ABSTRACT:

Introduction:

Drug-related poisonings have a high impact on morbidity and mortality, representing the first cause of intoxication in Brazil.

Objective:

To describe the trends of cases of drug-related poisonings attended to by a poison control center.

Method:

A quantitative approach (cross-sectional trend study) with data analysis of cases of drug-related poisonings attended to at the Poison Control Center of University Hospital of the State University of Londrina. Data were collected from service notification records for the period 1985 to 2014. For statistical analysis, a simple linear regression model was used.

Results:

Of the 36,707 cases attended to by the service, 22.5% (n = 8,608) were drug-related poisonings. There was an increase in the proportion of cases for both sexes (R² = 0.195, p = 0.014) and males (R² = 0.403, p < 0.001). There was a trend towards a higher proportion of cases involving the analgesic, anti-inflammatory and immunosuppressive drug classes (R² = 0.521, p = 0.018), antidepressants (R² = 0.923, p < 0.001) and antipsychotics (R² = 0.869; p < 0.001). Antibiotics showed a trend toward a lower proportion of cases (R² = 0.773, p = 0.001).

Conclusions:

There was a trend for a higher proportion of cases of drug-related poisonings in males. Also, there was an increased trend towards cases involving analgesics/anti-inflammatories/immunosuppressants, antidepressants and antipsychotics.

Keywords:
Poisoning; Drugs; Trends

INTRODUCTION

Human poisoning involves a wide variety of pathophysiological processes related to the interaction between a chemical or biological agent and the body. Poisoning is a serious global public health problem¹1. Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 32st Annual Report. Clin Toxicol (Phila) 2015; 53(10): 962-1147. http://dx.doi.org/10.3109/15563650.2015.1102927
http://dx.doi.org/10.3109/15563650.2015.... , victimizing approximately 500,000 people per year according to the World Health Organization (WHO) ²2. World Health Organization. Guidelines for poison control. Genebra: World Health Organization; 1997.^,33. Bitencourt NKS, Borges LM, Alves SMF, Souza FHHV. Intoxicações medicamentosas registradas pelo Centro de Informações Toxicológicas de Goiás, 2007. In: Anais do VI Seminário de Iniciação Científica. Anápolis: Universidade Estadual de Goiás; 2008. p. 1-6..

Drugs are important therapeutic tools used for the prevention of health problems and recovery and maintenance of health; however, their irrational and indiscriminate use causes many negative consequences, such as not controlling or resolving the health problem, poisoning and even death. Drugs rank first in poisoning records and are the second cause of mortality related to human poisoning⁴4. Bortoletto ME, Bochner R. Impacto dos medicamentos nas intoxicações humanas no Brasil. Cad Saúde Pública 1999; 15(4): 859-69. http://dx.doi.org/10.1590/S0102-311X1999000400020
http://dx.doi.org/10.1590/S0102-311X1999... ^,55. Sistema Nacional de Informações Tóxico-Farmacológicas. Dados de intoxicação [Internet]. [acessado em mar. 2017]. Disponível em: http://sinitox.icict.fiocruz.br/dados-nacionais
http://sinitox.icict.fiocruz.br/dados-na... . Besides, the potential years of life lost due to drug intoxication indicate large social and economic losses for the public⁶6. Mota DM, Melo JRR, Freitas DRC, Machado M. Perfil da mortalidade por intoxicação com medicamentos no Brasil, 1996-2005: retrato de uma década. Ciênc Saúde Coletiva 2012; 17(1): 61-70. http://dx.doi.org/10.1590/S1413-81232012000100009
http://dx.doi.org/10.1590/S1413-81232012... .

A study based on poisoning cases at the National Network of Poison Control Centers in Brazil points to suicide attempt (41%) and individual accidents (35.3%) as the main circumstances of drug poisoning. Regarding the therapeutic classes, benzodiazepines are the drugs that most resulted in intoxication, followed by anticonvulsants, antidepressants and analgesics³3. Bitencourt NKS, Borges LM, Alves SMF, Souza FHHV. Intoxicações medicamentosas registradas pelo Centro de Informações Toxicológicas de Goiás, 2007. In: Anais do VI Seminário de Iniciação Científica. Anápolis: Universidade Estadual de Goiás; 2008. p. 1-6..

However, studies conducted in Brazil on drug poisoning are commonly performed on children and adolescents⁷7. Oliveira FF, Suchara EA. Epidemiological profile of exogenous poisoning in children and adolescents from a municipality in the state of Mato Grosso. Rev Paul Pediatr 2014; 32(4): 299-305. https://dx.doi.org/10.1016%2Fj.rpped.2014.06.002
https://dx.doi.org/10.1016%2Fj.rpped.201... ^,88. Werneck GL, Hasselmann MH. Profile of hospital admissions due to acute poisoning among children under 6 years of age in the metropolitan region of Rio de Janeiro, Brazil. Rev Assoc Med Bras 2009; 55(3): 302-7. http://dx.doi.org/10.1590/S0104-42302009000300023
http://dx.doi.org/10.1590/S0104-42302009... or elderly⁹9. Paula TC, Bochner R, Montilla DE. Clinical and epidemiological analysis of hospitalizations of elderly due to poisoning and adverse effects of medications, Brazil from 2004 to 2008. Rev Bras Epidemiol 2012; 15(4): 828-44. http://dx.doi.org/10.1590/S1415-790X2012000400014
http://dx.doi.org/10.1590/S1415-790X2012... . Only the study by Margonato et al.¹⁰10. Margonato FB, Thomson Z, Paoliello MMB. Acute intentional and accidental poisoning with medications in a southern Brazilian city. Cad Saúde Pública 2009; 25(4): 849-56. http://dx.doi.org/10.1590/S0102-311X2009000400016
http://dx.doi.org/10.1590/S0102-311X2009... , carried out on poisoning cases occurring in 2004, evaluated drug intoxications in the general population. Nevertheless, studies have not shown trends in the outcome of drug poisoning cases over years.

With regard to drug poisoning, the most important services are those provided by a poison control center (PCC) for critical instances of guidance for cases of poisoning and envenomation¹¹11. Azevedo JLS. A importância dos centros de informação e assistência toxicológica e sua contribuição na minimização dos agravos à saúde e ao meio ambiente no Brasil [dissertação]. Brasília: Universidade de Brasília; 2006.. Thus, it is essential to systematize the cases reported by these services, especially drug-related ones, which are little explored in scientific studies. Knowledge of drug poisoning profiles may lead to control strategies and implementation of appropriate assistance for the inappropriate and indiscriminate use of these therapeutic resources. Therefore, the aim of this work was to investigate the cases of drug-related poisoning (DRP) seen at a PCC.

METHOD

This was a cross-sectional trend study, conducted with data from the PCC of the University Hospital of the State University of Londrina (CIT/HU/UEL), in the city of Londrina, Brazil. CIT/HU/UEL provides guidance in the event of accidents with poisonous animals and intentional or accidental intoxications, as well as any contact with an exogenous substance, even if it does not generate clinical manifestations. For this study, the term “drug-related poisoning (DRP)” was used, not “drug intoxication”,¹²12. Gandolfi E, Andrade MGG. Eventos toxicológicos relacionados a medicamentos no Estado de São Paulo. Rev Saúde Pública 2006; 40(6): 1056-64. http://dx.doi.org/10.1590/S0034-89102006000700014
http://dx.doi.org/10.1590/S0034-89102006... since not only cases of intoxication were analyzed, but all drug-related toxic events, including exposures and adverse reactions.

All the cases of DRP treated by the CIT/HU/UEL in the period from 1985 to 2014 were analyzed. These cases were attended to in person (emergency room of University Hospital) or long distance (telephone service), giving clinical support to the health care professional caring for the patient.

The data were collected from the service’s notification forms and outcome of cases of intoxications and poisonings. The study variables used to describe the cases were the following: age (in years); age group (4 years or less, 5 to 9 years, 10 to 14 years, 15 to 19 years, 20 to 39 years, 40 to 59 years, 60 years and older); sex (male or female); exposure (acute, chronic); circumstance (suicide attempt, accidental, administration error, therapeutic use, self-medication, medical prescription, other), occurrence (intoxication, exposure only, adverse reaction, other), exposure route (oral only, parenteral only, other), toxicological analysis (yes, no), hospitalization (yes, no), time of hospitalization (in days), outcome (discharge, death, other) and drug classes, which were defined on the basis of the criteria used by the service itself (CIT/HU/UEL). The service notification forms allowed the inclusion of only three agents, so for intoxications involving four or more agents (only drugs or drugs in combination with other substances), it was not possible to identify some of these agents. In these situations, the notifying professional was directed to record the substances that could be more serious.

Trends were calculated according to the proportion of cases of DRP according to sex (male and female), in relation to total cases (dependent variable) and per year of analysis (1985 to 2014) (independent variable). The trends in drug classes were calculated on the basis of the proportion of cases per class in relation to total cases of DRP (dependent variable), for three years of analysis (1985-1987 to 2012-2014) (independent variable). Trend analyses throughout the three-year periods were carried out only with the five classes of drugs that showed the highest frequency. The choice of the period from 1985 to 2014 was due to the option for three-year periods in the trend analyses of drug classes, starting in the year of operation of the CIT/HU/UEL (1985), forming ten triennia.

The data were entered in a database created in Epi Info version 3.5.4 for Windows^®, and statistical analysis was performed using the Statistical Package for Social Sciences (SPSS), version 19.0 for Windows^®. The simple and relative frequencies of the qualitative variables and the measures of central tendency of the quantitative ones (mean and standard deviation) were then determined. Trend analysis was performed using simple linear regression models. Statistical modeling considered the proportion of cases in the study outcomes as a dependent variable and the chronological time under analysis as an independent variable. The estimated model could be written as: Y = β0 + β1 (X - 1985 [ou 1985-1987]). In these models, Y corresponds to the proportion of cases, β0 the mean annual rate, β1 the coefficient of linear effect (velocity) and X the year or triennium¹³13. Neter J, Kutner MH, Nachtschiem CJ, Wasserman W. Applied Linear Statistical Models. 4ª ed. Chicago: Irwin Series in Statistics; 1996.. The trend was considered significant when the model resulted in p < 0.05. As a measure of the accuracy of the models, the coefficient of determination (R²) was used. This research was approved by the Ethics Committee on Research Involving Human Beings of the State University of Londrina ­(CEP-UEL) (CAAE No. 45986415.1.0000.5231).

RESULTS

During 1985 to 2014, CIT/HU/UEL registered 36,707 cases involving intoxications or poisonings. Of these cases, medications accounted for 8,608 (23.5%). Of the cases of DRPs (n = 8,608), there was a combination with other chemical agents in 7.4% (Table 1). Of the cases only with medications (n = 7,972), 1,994 (25%) involved 2 or more drugs.

Females accounted for the majority of DRPs (n = 5,138; 65.1%). The mean age was 19.1 ± 16.3 years, ranging from newborn to 90 years. The most frequent age groups were those of 4 years or less (30.6%) and 20 to 39 years (32.0%). Acute exposure was the most frequent (99.4%). Suicide attempt (53.1%) and accidental occurrence (35.1%) represented the main circumstances of DRPs (Table 2).

In addition, 31.4% (n = 2,702) of patients with DRPs required hospitalization, with 0.6% (n = 50) resulting in death. Regarding the number of days of hospitalization, a mean of 2.7 ± 4.6 days, with a maximum of 103 days, was obtained. The majority of cases were by telephone (n = 6,313, 73.3%) and in the urban area (n = 8,234, 95.7%). Toxicological analyses were conducted in 1.2% (n = 107) of patients with DRPs.

Regarding the medications, anticonvulsants, sedatives or hypnotics (29.5%), analgesics, anti-inflammatories or immunosuppressants (13.0%) and antidepressants (12.8%) were the main classes involved with a total number of 11,162 (Table 3).

In the analysis of the proportion of cases of DRPs according to sex, there was a trend for an increase in the proportion of total cases in both sexes (R² = 0.195, p = 0.014) and in males (R² = 0.403, p <0.001) (Figure 1). In proportional numbers, the increase for the period 1985-2014 was 2.3% for both sexes and 64.0% for males. We should also point out the proportional decline in cases (total, male and female) in 1997.

Among the five main classes involved in the DRPs according to the predetermined triennia, there was a trend for an increase in the proportion of cases with analgesics, anti-inflammatories and immunosuppressants (R² = 0.521; p = 0.018), antidepressants (R² = 0,923; p < 0.001) and antipsychotics (R² = 0.869; p < 0.001). The antibiotics showed a trend towards a reduced proportion of cases (R² = 0.773; p = 0.001) (Table 4).

DISCUSSION

The proportion of cases involving drugs (23.5%) is similar to the results of other studies conducted in Brazil⁴4. Bortoletto ME, Bochner R. Impacto dos medicamentos nas intoxicações humanas no Brasil. Cad Saúde Pública 1999; 15(4): 859-69. http://dx.doi.org/10.1590/S0102-311X1999000400020
http://dx.doi.org/10.1590/S0102-311X1999... ^,1414. Morais ICO, Brito MT, Mariz SR, Fook SML, Rabello IP, Oliveira FN. Perfil epidemiológico das intoxicações medicamentosas registradas pelo Centro de Assistência e Informação Toxicológica de Campina Grande (PB) no período de 2005 a 2007. Rev Bras Farm 2008; 89(4): 352-7.^,1515. Malaman KR, Paranaíba ASC, Duarte CMS, Cardoso RA. Perfil das intoxicações medicamentosas, no Brasil. Infarma 2009; 21(7/8): 9-15.^,1616. Teles AS, Oliveira RFA, Coelho TCB, Ribeiro GV, Mendes WML, Santos PNP. Papel dos medicamentos nas intoxicações causadas por agentes químicos em município da Bahia, no período de 2007 a 2010. Rev Ciênc Farm Básica Apl 2013; 34(2): 281-8. and the data published by the National System of Toxic-Pharmacological Information (Sinitox) (28.5%)⁵5. Sistema Nacional de Informações Tóxico-Farmacológicas. Dados de intoxicação [Internet]. [acessado em mar. 2017]. Disponível em: http://sinitox.icict.fiocruz.br/dados-nacionais
http://sinitox.icict.fiocruz.br/dados-na... . It is also worth noting the combination of medications with other agents, especially drugs of abuse, which tends to make intoxication more serious. In addition, it may be suggested that the use of drugs of abuse increases the risk of DRPs, especially in the circumstances of attempted suicide¹⁷17. Rocha CN, Silveira DB, Camargo RS, Fernandes S, Ferigolo M, Barros MMT. Risco de suicídio em dependentes de cocaína com episódio depressivo atual: sentimentos e vivências. SMAD, Rev Eletrônica Saúde Mental Alcool Drog 2015; 11(2): 78-84..

In relation to the age group most affected by the MES, we highlight the 20-39 years, probably related to intentional circumstances (such as attempted suicide)¹⁸18. Klinger EI, Schmidt DC, Lemos DB, Pasa L, Possuelo LG, Valim ARM. Intoxicação exógena por medicamentos na população jovem do Rio Grande do Sul. Rev Epidemiol Controle Infecç 2016; 6 (Supl. 2): 1-8. http://dx.doi.org/10.17058/reci.v1i1.8216
http://dx.doi.org/10.17058/reci.v1i1.821... and to children aged 4 years or less, who are more subject to administration errors or to accidental causes¹⁹19. Matos GC, Rozenfeld S, Bortoletto ME. Intoxicações medicamentosas em crianças menores de cinco anos. Rev Bras Saúde Matern Infant 2002; 2(2): 167-76. http://dx.doi.org/10.1590/S1519-38292002000200009
http://dx.doi.org/10.1590/S1519-38292002... ^,2020. Amador JC, Thomson Z, Guilherme CES, Rocha SF. Perfil das intoxicações agudas exógenas infantis na cidade de Maringá (PR) e região, sugestões de como se pode enfrentar o problema. Pediatria 2000; 22(4): 295-301.. Other studies in Brazil have identified children and young adults as the main age groups involved in DRPs¹⁹19. Matos GC, Rozenfeld S, Bortoletto ME. Intoxicações medicamentosas em crianças menores de cinco anos. Rev Bras Saúde Matern Infant 2002; 2(2): 167-76. http://dx.doi.org/10.1590/S1519-38292002000200009
http://dx.doi.org/10.1590/S1519-38292002... ^,2121. Monte BS, Nunes MST, Nunes MDS, Mendes CMM. Estudo epidemiológico das intoxicações por medicamentos registrados pelo centro de informações toxicológicas do Piauí: 2007 a 2012. Rev Interdisciplin 2016; 9(3): 96-104.. Information from Sinitox also reinforces the notion that these age groups are exposed the most to this type of intoxication⁴4. Bortoletto ME, Bochner R. Impacto dos medicamentos nas intoxicações humanas no Brasil. Cad Saúde Pública 1999; 15(4): 859-69. http://dx.doi.org/10.1590/S0102-311X1999000400020
http://dx.doi.org/10.1590/S0102-311X1999... ^,2222. Brasil. Ministério da Saúde. Departamento de Informática do SUS. Informações de saúde. Epidemiológicas e morbidade. Intoxicação exógena [Internet]. [acessado em mar. 2017]. Disponível em: http://www2.datasus.gov.br/DATASUS/index.php?area=0203&id=29878153
http://www2.datasus.gov.br/DATASUS/index... .

According to Datasus, suicide attempt (35.6%), accidental cause (40.1%) and therapeutic use (8.7%) have been the main causes of exogenous intoxication by medications since 2007²²22. Brasil. Ministério da Saúde. Departamento de Informática do SUS. Informações de saúde. Epidemiológicas e morbidade. Intoxicação exógena [Internet]. [acessado em mar. 2017]. Disponível em: http://www2.datasus.gov.br/DATASUS/index.php?area=0203&id=29878153
http://www2.datasus.gov.br/DATASUS/index... . These circumstances were highlighted in a study of DRP cases attended to by a PCC in the state of Rio Grande do Sul²³23. Ramos CLJ, Targa MBM, Stein AT. Perfil das intoxicações na infância atendidas pelo Centro de Informação Toxicológica do Rio Grande do Sul (CIT/RS), Brasil. Cad Saúde Pública 2005; 21(4): 1134-41. http://dx.doi.org/10.1590/S0102-311X2005000400015
http://dx.doi.org/10.1590/S0102-311X2005... . Among these three circumstances, suicide attempt tends to be the most serious, since the individual has intentionality in taking a large amount of the drug²⁴24. Oliveira MLF, Buriola AA. Gravidade das intoxicações por inseticidas inibidores das colinesterases no noroeste do estado do Paraná, Brasil. Rev Gaúcha Enferm 2009; 30(4): 648-55. http://dx.doi.org/10.1590/S1983-14472009000400010
http://dx.doi.org/10.1590/S1983-14472009... , which requires a more careful handling of the cases.

There has been a trend towards an increase in the proportion of cases of DRPs over the years, as seen specifically for males. The reason for the increase in this trend may be related to the easy acquisition of these products and their great availability in households, as well as the wide variety of drugs in the retail pharmacy⁷7. Oliveira FF, Suchara EA. Epidemiological profile of exogenous poisoning in children and adolescents from a municipality in the state of Mato Grosso. Rev Paul Pediatr 2014; 32(4): 299-305. https://dx.doi.org/10.1016%2Fj.rpped.2014.06.002
https://dx.doi.org/10.1016%2Fj.rpped.201... . In addition, the precariousness of some public services, combined with the ease of obtaining medicines in pharmacy, which still have a commercial character to the detriment of care, increases the availability of these products to society²⁵25. Aquino DS. Por que o uso racional de medicamentos deve ser uma prioridade? Ciênc Saúde Coletiva 2008; 13(Supl. 1): 733-6. http://dx.doi.org/10.1590/S1413-81232008000700023
http://dx.doi.org/10.1590/S1413-81232008... .

In addition, many health care professionals and patients ignore the dangers of drug combinations, increasing the risk of administration errors or adverse reactions. Also, it should be mentioned that drug advertising has been a frequent stimulus for inappropriate drug use, above all by highlighting benefits and omitting or minimizing risks and possible adverse effects, giving the impression that they are innocuous products, thereby influencing consumption as with any other commodity²⁵25. Aquino DS. Por que o uso racional de medicamentos deve ser uma prioridade? Ciênc Saúde Coletiva 2008; 13(Supl. 1): 733-6. http://dx.doi.org/10.1590/S1413-81232008000700023
http://dx.doi.org/10.1590/S1413-81232008... ^,2626. Rabello ET, Camargo Junior KR. Propagandas de medicamentos: a saúde como produto de consumo. Interface (Botucatu) 2012; 16(41): 557-67. http://dx.doi.org/10.1590/S1414-32832012000200006
http://dx.doi.org/10.1590/S1414-32832012... .

Although women represent the main group affected by DRPs, as demonstrated in this study and in others conducted in Brazil⁴4. Bortoletto ME, Bochner R. Impacto dos medicamentos nas intoxicações humanas no Brasil. Cad Saúde Pública 1999; 15(4): 859-69. http://dx.doi.org/10.1590/S0102-311X1999000400020
http://dx.doi.org/10.1590/S0102-311X1999... ^,1414. Morais ICO, Brito MT, Mariz SR, Fook SML, Rabello IP, Oliveira FN. Perfil epidemiológico das intoxicações medicamentosas registradas pelo Centro de Assistência e Informação Toxicológica de Campina Grande (PB) no período de 2005 a 2007. Rev Bras Farm 2008; 89(4): 352-7.^,1515. Malaman KR, Paranaíba ASC, Duarte CMS, Cardoso RA. Perfil das intoxicações medicamentosas, no Brasil. Infarma 2009; 21(7/8): 9-15.^,1616. Teles AS, Oliveira RFA, Coelho TCB, Ribeiro GV, Mendes WML, Santos PNP. Papel dos medicamentos nas intoxicações causadas por agentes químicos em município da Bahia, no período de 2007 a 2010. Rev Ciênc Farm Básica Apl 2013; 34(2): 281-8.^,1818. Klinger EI, Schmidt DC, Lemos DB, Pasa L, Possuelo LG, Valim ARM. Intoxicação exógena por medicamentos na população jovem do Rio Grande do Sul. Rev Epidemiol Controle Infecç 2016; 6 (Supl. 2): 1-8. http://dx.doi.org/10.17058/reci.v1i1.8216
http://dx.doi.org/10.17058/reci.v1i1.821... ^,2323. Ramos CLJ, Targa MBM, Stein AT. Perfil das intoxicações na infância atendidas pelo Centro de Informação Toxicológica do Rio Grande do Sul (CIT/RS), Brasil. Cad Saúde Pública 2005; 21(4): 1134-41. http://dx.doi.org/10.1590/S0102-311X2005000400015
http://dx.doi.org/10.1590/S0102-311X2005... , the trend towards an increase in the proportion of male cases may be related to the higher consumption of these products by men in the last decade¹⁶16. Teles AS, Oliveira RFA, Coelho TCB, Ribeiro GV, Mendes WML, Santos PNP. Papel dos medicamentos nas intoxicações causadas por agentes químicos em município da Bahia, no período de 2007 a 2010. Rev Ciênc Farm Básica Apl 2013; 34(2): 281-8.^,2727. Bertoldi AD, Dal Pizzol TS, Ramos LR, Mengue SS, Luiza VL, Tavares NUL, et al. Perfil sociodemográfico dos usuários de medicamentos no Brasil: resultados da PNAUM 2014. Rev Saúde Pública 2016; 50 (Supl. 2): 5s. http://dx.doi.org/10.1590/S1518-8787.2016050006119
http://dx.doi.org/10.1590/S1518-8787.201... ^,2828. Prado MAMB, Francisco PMSB, Bastos TF, Barros MBA. Uso de medicamentos prescritos e automedicação em homens. Rev Bras Epidemiol 2016; 19(3): 594-608. http://dx.doi.org/10.1590/1980-5497201600030010
http://dx.doi.org/10.1590/1980-549720160... compared to previous decades²⁹29. Bertoldi AD, Barros AJD, Hallal PC, Lima RC. Utilização de medicamentos em adultos: prevalência e determinantes individuais. Rev Saúde Pública 2004; 38(2): 228-38. http://dx.doi.org/10.1590/S0034-89102004000200012
http://dx.doi.org/10.1590/S0034-89102004... ^,3030. Simões MJS, Farache Filho A. Consumo de medicamentos em região do Estado de São Paulo (Brasil), 1985. Rev Saúde Pública 1988; 22(6): 494-9..

It should also be noted that there was a general reduction in the proportion of DRPs registered in 1997. This decrease was due to the systematic reporting of exogenous intoxications, which in 1997 became the obligatory notification of injuries, being included in the Brazilian Information System for Notifiable Diseases (SINAN).

As regards the most common classes of drugs in the DRPs during the period of analysis (1985-2014), those that act on the central nervous system, the analgesic/anti-inflammatory/immunosuppressive drugs and antibiotics were the most prominent. These data corroborate the National Survey on Access, Use and Promotion of the Rational Use of Medicines (PNAUM), which identified that drugs acting on the nervous system (with analgesics representing 40.8% of them) and on the musculoskeletal system (including inflammatory and antirheumatic drugs) are respectively used by 18.6 and 8.7% of the population surveyed³¹31. Bertoldi AD, Arrais PSD, Tavares NUL, Ramos LR, Luiza VL, Mengue SS, et al. Utilização de medicamentos genéricos na população brasileira: uma avaliação da PNAUM 2014. Rev Saúde Pública 2016; 50(Supl. 2): 11s. http://dx.doi.org/10.1590/S1518-8787.2016050006120
http://dx.doi.org/10.1590/S1518-8787.201... . The high consumption of analgesics, anti-inflammatories and antirheumatics, shown by PNAUM³¹31. Bertoldi AD, Arrais PSD, Tavares NUL, Ramos LR, Luiza VL, Mengue SS, et al. Utilização de medicamentos genéricos na população brasileira: uma avaliação da PNAUM 2014. Rev Saúde Pública 2016; 50(Supl. 2): 11s. http://dx.doi.org/10.1590/S1518-8787.2016050006120
http://dx.doi.org/10.1590/S1518-8787.201... , indicates that the public is exposed to a greater risk of DRPs by these therapeutic groups.

The fact that many DRPs involve those that act on the central nervous system may be related to the increasing use of these substances³²32. Loyola Filho AI, Castro-Costa E, Firmo JOA, Peixoto SV. Tendências no uso de antidepressivos entre idosos mais velhos: Projeto Bambuí. Rev Saúde Pública 2014; 48(6): 857-65. http://dx.doi.org/10.1590/S0034-8910.2014048005406
http://dx.doi.org/10.1590/S0034-8910.201... , mainly due to the increase in the number of patients diagnosed with psychosomatic illnesses, such as depression, anxiety, panic syndrome and others ³³33. Mojtabai R, Olfson M, Han B. National Trends in the Prevalence and Treatment of Depression in Adolescents and Young Adults. Pediatrics 2016; 138(6): e20161878. https://doi.org/10.1542/peds.2016-1878
https://doi.org/10.1542/peds.2016-1878... ^,3434. John A, Marchant AL, McGregor JI, Tan JO, Hutchings HA, Kovess V, et al. Recent trends in the incidence of anxiety and prescription of anxiolytics and hypnotics in children and young people: An e-cohort study. J Affect Disord 2015; 183: 134-41. https://doi.org/10.1016/j.jad.2015.05.002
https://doi.org/10.1016/j.jad.2015.05.00... .

Analgesics, which have also been highlighted in cases of intoxication, are the most popular and safe medications when administered under recommended therapeutic conditions³⁵35. Mastroianni PC, Lucchetta RC, Sarra JR, Galduróz JCF. Estoque doméstico e uso de medicamentos em uma população cadastrada na estratégia saúde da família no Brasil. Rev Panam Salud Publica 2011; 29(5): 358-64., but they have been an important cause of drug intoxication among children and adults, since they are sold without the need for a prescription³⁵35. Mastroianni PC, Lucchetta RC, Sarra JR, Galduróz JCF. Estoque doméstico e uso de medicamentos em uma população cadastrada na estratégia saúde da família no Brasil. Rev Panam Salud Publica 2011; 29(5): 358-64., which makes access easy.

The trends towards an increased proportion of cases involving antidepressants and antipsychotics found in this study refer to the process of medicalization of society. Medicalization exposes the public to too much to medical sciences³⁶36. Ignácio VTG, Nardi HC. A medicalização como estratégia biopolítica: um estudo sobre o consumo de psicofármacos no contexto de um pequeno município do Rio Grande do Sul. Psicol Soc 2007; 19(3): 88-95. http://dx.doi.org/10.1590/S0102-71822007000300013
http://dx.doi.org/10.1590/S0102-71822007... to the detriment of social, cultural and behavioral issues, which increases the prescription of psychotropic drugs for the treatment of psychosomatic disorders³⁶36. Ignácio VTG, Nardi HC. A medicalização como estratégia biopolítica: um estudo sobre o consumo de psicofármacos no contexto de um pequeno município do Rio Grande do Sul. Psicol Soc 2007; 19(3): 88-95. http://dx.doi.org/10.1590/S0102-71822007000300013
http://dx.doi.org/10.1590/S0102-71822007... .

A report by the National Health Surveillance Agency (ANVISA) in Brazil showed that amitriptyline (antidepressant) was the fourth most used psychoactive drug in the country in 2010³⁷37. Agência Nacional de Vigilância Sanitária. Boletim de farmacoepidemiologia. Brasília: Agência Nacional de Vigilância Sanitária; 2011.. A study carried out in the city of Pelotas (RS) found that, among psychoactive drugs, the use of antidepressants increased from 8.4% in 1994 to 31.6% in 2003³⁸38. Rodrigues MAP, Facchini LA, Lima MS. Modificações nos padrões de consumo de psicofármacos em localidade do Sul do Brasil. Rev Saúde Pública 2006; 40(1): 107-14.. This increasing trend is also observed in other studies³⁹39. Hemels ME, Koren G, Einarson TR. Increased use of antidepressants in Canada, 1981-2000. Ann Pharmacother 2002; 36(9): 1375-9. https://doi.org/10.1345/aph.1A331
https://doi.org/10.1345/aph.1A331... ^,4040. Olfson M, Marcus SC, Druss B, Elinson L, Tanielian T, Pincus HA. National trends in the outpatient treatment of depression. JAMA 2002; 287(2): 203-9., and is associated with the increased diagnosis of depressive illnesses and the expansion of treatment options for treatment³⁸38. Rodrigues MAP, Facchini LA, Lima MS. Modificações nos padrões de consumo de psicofármacos em localidade do Sul do Brasil. Rev Saúde Pública 2006; 40(1): 107-14..

Studies have reported increasing trends in cases and hospitalizations for psychoses in recent years⁴¹41. Medel-Herrero A, Amate JM, Saz-Parkinson Z, Gómez-Beneyto M. Changing trends in hospitalization rates associated with psychosis: Spain, 1980-2009. Soc Psychiatry Psychiatr Epidemiol 2015; 50(12): 1843-55. https://doi.org/10.1007/s00127-015-1128-9
https://doi.org/10.1007/s00127-015-1128-... , which tends to increase the use of antipsychotics, associated with the greater extent of the therapeutic arsenal for the treatment of this group of diseases. This situation exposes individuals to an increased risk of DRPs with antipyschotics, as demonstrated in the present study.

On the other hand, there was a decreasing trend in DRPs with antibiotics, which refers to the rational prescription of this therapeutic group, but also to new regulations that govern the prescription and acquisition of these products. In 2011, ANVISA issued a resolution regarding a mandatory doctor’s prescription to obtain antibiotics, and the need for pharmacies to retain the prescription⁴²42. Agência Nacional de Vigilância Sanitária. Resolução RDC nº 20, de 5 de maio de 2011. Dispõe sobre o controle de medicamentos à base de substâncias classificadas como antimicrobianos, de uso sob prescrição, isoladas ou em associação. Brasília: Agência Nacional de Vigilância Sanitária; 2011.. Previous studies demonstrated that the acquisition of these products occurred without the need for a prescription⁴³43. Vilarino JF, Soares IC, Silveira CM, Rödel APP, Bortoli R, Lemos RR. Perfil da automedicação em município do Sul do Brasil. Rev Saúde Pública 1998; 32(1): 43-9. http://dx.doi.org/10.1590/S0034-89101998000100006
http://dx.doi.org/10.1590/S0034-89101998... ^,4444. Sá MB, Barros JAC, Sá MPBO. Automedicação em idosos na cidade de Salgueiro-PE. Rev Bras Epidemiol 2007; 10(1): 75-85., which could result in the irrational use of antibiotics.

Some methodological aspects should be pointed out in relation to this study. Because it was a study using secondary data (PCC notification forms), the information may have been erroneously recorded and/or illegible, in addition to being “ignored” or “ lacking information”. In this regard, it is noteworthy that only three records had no entry for the item “age”. Also important was the limitation in the number of medications to be registered on the CIT/HU/UEL forms (maximum of three), which affects the completeness and consistency of the information. In addition, non-notification of injuries, especially mild ones, may lead to underreporting of cases. Nevertheless, despite the limitations presented, the study gathered consistent and unpublished data on the trends of DRPs, which can contribute to new explorations of secondary data on these diseases.

The results obtained raise a concern about the access and use of psychoactive drugs, indicating the need for measures to promote the rational prescription of these products and more control in their acquisition. In addition, they reveal the need for a more rigorous follow-up of the patient to achieve therapeutic goals, reducing the risk of suicidal thoughts. In addition, easy access to analgesics and anti-inflammatories can be an important contributor to the increasing trend towards intoxications with these drugs, and therefore, policies that foster their rational use can contribute to a decrease in DRPs in this group.

CONCLUSIONS

DRP cases showed a predominance of women, individuals aged 20 to 39 years and children 4 years or less, and suicide attempts and accidental causes as the main circumstances for their occurrence. The proportion of DRPs showed an increasing trend, especially in males. The main medications involved were those that work on the central nervous system, with antidepressants and antipsychotics showing the greatest proportional increase between 1985 and 2014.

ACKNOWLEDGMENTS

To the trainees of the PCC of the University Hospital of the State University of Londrina and the technical administration Miriam de Cássia Tóffolo for their assistance with data collection.

References

Publication Dates

History