How paracetamol and aspirin work

Both these drugs, used to treat minor aches and pains and to reduce fever, have a similar mode of action. They inhibit an enzyme called cyclo-oxygenase, or COX. This produces substances called prostaglandins, which are mediators produced in response to damage to cells and which tell the body that there is damage, which we feel as pain. Blocking the production of the prostaglandins therefore reduces the sensation of pain. They also cause relaxation of blood vessels in the brain which causes headache; drugs such as aspirin reduce this by reducing the amount of prostaglandin present. The prostaglandins can also increase the temperature by acting on a particular area in the brain. If there are fewer of these mediators, the temperature will remain more or less normal and fever will be reduced. The prostaglandins, along with other mediators such as kinins and histamine, are also involved with the inflammation that occurs when tissue is damaged and infected by bacteria. Therefore aspirin will reduce inflammation by reducing the amount of prostaglandin available. Paracetamol does not do this because it is less effective at inhibiting COX; it mainly inhibits this in the brain, allowing the pain relief and temperature reduction. Therefore paracetamol does not reduce inflammation.

At first paracetamol (acetaminophen in the USA) was considered a safe and effective drug. It became increasingly popular and was used by millions worldwide. A problem then began to appear, as some people began to take overdoses of the readily available drug.1

The drug, unfortunately, causes serious toxic effects at high doses. Although two tablets, the normal recommended dose for an adult, are perfectly safe, twenty-two could be a lethal overdose. The number of deaths worldwide amounts to hundreds and many more are made seriously ill. However, paracetamol is a safe drug, provided it is used at the correct dose. (Remember there are no safe drugs, only safe ways of using them.) Here we have yet another illustration of the Paracelsus principle: 'All substances are poisons; there is none that is not a poison. The right dose differentiates a poison from a remedy.' Thus even a drug like paracetamol, which is safe enough to be sold over the counter in pharmacies, is capable of becoming a poison. The number of deaths caused by this relatively very safe drug, as well as the illness it has caused, have, unfortunately, led to calls for it to be withdrawn (see case notes).

Any drug taken in overdose is likely to cause death and illness, and there are many other drugs readily available over the counter that are

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