Defining paracetamol

What is paracetamol?

Paracetamol, also known as acetaminophen or APAP (which is the active ingredient), is a commonly used medication for the treatment of mild to moderate pain and fever. Paracetamol thus belongs to the medication class known as analgesics (non-opioid / non-narcotic pain relievers) and antipyretics (fever reducers). Paracetamol may be recommended by medical doctors but is widely available in a range of products available over the counter. It is generally taken as needed for treatment but can sometimes be recommended as part of a dosing schedule over a more extended period of time. 

Inactive ingredients in paracetamol products generally include:

• Povidone (or polyvinylpyrrolidone / PVP): This ingredient is typically used as a synthetic water-soluble polymer involved in the dispersion (distribution) and suspension of a medication. The ingredient functions as a binder and helps the tablet to disintegrate (dissolve) so that it can be broken down for easier absorption in the small intestine.
• Pregelatinized starch: This ingredient is produced from pre-cooked, dried and ground (powdered) starch (normally corn or potato). Starches are useful for absorbing water quickly and helping to facilitate the disintegration process.
• Sodium starch glycolate: Ingredients used to create sodium starch glycolate include corn, potato, rice or wheat. Sodium starch glycolates are tasteless and odourless and function as a dissolution excipient (‘buking agent’), absorbing water quickly and bulking up the ingredient. This contributes to rapid disintegration of the medication.
• Stearic acid (a saturated fatty acid): This ingredient is also known as n-octadecanoic acid (C18H36O2) and is typically derived from animal or vegetable fats and oils. It functions as an emulsifying or solubilising agent, enabling disintegration.

What is paracetamol used for?

Common ailments paracetamol is frequently used for include:

• Mild fever
• Headaches
• Sore throats
• Muscle aches
• Toothaches
• Backaches
• Menstrual cramps (including premenstrual cramps or discomfort)

Such symptoms may be experienced during bouts of colds and flu (influenza) and various other illnesses, as well as reactions following vaccinations. Some individuals may also find some relief for mild pain associated with osteoarthritis. Paracetamol is not, however, a preferred pharmacological treatment for this condition as it does not treat the underlying swelling and inflammation which causes the characteristic symptoms of this condition (paracetamol is considered to have weak anti-inflammatory properties and thus cannot appropriately control such symptoms).

In general, paracetamol is regarded as having a very good safety profile (i.e. a low risk of side-effects) when taken at the recommended therapeutic dosages. A commonly taken medication with such a sound safety profile in comparison to many other pain-relieving medications, paracetamol can easily be underestimated when it comes to the potential risks of its use. Despite the fact that it is sold over-the-counter, like any other medication, there are still risks associated with its use and misuse.

Misuse can result in an array of side-effects, some of which may require medical monitoring. Overdosage of paracetamol is possible and can result in hepatotoxicity and severe liver damage, which can be life-threatening. Overdosage can easily occur as many over-the-counter medications contain paracetamol as an ingredient. If such medications are taken concurrently, more than the recommended daily dose may be absorbed into the system, resulting in overdosage.

Taken at low or recommended dosages, paracetamol does not result in the kinds of gastrointestinal side-effects that other pain-relieving medications, like NSAIDs (non-steroidal anti-inflammatories) are associated with. These include the likes of bleeding problems, ulcerations or perforations in the gastrointestinal system.

Available at a relatively low cost, paracetamol can sometimes be safely combined with other medications, like NSAIDs and opioids, for the treatment of more severe pain. Drug interactions and dosages should be carefully taken into account, however, to avoid unwanted effects.

How does paracetamol work?

Paracetamol targets the hypothalamus in the brain in order to help reduce fever and pain symptoms. This region of the brain is situated beneath the thalamus and above the pituitary gland, playing a fundamental role in the nervous and endocrine systems. The medication works to block pain impulses and inhibit the synthesis of prostaglandin (lipid compounds) in the central nervous system. Prostaglandins naturally assist with healing in the body when injury occurs. However, excessive production of these lipids can lead to unwanted inflammation and chronic pain. Blocking the production of these thus eases these symptoms.

The time it takes for paracetamol to achieve peak concentration levels in the blood is normally between 10 and 60 minutes (in both orally taken immediate release medications and intravenous infusions). Extended-release varieties can peak at between 60 and 120 minutes. Orally taken tablets at quantities of 500mg or 650mg (extended-release) can take longer (6 and 8 hours respectively).

Paracetamol has a half-life (i.e. the period of time it takes for the concentration level of the drug to be halved) of about 7 hours (in new-borns), 4 hours (in infants), 2 to 5 hours (in children), 3 hours (in adolescents) and 2 hours (in adults).

Paracetamol is metabolised by the microsomal enzyme system of the liver which consists of two protein components - cytochrome P-450 and NADPH-cytochrome c reductase, as well as the lipid, phosphatidylcholine. The conjugation of glucuronic and sulfuric acid in this process helps to make the medication more soluble in water. This helps to achieve easier elimination of the medication through urine. Paracetamol is mainly absorbed in the small intestine.

Some paracetamol brand names include:

Brand combination products (containing acetaminophen / paracetamol and other active ingredients)