Ibuprofen

Everyone experiences pain from a variety of sources on a day-to-day basis.  When this pain becomes more severe or distracting, many people turn to painkillers.  Ibuprofen, more commonly known as Motrin, Advil or Nurofen, is an example of a widespread analgesic drug used to alleviate pain caused by a variety of illnesses and injuries.  How does it work?

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Structure & Synthesis

First, it is important to discuss the structure and synthesis of ibuprofen.  The name “ibuprofen” comes from the conventional chemical name of the compound: iso-butyl-propanoic-phenolic acid.Ibuprofen is synthesized in a series of four steps through which 2-methylpropylbenzene (pictured left) is converted to iso-butyl-propanoic-phenolic acid (pictured to the right).  A more in depth description of the synthesis of ibuprofen can be read on the Royal Chemistry Society website.

How does it work?

When ibuprofen is taken, it is broken and absorbed into the bloodstream through the wall of the stomach.  Ibuprofen affects two cyclo-oxygenase enzymes (usually abbreviated COX-1 and COX-2).  These enzymes form prostaglandins from arachidonic acid, which is released when cells are damaged.  Prostaglandins cause the body’s response to pain, including inflammation, redness, increased temperature, and lower pain threshold.  Ibuprofen attaches to the active site of COX-1 and COX-2, preventing the synthesis of prostaglandins.  However, the enzymes eventually reject the ibuprofen, which is why the effects wear off after a few hours.  This video by Baxter Films has a great visual explanation of this process.

Optical Isomers

One interesting aspect of ibuprofen is that it has an optical isomer.  Optical or mirror image isomer includes a (+) or (-) in the notation, which is based on the direction that the isomer rotates polarized light. Ibuprofen has an S+ and an R- isomer.  The optical isomers of ibuprofen have many identical properties, including identical boiling points, freezing points, and solubility.

Although these isomers are nearly the same, they interact with molecules in different ways.  The S+ form of ibuprofen is pharmacologically active, or produces the desired pain-relieving effects, which are discussed below.  The R- form is unable to block the formation of prostaglandins because it is unable to bond to the active site of the COX enzymes.

Interestingly enough, the body has an enzyme that is able to convert the R- isomer of ibuprofen to the S+ isomer.  Thus, a typical 400 mg dose of ibuprofen contains 200 mg of the S+ isomer and 200 mg of the R- isomer, 60% of which is synthesized to S+ ibuprofen by the body.  Since stereospecific synthesis, or producing only one specific isomer, is more expensive and time consuming and enzymes in the body are able to convert the R- isomer to the S+ isomer, ibuprofen is usually sold as a mix of the two isomers.

Fast-Acting?

Despite the fact that ibuprofen has a carboxylic acid (COOH) group, it is not very soluble in water because it consists mostly of hydrocarbon groups, as seen in the structural image above.  This is bad news for users because the acting time of a drug depends on its solubility in water.  Before a drug reaches the bloodstream, it must first be absorbed through the wall of the stomach, which is achieved after the compound is dissolved in water.  But ibuprofen are generally felt within 15-30 minutes of taking it, so how is it able to enter the bloodstream so quickly?

In order to increase the solubility of ibuprofen, it is reacted with the amino acid lysine (shown below) to form ibuprofen lysinate.  This compound is more soluble than ordinary ibuprofen because it is ionic and has NH2 groups as well as the COOH group, making it more attractive to water.

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Side Effects

Ibuprofen can have side effects when taken, especially over a prolonged period of time.  This is because taking ibuprofen blocks the synthesis of prostaglandins, which have multiple roles in the body.  The two common negatively affected areas of the body are the stomach, since prostaglandins help protect the lining of the stomach, and blood clotting, since prostaglandins stimulate constriction of the blood vessels and clotting of platelets.  These websites provide more information on the roles of prostaglandins and side effects of ibuprofen.

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