO,IV,IM or aerosol, should not be used in horses with cushings because the horse already has a high level of cortisol.
cushings syndrome symptoms
fat deposition, obesity, excessive hair coat, poor wound healing, osteoporosis, insulin resistance and laminitis. caused by a tumor in the pituitary gland that results in excessive ACTH production
dexamethasone suppression test
used to test for cushings, if the horse does not have cushings, the horse will not produce ACTH. In true cushings cases, negative feedback does not occur so ACTH continues to be produced even when dex is given
Side effects of synthetic corticosteroids
usually occur with long term use of the drug, especially when high doses are used. Alternate day therapy with short acting preparations is preferred. withdraw drug slowly by tapering the dosage and prolonging interval between doses. corticosteroids suppress the immune system response so animals are more susceptible to infection, may mask signs of infection such as fever. polyuria, polydipsia and muscle wasting can be seen with prolonged use, may cause or worsen gastric ulcers, laminitis
dexamethasone
used in high doses in emergencies for anaphylactic reactions, spinal cord injuries or shock, used in lower doses to treat allergic reactions such as heaves, hives itching and inflammatory diseases like arthritis
prednisone and prednisolone
horses do not absorb prednisone so use prednisolone when choosing a short term steroid
fluticasone
used to control heaves, given as aerosol
