Paracetamol

Acetaminophen (INN Paracetamol) is one of the most widely used over-the-counter antipyretic and analgesic drugs worldwide.
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Although discovered more than 100 years ago, and used extensively for ~ 50 years, its mode of action is still unclear

Source : The FASEB Journal Volume 22, Issue 2

One of the most widely prescribed drugs in history works by mechanisms which have not yet been agreed upon by the medical establishment. It‘s currently thought that paracetamol acts via more than one neurological pathway, one of which may be by inhibiting the COX-2 network (see link above). The COX-3 isoform of the COX family of enzymes is also implicated (Ref. Wikipedia)

The fact is, despite its ubiquity, we still don’t really understand how paracetamol works. A leading theory is that, in part, it works like aspirin and ibuprofen, by blocking enzymes known as cyclooxygenases.
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These enzymes are responsible for making hormone-like compounds called prostaglandins, which trigger pain and swelling in the body as well as stimulating production of the mucous that shields our stomachs against digestive acids."

Source : New Scientist, link below

Uncertainties regarding its efficacy

Recent research suggests that paracetamol does have a marginal effect for pain relief - but only in around 25% of individuals - and that its beneficial action in others is due to placeboplugin-autotooltip__plain plugin-autotooltip_bigPlacebo effect

Placebos are faux medications - typically lactose or microcrystalline cellulose - designed to act as inert, non-functional 'controls' in medical experiments. (There are also faux medical procedures, see section below)

From the beginnings of their use in research, experimenters had assumed that they could not possibly have any medical effect. But they are now being taken seriously as treatments, after it was discovered that totally inactive substances effects.

It's proven, however, to have some 'anti-pyretic' (fever reducing) properties - but is less efficient than either aspirin or ibuprofen.

The drug has significant side-effects, including stomach-lining damage. Overdoses - which can cause severe liver damage - run into 80,000 each year in the US alone.

A May 2014 cover story from New Scientist 'Cure-all no more' drew attention to a review of research regarding the use of paracetamol to relieve chronic joint pain, examining seven studies that compared the drug with a placebo. Five of these found it to be marginally more effective, but two found no difference.

“Why are we bothering to give a drug to people that’s toxic, that has significant potential problems, when it doesn’t work?” asks Andrew Moore, an anaesthetist and director of pain research at the University of Oxford. “It’s unethical.”

Anecdotal evidence from medical professionals suggests that some doctors are, in effect, using paracetamol as a 'prescribed placebo' (many countries have legislation to prohibit doctors from prescribing actual placebos.)

Also see : Tolmetinplugin-autotooltip__plain plugin-autotooltip_bigTolmetin

Tolmetin, a.k.a. Tolectin is a nonsteroidal anti-inflammatory drug (NSAID) of the heterocyclic acetic acid derivative class.

It was developed in the 1970's, and is used to treat conditions such as osteoarthritis, Rheumatoid Arthritis, and Ankylosing Spondylitis

Its mechanism of action is unclear..

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