New Pharmacological and Epidemiological Data in Analgesics Research

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The use of analgesics was significantly higher among women, adults and elderly 20 years or more , highly educated individuals and respondents who referred: diagnosis of one or more chronic diseases, using three or more medications, possession of health insurance and with one or more emergency care admittances or hospitalizations within the last year.

Non-opioid analgesics were the agents most used The most commonly used drugs were metamizole These drugs were used mainly to manage occasional health conditions, particularly pain. One in five Brazilians used some analgesic, especially non-opioid analgesics, to manage acute health problems such as painful conditions. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Competing interests: The authors have declared that no competing interests exist. Pain is the most common complaint that leads individuals to seek healthcare services. Agents with analgesic action including non-opioids, opioids and non-steroidal anti-inflammatory drugs [NSAIDs] are among the most commonly used drugs for self-medication among the Brazilian population [ 1 ]. In Brazil and internationally, non-opioid analgesics and some non-steroidal anti-inflammatories are easy to acquire because of the affordable price and because they are sold without prescription.

Another factor contributing towards consumption of analgesics is that some analgesics also have therapeutic indications other than treatment of acute and chronic pain, such as management of fever for which non-opioid analgesics and NSAIDs are used and treatment of inflammatory conditions, such as temporomandibular joint arthritis also using NSAIDs.

North American data have shown that pain medications stand out in both sales volume and volume of prescriptions. In and , they were the third best-selling category in the USA, after cancer and antidiabetic agents [ 2 , 3 ]. In terms of number of prescriptions, they were the second most prescribed therapeutic category in , only behind treatments for systemic arterial hypertension [ 4 ]. It is important to emphasize that studies have shown that the prevalence of non-prescription use is higher than use under prescription [ 5 — 7 ].

Population-based studies, with national samples estimating prevalence and characterizing users, the drugs most commonly used and the ways in which these drugs are used, are essential for assessing to what extent such use may represent a public health problem. Studies of this nature have point out that analgesic and NSAID use occurs frequently, with higher prevalence of over-the-counter OTC drugs than of prescription medications [ 5 — 7 ]. However, no population-based studies published in Medline or EMBASE have been conducted in countries where the use of analgesics and NSAIDs that are subject to prescription Rx is facilitated by the practice of selling them in pharmacies without requiring presentation of the prescription.

In this situation, the potential risks to which this population is subject may be even greater than those already pointed out in other scenarios. The study population comprised people of all ages residing in permanent private households, chosen in a complex survey with a probabilistic sample in three stages, in which the primary sampling unit corresponds to the municipalities, the second stage to the census sectors, and the third to domiciles.

As the use of medicines varies according to age and gender, before starting the interview, these information of all household residents were recorded in order to identify who to be interviewed. The sample included eight demographic domains: 1 ages 0—4, both genders; 2 ages 5—19, both genders; 3 ages 20—39, female; 4 ages 20—39, male; 5 ages 40—59, female; 6 ages 40—59, male; 7 ages 60 or over, female; 8 ages 60 or over, male.

That were replicated for each of the five Brazilian geographical regions. Sample size was defined based on estimates of access and use of medicines obtained from previous surveys. By the end, PNAUM interviewed 41, people who, following adjustments by region, gender and age, represent approximately million Brazilians living in urban areas of the country. The survey was performed face-to-face. The research instruments were developed by researchers from seven universities in Brazil, having been standardized and tested previous to their implementation.

The questionnaires included questions regarding the current use of medicines for chronic diseases and the use 15 days prior to the research to investigate signs, symptoms and acute conditions treated with medicines. The questions were adapted to be answered by the person responsible for the care of children persons below 15 years of age and those unable to communicate or self-report information due to physical or mental illness, speech impediment or lack of discernment to answer questions.

The data were recorded on tablets, using software that had been developed specifically for the study. All the participants signed two copies of the consent form before giving responses in the interview. The main person responsible for the children or incapable person, present in the face-to-face interview, gave informed consent and completed the interview. We investigated the use of drugs to treat chronic diseases, based on information about previous diagnoses and medical indications for pharmacological therapy, along with the use of drugs to treat acute diseases or events, within the 15 days prior to the interview.


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The investigation on chronic diseases contained specific questions about high blood pressure, diabetes, heart diseases, hypercholesterolemia, stroke, lung disease, arthritis, arthrosis or rheumatism, depression and other chronic diseases lasting six months or longer. The investigation on acute diseases or events treated with medicines contained questions about the use of medications for the following conditions: infection, sleeping or anxiety problems, stomach or bowel problems, fever, pain, flu, cold or allergic rhinitis; along with use of vitamins, mineral supplements, appetite stimulants or tonics.

In the present study, we included occasional or continuous use of analgesics, irrespective of origin through prescription or self-medication. The main outcome was the use of at least one analgesic yes or no. The outcome variable considered the self-reported use of analgesics either for the treatment of chronic conditions or in the previous 15 days for the treatment of acute events or diseases. Whenever possible, the drug names were copied from the packaging or prescription, to avoid misclassification. When no packaging or prescription was available, the names declared by the interviewees were recorded.

In the present study, this last group was referred to as non-opioid analgesics, encompassing the following groups proposed in the ATC system: salicylic acid and derivatives, pyrazolones, anilides and other analgesics and antipyretics. Combination drugs products containing more than one analgesic ingredient were categorized as a separate drug. The most commonly reported drugs and their patterns of use were identified according to their use in treating acute or chronic conditions and the reasons for their use. Sociodemographic and health-related variables were evaluated.

The economic classification took into account the conditions of the household, the number of goods acquired and the schooling of the person in charge of the household. The health-related variables included the number of chronic diseases reported none; 1; 2; or 3 or more ; number of drugs in use excluding analgesics none; 1; 2; 3 to 4; or 5 or more ; health insurance coverage yes or no ; emergency visits within the previous 12 months yes or no ; and hospitalizations within the previous 12 months yes or no.

Specifically among users of analgesics, use of multiple analgesics i.

Correction

For this, concomitant use of the following was assessed: a analgesics belonging to different groups; and b analgesics belonging to the same group. Descriptive analyses were performed using SPSS version The chi-square test for independence was performed to evaluate possible associations. The sociodemographic and health-related characteristics of the sample are presented in Table 1.

Among adults 18 years or older , it was The prevalence of use of non-opioid analgesics was The prevalence of use was higher among women, individuals aged 60 years and over more and those with higher levels of schooling. The prevalence was higher in the following situations: presence of chronic disease irrespective of how many of them: from one to three or more ; use of five or more drugs other than analgesics , possession of health insurance coverage; use of emergency services within the last year; or occurrence of hospitalizations within the last year Table 1. The prevalence of use of the three groups of analgesics, categorized according to age group, is shown in Fig 1.

In all of the three groups of analgesics, the prevalence of use was higher among individuals aged 60 years and over. Caution is suggested in the interpretation. In a specific analysis that only included users of analgesics, most of these individuals reported consumption of only one analgesic The proportions of analgesics used alone or in combination by the individuals who cited the use of analgesics are shown in Fig 2. Among all the analgesics used, the ones most commonly used were non-opioid agents The ten most commonly used drugs are presented in Table 3.

Chemical ATC classification. Regarding health conditions, most of the interviewees used analgesics to treat acute diseases The pattern of analgesic use, in relation to chronic or occasional health conditions, motives and frequency of use, is presented in Table 4. Pain was the main reason cited for consumption, regardless of the group of analgesics. The prevalence of analgesic use in our study reveals that one in five Brazilians of all ages was using analgesics and that this use occurred mainly for treatment of occasional health conditions. The use was greater among women, adults and the elderly.

Opioids were infrequently used, compared with the other groups. Metamizole, paracetamol and diclofenac were among the most commonly used drugs, representing alone about three-quarters of all analgesics cited. We did not find any previous studies with sufficient methodological similarities to make direct comparisons with estimates of overall prevalence of analgesic use. Among the differences between the studies, we can highlight the recall period for the evaluation of medicine use, the ages of the participants and the drugs analyzed.

In our study, we evaluated current use or use within the 15 days prior to the interview, while other studies used periods of 7 days [ 6 , 11 ] or 30 days [ 5 , 7 , 12 ]. Previous studies found that different recall periods influenced the prevalence of occasional use of analgesics and NSAIDs, and the authors of those studies recommended the use of shorter reminder periods [ 13 , 14 ].

Women consumed more analgesics than men, and our finding was in line with the results from previous studies conducted in the USA [ 5 ] and in European countries [ 6 , 7 , 11 , 12 , 15 ]. The difference in use between men and women is due not only to biological differences such as hormonal differences and differences in the prevalence of certain pathological conditions such as migraine, menstrual cramps and low back pain, among others [ 16 ], but also to different behavior regarding health care [ 15 , 17 ].

The prevalence of use among adults and the elderly was higher, independently of the analgesic group. This finding was consistent with the epidemiological distribution of certain health conditions, such as muscle and back pain, headache and migraine, which occur more frequently in the economically active age range [ 18 , 19 ]. However, when the prevalence of use was stratified according to analgesic groups, the use of NSAIDs was found to be significantly higher among individuals aged 60 years and over, and the use of non-opioid analgesics was greater among those aged 20 years and over.

Use of analgesics was more frequent among people with higher schooling levels and among those with health insurance. This result may be related to greater access to healthcare services and medications. Individuals with greater numbers of chronic diseases, those using polymedication and those who had been seen in emergency or hospitalized consultations within the last 12 months also presented higher prevalence of use.

These results were consistent with the widespread use of analgesics to treat the painful and inflammatory conditions that are present in several chronic diseases; and with the presence of pain as part of the set of symptoms of various emergency or hospitalization situations.

Pharmacological Management of Neuropathic Pain: Current Trends and Possible Approaches

The predominant use of non-opioid analgesics, particularly metamizole, paracetamol and acetylsalicylic acid, is consistent with their indication for very common acute and chronic pains, their widespread availability as over-the-counter medications and the fact that they are freely available in the public healthcare system. In addition, they are cheaper, have large use in the management of fever and are safer than other analgesics. The consumption of metamizole by approximately half of the users of non-opioid analgesics is noteworthy. The adequacy of this drug remains a topic of discussion in the literature.

Metamizole has been banned in many countries due to uncertainties regarding its safety, while in other countries it is still widely used, as is the case of Brazil [ 21 , 22 ]. NSAIDs, in turn, were consumed by We would suggest that the lower prevalence of NSAID use, compared with use of non-opioid analgesics, is appropriate, because although effective in managing various painful conditions, they present higher potential for adverse reactions.

II. The Key Questions

The pharmacology of pain remains a very active field of research and development, and new analgesics and targets are being evaluated all the time in three complementary areas. First, there is continuing interest in the role of ion channels in analgesia research. However, its mode of administration intrathecal and adverse side-effects have restricted its clinical use. Novel Cav2. A variety of transient receptor potential TRP channels are also involved in both pain signaling 75 and cancer. A particular analgesic focus is nerve growth factor and its receptors. In overall conclusion, cancer pain, originating from a variety of sources in the body, continues to be a major problem in reducing the quality of life of cancer patients and survivors.

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