Health writers information on paracetamol

Q	How long has paracetamol been in use?
A	The pain and fever relieving properties of paracetamol were discovered in 1893 (1), but it first became available, on prescription only, in 1956, and then as an OTC medicine in 1963. It is now the most widely used pain reliever in Britain (2).
Q	How does paracetamol work?
A	As with many medicines, the effectiveness of paracetamol was discovered without knowing how it works. Its mode of action is known to have differences from other pain relievers, but although it is thought that pain relief works throughout the body and in the brain, the exact nature of the mechanism is not clear (3). However, the temperature lowering effects are known to be produced by prostaglandin inhibition in the brain (4).
Q	What is paracetamol useful for?
A	Paracetamol products give relief for all kinds of mild to moderate pain, including headache, rheumatic pains, pains from minor injuries, and all the everyday aches and pains of normal life. Paracetamol products are also very effective for bringing down high temperature in fevers, including colds and flu, and for relieving the aches and pains associated with these common illnesses.
Q	Who can use paracetamol products?
A	Paracetamol products are suitable for most people including the elderly and young children (5). Interactions with other treatments are not a problem, and they can generally be taken by people who are sensitive to aspirin. Paracetamol is well tolerated by people with peptic ulcers and in general those who suffer from asthma (6,7). Liquid paracetamol products are particularly suitable for children, and can be given to babies to treat the raised temperatures that may follow immunization(8).
Q	Can paracetamol be taken during pregnancy?
A	Paracetamol products can normally be used at recommended dosages during pregnancy, although it is always wise to consult a doctor about taking any medicines at this time, and mothers who are breast feeding may use paracetamol products (4,6,9). One report (10) has suggested an association between very heavy paracetamol use during the later stages of pregnancy and an increased risk of wheezing in the offspring, but this did not occur with normal occasional use at recommended dosages.
Q	What is the correct dosage?
A	For adults the recommended dosage is two 500mg tablets or capsules every four to six hours. No more than eight tablets or capsules should be taken in 24 hours. As with other medicines, paracetamol should not be taken on a long term basis unless under the supervision of a doctor. Children's medicines are available in different strengths for different ages and the instructions on the pack should always be followed. In general, children's dosages are based on 10-15mg paracetamol per kilogram body weight (8,11)
Q	What is the maximum amount that can be bought?
A	Paracetamol products are available in pharmacies up to a maximum pack size of 32 tablets or capsules, and in shops other than pharmacies up to a maximum pack size of 16 tablets or capsules. Multiple packs can be purchased provided the total does not exceed 100 tablets or capsules. For quantities of more than 100, a doctor's prescription is necessary. However, pharmacies and many retailers operate a voluntary restriction on the number of packs that can be purchased in a single transaction. For paracetamol products in the form of liquids, effervescent tablets or powders there is no limit on the pack sizes or quantities that can be purchased(12).
Q	If paracetamol products are used long term, is there a risk of liver damage?
A	Many people use paracetamol for extended periods under supervision of their GP. There is no evidence to show that, at recommended dosages, paracetamol causes liver injury when used for long periods (4).
Q	Will frequent use of paracetamol products cause addiction?
A	No. There is no physiological mechanism by which anyone can become addicted to paracetamol. There have been reports of addiction to combination products where paracetamol is combined with an opioid medicine, but this has nothing to do with the paracetamol component (4).
Q	Does paracetamol cause irreversible liver damage in overdose?
A	In large, untreated overdoses paracetamol may cause liver damage, but the liver recovers completely within a matter of months with no permanent damage (13,14). If the overdose is large enough to completely overwhelm the liver it cannot recover and death will follow. This is what is meant by the term 'irreversible liver damage.'
Q	Does a paracetamol overdose inevitably lead to death?
A	No. Death is a rare event following paracetamol overdose (15,16). Of all people in the UK who attend hospital each year for paracetamol overdose, 99.7% recover fully with no long term effects (17). Where death does occur following a paracetamol overdose it is usually because of delay before antidote treatment is received.
Q	How are paracetamol overdoses caused?
A	Most paracetamol overdoses are deliberate. Some overdoses are claimed to be 'therapeutic misadventure' but in reality this is extremely uncommon and the facts are often misinterpreted (18). It has also been suggested that several paracetamol containing products may be unwittingly taken together leading to an overdose but there are no substantiated cases of this ever resulting in liver injury.
Q	Is it dangerous to take paracetamol and drink alcohol?
A	No. Indeed paracetamol and alcohol are metabolised by the same oxidative enzymes and alcohol may even confer some protection to the liver in the event of a paracetamol overdose (19). In certain circumstances, alcoholics may be at higher risk of liver injury in the event of a paracetamol overdose. However, paracetamol is used as an analgesic for patients in hospital liver units, including alcoholic patients (20).
Q	Does paracetamol cause asthma?
A	There is no evidence that taking paracetamol causes asthma. One study has shown that people with severe asthma take more paracetamol than average, but this may be because they suffer from more headaches (21). The Committee on Safety of Medicines has reviewed this study and advised that'There is no reason for advising any change in the use of paracetamol. Paracetamol is a safe and effective pain killer for many patients including asthmatics' (6). In some rare cases, established asthmatics may be sensitive to paracetamol. In these patients, taking paracetamol may precipitate an asthma attack (7).
Q	Does paracetamol have anti-inflammatory action?
A	Paracetamol has very little anti-inflammatory activity, not enough to be clinically useful. However, paracetamol is now recommended as first line treatment for effective pain relief in osteoarthritis because of its lack of gastrointestinal side-effects, and although an anti-inflammatory action is not necessary in this particular condition, the wide use of paracetamol for osteoarthritis may have led to confusion amongst the general public (22).
Q	Are there any health benefits from using paracetamol products?
A	Paracetamol is virtually free of side-effects at recommended dosages and is therefore a healthy choice as a pain reliever, and to reduce fevers (4). Also, there is increasing evidence that using paracetamol may help to protect from hardening of the arteries, by inhibiting the oxidation of certain low-density lipoproteins which carry the 'bad' form of cholesterol, preventing one of the main processes involved in the formation of arterial plaque. Arterial plaque contributes to many deaths per year from stroke and heart disease(23). In addition, early studies have shown that frequent use of paracetamol appears to give significant protection from ovarian cancer(24).
REFERENCES
1	Mering, von, J., 1893, Beiträge zur Kenntniss der Antipyretica, Therap. Monatshefte, 7, 577-578.
2	Spooner, J. B. and Harvey, J. G., 1993, Paracetamo overdosage &endash; facts not misconceptions, Pharm. J., 250, 706-707.
3	Guzman, F. and Lim, R. K. S., 1967, Central and peripheral mechanisms of analgesia and pain, Arch. Bio. Med. Exper., 4, 180-186.
4	Prescott, L. F., 1996, Paracetamol (Acetaminophen) A Critical Bibliographic Review, Pub. Taylor & Francis Ltd.
5	Day, R. O. et. al., 2000, The Position of Paracetamol in the World of Analgesics, Am. J. Therap., 7, 51-54.
6	MCA information bulletin re Thorax paper, March 21, 2000.
7	Jenkins, C., 2000, Recommending Analgesics for People with Asthma, Am. J. Therap., 7, 55-61
8	Medicines for Children, 1999, RCPCH.
9	Heymann, M. A., 1986, Non-narcotic analgesics. Use in pregnancy and fetal and perinatal effects, Drugs, 32(suppl. 4), 164-176.
10	Shaheen S.O. et al., 2002, Paracetamol use in pregnancy and wheezing in early childhood, Thorax, 57, 958-963.
11	BNF 44, 2002.
12	Dept. of Health Sale or Supply Regulations, SI 1997, No. 2044.
13	Proudfoot, A. T. and Wright, N., 1970, Acute paracetamol poisoning, BMJ, 3, 557-558.
14	Prescott, L. F., 1983, Paracetamol overdosage: pharmacological considerations and clinical management, Drugs, 25, 290-314.
15	Thomas S. H. L. et al., 1997, Paracetamol poisoning in the North East of England: presentation, early management and outcome, - Hum. & Exp. Toxicol., 16, 495-500.
16	Gow, P. J. et .al., 1999, Paracetamol overdose in a liver transplantation centre: An 8-year experience, J. Gastroenterol. Hepatol., 14, 817-821.
17	Office of National Statistics and PIC files.
18	Prescott, L. F., 2000, Therapeutic Misadventure with Paracetamol: Fact or Fiction?, Am. J. Therap., 7, 99-114.
19	Prescott, L. F., 2000, Paracetamol, alcohol and the liver, Br. J. Clin. Pharmacol., 49, 291-301.
20	Dart, R. C., et. al., 2000, Treatment of Pain or Fever with Paracetamol (Acetaminophen) in the Alcoholic Patient: A Systematic Review, Am. J. Therap., 7, 123-134.
21	O Shaheen S. et al., 2000, Frequent paracetamol use and asthma in adults, Thorax, 55; 266-270.
22	Brandt, K. D., 2000, The Role of Analgesics in the Management of Osteoarthritis Pain, Am. J. Therap., 7, 75-90.
23	Greenspan, P., 2000, First Conference on Arteriosclerosis, Thrombosis and Vascular Biology, Denver, Colorado, USA.
24	Cramer, D. W., 1998, Over-the-counter analgesics and risk of ovarian cancer, The Lancet, 351, 104-107.