NSAIDs Flashcards
Describe the WHO analgesic ladder
Step 1 - non opioid analgesic +/- adjuvant analgesic
Step 2 - opioid analgesic for mild to moderate pain +/- non opioid analgesic +/- adjuvant analgesic
Step 3 - opioid analgesic for moderate to severe pain +/- non opioid analgesic +/- adjuvant analgesic
Name some non opioid anlagesics
NSAIDs
Paracetamol
Name an opioid analgesic for mild to moderate pain
Codeine phosphate
Name an opioid analgesic for moderate to severe pain
Morphine sulfate
Where is aspirin derived from?
Willow trees
Where is Ibuprofen derived from?
Propionic acid
Name some NSAIDs
Naproxen Diclofenac Ibuprofen Aspirin (salicylate) Indomethacin Phenylbutazone Meloxicam Ketoprofen Etoricoxib
What does the term NSAID stand for?
Non steroidal anti inflammatory drug
Describe the mechanism of action of all NSAIDs
Exert effects on inhibition of prostaglandin synthesis
What is the primary site of action of NSAIDs?
Cyclooxygenase enzyme - COX1 and COX2
What is the role of prostaglandins?
Modulate components of inflammation Control of body temperature - fever Platelet aggregation - thromboxane A2 Pain transmission Support renal function
Describe the storage and release of prostaglandins
They are not stored. They are produced and released on demand
How long is the half life of prostaglandins?
minutes
What does COX catalyse?
Conversion of arachidonic acid to prostaglandins and endoperoxide
What does constitutively mean?
Produced at a steady rate regardless of physiological demand
Where is COX 1 expressed?
Most tissues
What is the function of COX 1?
Protects the gastric mucosa
Where is COX 2 expressed?
Brain and kidney, is induced in sites of inflammation
Which COX is present in platelets?
COX 1
What do older NSAIDs block?
Both COX isoforms
What NSAID blocks both COX isoforms
Ibuprofen
Blocking which COX isoform is undesirable and why?
COX 1
Stomach (PGE2,PGI2), intestine, kidney (PGE2, PGI2), platelet (thromboxane A2)
Which NSAID works on blocking thromboxane A2?
Aspirin
What do glucocorticoids do?
Block mRNA expression of COX2
How does celecoxib act?
Blocks COX2 - blocks the inflammatory effect of macrophages
Describe the metabolism of arachidonic acid
Arachidonic acid is metabolised by either COX1/2 to PGG2 and then PGH2 which is then converted to thromboxane A2 and prostaglandins (PGE2 and PGI2) (BY COX 1) or Prostacyclin (PGI2) and prostaglandins (inflammation, pain and fever)
Describe the action of thromboxane A2
Vasoconstriction
Stimulates platelet aggregation
Describe the action of PGI2
Vasodilation
Inhibits platelet aggregation
Name some COX 2 inhibitors
Etoricoxib and celecoxib
Why are COX 2 inhibitors more preferable as NSAIDs in patients with a history of GI bleeds
Reduced risk of serous upper GI bleed
Do not inhibit platelet aggregation
What is the first line treatment of gout
NSIADs
What drug is given to someone with out who can not tolerate NSAIDs
Colchicine
How long can the anti-inflammatory effect take to show in NSAIDs
3 weeks
What conditions are NSAIDs used for their anti-inflammatory properties?
Gout
Sero negative arthritis
Rheumatoid arthritis
SLE
What must be prescribed in addition to NSAIDs for long term use?
Gastroprotective drugs
Describe when the effect should be present for NSAIDs used as analgesics
Effect after first dose, full affect takes up to 1 week
Give the indications for using NSAIDs as analgesics
Osteoarthritis Rheumatoid arthritis Soft tissue rheumatism and back pain Minor trauma Soft tissue injury and sports injury Headache Dysmenohrrhea Oeri-/post- operatively Ureteric colic
Describe the mechanism of pyrexia
During inflammation Interleukin 1 releases prostaglandins into the CNS
Prostaglandins elevate the hypothalamic set point for temperature control
Describe how NSAIDs have anti pyrexic properties
Prevent prostaglandins synthesis so prevent hypothalamic set point of temp control from being raised
Name an NSAID indicated in cardiovascular disease
Aspirin
Describe the action of aspirin
Reduces platelet aggregation and therefore reduces the bloods ability to clot
Give some indications of aspirin
Unstable angina STEMI NSTEMI TIA Ischaemic stroke Secondary prevention
Describe the cyclo oxygenase pathway
Injury/infection/trauma
Attacks the cell membrane of the cell
Cell membrane contains phospholipids
Activation of phospholipase occurs
It causes formation of arachidonic acid
Arachidonic acid is further metabolised by cyclooxygenase pathway to produce prostaglandins and the lipoxygenase pathway to produce leukotrienes
List some common side effects of NSAIDs
GI discomfort - nausea, diarrhoea, oesophagitis, gastritis
Renal impairment
List some less common side effects of NSAIDs
Upper GI - bleeding and Peptic ulceration
Renal - fluid retention, papillary necrosis, interstitial nephritis
Increased BP and fluid retention - CCF
Hypersensitivity rashes - erythema multiforme, angioedema and bronchospasm
Headache, dizziness
Blood disorders
Cardiovascular events
Describe how NSAIDs can sometimes cause bronchospasm
COX inhibition and shunting of arachiodonic acid metabolism across the lipoxygenase pathway with resultant production of asthmogenic cysteinyl leukotreines
Describe the steroid and NSAID drug interaction
Increased risk of GI bleeding
Describe the anticoagulant and NSAID drug interaction
Increased risk of GI bleeding
Increased anticoagulant effect
Describe the ACE inhibitor and NSAID drug interaction
Increased risk of renal impairment, hyperkalaemia and antagonism of hypotensive effect
Describe the digoxin and NSAID drug interaction
May increase plasma digoxin concentrations
Increase risk of heart failure
Decrease renal function
Describe the interaction between NSAIDs and sulfonylureas
Enhances sulfonylureas effect
Describe the interaction between NSAIDs and quinolone antibiotics
Increased risk of seizures
Describe the interaction between NSAIDs and phenytoin
Increased risk of phenytoin toxicity
Describe the interaction between NSAIDs and SSRIs and venlafaxine
Increased risk of bleeding
Describe the interaction between NSAIDs and diuretics
Increased nephrotoxicity risk
Which patient groups are at risk of GI bleeding with NSAIDs
History of GI ulceration
Age >65
Concomitant drugs - anticoagulants, SSRIS, Steroids
Multiple NSAIDs
Which patients are at risk of cardiovascular or renal side effects of NSAIDs
Patients aged over 65
Established CVD
Hypertension
Renal and hepatic impairment
What groups of patients should be cautious of using NSAIDs
Pregnant Breast feeding Asthmatics Hypersensitivity Coagulation defects
