quarta-feira, março 16, 2005

O Uso dos Analgésicos

1: J Intern Med. 1990 Jun;227(6):423-8.

Consumption, overdose and death from analgesics during a period of over-the-counter availability of paracetamol in Denmark.

Ott P, Dalhoff K, Hansen PB, Loft S, Poulsen HE.
Department of Medicine A, Rigshospitalet, Copenhagen, Denmark.

During the period 1978-1986, annual sales of paracetamol in Denmark increased from 1 million defined daily doses (DDD) (3 g) to 47 million DDD, while the number of admissions and deaths from overdose increased from 26 to 202 and from 1 to 3-4, respectively. The corresponding figures for salicylates are a decrease in sales from 113 to 94 million DDD, an increase in admissions from 282 to 595, and an increase in deaths from 5 to 22. From 1 January 1984 paracetamol became available on an over-the-counter basis. The figures for 1983 and 1984 were an increase in sales from 14 to 28 million DDD, an increase in admissions from 114 to 198, and an increase in deaths from 0 to 4. The number of deaths from opioid overdose remained constant at a value of about fifty during this period, the mortality per dose being about 20-fold higher than for paracetamol and salicylates. Dextropropoxyphene-related deaths increased twofold to 121 in 1986, with unchanged sales figures. A campaign launched by the National Board of Health resulted in a reduction in the number of deaths from dextropropoxyphene to 66 in 1987. The main effect of over-the-counter release of paracetamol was a dramatic increase in sales, without the epidemic of deaths observed a decade ago in the UK. It is suggested that the higher mortality of paracetamol poisonings in the UK compared to Denmark is related to the dextropropoxyphene content of the combination product, which is not available in Denmark. From an epidemiological toxicological viewpoint such combinations are not justified.

PMID: 2351928 [PubMed - indexed for MEDLINE]

2: J Epidemiol Community Health. 1997 Apr;51(2):175-9.

Comment in: J Epidemiol Community Health. 1997 Dec;51(6):731-2.

Use of paracetamol for suicide and non-fatal poisoning in the UK and France: are restrictions on availability justified?

Gunnell D, Hawton K, Murray V, Garnier R, Bismuth C, Fagg J, Simkin S.
Department of Social Medicine, University of Bristol.

OBJECTIVE: To investigate the relationship between the availability of paracetamol and its use for overdose and suicide. DESIGN: Analysis of routinely collected information on time trends for paracetamol suicides, non-fatal overdoses, and sales. SETTING: England and Wales and France. RESULTS: There were strong correlations between trends in paracetamol sales in the UK and trends in non-fatal paracetamol overdose in Oxford between 1976 and 1993 (Spearman's r = 0.86; 95% confidence interval (CI) 0.54, 0.96) and between paracetamol sales and non-fatal overdoses in France between 1974 and 1990 (r = 0.99; 95% CI 0.97, 1.00). Sales figures were also correlated with paracetamol related suicides in both England and Wales, 1983-91 (r = 0.72; 95% CI 0.11, 0.94) and France, 1974-90 (r = 0.79; 95% CI 0.50, 0.92). Similarly strong relationships were observed between trends in non-fatal overdoses and suicide by paracetamol poisoning in England and Wales (r = 0.85; 95% CI 0.61, 0.95) and France (r = 0.79; 95% CI 0.50, 0.92). It is estimated that approximately 32,000 overdoses involving paracetamol occur annually in England and Wales. Fatality rates from paracetamol overdose were four times as high in England and Wales (0.4%, 95% CI 0.38, 0.46) as in France (0.1%, 95% CI 0.06, 0.17). CONCLUSION: Trends towards greater availability of paracetamol are paralleled by increases in its use for both non-fatal overdose and suicide. Paracetamol related morbidity and mortality seem to be less frequent in France where the quantity of paracetamol in a single purchase is limited. Although not conclusive, these data add to a body of
evidence which suggests that restrictions in the quantity of paracetamol available as a single purchase in the UK may reduce suicide and liver failure related to paracetamol.

PMID: 9196648 [PubMed - indexed for MEDLINE]

3: Br J Clin Pharmacol. 2002 Oct;54(4):430-2.

Paracetamol-related deaths in Scotland, 1994-2000.

Sheen CL, Dillon JF, Bateman DN, Simpson KJ, MacDonald TM.
Medicines Monitoring Unit, Department of Gastroenterology, Ninewells Hospital, Dundee, DD1 9SY. chris@memo.dundee.ac.uk

AIMS: To investigate the death rate due to paracetamol poisoning in Scotland and what effect the reduction in over-the-counter paracetamol pack sizes in 1998 had on the death rate. METHODS: Records from 1994 to 2000 were examined to identify
the number and annual incidence of paracetamol-related deaths. Numbers of deaths before and after the pack size reduction were compared. RESULTS: No significant differences were shown due to the pack size reduction. The Scottish paracetamol-related death rate was twice as high as in England and Wales.
CONCLUSIONS: Further measures to reduce paracetamol-related morbidity and
mortality in Scotland should be considered.

PMID: 12392592 [PubMed - indexed for MEDLINE]

4: Scott Med J. 2004 Nov;49(4):142-3.

Restricting sales of paracetamol tablets: effect on deaths and emergency
admissions for poisoning in Scotland 1991 - 2002.

Inglis JH.
NHS Health Scotland, Woodburn House, Canaan Lane, Edinburgh. jamie.inglis@hebs.scot.nhs.uk

OBJECTIVE: To identify any effect on deaths and emergency admissions for poisoning resulting from the restriction on paracetamol sales introduced in September 1998. SETTING: Scotland. DATA: Deaths from poisoning were extracted from the General Registrar (Scotland) Office annual reports for 1991 to 2001 and emergency admissions data for 1990/91 to 2001/02 was supplied by the Information and Statistics Division of NHS Scotland. RESULTS: Deaths in the early 1990s, deaths from all poisonings and deaths from paracetamol poisoning were stable.
After the restrictions deaths from all poisonings remained stable. Deaths from paracetamol poisoning fell by 45% in 1998 but have risen in each of the three years since to reach pre-restriction levels. RESULTS: Emergency admissions in the early 1990s all poisonings rose steadily. Following the restrictions all admissions fell by 10% and paracetamol poisonings fell by 14%. All admissions remained lower for a further two years but are now rising again. Paracetamol poisonings remained lower for a second year but the last two years have both seen 10% increases to reach record levels. DISCUSSION: The restrictions caused a dramatic 45% fall in deaths from paracetamol poisoning and reversed a relentless upward rise in all admissions for poisoning. The benefits were short-lived lasting about two years. Deaths and admissions are rising again and admissions are at record levels. CONCLUSIONS: Restricting paracetamol sales resulted in significant health gain. Further restrictions and public education on this valuable but dangerous drug are both urgently needed.

PMID: 15648708 [PubMed - in process]

5: Am J Ther. 2002 May-Jun;9(3):245-57.

Over-the-counter analgesics: a toxicology perspective.

Jones A.
National Poisons Information Service, Guy's and St Thomas' NHS Trust, United Kingdom. allison.jones@gstt.sthames.nhs.uk

The decision to use any analgesic is a balance of benefit and risk. In the case of analgesics, it is important to balance the therapeutic benefit against both the risk in therapeutic use and the risk (and ease of treatment) in overdose.
Paracetamol in therapeutic dose carries little risk of adverse events. Less than 0.1% of the estimated 30 million paracetamol users in the United Kingdom attend hospital with a paracetamol overdose each year, and approximately 200 people die, most of whom presented late or did not receive antidote, N-acetylcysteine, within 12 hours. Nonsteriodal anti-inflammatory drugs (NSAIDs) have greater adverse effects in therapeutic use than paracetamol but also have a lower incidence of severe features or death in overdose. There is no antidote available for NSAID poisoning. Aspirin carries both significant adverse effects in therapeutic dose and a substantial risk in overdose, for which there is no antidote. Its risk-benefit profile is probably the poorest of all analgesics currently available over-the-counter (OTC); this is reflected in current trends both in analgesic use and overdose figures. Although a number of options to reduce deaths from poisoning by OTC analgesics have been considered, few are practical, and all must take account of the public health benefits provided by these drugs. A perspective should be retained that the vast majority of the population in Australia, the United States, the United Kingdom, and Denmark derive therapeutic benefit from OTC analgesics and do not take them in overdose.
The majority of those who do take overdoses come to little or no harm.
Management of serious poisoning by paracetamol, aspirin, or NSAIDs remains a medical challenge.

Publication Types:
Review, Tutorial
PMID: 11941384 [PubMed - indexed for MEDLINE]

6: Tidsskr Nor Laegeforen. 2004 Jun 17;124(12):1624-8.

[Paracetamol poisonings in Norway 1990-2001]

[Article in Norwegian]
Boe GH, Haga C, Andrew E, Berg KJ.

Avdeling for giftinformasjon (Giftinformasjonen), Sosial- og helsedirektoratet, Postboks 8189 Dep, 0034 Oslo. g.h.boe@shdir.no

BACKGROUND: After the introduction of new regulations in 1981 and 1990 in
Norway, over-the-counter sales of paracetamol and acetylsalicylic acid have been limited to 10 grams. From 1990 the sale of paracetamol has increased dramatically; that of acetylsalicylic acid has accordingly been reduced. We have investigated the morbidity and mortality from overdoses of analgesics, especially paracetamol, in the period 1990-2001. MATERIAL AND METHOD: We collected data from the inquiries received by the National Poisons Information
Centre in Norway. Data on hospital admissions and deaths have been recorded from the Norwegian Patient Register. These data have also been used to collect anonymous case records from all patients who died following intake of paracetamol. We also sent questionnaires to 57 hospital departments in a survey of deaths from paracetamol poisoning. RESULTS: Calls concerning paracetamol poisonings to the National Poisons Information Centre doubled to about 400 calls per year over the period. In 30% of cases serious poisoning was suspected.
Hospital admissions diagnosed primarily as analgesic poisoning increased from 848 to 1162. On average, 52% of poisonings were caused by paracetamol, 13% by opioids, 5% by acetylsalicylic acid; in 27% the analgesic involved was not specified. 59 deaths were diagnosed as poisoning from analgesics as primary cause, 13 of them due to paracetamol, 26 to opioids, 2 to acetylsalicylic acid; in 18 cases the analgesic involved was not specified. The questionnaires gave insignificant additional information. INTERPRETATION: The number of paracetamol poisonings has increased since 1990 in accordance with the dramatic increase in sales of paracetamol in Norway. Although the mortality of paracetamol poisoning is low (1-2 deaths annually), it represents the most critical poisoning problem among non-opioid analgesics. It is important to monitor the morbidity and mortality of paracetamol poisoning, as new regulations introduced from 2003 will
increase the availability of paracetamol and other selected non-opioid

PMID: 15229706 [PubMed - indexed for MEDLINE]

7: J Public Health (Oxf). 2005 Mar;27(1):19-24. Epub 2005 Jan 6.

Impact of paracetamol pack size restrictions on poisoning from paracetamol in England and Wales: an observational study.

Morgan O, Griffiths C, Majeed A.
Office for National Statistics, London SW1V 2QQ.

BACKGROUND: About 500 drug poisoning deaths involving paracetamol (acetaminophen) occur every year in England and Wales. To reduce the number of deaths, regulations were introduced in 1998 to restrict the sale of paracetamol.
In this paper, we evaluate the impact of these regulations. METHODS: Mortality data for England and Wales were provided by the Office for National Statistics.
Deaths were defined as due to compound paracetamol (paracetamol in combination with another analgesic, a low dose opioid or other ingredients) or paracetamol only, with or without alcohol or other drugs. The Department of Health provided data on all hospital admissions with a primary diagnosis of paracetamol poisoning. RESULTS: Mortality rates for paracetamol only were similar for males and females, and decreased from about 4.5 to 2.8 per million between 1997 and 1999 and again from about 3.1 to 2.2 per million between 2001 and 2002. These falls may be attributable to random variation in the rates. Deaths involving compound paracetamol, which were not subject to the 1998 regulations, remained relatively constant over the study period. There was evidence of a decreasing trend in paracetamol only mortality rates and this followed overall trends for other drug poisoning excluding opioids and drugs of misuse. Hospital admissions due to paracetamol poisoning increased from about 27 000 to 33 000 between 1995/1996 and 1997/1998 and then decreased to 25 000 in 2001/2002. There were almost 50 per cent more admissions for females than males, with the highest admission rates amongst females aged 15-24 years old. CONCLUSIONS: Between 1993 and 2002, mortality rates and hospital admissions due to paracetamol poisoning declined. However, the contribution of the 1998 regulations to this decline is not clear. Paracetamol poisoning continues to be an important public health issue in England and Wales and represents significant workload for the NHS in England.

PMID: 15637104 [PubMed - in process]

8: Ir J Med Sci. 2002 Jul-Sep;171(3):148-50.

Ease of access is a principal factor in the frequency of paracetamol overdose.

O'Rourke M, Garland MR, McCormick PA.
Liver Unit, St Vincent's University Hospital, Dublin, Ireland.

BACKGROUND: In Ireland, 30% of non-fatal overdoses involve paracetamol. AIMS: To determine how and where patients obtained paracetamol, to assess awareness of toxicity and examine the relationship between dose and suicidal intent. METHODS:
A prospective study of patients admitted following a paracetamol overdose
recording their reasons for using paracetamol, their knowledge of its toxicity and their suicidal intent scale (SIS). RESULTS: Of 100 patients, 66% obtained paracetamol in non-pharmacy outlets, 82% cited ease of availability as the reason, 55% were aware of its toxicity, 31% of liver damage and 68% did not read the warning on packets. The mean number of tablets taken was 51.3 for males and 37.2 for females (p < 0.01). Males presented later than females for medical attention (12.5 versus seven hours [p < 0.02]) and more males than females took alcohol (p < 0.03). The mean SIS score was 14.71 for males and 12.38 for females. There was a significant correlation between the SIS and the amount of paracetamol consumed (r = 0.28; p < 0.01). CONCLUSION: The majority obtained paracetamol in local shops or at home. Knowledge of toxicity and the need for early antidote was poor. There was a significant relationship between suicidal intent and number of tablets consumed. Limiting availability could reduce number of overdoses.

PMID: 15736354 [PubMed - in process]