NSAIDs Flashcards
What is COX-1 and what are its homeostatic and pathological functions
COX-1 - cyclo-oygenase 1. Constitutively active in most tissues
Homeostatic function - GI protection, platelet aggregation, vascular resistance, renal blood flow
Pathological functions - chronic inflammation, chronic pain, raised BP
What is COX-2 and what are its homeostatic and patholgical functions
COX-2 - cyclo-oxygenase 2. Inducible but typically active in active/inflamed tissue
Homeostatic functions - renal homeostasis, tissue repair/healing, reproduction, inhibition of platelet aggregation
Pathological functions - chronic inflammation, chronic pain, fever, blood vessel permeability
What are the general functions of prostagladins E2, F2-alpha and D2
Pain, pyrexia and inflammation
What are the differences between prostaglandin I2 and thromboxane A2
PGI2 protects the CVS - inhibits platelet aggregation, vasodilates
TXA2 is generally bad for the CVS - platelet aggregation, vasoconstriction
By what mechanism do NSAIDs act to inhibit COX
NSAIDs compete with arachidonic acid for hydrophobic site of COX to decrease prostaglandin, prostacyclin and thromboxane synthesis
Describe the analgesic effects of NSAIDs
Local peripheral action at site of pain with increased efficacy if inflamed
Central component associated with decreased PGE2 synthesis in dorsal horn - PGE2 used as neurotransmitter so decreased synthesis means decreased excitability of neurones in pain relay
Describe the anti-inflammatory effects of NSAIDs
NSAIDs decrease prostaglandin production during injury
Cause symptomatic relief by COX inhibtion though have little effect on underlying condition
Describe the anti-pyretic and platelet effects of NSAIDs
NSAID inhibit hypothalamic COX-2 where cytokine induced prostaglandin synthesis is elevated
Inhibition of COX-2 prevents stimulation of fever
COX-1 inhibition inhibits platelet aggregation by decreasing TXA2 synthesis
What are the differences between the COX-2 selective and non-COX-2 selective drugs
COX-2 selective have a higher selectivity for COX-2
COX-1 inhibitors can disrupt physiological actions fo COX-1 - harmful side effects
COX-2 have less GI ADRs but renal ADRs similar to non-selective
COX-2 do not have any anti-platelet effects but do impair PGI2 which may lead to unopposed aggregatory effects
Name some non-selective NSAIDs
Aspirin
Ibuprofen
Naproxen
Diclofenac
Name some COX-2 selective NSAIDs
Celecoxib
Parecoxib
Etoricoxib
Describe the pharmocokinetic properties of NSAIDs
Have complete GI absorption and don’t undergo 1st pass elimination
t1/2 generally either short or long - though NSAID may exceed t1/2 as they tend to accumulate at site of inflammation and may not be eliminated
Are highly protein bound -> small Vd
Are metabolised by the liver
Name some GI ADRs of NSAIDs and the effects that NSAIDs cause in the GI tract
NSAIDs decrease mucus and bicarb secretion and increase acid produciton
NSAIDs decrease mucosal blood flow (enhanced cytotoxicity and hypoxia) and decrease hydrophobicity of mucus layer due to acidic nature
ADRs: dyspepsia, nausea, peptic ulceration, bleeding, perforation
Name some renal ADRs of NSIADs and the effects of NSAIDs on the kidneys
NSAIDs decrease GFR, decrease renal medullary blood flow and increase creatinine in the blood
This is due to inhibition of prostaglandin production which are used for vasodilation
Have increased salt and water retention -> oedema and hypertension
Decreased renin secretion results in hyperkalaemia
Name some cardiovascular ADRs of NSAIDs and the effects of NSAIDs on the CVS
Increased salt and water retention increases BP and may exacerbate HF
Decreased prostaglandins means there is vasoconstriction - unopposed action of ADH
Increase risk of acute MI
