NSAIDs Flashcards
What are the 2 classifications of NSAIDs?
- inhibitors of prostanoids (PGs, TXA2)
- miscellaneous anti-inflammatory drugs
NSAID mechanism of action:
What 5 NSAIDs commonly used in humans can cause poisoning in small animals?
- Aspirin
- Acetaminophen
- Ibuprofen
- Indomethacin
- Naproxen
What are 9 signs of NSAID toxicity in animals?
- GI ulceration, hemorrhage, and perforation**
- vomiting
- diarrhea
- hepatotoxicity
- renal toxicity
- cardiovascular and blood toxicity
- CNS depression
- circulatory disturbances
- drug-drug interactions
What does COX-1 usually due in the GI mucosa? What happens when it is inhibited?
produces PGE2 responsible for gastric protection
- increases mucus secretion
- increases bicarbonate
- increases mucosal blood flow
peptic ulcers, GI bleeding
What do COX-1 and COX-2 do in the kidneys? What happens when they’re inhibited?
produces PGE2 and PGI2 responsible for afferent arteriolar vasodilation which increases GFR and increases Na and water excretion
- Na and water retention
- hypertension
- hemodynamic acute kidney injury
What do COX-1 and COX-2 do in the cardiovascular system? What happens when they’re inhibited?
produces PGI2
- vasodilation
- inhibition of platelet aggregation
produces TXA2
- vasoconstriction
- platelet aggregation
COX-2 > COX-1 —> stroke, myocardial infarction
NSAID side effects:
What are the 8 desirable features of NSAIDs?
- deactivate/desensitize nociceptors - decreases pain
- attenuates inflammatory response
- synergistic with opioids
- no addiction or dependence
- no respiratory depression
- minimal nausea/vomiting
- long duration of action
- no cognitive side effects
How do COX-1 and COX-2 compare? Why is drug selectivity important?
COX-1 = mediates physiological responses, like GI protection and platelet aggregation
COX-2 = expressed by cells involved in inflammation, like macrophages and monocytes and is responsible for the synthesis of PGs and TXA2
selective inhibition of COX-2 may have better therapeutic responses
How is the selectivity of an NSAID expressed? What is the inhibitory effect?
selectivity of COX-2 vs COX-1 = COX1/COX2
(IC50) = COX1/COX2 > 1 = drug more specific for COX2
What are 5 dual inhibitors of the LOX and COX pathway?
- Tepoxalin (Zubrin)* - approved in Europe and America for osteoarthritis in dogs
- Benoxaprofen
- Ketoprofen
- Licofelone
- Corticosteroids - adverse effects
What are the 4 major classifications of NSAIDs? What are some examples of each?
- selective COX-1 inhibitors - low-dose aspirin
- non-selective COX inhibitors - Naproxen (Aleve), Ibuprofen (Motrin, Advil), Ketoprofen (Anafen), Aspirin, Flunixin meglumine
- selective COX-2 inhibitors - Meloxicam, Etodolac, Phenylbutazone, Carprofen, Deracoxib, Firocoxib, Robenacoxib
- dual inhibitors - Tepoxalin
What are the main side effects associated with the different classifications of NSAIDs?
- selective COX-1 inhibitors - GI ulceration, excessive bleeding
- non-elective COX inhibitors - paradoxical hyperpyrexia
- selective COX-2 inhibitors - increased blood clotting, stroke
- dual inhibitors - none to note
NSAID classification and adverse effects:
Currently available NSAIDs for dogs:
What are the 4 main uses of Aspirin? How is it used in low doses?
reduces pain, fever, inflammation, and platelet aggregation
prevents heart attacks and strokes (myocardial infarction)
What is Aspirin derived from?
salicylic acid from willow bark is modified into acetyl salicylic acid (ASA) = Aspirin
What is the mechanism of action of Aspirin? What are the 4 major effects?
irreversibly inhibits COX-1, resulting in decreased PG and TXA2 synthesis
- analgesic
- antipyretic
- anticoagulant - reduced platelet aggregation
- anti-inflammatory - reduced PG expression
What adverse effects are common with Aspirin usage in cats, dogs, and sheep?
CATS: sensitive to aspirin toxicity (long half-life)
DOGS: sensitive to GI effects (bleeding), chronic use in dogs with OA can aggravate joint disease
SHEEP: pulmonary edema
What are 6 common adverse effects of Aspirin? What drug does Aspirin commonly interact with?
- GI distress: vomiting, diarrhea, anorexia, ulceration
- paradoxical hyperpyrexia (>106.7 F)
- hyperventilation, respiratory acidosis
- metabolic acidosis
- dehydration
- chronic use = bleeding during surgery
Warfarin
In what 4 ways is Aspirin toxicity treated?
- induce emesis in cases of acute toxicity
- increase removal of the drug by gastric lavage followed by administration of activated charcoal
- increase urinary excretion by administering alkalizing agents
- initiate IV fluid therapy to address dehydration and metabolic acidosis
In what 4 situations is it contraindicated to use Aspirin?
- active GI bleeds
- bleeding disorders
- asthma
- renal insufficiency
What is Flunixin meglumine (Banamine)? How does its mechanism of action compare in horses and dogs?
non-selective COX inhibitor with potent analgesic and anti-inflammatory effects
HORSES = greater COX-2 selectivity
DOGS = greater COX-1 selectivity
What exceptional property does Flunixin meglumine (Banamine) have? How is it used in horses and cattle?
alleviates visceral pain related to colic
- treats acute, visceral, and surgical pain
HORSES = longest duration of postoperative analgesia (~13 hrs)
CATTLE = controls pyrexia associated with respiratory disease, endotoxemia, and mastitis (not FDA-approved)
What are 3 adverse effects of Flunixin meglumine (Banamine)?
- myonecrosis upon IM injection
- overdose in horses causes ulcers on the tongue, gingiva, lips, and stomach; CNS depression, and anorexia
- dogs: renal failure and GI damage
What is Ketoprofen (Ketofen)? What is its mechanism of action? When is it most commonly used?
non-selective COX inhibitor with anti-inflammatory and analgesic effect
inhibits COX-1, COX-2, and LOX pathway (lowers LTB4 synthesis)
horses with acute and chronic musculoskeletal disorders
How does Ketoprofen (Ketofen) compare to flunixin and phenylbutazone? What are 3 possible adverse effects?
safer profile
- PO administration can cause GI injury including ulceration and bleeding
- caution in animals with hemostatic disorders
- caution in animals with compromised renal function
What is the most commonly used NSAID in horses? What is its mechanism of action?
phenylbutazone, especially used as an analgesic for racehorses due to its safety, efficacy, and affordability
preferential COX-2 inhibitor in both horses and dogs
What are the 5 most common uses of Phenylbutazone?
- osteoarthritis
- lameness
- rheumatism
- other painful conditions of the limbs
- nonspecific inflammation in other conditions
What active metabolite does Phenylbutazone produce? What are 3 adverse effects?
oxyphenylbutazone
- GI distress: erosions, ulcers, anorexia, colic, diarrhea
- renal papillary necrosis
- death by hypovolemia, shock, and ulcer-mediated sepsis
When is it contraindicated to use Phenylbutazone?
patients with serious cardiac, renal, or hepatic injury, or hematologic disorders
What is Carprofen (Rimadyl)? What is its mechanism of action? What is it commonly used for?
preferential COX-2 inhibitor with analgesic and anti-inflammatory effects
potency for canine COX-2 is more than 100x relative to canine COX-1
short- and long-term pain management and musculoskeletal disorders
What are the main 3 adverse effects of Carprofen (Rimadyl)? How does this compare to other NSAIDs? In what patients is it not recommended for use?
diarrhea, anorexia, vomiting
lower frequency of GI ulceration and hemorrhage
- patients with hepatic or renal dysfunction and hemostatic disorders
- pregnant, lactating, or breeding bitches
What is Meloxicam (Metacam)? What is its selectivity ratio? When is it used?
preferential COX-2 inhibitor with analgesic and anti-inflammatory effects
COX-2/COX1 = 10
chronic pain and inflammation related to osteoarthritis and surgery (FDA-approved in cats)
Meloxicam (Metacam) is a relatively safe NSAID in dogs and cats. What are 3 possible adverse effects? What caution should be taken with cats?
- GI distress
- anemia
- lethargy
- rare and transient
repeated use can evoke acute renal failure and death
When is it contraindicated to use Meloxicam (Metacam)?
pregnant, lactating, or young animals < 4 months
What is Etodolac (EtoGesic)? When is it most commonly used?
preferential COX-2 inhibitor with analgesic and anti-inflammatory effects
dogs with osteoarthritis
What is a unique adverse effect of Etodolac (EtoGesic)? What else can it cause? When is use contraindicated?
may cause keratoconjunctivitis sicca in dogs (monitor tear production)
GI distress, CNS depression, hepatotoxicity, nephrotoxicity
patients with hematological, renal, or hepatic impairment
What is Tepoxalin (Zubrin)? What is its mechanism of action?
dual inhibitor: non-selective COX inhibitor with potent effect on LOX
inhibits COX-1, COX-2, and 5-LOX, which reduces the production of prostaglandin mediators of pain, fever, and inflammation
In what 3 situations is Tepoxalin (Zubrin) used?
- osteoarthritis in dogs
- allergic conditions in dogs
- postoperative pain control
What are 4 common adverse effects of Tepoxalin (Zubrin)?
- GI distress: vomiting, diarrhea, anorexia, ulceration
- CNS depression
- hepatotoxicity
- nephrotoxicity
What are the 2 selective COX-2 inhibitors?
(“coxibs”)
1. Deracoxib (Deramaxx) - dogs
2. Firocoxib (Previcox, Equicox) - dogs, horses
When is Deracoxib and Firocoxib used?
D = osteoarthritis and post-operative pain/inflammation in dogs
F = osteoarthritis in horses and dogs
What are the most common adverse effects of Deracoxib? Firocoxib?
D = GI distress
F = horses: diarrhea, mouth ulcers, excitation
dogs: vacuolization in the brain at high doses
Which NSAIDs are rarely used in veterinary medicine?
non-selective COX inhibitors
- Aspirin
- Acetominophen (Tylenol): particularly unsafe in cats
- Ibuprofen (Motrin, Advil)
- Naproxen (Aleve): can treat myositis and lameness in horses
- Indomethacin
What is dimethyl sulfoxide (DMSO)? What are 6 common effects?
miscellaneous anti-inflammatory that is a solvent for many aromatic, organic, and inorganic compounds (colorless, straw-yellow, highly hygroscopic)
- anti-inflammatory: inhibits PG synthesis and traps free radicals
- diuretic
- analgesic
- skin penetrating
- anticholinesterase
- weak antibacterial/antifungal
In what 9 situations is dimethyl sulfoxide (DMSO) commonly used?
- acute swelling (musculoskeletal trauma)
- cerebral edema and paralysis from spinal cord trauma
- cystitis (urethral obstruction in cats)
- superficial burns
- skin grafts
- transient ischemic conditions
- edema of limbs from fractures
- swelling and engorgement of mammary glands
- severe inflammation resulting from extravascular injection of irritating drugs or lick granulomas
What are 5 possible adverse effects of dimethyl sulfoxide?
- transient local effects
- high dose, long usage = myopia
- IV = hemolysis, hemoglobinuria
- hepatic and renal damage, pulmonary edema
- CNS: sedation, coma, seizures
What is osteoarthritis? What usually protects joints from this?
degenerative joint disease that affects the spine and lower limbs leading to stiffness and excruciating pain
synovial lining and synovial fluid usually ensure smooth and easy bothy movement (hyaluronic acid is the natural lubricant of the joints and found in SF)
What is polysulfated glycosaminoglycan (PSGAG), or Adequan? What are its 2 mechanisms of action?
disease-modifying osteoarthritis drug (DMOAD)
modulates clinical signs of OA by indirectly promoting chondroprotective effects
- improves joint articular function by affecting synovial fluid
- anti-inflammatory: inhibits PGE2 biosynthesis, leukocyte migration, and IL levels
How is polysulfated glycosaminoglycan (PSGAG), or Adequan used in dogs and horses? What is the most common adverse effect?
DOGS = treat OA and prevent hip dysplasia
HORSES = treat traumatic joint dysfunction
associated with drug administration - septic arthritis
What are the 3 mechanisms of action of hyaluronate sodium? How is it used in dogs and horses?
- cushioning - reduces cell migration
- lubricating effect on articular soft tissue
- scavenges and removes O2-derived free radicals
treats synovitis associated with OA
What are 6 general guidelines for the safe use of NSAIDs?
- individualize dosage based on drug’s efficacy, age of the animal, and duration of action
- screen patients for underlying renal and hepatic dysfunction
- monitor hydration status - hypovolemic animals should not be placed on NSAIDs
- allow an adequate wash out period prior to administering
- administer the lowest possible dose for the shortest period of time to minimize injury risk
- concurrent use of glucocorticoids and NSAIDs should be avoided due to increased risk of GI complication
