Tdm And Nsaids

Front 1

why is therapeutic drug monitoring (TDM) needed?

Back 1

some drugs have a very low therapeutic index (LD50/ED50) hence can easily OD. sometimes there can be a poor correlation between dose and circulation concentration, and therapeutic and toxic effects

Front 2

how do you work out TDM and what samples do you need?

Back 2

usually need 6 intervals to get steady state and multiply by the half life of the drug to work out how long to monitor for (normally about 2 weeks). with repeated dosing, a steady plasma concentration is attained (Cmax and Cmin unchanged). need venous blood for plasma or serum

Front 3

in what stage of inflammation to NSAIDS have their greatest effect?

Back 3

In the acute transient phase when there is local vasodilation, and increased capillary permeability

Front 4

What are the main effects of NSAIDS? what are their benefits?

Back 4

analgesic, anti inflammatory, anti pyretic, used for pain and inflammation in chronic osteoarthritis, post trauma and perioperatively.
they are non-narcotic, non sedating, not ataxia inducing and can be used with narcotics.

Front 5

what are some other uses of NSAIDS?

Back 5

anti-tumour effects via COX-2 inhibition for transitional cell carcinomas (-oxicam family)
antithrombotic (reduce risk of thromboembolism)
ophthalmic (keratitis and scleritis)
immune modulating (decrease autoantibody producing B cells) ie rheumatoid arthritis
antipyretic is cattle, endotoxic shock

Front 6

how to NSAIDS work:

Back 6

Inhibit COX 1 and COX 2 and also LOX.
cell damage→ phospholipids→ phospholipase(inhibited by corticosteroids)→ arachidonic acid→ COX 1 and 2 to produce thromboxane and prostaglandins or LOX to produce leukotrienes

Front 7

describe the differences between COX 1 and 2

Back 7

COX 1 is constitutively produced and has many protective roles, present in BV, GI, mucosa and kidney, produces PGE2 and PGI2.
COX 2 is induced after an injury (ie ischaemia, infec, trauma) to produce mediators of pain, inflammation and pyrexia.

Front 8

what can NSAIDS have adverse effects on?

Back 8

GI tract (ulceration)
kidneys
blood
liver toxicity
inhibit proteoglycan synthesis

Front 9

describe how NSAIDS cause gastric ulceration

Back 9

prostaglandins (PGI2 and PGE2)have protective function by inhibiting mucous secretion, increasing mucosal blood flow and production. to alleviate the side effects, omeprazole (H2 blocker) can reduce acid secretion, misoprostal is a PGE analogue hence prevents ulceration. USE COX-2 inhibitors

Front 10

describe how NSAIDS have adverse effects on kidneys

Back 10

normally PGE2 and PGI2 increase salt and water excretion and increase renal vasodilation. increased water retention→ hypertension→ decreased renal blood flow→ interstitial necrosis and nephritis. Animals with heart dis (hence lower CO) at increased risk.

Front 11

why should you not use NSAIDS in volume depleted animals?

Back 11

can lead to renal compromise, failure and death

Front 12

describe how NSAIDs can have an adverse reaction on blood

Back 12

thromboxane is a proaggregator of platelets needed for thrombus formation and haemostasis. older drugs inhibit hence cause prolonged bleeding time. (Not COX2 specific drugs)
removal of PGI2 inhibits platelet aggregation, hence can cause abnormal bleeding.

Front 13

how to NSAIDS cause liver toxicity?

Back 13

accumulation of toxic metabolites?

Front 14

when would you use NSAIDS in cats and when would you not?

Back 14

if severe inflammation ok, give with IV fluid is dehydrated. Not if has kidney or bleeding problems. Moderate pain relief may be ok to give, but not to replace antinflammatory. meloxicam is the only NSAID safe to use in cats.