Lec7 Flashcards
What is inflammation?
a natural response of living tissue to injury and infection to initiate the healing process; Is the protective response elicited by injury or destruction of tissues
May be caused by chemical, physical or biologic agents
Serves to destroy, dilute, and sequester both the injurious agent and the injured tissue
What are the characteristics of Inflammation?
Pain – due to tissue swelling and release of prostaglandins
Heat – due to increased blood accumulation
Redness – due to blood accumulation
Swelling – increased capillary permeability allows plasma to leak into the interstitial tissue at the injury site
Loss of Function or Decreased Range of Motion – pain and fluid accumulation
What is the Inflammatory Pathway
Tissue trauma –> Phospholipase release –> break down to Arachidonic Acid –> enzyme reactions (Cyclogenase, Lipoxygenase) –> Cylogenase rxns: Prostaglandins and Thromboxanes, Lipoxygenase rxns: Leukotrienes
How does Cyclogenase act in inflammation?
–> Prostaglandins (inflammation mediator/vasodilation) and Throboxanes (platelet aggregation/ smooth muscle constriction)
How does Lipoxygenase act in inflammation?
–> Leukotrienes (induce inflammation / increased vascular permeablilty, WBC migration)
How does histamine participate in inflammation
- Released by mast cells when mast cell membranes come in contact with extracellular fluid involved with tissue trauma
- Dilation of Capillaries (Increases blood vessel permeability/Decreases blood pressure )
- Contraction of Smooth Muscle (Bronchial/Increased Gastric Contraction/Increased Heart Rate)
Corticosteroids
- produced by the adrenal gland
- Can usually be recognized by the ending “sone”
- Two Groups of Corticosteroids Produced by the Adrenal Cortex
- Affect glucose metabolism
- Generally cause an increase in blood glucose levels
- Raise concentration of liver glycogen
- Affect carbohydrate, protein, and fat metabolism
What are the different Corticosteroids based on the duration of action?
Short Acting (Less than or Equal to 12 Hour Duration)
- Hydrocortisone (Usually Topical)
- Cortisone (Converted by the Liver into Active Hydrocortisone)
Intermediate Acting (12 – 36 Hour Duration)
- prednisone (Converted in the Liver into Prednisolone)
- prednisolone – Tablets, Injection, Opthalmic Ointment
- triamincinolone (Vetalog®) - Tablet, Topical, Suspension for Inj.
- methylprednisolone (Medrol®) - Tablets
- isoflupredone (Predef 2X®)
Long Acting (48 Hour or Longer)
- dexamethasone (Azium®) - Tablets, Injection, Opthalmic Suspension
- betamethasone (Betasone®) - Injection, Topical
- flumethasone (Synalar®) - Topical Cream and Solution
- mometosone (Mometomax®) - Topical
How are the Corticosteroid preparations made?
Usually a Steroid Combined with a Salt to Make It More Soluble in Water
- Aqueous Solutions
What are the advantages of Corticosteroid preparations?
Can Be Given in Large Doses IV
Relatively Rapid Onset Because of Route
Especially Important in Shock,
IHA/ITP and Severe Allergic Reactions
Indications of Corticosteroids
Reduce Inflammation
Reduce Pain
“Feel Good” Drugs
Relive Pruritis (Itching)
Reduce Scarring by Delaying Healing
Reduce Tissue Damage
Treats Shock
Contraindications / Side Effects of Corticosteroids
Stimulate Breakdown of Glucose Stores Causing Hyperglycemia
Inhibit Fibrocartilage Growth
Decrease Immune Response by Inhibiting Lymphocytes
Also Neutrophils and Macrophages
Catabolic Effects – Break Down Protein
Weakened Musculature
Thinning of Skin
Hair Loss
Decreased Bone Density
“Iatrogenic” Cushing’s Disease
Induced Abortions
Polyuria/Poldipsia/Polyphagia
Decrease or Inhibit the Release of Stomach Protective Prostaglandins
May Result in Stomach Ulcers due to Increase in Gastric Acid Volume and Decrease in Gastric Acid pH
Elevated Liver Enzymes
Steroids Should Be Discontinued Slowly When Used Long Term
Quick Withdrawal = Negative Feedback on Hypothalmus = Addisonian Crisis
Leads to Imbalance of Electrolytes
Increased Potassium / Decreased Sodium
What precautions should be taken for the safe use of steroids
Use of Nonsteroidal Antiinflammatory Medications whenever possible
Use of Herbal and Nutraceutical Therapies
Omega 3 Fatty Acids
Smallest Dose Possible That Provides Clinical Response
Apply Locally Whenever Possible
Maintains Normal Adrenal Cortex Function
Still Maintains a High Local Level of Corticosteroid
Avoid Continuous Use Due to Negative Feedback and Adrenal Atrophy
Iatrogenic Cushing’s Disease
Caution With Pregnant Animals
Will Terminate Late-Stage Pregnancy
Remember Steroids DO NOT Cure Any Specific Disease!!
What are NSAIDs
Nonsteroidal Anti-Inflammatory Drugs
Decrease Inflammation Without the Use of Steroids
Work By Inhibiting Two Forms of Cyclogenase
List the differences between Cyclogenase-1 and Cyclogenase-2
Cyclogenase-1
Commonly Called COX-1
More Involved With the Stomach Hence GI Effects
Gastric Ulceration and Bleeding
Cyclogenase-2
Commonly Called COX-2
More Involved in Inflammation
What are the adverse effects associated with NSAIDs?
Some Species Are More Tolerant Than Others (Horses > Dogs > Cats /Also Individual Variation Between Patients)
Highly Bound to Albumin in the Blood Stream
Low Albumin May Increase Circulating NSAID’s
Liver Disease
Young or Old Animals
Supposedly Fewer Side Effects Than Glucocorticoids
Main Adverse Effect is GI Distress
Vomiting/Diarrhea
Gastric Ulcers and Bleeding Due to Inhibition of Prostaglandins
Increase in Gastric Acid Volume
Decrease in Gastric Acid pH
Increase Pepsin
Decrease Gastric and Enteric Mucus Production
Hepatotoxic
Bone Marrow Suppression
Reduced Platelet Aggregation Causing Decreased Clotting Ability
What are the need to know NAIDS?
Phenylbutazone, Aspirin, etodolac, flunixin meglumine, meclofenamic, Propionic Acid Derivatives, carprofen
phenylbutazone
(Butazolidin® = “Bute”)
- Pyrazolone derivative
- Commonly Used in Horses
- Pain Associated With Musculoskeletal System
- Mild to Moderate Analgesic, Antipyretic, and Anti-Inflammatory
- Metabolized by Liver to Form Oxyphenbutazone
- Highly Protein Bound
- Careful Giving to Animals With Low Albumin
- Adverse effects include GI ulcers in horses if used in high doses, and renal papillary necrosis if dehydrated or pre-existing renal compromise
- Well tolerated in dogs, less data available for cats
- Not used in humans due to bone marrow suppression
- Paste, Tablet, Powder, Bolus for Oral use, Topical Gel, IV injectable, Tissue necrosis if injected S.C. or I.M.
Aspirin
(Acetylsalicylic Acid)
- The Oldest Anti-inflammatory Agent
- Family of salicylate including bismuth subsalicylate (Pepto Bismol®)
- Inhibits the Cyclogenase Inflammatory Pathway Resulting in Decreased Prostaglandin Formation and Decreased Platelet Function
- Useful in Decreasing Platelet Aggregation by Blocking Thromboxane
- An Adjunct to Postadulticide Treatment of Heartworm Parasites (Reduces Platelet Clumping Associated With Narrowed Pulmonary Arteries)
- Heart Wall Disease (Anywhere There is Blood Turbulence)
- Blood Clots – Cats With Saddle Thrombus Disease
- Caution: Cats can’t Metabolize Aspirin as Rapidly as Dogs (Half Life in Dog = 8 Hours /Half Life in Cat = 30 Hours )
etodolac
(Etogesic®)
- Indol Acetic Acid Derivative
- Anti-inflammatory and Analgesic for Osteoarthritis in Dogs
- Oral Preparation with Once Daily Dosing
- Side Effects: Vomiting, Diarrhea and Lethargy
- Is believed to be More Selective Inhibitor of COX-2
- Inhibits the Prostaglandins for Inflammation without affecting COX-1 (Therefore More Protective Effects of Prostaglandins for Stomach and Kidney)
flunixin meglumine
(Banamine®)
- A Potent Inhibitor of Cyclogenase
- Potent Analgesic (onset in 15 minutes), Antipyretic, and Anti-Inflammatory
- Mainly Used for Musculoskeletal and Colic Pain (No. 1 Use in Horse for Colic)
- Also used for Shock, Intervertebral Disc Disease, and Pain Secondary to Surgery
- Blocks the Effects of Endotoxins (parvovirus)
- Labeled for Horses and Cattle (Used Off-label in Dogs and Other Species With Extreme Caution / Typically Only for Single Dose /Common to Have GI Side Effects)
- Although still labeled for both IV and IM injection, most equine clinicians avoid IM use due to risk of Clostridial infection
- Injectable solution is being used orally, but is off- label use
meclofenamic acid
(Arquel®)
- Representative Drug of the Fenamate Group
- Cyclogenase Inhibitor
- Primarily an Analgesic and Anti-Inflammatory in Horses for joint pain and osteoarthritis (Accumulates in the Joint Fluid After Oral Administration)
- Comes in Granule Form that is Mixed in the Feed
Propionic Acid Derivatives
The “fen” Group of NSAID’s
ibuprofen, ketoprofen, carprofen,naproxen
- Block Both Cyclogenase and Lipogenase
- Mainly used as analgesics
- Some are antipyretic and anti-inflammatory
- Adverse effects include nephrotoxicity and hepatotoxicity
carprofen
(Rimadyl®)
- Commonly used for osteoarthritis pain, musculoskeletal pain and acute pain related to surgery or trauma in dogs (Believed to target COX-2, so less inhibition of prostaglandins associated with GI protection and renal blood flow)
- Liver toxicities have been documented, especially in Labrador Retrievers (Blood work to assess liver enzymes should be done 7-14 days after initiating therapy and periodically thereafter (every six months) )
- Injectable and tablets
- Approved for BID or SID dosing
NSAIDs “Coxib Class”
- COX-2 Inhibitors Newer category of NSAIDs developed to be more specific in their inhibition of COX-2, without interfering with the protective COX-1
- Members include deracoxib (Deramaxx®), firocoxib (Previcox®, Equioxx®), and meloxicam (Metacam®), robenacoxib (Onsior®)
- Uses in veterinary medicine mainly for control of inflammation and postoperative pain
deracoxib
(Deramaxx®)
- Member of the COXIB class
- Used to decrease pain, inflammation, and fever
- Also indicated for osteoarthritis and control of postoperative pain associated with orthopedic surgery in dogs
- Available as chewable tablets that should be given after eating to increase bioavailability
- Adverse effects include v/d, anorexia, and elevated kidney and liver values
- Should perform bloodwork prior to initiating therapy
firocoxib
(Previcox®, Equioxx®)
- Member of the COXIB class with the same indications for use in dogs as deracoxib
- Chewable tablets can be administered with or without food
- Formulated as an oral paste for horses to be given once daily for osteoarthritis (maximum 14 day regimen)
- Used in cats as single dose for fever reduction
meloxicam
(Metacam®)
- Member of the oxicam class of COX-2 inhibitors
- Has anti-inflammatory, analgesic and antipyretic effects (Also inhibits leukocyte infiltration into the inflamed area)
- Used in dogs for alleviation of pain and inflammation due to acute/chronic musculoskeletal disorders and postoperative pain (Available as an oral suspension that is best applied to food)
- Used in cats as a one-time SQ injection for control of postoperative pain and inflammation
- Should not be used in animals with liver, cardiac, kidney or GI problems, or pregnant/lactating animals
- Adverse effects include v/d, anorexia, and lethargy
- Used in horses for pain/inflammation associated with surgery
- Used in pigs for mastitis/metritis
robenacoxib
(Onsior®)
- Potent and selective COX-2 inhibitor
- Used for pain/inflammation of osteoarthritis in dogs and postoperative pain/inflammation in CATS
- Used orally or SQ injectable for three days in cats and long term for osteoarthritis in dogs (not approved for dogs in USA)
- Adverse side effects include v/d, GI ulcers, anorexia, behavior changes in cats (depression/restlessness)
How do dual pathway NSAIDs work?
block both COX and LOX in the inflammatory pathway
What is LOX inhibition?
LOX inhibition leads to decreased synthesis of inflammatory leuokotrienes along with inhibition of prostaglandins
Diclofenac sodium
(Surpass®)
- is a non-specific COX-1 and 2 and has some LOX inhibition
- Available as a topical cream approved for use in horses to reduces pain and inflammation
- Local control of joint pain when applied topically to the hock, knee, fetlock and pastern joints
- Can be used for up to 10 days with minimal side effects
- Rubber gloves should be worn during application due to human absorption
Superoxide Radical Deactivation
- Superoxide radicals are produced by inflammation
- Destroy tissue cells / Degrade hyaluronic acid (Main component of joint fluid, Is responsible for joint fluid viscosity/lubrication)
- Agents in this group convert superoxide radicals into oxygen and water, thereby reducing cellular damage
- Also called “free radical scavengers”
- Includes dimethyl sulfoxide (DMSO, Domoso®) and orgotein (superoxide dismutase, Palosein®)
dimethyl sulfoxide
(DMSO, Domoso®)
- Known for its ability to penetrate skin and is used off label frequently as a carrier of other medications
(Labeled for reduction of swelling via topical application for things such as lick granulomas and constricted ear canals / Used IV for treatment of various inflammatory conditions including CNS swelling )
- Available as a gel and solution
- WEAR GLOVES when applying topically as it will absorb readily into human skin
- Leaves a garlic smell/aftertaste
- Teratogenic in some species
- May cause skin irritation/burning of treated area
orgotein
(superoxide dismutase, Palosein®)
- Similar in action to DMSO
- Used IM and Intra-Articularly in horses for joint disease (SQ in Dogs)
- Prevents destruction of hyaluronic acid /Prevents or reduces joint damage
Glycosaminoglycans
- Glycoproteins (proteoglycans) form part of the extra-cellular matrix of connective tissue such as cartilage
- Proteoglycans resemble polysaccharides
- Includes hyaluronic acid, glucosamine, chondroitin, and polysulfated glycosaminoglycans (PSGAGs)
Essential Fatty Acids
- Omega 3 and Omega 6 unsaturated fats
- Increase cell membrane stability and have antioxidant activity
- Found in fish and linseed oils
- Good for skin, hair coat, joint and heart health
Glucosamine and Chondroitin Sulfate
- Considered Nutraceuticals
- Play a role in the maintenance of cartilage structure and function
- Help stimulate cartilage cell growth
- Helps maintain cartilage strength and resilience
- Helpful in the control of inflammation and pain associated with Osteoarthritis /Degenerative Joint Disease (DJD)
- Many products and combinations available in tablet, capsule and food supplement forms
hyaluronic acid supplement
- hyaluronate sodium (Legend®, Hyalovet®)
- Normally a part of joint fluid
- Administered intra-articularly in horses to help cushion degenerating joints (Relieves joint pain and improves mobility)
- Can also be administered IV in horses
- Oral supplements available for small animals
Polysulfated glycosaminoglycans
(PSGAGs)
- Appear in a drug called Adequan® that is a semisynthetic mix of glycosaminoglycans from bovine cartilage
- Can be given intra-articularly or IM in horses and dogs
- Similar to natural mucopolysaccharides found in cartilaginous tissues
- Inhibits proteolytic enzymes which degrade proteoglycans
- Promotes production of joint fluid from the synovial membrane and has some anti-inflammatory action
methyl sulfonyl methane
“MSM”
- Dietary supplement form of sulfur that supports healthy connectibve tissue like tendons, ligaments, and muscles
- Adjunct therapy for arthritis seem in many combination products
acetaminophen
(Tylenol®)
- Non-narcotic analgesic (NOT an NSAID)
- Limited antipyretic and anti-inflammatory effects
- Rarely used in veterinary medicine
- Conjugated with glucuronic acid in liver metabolism (Contraindicated in cats at any dosage / Toxic metabolites build up and cause the conversion of hemoglobin to methemoglobin)
- Can cause liver and kidney dysfunction in any animal
- Warn clients that it is toxic to animals!
Antihistamines
- Drugs that counteract the effect of Histamine
- Histamine causes bronchoconstriction and inflammatory changes when released from mast cells
- Antihistamines or H1 blockers compete with histamine for receptor sites, preventing histamine response (act as competitive antagonists)
- Do not have an effect after histamine attaches to its receptor site
- Does NOT prevent histamine release like steroids do
- The three most commonly used in veterinary medicine are diphenhydramine (Benadryl®), chlorpheniramine (Chlortrimeton®), and hydroxyzine (Atarax®)
- Have been shown to decrease steroid dose by as much as 50% when used in combination
- Adverse effects include drowsiness, dry mucous membranes, decreased GI secretions, and CNS stimulation in high doses
What are the two types of histamine receptors?
H1 - Constrict extravascular smooth muscles when stimulated, H1 blockers are used to treat pruritis, laminitis (large animals), motion sickness, anaphylactic shock and some respiratory conditions
H2 - Increase Gastric Secretions
