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What are "NSAIDs"?
non-steroidal anti-inflammatory drugs
What are the advantages of NSAIDs over glucocorticoids?
- fewer side effects
- fever reduction
How do NSAIDs work?
- by blocking COX (cyclooxygenase) to prevent formation of prostaglandins and thromboxanes
- some also block LOX (lipoxygenase) to prevent formation of leukotrienes
What are the 2 types of cyclooxygenase, and what do they do?
- COX 1 - found in GI tract and kidneys - cause formation of "good" protective prostaglandins
- COX 2 - functions in tissue damage - causes formation of "bad" inflammatory prostaglandins
If we give an NSAID that block both COX 1 and COX 2, what are the general effects?
we get the desirable anti-inflammatory effects, and also get undesirable GI effects (upset stomach, GI ulcers) due to lack of protective effects due to lack of GI prostaglandins
In general, which is better to use for anti-inflammatory purposes - a general COX blocker, a selective COX 1 blocker, or a selective COX 2 blocker, and why?
a selective COX 2 blocker - leaves the protective GI prostaglandins alone, less GI side effects
Are NSAIDs effective analgesics for inflammatory pain? Are NSAIDs effective analgesics for pain due to broken bones?
yes for inflammatory pain, no for broken bone pain
In general, what are the side effects of NSAIDs?
mainly GI origin - diarrhea, anorexia, melena, GI ulcers, nephrotoxicity, bone marrow suppression, bleeding disorders, idiosyncratic hepatopathy
Do NSAIDs interact with other drugs? Why? Should we look up interactions when using NSAIDs with other drugs in a patient?
- yes - NSAIDs have tight plasma protein binding
- yes - look up interactions
List dogs, cats, and horses in order from most tolerant of NSAIDs to least tolerant
List 5 specific COX 2 inhibitor (blocker) drugs
- carprofen - Rimadyl
- etodolac - Etogesic
- deracoxib - Deramaxx
- meloxicam - Metacam
- firocoxib - Previcox
What are the indications for carprofen - Rimadyl and the newer COX inhibitor drugs?
- hip dysplasia
- other forms of degenerative joint diseases in dogs
List the non-selective COX inhibitor drugs - block both COX 1 and COX 2 - discussed in class.
- tepoxalin - Zubrin
- phenylbutazone - "bute"
- acetylsalicylic acid - aspirin
- the propionic acid derivatives (ketoprofen - Ketofen, naproxen - Equiproxen, Aleve, ibuprofen - Advil, Motrin)
- flunixin meglumine - Banamine
- meclofenamic acid - Arquel
What is tepoxalin - Zubrin's claim to fame?
blocks COX 1 COX 2 and LOX - lipoxygenase - to block formation of all of the eicosanoids - prostaglandins, thromboxanes, and leukotrienes
What is phenylbutazone's "nickname"? Why should we care?
- "bute" - do not get it confused with butorphanol
- phenylbutazone (1949) has been around longer than butorphanol (1980's? "torb"), and it got the good nickname first.
Phenylbutazone is used in what species for what indication most commonly?
equine - musculoskeletal pain
How is phenylbutazone administered? Is it OK to give it IM?
- should be given PO or IV
- do not give perivascular, SQ, or IM - causes tissue damage, slough
What is the first NSAID developed?
aspirin - acetylsalicylic acid - 1875
What are the indictions for the use of aspirin?
analgesic for mild or superficial pain, joint or musculoskeletal pain, headaches in people, antipyretic, anti-inflammatory, blood thinner - reduces blood clotting
How does aspirin reduce blood clotting?
inhibits formation of thromboxane, which normally promotes platelet aggregation
What type of patients may benefit from aspirin administration for "blood thinning" purposes?
- people at risk of heart attack
- dogs with HWD
- cats with hypertrophic cardiomyopathy
Describe use of aspirin in cats.
- do not use for general anti-inflammatory purposes
- generally used only in cats with hypertrophic cardiomyopathy, at a very low dose, once or twice a week - since cats metabolize aspirin very slowly. high dose or frequent administration cause toxicity
List the side effects of aspirin administration. Does buffering or enteric coating of aspirin help to reduce side effects?
- gastric irritation
- GI ulcers
- buffered, enteric coated are supposed to help
What is the main point to remember about use of the propionic acid derivatives in house pets? (ketoprofen-Ketofen, naproxen-Equiproxen, Aleve, and ibuprofen-Advil, Motrin)
- don't do it
- we have better and safer drugs that we can recommend to our clients
What species is ketoprofen-Ketofen and naproxen-Equiproxen used in?
What species is flunixin meglumine - Banamine used in? For what indictaions? How analgesic is it?
horses - musculoskeletal disorders and colic. is a potent analgesic
Why don't we use flunixin meglumine very much in dogs?
because it causes severe GI side effects
What species is meclofenamic acid-Arquel used in? For what indications? How is it administered?
- joint inflammation
- given PO-granules on food
List the non-COX inhibitor NSAIDs discussed in class.
DMSO, the chondroprotective agents (polysulfated glycosaminoglyan, hyaluronic acid, glucosamine and chondroitin sulfate), orgotein
How does DMS - dimethyl sulfoxide - work?
inactivates superoxide radicals an hydroxide radicals, which cause cell damage
How is DMSO labeled for administration?
What are the indications for use of DMSO?
topical application to reduce acute swelling due to trauma in horses and dogs. anti-inflammatory in otic preparations. many off-label uses
Should we apply a bandage to an area where DMSO has been applied?
no-causes skin irritation
What problems can DMSO cause?
- some drugs dissolved in DMSO can be carried across the patient's skin.
- penetrates intact skin, we need to clean the patient's skin well before applying DMSO
- we also need to wear gloves when handling DMSO - can cause skin irritation
- is teratogenic (causes birth defects)
- may taste or smell garlic odor on patient's breath
Since industrial grade DMSO is cheaper than medical grade DMSO, we should buy the industrial grade for use in our veterinary hosptials. True or false. Why?
false - industrial grade may have toxic impurities in it that can be detrimental to the patient's health
What dosage forms is DMSO commonly available as?
DMSO Gel and Solution, Synotic
List the chondroprotective agents used as anti-inflammatories.
polysulfated glycosaminoglycans, hyaluronic acid, glucosamine and chondroitin sulfate
What are some other names for polysulfated glycosaminoglycans? What is this type of drug derived from? How is it administered?
- semisynthetic drug derived from bovine cartilage
- administered IM or intra-articular
How do PSGAGs work?
- the large complex molecules trap water in joint cartilage, making it more springy, able to withstand activity better.
- PSGAGs also reduce degenerative joint changes, and promote activity of synovial membrane
What are the label indications for PSGAGS?
non-infectious joint lameness in horses, hip dysplasia and degenerative joint disease in dogs
List the proprietary names, method of action, and methods of administration of hyaluronic acid.
- Hyalovet, Legend
- hyaluronic acid is a component of synovial fluid that helps it to be viscous and lubricate well
- also anti-inflammatory
- given IV or intra-articular
Give the common proprietary name of glucosamine and chondroitin sulfate discussed in class. How does this compound work?
- Cosequin - precursors for PSGAG formation in the joings.
- chondroitin binds with and supports collagen strands in the joint cartilage
- glucosamine stimulates production of hyaluronic acid
Glucosamine and chondroitin sulfate is a nutraceutical. Is it regulated? Does regulation matter? Why or why not?
- nutriceutricals are not regulated since they are basically food.
- lack of regulation means that there is no assurance of quality or concentration or consistency in these products.
- advise clients to stick to the brand names - more likely to be higher quality
Acetaminophen - Tylenol is not an anti-inflammatory drug, but is discussed here for convenience. What does it do for patients?
Is acetaminophen safe to use in people?
- yes - does not block prostaglandins
- no GI side effects
Is acetaminophen regularly used in dogs? Why or why not?
no - risk of toxicity, other drugs are better
Is acetaminophen safe to use in cats?
What drug can be used to treat acetaminophen toxicity in cats?
acetylcysteine - Mucomyst
What is orgotein? How does it work?
superoxide dismutase - SOD
What is superoxide dismutase?
an enzyme, both naturally present and available as a drug. it catalyzes the conversion of superoxide radicals into O2 and H2O2.
What are superoxide radicals, and why are they a problem?
oxygen atoms with unpaired electrons. these are very reactive - when they occur in the patient's body, they take electrons from nearby molecules, leaving them one short, then the newly robbed molecules take electrons from other nearby molecules, in a chain reaction that tends to damage cells
What sort of cell damage is orgotein meant to prevent? In what species is it most commonly used?
- inactivate superoxide radicals associated with joint inflammation, which would otherwise degrade hyaluronic acid in the joint fluid, decreasing viscosity and lubrication.
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