Aspirin

One of the salicylates, acetylsalicylic acid.

Non steroidal anti-inflammatory drug.

Pharmacology

Irreversible inhibition of arachidonate cyclo-oxygenase inhibits syntheses of prostaglandins.

Anti-inflammatory activity is related to inhibition of the COX 2 isoenzyme.

Antipyretic effect is due to inhibition of prostaglandins in the hypothalamus.

Analgesic effect is due to lack of prostaglandins in the tissues causing neuronal hyperalgesia.

Benefits of low dose aspirin

Antiplatelet action on COX1 reduces incidence MI and stroke in high risk patients and improves mortality.

Improves patency of coronary graft vessels.

Reduces risk of venous thromboembolism.

Reduces by almost half the risk of colon cancer and probably rectal cancer.

May reduce pregnancy related hypertension and may help in radiation induced diarrhoea.

Unwanted effects

Inhibits prostaglandin activity in the gastric mucosa so causes localised vasoconstriction. This means digestive enzymes and HCl which have `diffused backwards` are not washed away. His may lead to ulceration and haemorrhage.

Dyspepsia, nausea, vomiting, skin reactions.

`Analgesic associated nephropathy` after long term high doses of NSAIDs

Reye’s syndrome in children is very rare.

High doses may lead to tinnitus, dizziness, decreased hearing, nausea, vomiting.

Paracetamol

A weak inhibitor of COX-1 and COX-2.

Analgesic and antipyretic activity, only very weak anti-inflammatory effects.

Non-steroidal anti-inflammatory drugs

Have an analgesic effect similar to paracetamol in single does.

In regular full doses they have a lasting analgesic and an anti-inflammatory effect which makes them useful for treating ongoing pain caused by inflammation.

Therefore they are more appropriate than paracetamol or opioids in RA and advanced OA.

May also be used in back pain and soft tissue disorders.

Patients who do not respond to one preparation may respond to another, individual patient tolerance also varies with the preparation.

Pain relief begins after the first dose and a full analgesic effect is gained after a week. Full anti-inflammatory effect may take up to 3 weeks.

Selective inhibition of COX-2 improves GI tolerance.

Pharmacology

Reversible inhibition of arachidonate cyclo-oxygenase.

Prevent formation of prostaglandins.

COX-1 found in most tissues and platelets.

COX-2 is induced in inflammatory cells when they are activated and synthesises the mediators of inflammation.

So therapeutic action is related to inhibition of COX-2 and side effects related to inhibition of COX-1.

Antipyretic effects due to inhibition of prostaglandin formation the hypothalamus

Analgesic effects due to lack of tissue based prostaglandins to sensitise local nociceptors. Also some CNS action. May work in headache by preventing prostaglandin induced vasodilation.

Cautions and Contra-indications

Use with caution in the elderly.

Contra-indicated in patients with hypersensitivity to other NSAIDs or aspirin, e.g. history of angioedema, urticaria or rhinitis caused by aspirin or other NSAID.

C.I. in pregnancy, breast feeding and coagulation defects.

C.I. in patients with previous active peptic ulceration.

May result in deterioration of renal function.

Use with caution in renal, cardiac or hepatic conditions.

Side effects

GI problems, dyspepsia, nausea, diarrhoea, discomfort with possible haemorrhage and gastric ulceration.

Gastric irritation is caused by systemic and local effects.

If the treatment must be carried on, gastro protective treatment may be needed.

Hypersensitivity, particularly rashes, angioedema and bronchospasm.

May include bronchospasm in sensitive individuals.

CNS features and possible tinnitus.

Renal failure may present especially if there is pre-existing renal compromise.

Rheumatoid arthritis and other inflammatory disorders

Symptomatic treatment with a NSAID, indicated in pain and stiffness caused by inflammatory processes.

In rheumatoid arthritis other drugs may be given to influence the disease process, these are called disease-modifying anti-rheumatic drugs e.g. penicillamine, gold salts, antimalarials and drugs which affect the immune response such as azathioprine or methotrexate.

Corticosteroids may also reduce the rate of joint destruction.

Osteoarthritis and soft tissue disorders

OA is degenerative joint disease.

Advise weight reduction and exercise.

Try paracetamol first.

Or low dose NSAID, egg ibuprofen 1.2 g / day.

Paracetamol 4g per day may also be given with NSAIDs.

Low dose opioids may also be given with paracetamol.

Topical NSAIDs or capsaicin may provide pain relief in OA.

Intra-articular corticosteroid injections may produce temporary relief in OA.