Anti-Inflammatory Agents Exam 1 Flashcards
3 phases of inflammtion:
- acute inflammation
- immune response
- chronic inflammation
STUDY THE INFLAMMATORY CASCADE
What is one of the biggest side effects of long-term anti-inflammatory use?
renal failure and gastric ulcers
What does low dose aspirin control?
platelet aggregation
The higher the dose of anti-inflammatories the more ______ _______
side effects
Effect of eicosanoids on muscle:
-vascular: vasodilation or vasoconstriction
-GI: contraction, colic
-uterus: contraction
-pulmonary: constriction (contraction)
The left side of the inflammatory cascade is only effected by what type of drug?
steroidal
The right side of the inflammatory cascade is only effected by what type of drug?
non-steroidal
What is the most important mediator of inflammation?
prostaglandin
What is the first mediator of inflammation?
arachidonic acid
NSAIDs stand for
non-steroidal anti-inflammatory drugs
What is activity of NSAIDs mediated by?
the inhibition of prostaglandins
During treatment, how is inflammation reduced with NSAIDs?
by decreasing the release of mediators from granulocytes, basophils, and mast cells
All NSAIDs are:
-analgesic (relieve pain by reducing inflammation)
-anti-inflammatory
-antipyretic
-anti-endotoxic
-anti-thrombotic (inhibit platelet aggregation)
-gastric irritants
NSAIDs can cause ______ problems
kidney
Why should NSAIDs not be taken after surgeries?
because we need the inflammation to be able to heal
How are NSAIDs different from opioids (pain killers)
opioids work on receptors in the brain
NSAIDs used in horses:
-flunixin meglumine (banamine)
-phenylbutazone (bute)
-ketoprofen
-naproxen
-firocoxib
-aspirin
-dypirone
Stacking
using more than 1 NSAID - increasing chances of side effects, usually done in the case of an emergency
Uses for NSAIDs:
-relieving pain
-reducing fever
-counteracting endotoxemia
-reducing excessive blood clotting
Analgesia (reducing pain) process
prostaglandin produce pain, by reducing prostaglandins NSAIDs provide pain relief
Anti-pyretic (reducing fever) process:
prostaglandins produced during both infection and inflammation cause fever
-fever is a natural mechanism the body uses to fight infection but when it is too high it can cause irreversible brain damage
Counteracting Endotoxemia process
endotoxemia is where bacteria toxins reach the bloodstream
-these toxins can be life-threatening
-generally flunixin meglumine is the preferred NSAID for this
Reducing excessive blood clotting process
by blocking thromboxane production, NSAIDs help maintain blood flow in situations where excessive blood clotting causes problems
Phenylbutazone
-aka bute
-potent pain reliever, antipyretic, and anti-inflammatory
What is bute commonly used for?
-lameness resulting from soft tissue injury
-muscle soreness
-bone and joint problems
-laminitis
How can bute be given?
IV or PO
How long does it take for bute to start relieving pain/reducing fever?
1-2 hours
What should you do for a horse that needs to be on bute for more than a few days?
use drugs that protect the GI tract
Drugs that help protect the GI tract while taking NSAIDs
-omeprazole
-cimetidine
-ranitidine
Flunixin Meglumine
-aka banamine
What are the uses for flunixin meglumine?
-pain relief in the treatment of colic
-protection from septic/endotoxic shock due to any GI insult
-used as an anti-inflammatory in the treatment of painful conditions of the eye
-may be used to reduce or control fevers due to viral or bacterial infections
What can banamine cause?
GI ulcers
How can banamine be administered?
IV or PO
What can happen if banamine is given IM?
clostridial myositis (C-diff)
anaerobic bacteria
How is cortisol produced?
produced by the adrenal cortex gland in a negative feedback loop
What is cortisol released by?
the hypothalamus and pituitary adrenal axis
What does cortisol do?
-proper glucose metabolism (gluconeogenesis = synthesis of new glucose)
-regulation of blood pressure
-insulin release for blood sugar maintenance
-immune function
-inflammatory response
When are cortisol levels naturally higher?
in the morning
What is the negative feedback loop of cortisol?
- hypothalamus (in brain) signals the release of corticotropin releasing hormone
- this gets sent to the pituitary and signals the release of adrino-corticotropic hormone
- This gets send to the adrenal gland (top of kidneys) and signals the release of cortisol
- Cortisol than signals the hypothalamus to either shut off or release more cortisol and the loop begins again
What does the adrenal gland release?
-cortisol
-epinephrine (adrenaline)
Cortisol
-called the stress hormone
-its levels increase in fight or flight responses (quick burst of energy for survival reasons, heightened memory functions, burst of increased immunity, lower sensitivity to pain, helps maintain homeostasis)
What happens when one has prolonged levels of cortisol in the blood stream (chronic stress)?
-impaired cognitive performance
-suppressed thyroid function
-blood sugar imbalances such as hyperglycemia
-decreased bone density
-break down of muscle tissue, muscle wasting
-higher blood pressure
-increased fat deposits
-lowered immunity and inflammatory responses in the body
What lowers stress and cortisol levels?
exercise
Metabolic effects of cortisol
-carbohydrate, protein, and fat metabolism
-increase serum glucose
-stimulate insulin release and lipogenesis (fat deposits)
Metabolism
cells doing their jobs to survive
Catabolism
breaking down
Catabolic effects of cortisol
-supraphysiologic amounts of steroids lead to decreased muscle mass and weakness
-osteoporosis (bone breaking down)
Anabolism
building up
What anti-inflammatory effects does cortisol have?
effects on concentration, distribution, and function of peripheral leukocytes
-reduced prostaglandin, leukotriene, etc.
What immunosuppressive effects does cortisol have?
inhibit functions of macrophages and antigen-presenting cells
-inhibit ability of macrophage to phagocytose and kill microorganisms
What does cortisol reduce the production of?
antibodies
PPID/Cushings
the excessive circulating glucocorticoids
-the pituitary continues to secrete cortisol even if triggered to shut off/there are already too high levels
Cushings symptoms
-fat deposition
-obesity
-excessive hair
-poor wound healing
-osteoporosis
-insulin resistance
-laminitis
When do horses usually get cushings?
when they get older
Uses for synthetic coricosteroids
-allergies: hives, heaves
-auto-immune disorders
-traumatic brain injuries
-recurrent uveitis (blindness)
-joints
-other inflammatory disorders
What are short and medium acting steroids?
-cortisone
-hydrocortisone
-prednisone (don’t use in horses)
-prednisolone
-meprednisone
What are long acting steroids?
-dexamethasone
-betamethasone
Formulations of steroids (how they can be given)
-PO
-IV
-IM
-aerosol
What steroid helps decrease brain swelling in traumatic brain injuries?
cortisol
When do severe side effects occur with steroid use?
with long-term administration of the drug
How should a horse stop taking a steroid drug?
withdrawing slowly and tapering the dosage and prolonging the interval between doses
Side effects of steroid
-suppressed immune response (if not the desired effect)
-polyuria,polydipsia (excessive urinating and drinking)
-cause or worsen gastric ulcers
-laminitis
In what horses should steroids not be used?
in horses with cushings
Steroids mimic what natural hormone?
cortisol
Process of steroids acting on the body
when they are given, CRH and CTRH are no longer being produced (the cortisol negative feedback loop is shut down), so it must be tapered down to allow the body to start naturally producing cortisol again (by activating the hypothalamus pituitary adrenal axis (HPA))
What does chronic administration of steroids suppress?
the pituitary release of ACTH, GH, TSH, and LH
What types of fat does steroids increase?
-visceral
-facial
-nuchal
-supraclavicular
Why does osteoporosis occur from steroid use?
antagonizes effects of vitamin D on calcium absorption
When is dexamethasone used in higher doses?
-in emergencies
-anaphylactic reactions
-spinal chord trauma
-shock
-any CNS trauma (helps shrink the brain)
When is dexamethasone used in lower doses?
-treat allergic reactions: heaves, hives, itching
-inflammatory diseases: arthritis
Why do horses not receive prednisone?
they do not absorb it
When choosing a short term steroid what should you use for horses?
prednisolone
What is fluticasone used for?
to control heaves
How is fluticasone given?
as aerosol (nebulizer or air mask)
-more localized effects so less chance of side effects
What is triamcinolone used for?
join injections
What is Methyl-prednisolone used for?
SI injections
