nsaidS

structure

Carboxylic acids

Salicylic acids

· aspirin

· difusinal

Acetic acids

· diclofenac

· indomethacin

Proprionic acids

· ketoprofen

· naproxen

Fenamic acids

· mefanamic acid

Enolic acids

Pyrazolones

· phenylbutazone

Oxicams

· piroxicam

mode of action

· have three actions

· analgesic

· antipyretic

· anti-inflammatory

· best understood action is inhibition of prostaglandin synthesis

· through inhibition of cyclo-oxygenase

· this has far-reaching effects

· other less-understood effects

· on inflammatory cells and mediators

kinetics

· all well orally absorbed

· extensively metabolised to inactive compounds

· half-life of 2-14 hrs

· highly bound to plasma proteins

· excretion via urine and bile

· elimination can be affected by

· renal failure

· hepatic failure

· old age

· often presented as enteric-coated or sustained release preparations

· to minimise GIT side-effects

· to increase half-life

clinical effect

· minor overall differences in efficacy among different NSAIDs

· marked individual variation

· basis for variability unclear

adverse effects

Gastrointestinal

· up to 50%

· major SEs are

· gastric erosions

· peptic ulceration

· GIT bleeding

· minor SEs are

· nausea

· vomiting

· dyspepsia

· diarrhoea

· combination with anti-ulcer agents may be used

· H₂-receptor antagonists (ranitidine)

· acid pump blockers (omeprazole)

· prostaglandin analogues (misoprostol)

· site-specific agents (sucralfate)

· no firm data to support this

Renal

· may cause renal toxicity

· impairment of glomerular function

· interstitial nephritis

· papillary necrosis

· decrease renal blood flow by inhibiting vasodilation induced by prostaglandins

· may produce sodium retention and oedema

· care in patients with renal dysfunction

Haematologic

· all NSAIDs interfere with platelet aggregation

· reversible with NSAIDs (platelet function normal after 3 half-lives)

· irreversible with aspirin (platelet function normal after 4 days)

· may see thrombocytopaenia with most NSAIDs

· severe reactions (eg. aplastic anaemia) with phenylbutazone

Respiratory

· may precipitate or exacerbate asthma

· most common with aspirin

Dermatological

· relatively mild

· pruritis and photosensitivity

CNS

· headache

· dizziness

· mood changes

· tinnitus with aspirin

interactions

Warfarin

· inhibit warfarin metabolism

· increase anticoagulant effect

Anticoagulants

· damage GIT mucosa and inhibit platelet function

· increase risk of GIT bleed

Lithium

· inhibit renal excretion

· increase serum level and toxicity risk

Oral hypoglycaemics

· inhibit metabolism and increase half-life

· increase risk of hypoglycaemia

Phenytoin

· inhibit phenytoin metabolism

· increase serum level and toxicity risk

Digoxin

· decrease renal digoxin clearance

· increase serum level and toxicity risk

Aminoglycosides

· decrease renal aminoglycoside clearance

· increase serum level and toxicity risk

Antihypertensives

· cause increased water retetention and vasoconstriction

· reduce hypotensive effect

Diuretics

· counteract diuretic effect

· lead to fluid retention