Exam 2: Lecture 11: NSAID's NOT FINISHED Flashcards
One of the most commonly used drug classes in veterinary medicine is?
NSAID’s
Which drug class provids
- analgesia
- Anti-inflammatory
- Antipyretic effects
- treats source of pain instead of making perception
NSAID’s
NSAID’s are beneficial for treating ______ and ______, is coming more understood in our profession and our clients are also demanding that we address their concerns about their pet?
acute and chronic
What is the MOA for NSAID’s
blocks cellular expression of COX enzymes in cell membranes
What is the difference between nonselective NSAID’s and NSAID’s COXIBs
nonselective NSAID’s: same amount of inhibition of COX 1 and COX 2
NSAID’s COXIB’s: Majority COX 2 inhibitor and slight COX 1 receptor
COX 1 and 2 from arachidonic acid produce ______ which can either help with gastric protection, homeostasis and renal function while also for pain inflammation
Prostaglandin
Inflammation is a response to tissue ______
damage
First step in the inflammation cascade is the release of ________, mediated by phospholipase A2 from injured cell membranes
arachidonic acid (AA)
AA is a substrate for generation of various ______ (PGs, leukotrienes, thromboxane, A2) the production of PGs and TXA2 is mediated by COX
eicosanoids
Inflammatory mediators lead to ???
- increased vascular permeability
- Heat
- Decreased nociceptor
Does COX 1 or COX 2 describe the following?
- Primary constitutive isoform of COX
- Responsible for basal prostaglandin (PG) production = homeostasis in tissues (housekeeping function)
COX 1
Does COX 1 or COX 2 describe the following?
- Present in stomach, kidney, platelets, and reproductive tract (gastroprotection, kidney, and platelet function, gestation and parturition)
- can be expressed at sites of inflammation
COX 1
Does COX 1 or COX 2 describe the following?
- Induced isoform of COX, but expressed constitutively in many tissues as neural, reproductive, and renal and has a homeostatic function
COX 2
______ has a bifunctional role depending on the isoform and target tissue
COX
______ work in both the CNS and peripheral tissue injured site
NSAIDS
inhibition of ______ enzymes peripherally blocks the function of PG’s which would normally dilate arterioles and sensitive peripheral nociceptors to inflammatory mediators
- EX: histamine and bradykinin
- produces localized pain and hypersensitivity
COX 2
Does COX 1 or COX 2 describe the following?
- expressed in the brain and spinal cord and becomes upregulated in response to traumatic injury and peripheral inflammation = neural plasticity and central sensitzation due to lowering of the threshold for nueronal depolarization
COX 2
_______ contributes to inflammatory response by causing vasdilation and enhancing inflammatory mediators and other cytokines
PGE2
Does COX 1 or COX 2 describe the following?
- production of PGE2
COX 2
drug therapy has tried to target inhibition of ______ in order to decrease unwanted side effects ….. however we now understand that COX 2 inhibition is detrimental to many normal physiological functions
COX 2
T/F: In general, most NSAIDs are water-soluble, and a weak organic acid that are well absorbed following oral adminstration
False!! they are lipid souble, weak organic acids that are well absrobed following oral adminstration
T/F: NSAIDS have the following characteristics
- Rapid oneset of action (around 30-60 min)
- Duration of effect can be up to 24 hours
- relatively small volumes of distribution attributable
to a high degree of plasma protein binding -
▪ High protein binding enables consistent
delivery to target tissue
true!!
Where do NSAIDS undergo extenisive metabolism to inactive metabolites
Heaptic metabolism
What Drug do the following characteristics define?
- Ubset of NSAIDS introducted in recent years that were developed to have anti-inflammatory effect, but reduced toxicity
- approved for use in animals:
deracoxib, firocoxib, mavacoxib, and
robenacoxib
Coxibs
What Drug do the following characteristics define?
- Cox 2 selective
- COX 1 sparing
- Strucutrally different from other NSADIS so it limits their ability to bind COX 1 site
Coxibs
What are the clinical uses of NSAIDS?
▪ Only use one NSAID at a time and do
not concurrently administer systemic
steroids!
▪ Baseline renal and hepatic function
prior to use
▪ Pay attention to dosages, frequency
and to offer it with food
▪ Use lowest effective dose for the
shortest duration possible, with
frequent monitoring of patient
response
▪ 5-7 day “wash out” period if
switching NSAIDs
What are Contraindications for NSAID’s
▪ Renal or hepatic insufficiency/impairment
▪ Active GI disease
▪ Coagulopathies
▪ Pregnant (or trying to become pregnant)
▪ Decreased circulating volume (ex. Congestive
heart failure, shock, dehydration , hypotension,
ascites or other cause of hypovolemia)
▪ Active hemorrhage or suspected blood loss
▪ Significant pulmonary disease
▪ Known sensitivity to NSAIDs
▪ Currently receiving systemic steroids or another
NSAID
What are the 9 ways to minimize risk when giving NSAIDS
- Obtain complete medical history
- Careful patient selection
- Provide verbal and written instructions
- Recognize adverse events and discontinue
immediately - Monitor labwork
- Use a balanced approach to analgesia
- Consider washout periods
- Consider gastroprotectants
- Dose optimization based on lean body weight
T/F: Pet owners need to be told what the
possible side effects are and their
clinical signs.
true
What Drug do the following characteristics define?
- COX 1 sparing
- COX 2 selective
- Approved to treat pain and inflammation due to OA and Otho and soft tissue surgery in DOGS
- Several studies support long term use and efficacy in DOGS
Carprofen
What is the major side effect of Carprofen
GI upset
What Drug do the following characteristics define?
- COX 1 sparing
- COx 2 selective
- Approved oral formaultion for DOGS for treatment of pain and inflammation associated with OA and post-op pain due to orthopedic surgery. Also effective for pain due to dental or soft tissue procedures
Deracoxib
What is the major side effect of Deracoxib
Gi complications
- Perforation of an ulcer
usually related to a higher dose
What Drug do the following characteristics define?
- Cox 1 sparing
- Cox 2 selective
- Approved as an oral formulation for the treatment of pain and inflammation associated with OA in DOGS
- also effective for postoperative pain control
- Injectable and oral paste for SID used in treatment of equine OA
Firocoxib
What are the side effects of Firocoxib
Minimal, mostly limited to GI upset
What Drug do the following characteristics define?
- Cox 1 sparing
- Cox 2 selective
- Approved for use in dogs for the treatment of pain and inflammation associated with OA
- Approved for use in CATS but only for a SINGLE DOSE to control pain and inflammation associated with orthopedic surgery, OHE, and casterations in the USA
Meloxicam
Which drug has a black box warning label issued by the FDA in 2010 for
- acute renal failure and death associated with repeated use in cats
Meloxicam
- However, long term use of low dose meloxicam is approved for cats in other countries
What are the side effects if Meloxicam
GI upset
What Drug do the following characteristics define?
- Cox 1 sparing
- Cox 2 selective
- Approved for use in dogs and cats for the treatment of pain and inflammation associated with OA, orthopedic surgery and soft tissue surgery
(Approved treatment in cats is less than 4 months is 3 days, Good safety profile in healthy young animals, and SQ injection)
Robenacoxib
What Drug do the following characteristics define?
- NON-COX-INHIBITING prostaglandin receptor antagonist (PRA)
- Approved for treatment of pain and inflammation in dogs with OA
- Galliprant does not inhibit the production of many housekeeping prostaglandings that maintain homeostatic functions
Grapiprant
What Drug do the following characteristics define?
- Specifically blocks the EP4 receptor which is the primary mediator of canine OA pain and inflammation
Grapiprant
What Drug do the following characteristics define?
▪ NOT an NSAID!
▪ Used in humans for antipyretic and analgesic
properties, with reduced risk of GI ulceration.
Lacks anti-inflammatory properties.
▪ Cats are more sensitive to __________
toxicosis → deficient in glucuronyl
transferase and therefore have limited
capacity to glucuronidate this drug
▪ Cats primarily develop
methemoglobinemia within a few hours,
followed by Heinz body formation
Acetaminophen
Define Acetaminophen in cats
Methemoglobinemia makes
mucous membranes brown or
muddy in color and is usually
accompanied by tachycardia,
hyperpnea, weakness, and
lethargy
▪ Other clinical signs of
acetaminophen toxicity include
depression, weakness,
hyperventilation, icterus, vomiting,
hypothermia, facial or paw edema,
cyanosis, dyspnea, hepatic
necrosis, and death
What Drug do the following characteristics define?
▪ Atypical NSAID
- Weake COX 1 and COX 2 inhibition
- COX 3?
- FDA approved for use in horses, but use has been described in several veterinary species
- Use caution in patients with co-morbitdities
Dipyrone (AKA metamizole)
What Drug do the following characteristics define?
- Nonselective NSAID
- FDA approved for treatment of inflammation and fever in food animals
- Most commonly used NSAID for treatment of colic and associated endotoxemia (in horses)
- Comes in an oral paste and injectable formualtion
Flunixin Meglumine
Why do you need to be cautious when giving Flunixin meglumine?
- DO NOT ADMINISTER IM - VERY IRRITATING AND COULD LEAD TO CLOSTRIDIAL MYOSITIS
What Drug do the following characteristics define?
- Nonselective NSAID
- used to treat musculoskeletal pain and inflmmation in horses
- Prohibited from use in dairy cattle females over 20 months of age
Phenylbutazone
What are the side effects of Phenylbutazone?
- gastric ulceration
- renal necrosis
- Anemia
The most common problem associated with use of NSAIDS
- Inhibiton of intestinal healing mechanisms
- gastric ulcerations
Inhibition of _______ prostaglandins from NSAID’s cause
- inhibition of healing mechanims
- gastric ulceration
Endogenous
What are gastric side effects of NSAIDS
- depression
- Lethargy
- inappetence
- nausea
- vomiting and/or diarrhea
- may include blood, and an ulcer that could lead to proliferation of the GI tract
What would you see on lab results for an animals with GI side effects
- decreased Hct and total protein
- increased BUN due to damage to GI
- Elevated luekocytes cound
- Consider concurent administration of gastroprotectants when NSAIDS are prescribed for chronic use
What NSAID causes right dorsal colitis in horses
PBZ
When giving your best friend an NSAID, rember these 4 sings:
▪ Behavior Changes
▪ Eating Less
▪ Skin Redness, Scabs
▪ Tarry
Stool/Diarrhea/Vomiting
▪ FRIEND
▪ STOP the Drug & Call your vet
Renal dysfunction may occur with NSAID administration due to
________ inhibition
prostaglandin inhibition
T/F: During normovolemia, there is a large need for production of PG
FALSE!!!
little need
Inhibition of COX enzymes can result in
____________ of afferent and efferent
blood vessels, glomerular dysfunction, and
abnormal tubuloglomerular feedback →
renal failure
vasoconstriction
Does Hypovolemia or Hypervolemia → PG production is increased and important for maintaining renal perfusion
Hypovolemia
T/F: If a patient is dehydrated or hypovolemix you have give them NSAIDs
FALSE!!!
Hold off on giving them NSAIDs until underlying problem is corrected
If you are concerned that patient may
become _________ during
anesthesia → do not give the NSAID
until stable in recovery period
* Institute corrective treatment for
hypotension promptly!
Hypotensive
Which drug is associated with idiosyncratic hepatocellular necrosis
- very rare
Carprofen
What are commonly seen Hepatic side effects of giving NSAIDS
- Anorexia
- Vomiting
- Icterus
- Increased hepatic enzymes
T/F: Liver functions should be monitored with the use of ALL NSAIDS
true
T/F: prostaglanids play an important role in bone repair and normal bone homeostasis
True
Small mammal models indicate that _____ potentially
alter bone healing, but after discontinuation of the drug
the rate of healing in a fracture returns to normal….so it
is still okay to use postoperative NSAIDs to manage
orthopedic pain, just don’t administer continuously for
weeks
NSAID’s
Experimental data suggests NSAIDs can (Pick one: Increase of decrease) the
progression of OA
Decreases
T/F: Available published studies suggest that
the NSAIDs approved in the United States
that have been evaluated do not have a
significant clinical effect on bleeding
time following perioperative
administration.
true
_________ is the only drug of concern due to
irreversible effect on platelet function that
persists until the platelets are replaced
Aspirin
▪ Discontinue use 7-10 days prior to surgery
Which drug category is descried as:
Drug:
- Famotidine
Comments:
- Decrease dose in renal failure
H2 receptor blocker
Which drug category is descried as:
Drug:
- Sucralfate
Comments:
- Seperate from administration of abx and antacids
Mucosal protectant
Which drug category is descried as:
Drug:
- Omeprazole
- Pantoprazole
Comments:
- Do not admin a partial tablet/capsule unless dissolved in HCO3 (Bicarbonate)
Proton pump inhibitor
Which drug category is descried as:
Drug:
- Misoprostol
Comments:
- Do not give if pregnant
Prostaglandin analogue
Which drug category is descried as:
Drug:
- Metoclopramide
Comments:
- Do not administer if GI FB or other mechanical obstruction suspected
Promotility Agent
