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PubMed2004

Chronic daily headache with analgesic overuse: epidemiology and impact on quality of life.

OBJECTIVE: To analyze the prevalence and demography of chronic daily headache (CDH) with analgesic overuse. METHODS: A population of 9,984 inhabitants aged 14 or older living in Santoña, Spain, was studied. The authors personally interviewed 4,855 subjects, using a quota sampling approach. Those with headache for > or = 10 days/month and some analgesic use were asked to fill in a diary over the course of 1 month. Then, subjects were classified into CDH with or without analgesic overuse subtypes. Quality of life (Short Form-36 Health Survey [SF-36]) was also assessed in this second interview. RESULTS: Headache for > or = 10 days/month with analgesic consumption was reported by 332 subjects. Seven had secondary headache. Seventy-four (standardized prevalence 1.41%, 95% CI 1.1 to 1.8) fulfilled criteria for CDH with analgesic overuse. Prevalence in women (2.6%, 2.0 to 3.3) was much higher than in men (0.19%, 0.006 to 0.52). Mean age was 56 years (range 19 to 82 years). As recalled by the subjects, the mean age at onset of CDH was 38 years (range 9 to 82 years), whereas the mean age at onset of CDH with frequent analgesic consumption was 45 years (range 19 to 80 years) and that of primary headache was 22 years (range 5 to 60 years). CDH subjects showed a significant decrease in each SF-36 health-related score as compared with healthy control subjects. Transformed migraine was diagnosed in 49 (prevalence 0.9%), chronic tension-type headache in 20 (0.4%), and new daily persistent headache in 5 (0.1%). Thirty-five percent of patients overused simple analgesics, 22% ergotics, 12.5% opioids, and 2.7% triptans; the remaining 27.8% were overusing different combinations. CONCLUSION: CDH with analgesic overuse is a common disorder in the general population, mainly in women in their fifties, in whom 5% meet its diagnostic criteria.

Adolescent↗
PubMed1978

[Pharmacological studies of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M73101). (1). Analgesic activity (author's transl)].

The analgesic activity and the mode of action of M73101, a new analgesic anti-inflammatory agent, were investigated in mice and rats and compared to those of reference drugs. M73101 showed a marked analgesic activity against noxious stimuli induced by pressure (Haffner method and Randall-Selitto method), thermal (hot plate method), electric and chemical (acetic acid-stretching method and bradykinin-induced responses) stimulation, in a manner similar to those of basic anti-inflammatory drugs (BAD) such as aminopyrine, mepirizole, tiaramide HCl, and benzydamine HCl. The activities of M73101 were equal to and/or more potent than those of BAD, and more potent than those of acidic anti-inflammatory drugs. In addition, the analgesic activity of M73101 was not decreased by the pretreatment with levallorphan and showed no cross-tolerance to morphine in mice, indicating that the analgesic properties of M73101 differ from those of morphine. On the other hand, the analgesic activity of M73101 as well as BAD was decreased by repeated oral administration in mice, and the potency was weaker than mepirizole. Furthermore, the muscle relaxant effect of M73101 obtained by inclined screen test in mice was the weakest among the BAD, suggesting that analgesic activity of M73101 is not related to the muscle relaxant property. These results indicate that M73101 may be useful for clinical application as an anti-inflammatory drug possessing remarkable analgesic activity.

Administration, Oral↗
PubMed2004

Over-the-counter analgesics in older adults: a call for improved labelling and consumer education.

The use of analgesics increases with age and on any given day 20-30% of older adults take an analgesic medication. Over-the-counter (OTC) analgesics are generally well tolerated and effective when taken for brief periods of time and at recommended dosages. However, their long-term use, use at inappropriately high doses, or use by persons with contraindications may result in adverse effects, including gastrointestinal haemorrhage, cardiovascular toxicity, renal toxicity and hepatotoxicity. Many OTC drugs are also available through a prescription, for a broader range of indications and for longer durations of use and wider dose ranges, under the assumption that healthcare providers will help patients make safe choices about analgesics. Safe and effective use of medications is one of the greatest challenges faced by healthcare providers in medicine. More than 60% of people cannot identify the active ingredient in their brand of pain reliever. Additionally, about 40% of Americans believe that OTC drugs are too weak to cause any real harm. As a result of a recent US FDA policy, the conversion of prescription to OTC medications will result in a 50% increase of OTC medications. To reduce the risks of potential adverse effects from OTC drug therapy in older adults, we propose that the use of analgesics will be enhanced through the use of patient and healthcare provider education, as well as improved labelling of OTC analgesics. Improved labelling of OTC analgesics may help consumers distinguish common analgesic ingredients in a wide variety of preparations and facilitate informed decisions concerning the use of OTC drugs.

Aged↗
PubMed2003

Clinical pharmacology and rationale of analgesic combinations.

BACKGROUND AND OBJECTIVE: Oral fixed drug combination analgesics have potential advantages over monotherapy, but these can only be attained through careful design. RESULTS: The main reasons for developing combination analgesics are to gain efficacy and to reduce toxicity. Analgesic combinations interact pharmacokinetically, or pharmacodynamically, or both, in positive or negative terms. The t(max) value for both enantiomers of tramadol occur two hours following administration, and that for the active, (+)-M1 metabolite occurs after three hours. Thus, pairing tramadol with acetaminophen, a rapid-onset analgesic, represents a pharmacokinetically rational combination. Analgesic combinations should satisfy two important pharmacodynamic criteria: the components of the combination should display additive or synergistic analgesia; and this interaction should allow lower doses of each substance to be used in combination, resulting in an improved safety profile. Clinical studies of the pharmacodynamic between oral tramadol and acetaminophen in third molar extraction and cold pressor models have provided evidence that this combination provides better efficacy than either individual component of the combination. CONCLUSIONS: In summary, combination analgesics can play a valuable role in pain management. However, dubious combinations (directed against the same targets or with unwanted interactions) and 'old fashioned' fixed-dose multiple analgesic agent combinations should be avoided. Fixed-dose combination analgesics are of value only when they have been developed according to rational pharmacokinetic and pharmacodynamic criteria, and when claims for their benefits have been supported by evidence-based data and well-designed clinical studies.

Analgesics↗
PubMedDate not supplied

Use and abuse of analgesics in Nigeria: a community survey.

BACKGROUND: Chronic consumption of analgesics has been shown to increase the risk of end-stage renal disease. In Nigeria, these drugs are readily available as there is no legislation regulating their consumption. We report the use and abuse of analgesics in a Nigerian population. METHOD: Using a pre-tested questionnaire, subjects in Zawan B ward in Jos were interviewed regarding analgesic use. Cumulative lifetime dose of drugs consumed was calculated by obtaining the product of the average number of pills consumed in a week by duration of use in years. Analgesic abuse was defined as cumulative lifetime use of >5000 pills. RESULTS: Common analgesics regularly consumed were paracetamol in 58.1%, analgesic mixtures 28.9% and NSAIDS 13%. Common indications for use of these drugs were musculoskeletal pains, headache, fever and stress. Analgesic abuse was present in 22.6% of the respondents. CONCLUSION: Analgesic abuse is common in Jos, Nigeria. The sale and consumption of these drugs should be restricted by legislation.

Acetaminophen↗
PubMed2005

[Research on the analgesic effect and mechanism of bornyl acetate in volatile oil from amomum villosum].

OBJECTIVE: To study the analgesic effect and mechanism of bornyl acetate, the main ingredient of Amomum Villosum Volatile oil. METHODS: The analgesic effects were tested by pressing tail method. The I, and II phase pain were observed with the pain model caused by formalin test. Influence of naloxone antagonism test on analgesic effect of bornyl acetate. RESULTS: Bornyl acetate produced obvious analgesic effects on pain models induced by pressing tail. Bornyl acetate had inhibitory effect on I and II phase pain in formalin inducing pain model animals. Analgesic effect induced by Bornyl acetate wasn't significantly reduced by naloxone. CONCLUSION: Bornyl acetate shows analgesic effects. The analgesic site may locate in both central and peripheral nervous system. Its analgesic action way not be related to the opioid receptor.

Analgesics↗
PubMed1996

[Effectiveness of fixed analgesic combinations exemplified by thomapyrin].

Thomapyrin has been on the German market as analgesic for the past 50 years. It is the prescription-free preparation with the highest sales there. This is an occasion to survey current state of scientific knowledge concerning combination analgesics with acetyl salicylic acid, paracetamol and caffeine. For the assessment and registration of fixed preparations authorities of different European countries and also USA have defined special criteria. Analgesic preparations must agree with these defined criteria. The importance of these combination analgesics in pain therapy is described with the respect to the latest scientific results. Combination analgesics represent an important area of self-medication by the patient. The properties of the active substances alone and in combination are set forth, with respect to pharmacokinetics and efficacy. The experimental and especially clinical results clearly show a broader spectrum of action in consequence of the different modes of action of the individual active substances. Analgesic action is 1.4 fold higher owing to added caffeine. The fixed combination of active substances does not change the profile of side effects. The conclusion is that combination analgesics such as Thomapyrine show a positive benefit/risk ratio. Furthermore such combination analgesics are appropriate for self-medications and suited to combat pain of different kinds.

Acetaminophen↗
PubMed1998

[Analgesic nephropathy].

Analgesic nephropathy is a slowly progressive disease caused by the chronic abuse of analgesic mixtures containing two analgesic components combined with potentially addictive substances (coffeine and/or codeine). Pathologically, the nephropathy is characterized by renal papillary necrosis with calcification and chronic interstitial nephritis sometimes in association with transitional-cell carcinoma of the uroepithelium. In the early stage, the clinical characteristics are polyuria, sterile pyuria, sometimes renal colic and haematuria. With further progression of the disease, there are the nonspecific symptoms of advanced renal failure. The incidence of classic analgesic nephropathy among Hungarian patients on chronic renal replacement therapy has proven. There is an urgent need for the estimation of analgesic nephropathy among patients with chronic renal disease and among patients with chronic pain presumably regularly taking analgesics in Hungary. As long as analgesic mixtures containing phenacetin or paracetamol and/or nonsteroidal antiinflammatory drugs and addictive substances are available "over-the-counter", analgesic nephropathy will continue to be a problem also in our country.

Analgesics↗
PubMed1990

Effect of multiple dosing on the analgesic action of diflunisal in rats.

This investigation was designed to compare the analgesic effect of the initial dose of a repetitively dosed non-narcotic analgesic with the analgesic effect of a subsequent dose given 3 days later. To exclude gradual drug accumulation as a variable, the first ("loading") dose was larger than the maintenance doses. Male Sprague-Dawley rats received 100 mg/kg diflunisal i.v. as the first dose and 70 or 75 mg/kg every 12 hours thereafter. The analgesic effect of the first and seventh doses was determined as the pain threshold (voltage) upon electrical stimulation of the tail every 15 to 30 minutes from the third to the ninth hour after dosing. Blood samples for drug assay were obtained at 3 and 9 hours. A control group received injections of solvent for 6 doses and 100 mg/kg diflunisal as the seventh dose. There were no statistically significant differences between the area under the total or free (unbound) drug concentration versus time curves of the first and seventh dose but the average analgesic effect (area under the voltage increase versus time) of the seventh dose was only 28 percent that of the first dose. The areas under the drug concentration and analgesic effect versus time curves of the diflunisal dose given as the seventh injection to the control rats were similar to those produced by the first dose given to the multiple dosed rats. The results of this investigation show that the analgesic effect of a non-narcotic drug decreases substantially during repeated dosing in an animal model of experimental pain. This change in pharmacologic response has the characteristics of functional rather than pharmacokinetic tolerance in that there was no change in the drug concentration profile with time and no effect of the manipulations as such (i.e., repeated pain threshold determinations and blood withdrawals) on diflunisal-induced analgesia. These observations may have important implications for the evaluation and use of non-narcotic analgesics in the management of clinical pain.

Analgesia↗
PubMedDate not supplied

Musculoskeletal pain and analgesic therapy in a very old population.

The aim of this study was to examine the prevalence of musculoskeletal pain and use of analgesic drugs in a population of very old people. The investigation is based on data from the Kungsholmen project. Of the 2638 inhabitants aged 75 or more in a parish of central Stockholm 1800 were examined. Of the subjects. 60% reported trouble with pain at musculoskeletal locations, while only 40% of the pain reporting subjects used analgesics, one third of which were non-prescription minor analgesics. Prescription analgesics (non-steroidal antiinflammatory drugs or centrally acting drugs) were used by one fourth of the pain reporting subjects, and taken on a regular basis in only half of the cases. Potent opioids were used by less than 1% of the population. There was no increase in pain with increasing age, but an increase in use of minor analgesics with age >85. Women more often reported pain and had a higher consumption of analgesics. Light opioids were more often used by subjects with multifocal pain. Subjects living in sheltered accommodation used more analgesics, particularly light opioids, than did those living in their own homes or in institutions. Subjects with low or intermediate educational status more often reported pain and used light opioids to a larger extent than did the highly educated. These results indicate that musculoskeletal pain is relatively common among the very old, but does not seem to be a severe problem for the majority, considering the low proportion of subjects using prescription analgesics regularly. However, the very low use of potent opioids indicates that some of the elderly suffering from cancer and other severe pain causing diseases might be undertreated.

Journal Article↗
PubMed2003

Non-opioid analgesics and the risk of restless leg syndrome-a spurious association?

OBJECTIVES: The aim of this study was to evaluate the prevalence and risk factors of restless leg syndrome in a secondary care patient population maintained on tricyclic and serotonin re-uptake inhibiting antidepressants. STUDY DESIGN: Prospective observational study. STUDY POPULATION: Two hundred and forty-three patients of a single practice specializing in the treatment of affective and anxiety disorders. Patients younger than 30 years and those with neurologic diseases such as Parkinson's disease, multiples sclerosis and dementia were excluded, as well as those with schizophrenia or other illusional disturbances, eating disorders, histories of opioid or codeine-containing analgesic abuse or of alcohol or illicit drug abuse. Patients remained in the study population only if they had gained complete or partial recovery of their anxiety and/or depressive symptoms and been treated for at least 6 months in the practice's ambulatory care (85.0% of the patients were finally included). METHODS: Histories of leg discomfort, akathisia, medication use and socio-demographic factors were assessed at the time of enrolment. RLS was assumed if all minimal criteria of the international RLS study group were fulfilled. RLS patients also had a neurologic examination focusing on signs and symptoms of neuropathy. It is unclear whether those without RLS were also examined neurologically. RLS case status was assessed at 6-month intervals for patients in the study. It is unclear if the reported RLS prevalence reflects case status at enrolment and/or during the treatment course. The prevalence of various pain syndromes, as well as the intake of analgesics and average coffee intake per day was compared between those with and without RLS. Lifetime and current treatment exposure to antidepressants and dopamine antagonists was evaluated according to RLS status. It is unclear what the mean treatment time was. Various univariant, descriptive statistics were used. The statistical analysis and logistic regression was applied using RLS case status as the dependent and co-morbidities, and medications/treatments as independent variables. RESULTS: The prevalence of RLS among the patients included in the analysis was 27.0%, with female patients more often affected than men (31.0% vs. 19.0%). RLS symptom severity during the course of treatment was low for 43 of 65 cases. Somatic co-morbidities were more prevalent in RLS affected women and less prevalent in RLS affected men than in gender specific non-RLS patients. No significant differences were observed for lifetime exposure to dopamine antagonist between those with and without RLS (38.0% vs. 35.0%). Chronic pain syndromes were observed more often in RLS cases (women: 86.0% vs. 32.0%, men: 62.5% vs. 29.0%). Twelve percent of those without RLS and 75.0% of RLS cases had a history of regular intake of analgesics prior to study enrolment. In a multivariate logistic regression model the authors found RLS case status to be associated with the intake of analgesics (OR: 25.5, P<0.001), psychiatric co-morbidity (OR: 2.97, P=0.01) and an interaction between age and the intake of analgesics (OR: 2.6, P=0.03). CONCLUSIONS: A 27.0% prevalence of RLS was found in this highly selected population treated with tricyclic and serotonin re-uptake inhibiting antidepressants. The authors infer from their results that regular intake of analgesics is a risk factor for RLS and that the observed association of gender with RLS might be explained by a higher intake of analgesics in women compared to men. They further conclude that the intake of analgesics, rather than the pain co-morbidity itself, enhances the risk of RLS.

Journal Article↗
PubMed2006

How high should total pain-relief score be to obviate the need for analgesic remedication in acute pain? Estimation using signal detection theory and individual-patient meta-analysis.

BACKGROUND: A pain relief score 50% of the maximum is often used as a clinically meaningful outcome in meta-analyses of analgesic trials. This arbitrary value requires validation. OBJECTIVE: To determine the optimum pain relief score for predicting pain relief sufficient to obviate the need for analgesic remedication in acute post-surgical pain. DESIGN: Individual-patient meta-analysis of randomized controlled trials and use of signal detection theory to identify the optimum cut-off point on the total pain relief score (TOTPAR). Analgesic remedication was used as the clinical outcome. DATA SOURCES: Seven parallel-group, active and placebo-controlled trials of minor analgesics. RESULTS: The predictive value of the TOTPAR score [expressed as a percentage of the maximum score (%maxTOTPAR)] for remedication was excellent for all the trials. The pooled estimate of the area under the receiver operating curve, an index of discriminative power, was outstanding 0.96 (95% CI 0.95-0.97). The pooled estimate of the optimal %maxTOTPAR for predictive purposes was 44.11 (95% CI 44.00-44.23). CONCLUSION: The analysis suggests that the arbitrary 50% cut-off point TOTPAR score often used in meta-analyses of analgesic trials in dental pain is reasonably acceptable. This is different to the 33% cut-off point reported for analgesic trials of acute breakthrough cancer pain and some chronic pain states such as diabetic neuropathy and postherpetic neuralgia. These differences deserve careful consideration when reading reports of analgesic trials and meta-analyses. Remedication itself should be considered as the preferred outcome measure for analgesic trials.

Acetaminophen↗
PubMed1989

[The experiment studies of semiconductor GaAs-laser points irradiation the analgesic effect].

The article reported that Rabbits threshold of Pain were made a target of observing analgesic effect of the Semiconductor GaAs laser irradiation Znsanli (V36) points. The relations between meridian with peripheral nervous and analgesic mechanism had been explored. The result showed that GaAs laser irradiation at Znsanli (V36) points not only increase basic threshold of pain for Rabbits, but also had all over analgesic effect. After irradiation fifteen minutes obviousness effect in particular. That both the low-frequency electropulse and the laser affected points can raised analgesic effect, but it showed obvious analgesic-back-effect. GaAs laser irradiation nervis fibularis profundus were similar analgesic effect to the points irradiation indicated that points irradiation stimulus conduction had relation to peripheral nervous. After intravenous injection naloxone analgesic effect that GaAs laser irradiation points arose reversion were similar acupuncture analgesia. It indicated that analgesic effect had relation release of the internal source opiate-like substance (OLS).

Acupuncture Points↗
PubMed1994

End-stage renal failure due to analgesic nephropathy, its changing pattern and cardiovascular mortality. EDTA-ERA Registry Committee.

The changing pattern of prevalence and age distribution of analgesic nephropathy as a cause of end-stage renal failure (ESRF) in patients on RRT was analysed using the EDTA-ERA Registry's files. Comparing 1990 to 1981, the percentage of patients with analgesic nephropathy decreased in many European countries and the Registry's average came down from 3 to 2%. The highest prevalence was noted for Switzerland, which showed a decrease from 28 in 1981 to 12% in 1990. During the same interval the age distribution shifted to the right with an increase in median age from 57 to 63 at start of RRT for analgesic nephropathy. In Switzerland the age-specific acceptance rate to RRT for patients with analgesic nephropathy decreased to less than 1/3 in the age cohorts below 55 but increased in those aged 65 or older. This increase in the elderly cohorts appeared to be related to the growing acceptance rate to RRT of elderly patients in general rather than to an increasing incidence of ESRF due to analgesic nephropathy. Mortality in general and death rates due to cardiovascular causes were found not to differ in RRT patients with analgesic nephropathy from that of other standard primary renal diseases (excluding diabetic nephropathy and systemic diseases). Some 20 years after withdrawal of phenacetin from the analgesic market, analgesic nephropathy all but disappeared as a cause of ESRF in Sweden and Denmark, and the same may be expected to occur in countries like Switzerland, Belgium, and others in the not too far distant future.

Age Distribution↗
PubMed1994

Analgesic agents and strategies in the dental pain model.

Pain following removal of impacted third molar teeth has proven to be a useful clinical model for evaluating oral analgesics. Moreover, as the underlying pathophysiology becomes elucidated the model serves as a tool for monitoring the relative contributions of different pain events, including peripheral and central sensitization. Non-steroidal anti-inflammatory drugs (NSAIDs) demonstrate high potency in this model, reflecting the large contribution that peripheral prostaglandins may make to the pathophysiology of postoperative pain. However, other analgesic agents, with weak activity against peripheral prostaglandin synthesis (e.g. paracetamol, opioid analgesics), may also provide pain relief in the dental pain model. The activity of these agents is dependent on the time and method of administration, and may be related to more centrally located analgesic activity, or to peripheral actions other than inhibition of prostaglandin synthesis. In single dose studies it is possible to enhance pain relief by combining analgesic agents of different activities, e.g. ibuprofen 400 mg and codeine 20 mg. Such enhanced activity is also demonstrated by higher doses of certain NSAIDs, e.g. ketoprofen 100 mg. This may reflect the existence of complimentary analgesic activities within a single therapeutic agent. As a clinical research tool the dental pain model has several attributes which suggest that it will continue to be of value in identifying potentially improved analgesic strategies for postoperative pain.

Acetaminophen↗
PubMed2003

Chronopharmacology of analgesic effect and its tolerance induced by morphine in mice.

The influence of morphine dosing time on analgesic effect after acute or chronic treatment, recovery of analgesic effect after once developed tolerance, and their pharmacological mechanisms were investigated in ICR male mice under a 12-h light/dark cycle (light on from 7:00 AM to 7:00 PM). There was a significant 24-h rhythm in the latency of thermal response at 30 min after morphine injection. The analgesic effect was significantly greater at the dark phase than at the light phase. The rhythmic pattern resembled overall the rhythm occurring in the latency of thermal response under non-drugged state. The absolute value of morphine analgesic effect (the real time spent on the hot-plate) on days 1 and 2 after morphine daily injection was significantly larger after morphine injection at 9:00 PM than after saline injection at 9:00 PM or after morphine injection at 9:00 AM. The recovery from tolerance of analgesic effect was significantly faster at the dark phase than at the light phase. The time-dependent difference in the analgesic effect after chronic treatment or recovery from tolerance is closely related to that in the expression of mu-opioid receptor. The present study suggests that 24-h rhythm of morphine analgesic effect is consistent with 24-h rhythm of mu-opioid receptor expression.

Analgesia↗
PubMed1987

Rational use of analgesics in the treatment of the rheumatic disorders.

To the average arthritic patient, pain relief is usually his or her first priority in treatment. Thus, analgesics still have a part to play in the treatment of most arthritic conditions, even though the non-steroidal anti-inflammatory drugs (NSAIDs) have the major therapeutic role in most cases. In the treatment of acute gout, the NSAIDs are the most important, and simple analgesics are relatively unimportant, but in the treatment of rheumatoid and osteoarthritis and other arthropathies, analgesics taken as and if required to cover the more painful periods of a day do have a role, usually in conjunction with NSAIDs and other agents. In general, the simple analgesics are better tolerated than the NSAIDs and less likely to produce gastrointestinal irritation. Although many clinicians consider that simple analgesics have little part to play in the treatment of rheumatoid arthritis and other inflammatory arthropathies, the patient often takes them without the physician's knowledge, in addition to the prescribed treatment. Some recently introduced analgesics bridge the gap between the simple analgesics and the more potent potentially addictive drugs such as pethidine and morphine, which are only indicated in extremely painful crises or after traumatic episodes and surgical operations.

Analgesics↗
PubMed2005

Analgesic use and risk of subsequent hypertension in apparently healthy men.

BACKGROUND: Prospective studies have suggested that women who self-select for use of analgesics have an increased risk of hypertension, but data in men are sparse. We tested whether apparently healthy male physicians who reported analgesic use had an increased risk of subsequent hypertension. METHODS: Prospective cohort study of 8229 participants in the Physicians' Health Study who were free of hypertension and completed detailed analgesic questionnaires. Hypertension was defined as self-reported blood pressure of 140/90 mm Hg or higher or use of antihypertensive medication. RESULTS: After a mean of 5.8 years' follow-up, 2234 men (27.2%) reported subsequent hypertension. We categorized the cumulative analgesic use in quintiles. After adjusting for potential confounders, men in the highest quintile had no statistically significant increased risk of hypertension (hazard ratio, 1.12; 95% confidence interval, 0.97-1.31) when compared with those in the lowest quintile. In subgroup analyses, we evaluated the cumulative use of nonsteroidal anti-inflammatory drugs, acetaminophen, and aspirin. Compared with never users, men who reported consuming at least 2500 pills had hazard ratios of 1.05 (95% confidence interval, 0.89-1.24) for nonsteroidal anti-inflammatory drugs, 1.08 (95% confidence interval, 0.87-1.34) for acetaminophen, and 1.16 (95% confidence interval, 0.92-1.48) for aspirin. The results were similar for analgesic use in the year preceding the analgesic questionnaire. CONCLUSION: In this large cohort, apparently healthy male physicians who self-selected for analgesic use had no significantly increased risk of subsequent hypertension, although a small to moderately increased risk cannot be excluded in observational studies.

Acetaminophen↗