1) Destroy bacteria and direct other cells of the process
2) Start to clean up mess by removing dying cells
3) Pave the way for healing process
Main WBC involved in inflammation
Neutrophils followed by lymphocytes
WBC squeeze through a junction between endothelial cell
How do corticosteroids work?
Block action of phospholipase and stops the progression of inflammation
2 kinds of corticosteriods
Synthethic corticosteroids naturally are called..
Where are glucocorticoids released from?
How do glucocorticoids work?
Deposit glycogen in liver
Increase blood glucose levels
Have little or no effect of inflammation, associated with water and electrolyte balance
3 types of corticosteroids
Last less than 12 hours, hydrocortisone which is cortisone until it goes through biotransformation twice
Short acting corticosteroid
Lasts between 12 and 36 hours, Prednisone and Prednisolone.
Intermediate acting corticosteroid
Lasts longer than 48 hours, Dexamethasone. Called "methasones"
Long acting corticosteroids
3 liquid forms of corticosteroids
Combined with salt to make soluble in water
EX: Sodium phosphate and sodium succinate
No sallt and no additives
Suspended in diluent. Crystals suspension dissolve over several days and release small amounts of glucocorticoid each day and provide prolonged duration
Reduce capillary permeability
Catabolic effect on proteins
Causes stress triad
How do corticosteroids reduce inflammation?
By blocking conversion of arachidonic acid to eicosanoids
How do corticosteroids reduce capillary permeability?
By reducing production of cell factors that cause increased vascular permeability of the capillaries and so help maintain integrity of the capillaries and reduce some of the mechanisms of swelling in injured tissues
How do corticosteroids cause abortions?
Due to exogenous corticosteroids. After 20 days of gestation the bitch will abort in 2-5 days after steroids.
What is a stress triad?
Decreasing numbers of lymphocytes and eosinophils. Increase in neutrophils and thromboycytes.
Lymphopenia, eosionopenia and neutrophilia
Jugular is located between what two muscles?
Sternocephalicus and brachiocephalicus
Why do we not give a steroid shot before giving vaccines to patients who have reactions?
Steroids suppress immune system and allows virus to replicate inside the animal
Contraindications for steroids
Systemic or local fungal infection
Suppress immune system
Increase platelets and neutrophils
Decrease lymphocytes, eosinophils and monocytes
Iatrogenic diseases caused by steroids
Can occur naturally or by parenteral or oral Rx of corticosteroids by clinician. Selegiline hydrochloride suppresses MOTB which suppresses dopamine and cortisol from zona fasciculata
Symptoms of cushings disease
Alopeica, muscle wasting, polyuria, polydipsia, polyphagia, pot belly and thin skin
Results from animal being taken off steroids after years of administration can go from hyper to hypo over night
How do NSAID stop inflammation?
By blocking activity of cyclooxygenase and subsequent production of prostaglandins
Inhibiting COX-1 and COX-2 to varying degrees
Why are NSAID's not considered analgesics
They reduce discomfort and pain associated with inflammation but not visceral or somatic pain at the CNS level
Side effects of NSAID's
Bone marrow suppression
What was used to combat pain before modern medicine?
Willow bark, active ingredient is salicylic acid
How did Bayer make aspirin?
Added acetyl group to salicylic acid and created acetylsalicylic acid
What happened in 1971 in regards to NSAID's?
JR Vane discovered that NSAID's blocked production of prostaglandins from arachidonic acid, creating the Vane Model
What happened in 1976 in regards to NSAID's?
Prostaglandin synthase was identified as cyclooxygenase (COX) and showed NSAID exert their effects by inhibiting production of COX and prostaglandins
Phenylbutazone- inhibits COX
Acetylsalicylic acid (Aspirin)
Flunixin Meglumine (Banamine)- cattle/horses
Carprofen (Rimadyl)- used for degenerative joint disease or postoperative pain of soft tissue
Ibuprofen (Advil)- dont use on dog/cats
Ketoprofen- Horses inflammation of muscoskeletal disorders
Dipyrone- old NSAID horses for colic
COX-1 plays a role in...
Normal tissue function
COX-2 plays a role in...
With pain, fever, inflammation
Coxibs are compounds that target inhibition of COX-2, one of the main enzymes in inflammation pathway. Older NSAID targeted COX-1 as well causing gastric side effects.
What year was COX-1 and COX-2 first discovered?
Which COX has a larger active site?
COX-1 is always present in many tissues and therefore...
Enzymes are called “housekeeping” prostaglandins and are required for homeostatic activity in the GI tract, kidney, and platelets
Which COX inhibitors are less toxic?
Proinflammatory prostaglandins are produced by the induction of which COX?
COX-2, drugs producing specific COX-2 effects would be more effective in producing analgesic, anti inflammatory and antipyretic effects.
Functions of COX-1
Thromboxane A2 required for normal platelet function
Prostaglandin E2 required for sodium homeostasis in kidneys
Endogenous prostaglandins function to protect GI tract
Functions of COX-2
Apoptosis in cancer cells (shrinkage)
Bone response to mechanical stress
Receptors for pain
What happens if you inhibit COX-1 enzymes for a long time?
GI ulceration, erosion
Adverse effects on renal functions
Problems with homeostasis (platelets)
Inhibition of COX-1 and COX-2 produces what 2 things?
Decrease in pain
Decrease of inflammation
Joint injury and/or cartilage damage triggers inflammation and what...
COX-2 functions with increased production of inflammatory eicosanoids, PGE2 from arachidonic acid
PGE2 promotes production of what..?
Matrix metalloproteinases (MMPs), enzymes that break down cartilage
In regards to joint mobility inflammation promotes oxidative stress, what does that mean?
Inflammation decreases tissue inhibitor of metalloproteinase (TIMP) which normally reduces impact of cartilage-damaging MMPs
How does diet help with joint mobility?
Diet encourages COX-2 to convert eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into less inflammatory PGE3 resulting in less PGE2 and less cartilage damage
What are chondroprotective agents?
Medicines that slow the process of arthritis in joints by supporting the health of the joint cartilage
Examples of chondroprotective agents
Polysulfated glycosaminoglycans (PSGAGs)
Glucosamine and chondroitin sulfate
How do PSGAGs work for the joints?
Trap water and act as a moisturizer for cartilage
Adequan injectable reduces activites of MMPs in joint fluid that degrade cartilage
How does hyaluronic acid work for the joints?
Natural component found in synovial fluid and acts as a lubricant and suppresses PGE2
Legend or Hyalovet IV or injected into joint space
How do glucosamine and chondroitin sulfate work on joints?
Increase efficiency of chondrocytes to repair cartilage
Stimulates prodution of hyaluronic acid
Inhibit destructive MMP
Used to differentiate activity of NSAIDs and their effects on COX-1 and COX-2
Value is a result of an in vitro test tube under controlled conditions
The higher the value indicates preference for inhibiting COX-2 over COX-1
Coxib- class NSAIDs
Why not give cats or beagles aspirin?
The effect is on the liver metabolism, the alteration and number of RBCs, and the inability of the hemoglobin to carry oxygen and carbon dioxide.
Hemoglobin is converted to Methemoglobin which cannot carry oxygen or carbon dioxide.
Examples of drugs that can be used pre operation
Example of drugs that can be used post operation
Group of adrenocorticosteroids associated with antiinflammatory response
COX produced eicosanoids cause platelets to adhere to each other and thus contribute to the clotting mechanism
Means loss of hair and clinical sign of Cushings disease
Type of immunity provided by antibodies
Combination of NSAID use plus arterial hypotension can produce this kidney condition
Renal papillary necrosis
Lipoxygenase produced what eicosanoid
Diseases caused by the bodys own defense mechanisms turning against its own tissues, example would be lupus
Increase in neutrophils
Effect meaning that tissue is being destroyed or broken down
Type of cell that produces antibodies against invading pathogens
Refers to the outer part of the adrenal gland
Another name for hyperadrenocorticism
Enzyme that produces prostaglandins and thromboxanes
Collective term for all prostaglandins, leukotrienes, and thromboxanes produced by the arachidonic acid pathway
Means low numbers of eosionphils
Condition characterized by clinical signs consistent with insufficient amounts of glucocorticoids
Production of glycogen in the liver
Hormone released from the hypothalamus that stimulates pituitary to release ACTH
Means decreased monocytes
Means decreased size and seen in muscles and skin in animals with hyperadrenocorticism
Means that the animal has an elevated level of either natural cortisol or exogenous corticosteroids
Means the patient is exhibiting clinical signs consistent with low levels of corticosteroids
Means disease or condition caused by the vet
Hormone released by adrenal gland, is a mineralcorticoid
Arachidonic acid is acted on by COX and this enzyme to produce the eicosanoids
Group of adrenocorticosteroids affects mainly the electrolytes and water balance in the body with little or no antiinflammatory effect
Creation of glucose from amino acids
Decrease of lymphocytes in circulation
Ibuprofen, ketoprofen, naproxen all belong to the same group of compounds charaterized by this chemical structure
Type of body defense mechanism characterized by cells that attack pathogens or foreign proteins
Thromboxanes and these inflammatory mediators are produced by COX
Series of enzymes resulting in the production of eicosanoids after an injury
Arachidonic acid pathway
Cells involved in cell-mediated immunity, dont produce antibodies
Hormone released by the pituitary gland that stimulates the adrenal gland to produce corticosteroids
Adrenocorticotropic hormone (ACTH)
NSAID that comes in a rapidly disintegrating tablet, called a dual-pathway NSAID
Chondroprotective agent that is a component of the joint synovial fluid, acts a lubricant
Intermediate acting glucocorticoid that is not a pred
Older NSAID used on horses for relief of inflammation associated with the musculoskeletal system
First COX-2 selective inhibitor released for vet medical use in US
Intermediate acting corticosteroid in active form
Prednisolone, methylprednisolone, triamcinolone
Antiinflammatory that works differently from NSAIDs or glucocorticoids
Short acting glucocorticoid, topical
Besides carprofen the other three COX-2 selective inhibitors used in vet medicine
Long acting glucocorticoid that comes in aqueous solution, alcohol form, and suspension form
Prototype drug for the salicylates, OTC, hits both COX-1 and COX-2
Derivatives of propionic acid, OTC drug, high incidence of gastric ulcers when given to dogs
Ibuprofen, ketoprofen, naproxen
NSAID used primarily in horses for relief from colic, has more analgesic effect then phenylbutazone
Chondroprotective agent that mimics components of normal joint cartilage, traps water molecules and helps provide springy charateristics
Intermediate acting corticosteroid, must pass through liver to be converted to its active form, prednisolone
Nutriceutical chondroprotective agents, precursors for PSGAGs
Glucosamine and chondroitin sulfate
Human OTC drug used to relieve discomfort from pain but is not an NSAID
TRUE OR FALSE. Long acting glucocorticoid drug combined with acetate, diacetate, pivalate or valerate would identify it as an aqueous solution
TRUE OR FALSE. Vaccines should not be given to a dog that has been on prednisone for allergic skin reactions because the immune system will not be able to respond
TRUE OR FALSE. Hypoalbuminemic animals the dose of NSAIDs may have to be increased to achieve same effect on tissues
TRUE OR FALSE. Most common target organs for NSAID toxicity are the kidney and liver
False, kidney and GI tract
TRUE OR FALSE. NSAIDs should be able to provide enough analgesia to allow and animal with a broken leg to be positioned for a radiograph
Are increased retention of sodium associated with glucocorticoid effects?
Is maintain integrity of the capillaries associated with glucocorticoid effects?
Are decreased fibroblast activity associated with glucocorticoid effects?
Are decreased t-lymphocyte activity associated with glucocorticoid effects?
Are decreased scar tissue formation associated with glucocorticoid effects?
Yes, decreased fibroblasts
Are increased b-lymphocyte activity associated with glucocorticoid effects?
Is lymphocytosis associated with glucocorticoid effects?
No, caused lymphopenia
Are increased eosinophils and monocytes associated with glucocorticoid effects?
No, cause eosinopenia and monocytopenia
Are increased neutrophils associated with glucocorticoid effects?
Are muscle wasting and atrophy associated with glucocorticoid effects?
What effects do NSAIDs have on the stomach and intestinal mucus production?
Decrease mucus production
What effects do NSAIDs have on production of sodium bicarbonate by the GI tract wall?
Decrease sodium bicarbonate secretion
What effects do NSAIDs have on the repair of the GI epithelial cells?