Flashcards in pharmacology 8 - NSAIDS Deck (22):
inflammation is what? what are the cardinal signs.
common response to injury/insult. associated with chemical, physical, immunological, biological damage.
many mediators of this.
heat, pain , redness, swelling, loss of function (cardinal signs)
what are the benefits of inflammation? (5)
-increased blood flow to injury
-oedema which dilutes noxious stimuli
-attracts leucocytes and macrophages
generates antibodies at site
increased supply of O2 and nutrients.
what are adverse effects of inflammation?
-long lasting hyperalgesia
loss of function
-mediators released may induce a cycle - inflamm cells - further mediator release - chronic inflamm (won't stop when stimulus caesed.0
5 inflammatory mediators? what do the NSAIDS target?
-eicosanoids (PG's and leukotrienes)
PG's, TXA's, LT's.
what can you use the NSAIDS for? (5) eg?
to control the adverse effects of the inflammatory response.
-anti-thrombotic effects. (reduced platelet aggregation.) eg. aspirin.
what are the NSAIDS? hwat do they act on? inhibit what?
they act on the eicosanoids forming from arachidonic acid.
(PG, LT, TXA)
inhibit COX enzymes. (1&2)
give some examples of enolic acids - pyrazoles (phenylbutazone)
oxicams - piroicam/ meloxicam.
give some examples of carboxylic acids?
salicylic acid - aspirin
explain the COX enzyme?? however, NSAIDS are mainly non0selective and reversible.
cox 1 and cox 2.
cox 1 - constitutive enzyme (normal) - endogenous actions
cox 2 - inducible by inflammatory mediatorss/cells.
actions of nsaids? central? peripheral?
cetrally - analgesic, antipyretic (body temp)
peripheral - analgesic, anti-inflamm, anti-thrombotic, anti-endotoxic, cartilage effects.
how do nsaids work on analgesia? depends on?
depends on the type and cause of pain (any memory pain?/sentitivity) acute, persistent , chronic.
good for post-op pain
good for hyperalgesia
bradykinin and cytokines liberate PGS. (trigger release of)
how do nsaids work as an anti-pyretic? where regulates temperature?
hypothalamus regulates a set point. in pyrexia - this set point may be set to a higher level. (il-1 and pgs) so the body tolerates a higher temperature. nasaids - return this set point to normal.
explain endotoxic shock? what causes this and how?
caused by gram negative bacteria. LPS is generated by them and it causes damage to wbc's and the endothelium. releases vasoactive mediators (nsaids prevent this)
they reduce the permeability and leakyness. they therefore prevent shock. (species are not the same!)
pharmacokinetics comprises of? ADME. what is it?
the effect of the body on the drug!
explain absorbtion of nsaids? (A)
ORALLY /PARENTERALLY GIVEN.
weak acid so well absorbed in the stomach.
food may interfere with absorbtion!
explain distribution of nsaids? (D) ppb? vd? t1/2?
THEY ARE HIGHLY PROTEIN BOUND!99%
so if you displace a small amount then it leads to toxicity.
they have a small VD. (accululate at sites of inflammation) - proteins take them there. (ecf volume - 0.2l/kg)
often have a shirt half life
explain metabolism of nsaids? where done? and the excretion?
some excreted unaltered drug
some metabolites are active (oxyphenbutazone)
slow metabolism and excretion in young
some have 0 order kenetics.
what are the side effects of nsaids? linked to?
they inhibit COX 1.
GIT ULCERATION (reduce gi PG)
(inhibit gastric acid secretion and promote mucus secretion normally and bicarb,)
large intestin elesions and bute binds to feed and is carried there.
explain the nepphrotoxicity of nsaids? pgs? !!!!!!!!!!!!!!!!! what is their role.
Pg's act on renal blood flow. if you are hypotensive then pgs acton the afferent arteriole and dilate it. RAAS - contrict efferent. - therefore, higher GFR and less lost. it also prtects renal medullary cells from dehydration.
if you inihbit this then apoptosi of cells as they dehydrate and no GFR maintained.
explain the hepatotoxicity of nsaids?
have potential to prodcue hepatic injury. metabolised there. (labrador and carprofen.)
explain coagulation effects of nsaids ? eg?
aspirin. caused less platelet binding. see later lecture.