pharmacology 9 - NSAIDS Flashcards
when might you use the anti-thrombotic effects clinically?
hypertrophic cardiomyopathy in cats. causes thrombus formation 9use aspirin to de-coagulate) but use less frequently as they have a longer half life in cats than dogs (less metabolism) - cat has no means to perform glucuronidation. paracetamol = toxic!!
what are the main side effect sof nsaids?
- hepatotoxicity
- nephrotoxicity (pg)
- coagulation effects (aspirin)
- GIT ulceration. (PG)
expalin so,e drug interactions of nsaids? (4)
- if use 2 at same time then added efficacy and toxicity!
- may get slower clearance in using combination nsaids
- highly protein bound drugs may displace other drugs = toxicity. or if hypoalbuminaemic.
- if use drugs with hepatotoxicity then you will have reduced metabolism and so longer half life.
give some examples of nsaids? (6)
- paracetamol
- carprofen
- meloxicam
- fibrocoxib
- robenacoxib
- mavacoxib
aspirin - acetyl salicylic acid.
aspirin!!??…….properties? hydrolysed to? what does it mainly bind to? side effects? with cats? explain the antithrombotic effect?
hydrolysed to an active drug. inversibly binds Cox
mostly binds cox on platelets and they have no nucleus so cant reverse it and have to form new platelets to overcome the effects.
side effects - gi erosion, haemorrhage, emesis (vomit)
give cats less frequently as longer half life due to other means of metabolism (no glucuronidase enzyme.0
species variation in half life.
how does aspirin work as an anti-thrombotic drug? why do you NEED the correct dose?
reduces blood clotting by acting on the COX on platelts.
at low doses it work at inhibiting TXA2 - which is normally produced by platelets and promotes vasoconstriction and platelets to stick together. leads to clotting so if inhibit - no clotting!
at high doses it works on PGI2 - its synthesised by the endothelial cells and normally causes vasodilation and prevents clots forming. so if you inhibit this then causes clot to form.
paracetamol - why dont use in cats? what are the 3 steps of metabolism?
what does the 3rd one lead to ? NABQI? - binds to ? if this is saturated then binds to? auses? what can you treat this with?
why is it not a good anti-inflamm?
cats cant metabolise it as cant perform glucuronidation. toxic!!
- glucuronidation
- sulphate conjugation
- n-hydroxylation
- yields NABQi - this binds to glutathione but if this is saturated then it will bind to hepatic proteins and cause necrosis!!
treat by adding a precursor of glutathione - provide substrate.
paracetamol work at the next level down th epathway to cox - therefore it is a good antipyretic and analgesic but not a good anti-inflamm?
phenylbutazone? also called? used in? where does it concentate? what can it cause in ponies? why cant you use it in the food chain?
bute!! - cox inhibition. concentrates at site of inflamm.
causes protein losing enteropathy in ponies - Gi upset allows leakage of exudate into the GI tract. albumen lost via gut lesions.
cheap bbut cant use in food chain due to it being toxic in man.
pharmacokinetics in phenylbutazone?
absorbtion reduced by food.
has an active metabolite (oxyphenbutazone)
0 order kinetics
carprofen?? good at? poor? enantomers?
cox 1?
poor cox inhibitor but potent anti-inflamm, antipyretic, analgesic. racemic mix. (S and R enantomers) cox 1 sparing well tolerated used as perioperative analgesic
robenacoxib? specific to? increased safety why? dose? metabolism? excretion?
specific to COX 2. safety and efficiency as carpofen. increased GI safety. once daily. hepatic metabolism and biliary excreted.
mavacoxib? give how? kinetics? half life? ppb? eliminated?
COX2 inhibitor given orally. linear kinetics
highly protein bound.
extened half life. eliminated unchanged in bile.
drugs structurally similar to proeteoglycans? anti-inflamm effects.
give how? species? actions?
effects on bone/cartilage. hyaluronan/hylanuronic acid. ubiquitous. imparts structural characteristics to synovial fluid and cartilage. chondroprotective agent.
give i/v or intra-articular. dog/horse.
role of hyaluronan? (5)
free radical scavenger decreased PGE2 synthesis. decreased IL-1 proteoglycan release. high proteoglycan synthesis decreased leucocyte and macrophage (all reduced inflamm.)
polysulphated glycosaminoglycan. and pentosan polysulphate. (psg and pps)
reduce what?
similar to heparin. stimualtes matrix production. may reduce MMP. - pro-inflamm? drug excreted in kidney.
MMP’s - proteolytic enzymes. matrix degradation. there are some endogenous inhibitors called TIMPS. need a balance -if disrupted then cause joint or cv disease. (degenerative)
PPS - pentosan polysuphides - TIMPS. (MMP inhibitor)
