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
