NSAIDs and Cannabis Flashcards
what are the two arachadonic acid metabolites that are also inflammatory mediators that I should care about?
prostaglandins and leukotrienes
what are some general effects of prostaglandins?
vasodilation, ibhibits platelet aggregation, increased vascular permeability
briefly describe how NSAIDs work
NSAIDs act on cyclooygenase enzymes, COX1 and COX2 to ibhibit prostaglandin production
what is the effect of thromboxane?
it increases clotting
describe the differences in the actions of COX1 vs COX2
neither pathway is completely independent of each other, but:
- COX1 is expessed at constant levels in most tissues and makes prostaglandins that mediate normal homeostatis functions
- COX2 is synthesized by macrophages and other inflammatory cells after stimulation via cytokines, it also produces prostaglandins primarily involved with inflammation. COX2 also plays a role in maintaining renal perfusion.
COX1 helps produce postanoids with homeostatic functions. What are some of these functions?
- gastric mucosa (increased mucus production and enhances blood flow)
- kidneys (maintain adewuate renal perfusion)
- platelets (makes thromboxane, which increases platelets)
- vascular endothelium
non selective NSAIDs are considered “worse” than selective NDAIDs. why?
non selectives will block both COX1 and COX2 enzymes, do not only will there be a decrease in pain, fever, and inflammation (COX2), there will also be a decrease in GI mucosa integrity, decreased platelet function, and decrease in homeostatic functions (COX1)
what are the 6 clinical uses of NSAIDs?
- anti inflammatory
- analgesic
- antipyretic (fever)
- septic shock treatment
- antithrombotic
- anti cancer in certain cases
how does COX inhibition reduce the periperhal and central effects of prostaglandins and therefore provide analgesia?
- postaglandins normally sensitize nociceptors which increase the response to noxious (painful) stimuli, so this can be blocked
- COX1 and 2 are expressed in the spinal cord and during inflammation COX is upregulated leading to prostaglandin release, which lowers the spinaldepolarization thresholds, so this is blocked as well
how do NSAIDs provide an antipyretic effect?
PGE due to COX2 induction is what results in the hypothalamus reseting the body’s thermal set point and causing a fever, so decreasing PGE through COX inhibition lowers the thermal set point which reduces the fever.
how do NSAIDs help with septic shock?
shock is a result of a ton of inflammatory mediators going nuts at the same time, including prostanoids. NSAIDs can help reduce prostanoids, TNF, caspase, and other mediators, and improve clinical parameters in patients with shock.
if a patient is in shock and has poor perfusion, should you always give them NSAIDs?
no, the benefits of NSAIDs may not outweigh the risks in patients with poor perfusion
what drug is often used to treat septic shock in cows and horses?
flunixin
true or false: both non selective and selective NSAIDs have some COX1 inhibition
true
why do people take asprin for clotting disorders?
it selectively and irreversily inhbiits COX1 which normally produces thromboxane which increases platelet activation and aggregation, so by taking it, it reduces clotting
why are NSAIDs not a good choice for patients who are experiencing lots of hemorrhage?
they can exacerbate the hemorrhage by inhibiting the normal homeostasis and clotting that prostanoids usually regulate
how do NSAIDs provide an anti cancer effect in some cases?
COX2 is upregulated in some tumors, like:
- transitional cell carcinoma
- squamous cell carcinoma
- melaoma
NSAIDs suppress tumors via two main mechanisms:
- restore apoptosis
- inhibit angiogenesis
NSAIDs are highly protein bound, well absorbed orally, metabolized in the liver, and the half life can vary between species. there is no question here. just read this or write it down so you remember
DO ITTTT
what are the two big adverse effects of NSAIDs, and then what are the other 6 that are still important just less so?
**GI irritation/ulceration
**renotoxicity
- hepatotoxicity
- hemorrhage
- blood dyscrasis (blood disorder)
- delayed partuition
- delayed soft tissue healing
- delayed fracture healing
NSAIDs can cause acute renal failure which is particularily of concern when….
the patient is under anesthesia or in hypovolemic/dehydrated patients. porstaglandins normally maintain renal blood flow and GFR under these circumstances
why is giving NSAIDs to a pregant animal or a neonatal animal is concerning because….
COX2 is crucial for renal development
why should you NEVER give Asprin to patients with a risk of hemorrhage?
it is an irreversible COX1 inhibitor and platelets do not have a nucleus so they can’t make more COX1 enzymes
what NSAID would you use for:
a dog undergoing soft tissue sx
carprofen or meloxican
what NSAID would you use for:
a cat undergoing soft tissue sx
robenacoxib, or meloxicam post op
what NSAID would you use for: dog undergoing orthopedic sx
carprofen (add some opiods too)
what NSAID would you use for: a cat undergoing orthopedic sx
robenacoxib, sometimes meloxicam, (add opiods too)
what NSAID would you use for: a dog with osteoarthritis
meloxicam, firocoxib (may be the most effective), and carprofen
what NSAID would you use for: a cat with osteoarthritis
meloxicam (robenacoxib may cause more adverse effects if used long term)
what NSAID would you use for: a horse with musculoskeletal pain
phenylbutazone, flunixin, firocoxib for long term treatment
should you use NSAIDs to treat laminitis?
yes, acutely you can use a nonselective NSAID and chronically you can switch to a COX2 selective to reduce adverse effects
what NSAID would you use for: a horse with gastrointestinal pain or GI surgery?
Flunixin
why should you avoid using NSAIDs in foals?
they are very sensitive to getting GI ulcers
do not use ______ in production animals!!!!
phenylbutazone
when should you consider using NSAIDs in cattle?
for mastitis, to treat lameness, for castration, and dehorning
what NSAID would you use for: a cow undergoing castration or dehorning
meloxicam or flunixin
what kind of drug is Grapiprant (galliprant) and how is it different than other NSAIDs?
- it is a prostaglandin E2 E4P receptor antagonist, so it decreases inflammatory effects and reduces pain
- it does not work on COX enzymes like most other NSAIDs, and is said to have fewer side effects because of this!
what can Grapiprant (galliprant) be used for?
labelled for osteoarthritis in dogs
what is the proper way to switch NSAIDs?
- wait a week to allow washoit before starting a new one to reduce confusion if adverse effects occur
- do NOT give two NSAIDs at the same time and do NOT give them with steroids
what are the 3 big NSAIDs that are unapproved in animals but clients like to ask about?
- asprin (acetylsalicylic acid, can be used in animals to treat HCM/saddle thombus, and osteoarthritis)
- ibuprofen (causes erious GI and renal toxicity in small animals, do NOT use this!!
- acetominophen (few adverse effects in dogs but TOXIC to cats at low doses)
Gabapentin is not an NSAID, but can be used for pain. Explain how
it binds to Ca++ channels to inhibit excitatory neurotransmitter release. it is usually used together with opiods. usually used for chronic pain, specifically good for neuropathic pain
the main psychotropic compound in cannabis is _____
THC, it interacts with enodocannabinoid receptors
why are dogs more susceptible to the adverse CNS effects of THC?
dogs have way more endocannabinoid receptors in the CNS than humans by a factor of 1000
what is the major non-psychotropic component of cannabis?
CBD/Cannabidiol
how does CBD act to produce it’s analgesic, anxiolytic, antidepressant, anticonvulsant, anti inflammatory, etc effects?
it interacts with molecular targets other than just the CB receptors, it actually has a low affinity for the CB1 receptor. the mechanism of action is not fully understoof
what are the 4 possible uses of CBD in vet med?
- epilepsy
- anxiety
- pain
- antineoplastic effects
