Perfil de medicamentos descartados nas farmácias públicas de um município do leste de Minas Gerais / Profile of medicines discarded in the public pharmacies of an eastern municipality of Minas Gerais

O descarte inadequado de medicamentos pode levar a impactos ambientais negativos e deve ser considerado um problema de saúde pública. O presente estudo teve como objetivo levantar dados quantitativos e qualitativos relacionados ao perfil dos medicamentos descartados no município de Governador Valadares - MG. O trabalho foi desenvolvido nas UAPS/ESF que possuíam farmácias, e também na Farmácia Central/Policlínica Municipal. Nesses locais, foi realizada uma análise dos medicamentos descartados no período de julho de 2017 a maio de 2018. Por meio dos dados obtidos nesse período foi possível perceber que as principais classes de medicamentos descartadas foram os inibidores da enzima conversora de angiotensina, antagonistas da angiotensina II, agentes betabloqueadores, diuréticos, hipoglicemiantes, contraceptivos hormonais e agentes modificadores de lipídeos. Além disso, foi realizada uma ação de educação em saúde e aplicado um questionário semiestruturado aos usuários participantes dos grupos operativos. Dos 34 usuários respondentes do questionário, 23 (69,70%) não tinham acesso a informação sobre o local correto de descarte e armazenamento de medicamentos. Após a ação de educação em saúde verificou-se um aumento no quantitativo de medicamentos descartados pelos usuários nas UAPS/ESF Mãe de Deus I e II, Altinópolis III e IV, Santa Rita II, São Pedro I e II e Esperança e Nossa Senhora das Graças. O trabalho desenvolvido permitiu apresentar dados relevantes para a gestão municipal demonstrando a importância do farmacêutico no cuidado em saúde e o caráter epidemiológico local da prevalência das doenças crônico não transmissíveis.

The inadequate disposal of drugs can lead to negative environmental impacts and should be treated as a public health problem. This study aimed at surveying quantitative and qualitative data related to the profile of drugs discarded in the city of Governador Valadares - MG. The work was developed in the UAPS / ESF that had pharmacies, and also in the Central Pharmacy/Municipal Polyclinic. In these locations, an analysis of the drugs discarded between July 2017 and May 2018 was carried out. Through the data obtained in this period, it was possible to notice that the main classes of drugs discarded were angiotensin-converting enzyme inhibitors, angiotensin II antagonists, beta-blocking agents, diuretics, hypoglycemic agents, hormonal contraceptives, and lipid-modifying agents. In addition, a health education action was carried out and a semi-structured questionnaire was applied to users participating in the operating groups. From the 34 users who responded the questionnaire, 23 (69.70%) did not have access to information on the correct place to dispose and store medicines. After the health education action, there was an increase in the amount of drugs discarded by users in the UAPS/ESF Mãe de Deus I and II, Altinópolis III and IV, Santa Rita II, São Pedro I and II, and Esperança and Nossa Senhora das Graças. The work carried out made it possible to present relevant data for municipal management, demonstrating the importance of the pharmacist in health care and the local epidemiological character of the prevalence of chronic non-communicable diseases.

Noradrenaline induces peripheral antinociception by endogenous opioid release.

BACKGROUND: The aim of this study was to investigate this involvement in not inflammatory model of pain and which opioid receptor subtype mediates noradrenaline-induced peripheral antinociception. Noradrenaline is involved in the intrinsic control of pain-inducing pro-nociceptive effects in the primary afferent nociceptors. However, inflammation can induce various plastic changes in the central and peripheral noradrenergic system that, upon interaction with the immune system, may contribute, in part, to peripheral antinociception. METHODS: Hyperalgesia was induced by intraplantar injection of prostaglandin E2 (PGE2, 2µg) into the plantar surface of the right hind paw and the paw pressure test to evaluated the hyperalgesia was used. Noradrenaline (NA) was administered locally into right hind paw of Wistar rat (160-200g) alone and after either agents, α2-adrenoceptor antagonist yohimbine, α1-adrenoceptor antagonist prazosin, ß-adrenoceptor antagonist propranolol, µ-opioid antagonist clocinnamox, δ-opioid antagonist naltrindole and κ-opioid antagonist nor-binaltorfimina. In addition, the enkephalinase inhibitor bestatin was administered prior to NA low dose. RESULTS: Intraplantar injection of NA induced peripheral antinociception against hyperalgesia induced by PGE2. This effect was reversed, in dose dependent manner, by intraplantar injection of yohimbine, prazosin, propranolol, clocinnamox and naltrindole. However, injection of nor-binaltorfimina did not alter antinociception of NA after PGE2 hyperalgesia. Bestatin intensified the antinociceptive effects of low-dose of NA. CONCLUSION: Besides the α2-adrenoceptor, the present data provide evidence that, in absence of inflammation, NA activating α1 and ß-adrenoceptor induce endogenous opioid release to produce peripheral antinociceptive effect by µ and δ opioid receptors.

Eugenol Induces Phenotypic Alterations and Increases the Oxidative Burst in Cryptococcus.

Eugenol is a phenolic compound and the main constituent of the essential oil of clove India. Although there are reports of some pharmacological effects of eugenol, this study is the first that proposes to evaluate the antifungal effects of this phenol against both Cryptococcus gattii and C. neoformans cells. The effect of eugenol against yeast cells was analyzed for drug susceptibility, alterations in cell diameter, capsule properties, amounts of ergosterol, oxidative burst, and thermodynamics data. Data demonstrated that there is no interaction between eugenol and fluconazole and amphotericin B. Eugenol reduced the cell diameter and the capsule size, increased cell surface/volume, changed positively the cell surface charge of cryptococcal cells. We also verified increased levels of reactive oxygen species without activation of antioxidant enzymes, leading to increased lipid peroxidation, mitochondrial membrane depolarization and reduction of lysosomal integrity in cryptococcal cells. Additionally, the results showed that there is no significant molecular interaction between eugenol and C. neoformans. Morphological alterations, changes of cellular superficial charges and oxidative stress play an important role in antifungal activity of eugenol against C. gattii and C. neoformans that could be used as an auxiliary treatment to cutaneous cryptococcosis.

Estadiamento do câncer de mama em mulheres atendidas em um centro de referência em oncologia / Staging of breast cancer in women admitted for care in an oncology reference center

O objetivo do estudo foi avaliar a possível associação entre as características sociodemográficas e o estádio clínico do câncer de mama em mulheres, admitidas para atendimento em um centro de referência em oncologia. Os prontuários de 257 pacientes com diagnóstico de câncer de mama e atendidas entre novembro de 2009 a novembro de 2010 foram revisados. Os dados de interesse foram extraídos para um banco de dados e analisados por meio de regressão logística para identificação das variáveis associadas com o estádio clínico. As pacientes tinham em média 54,5 anos de idade e a maioria eram pardas (62,8%), sem história familiar de câncer de mama (78,2%) e com índice de massa corporal acima do ideal (57,2%). O diagnóstico do câncer foi tardio (estádio III e IV) em 32,7% das pacientes. Não houve associação significativa entre o estádio clínico e a idade, cor da pele, estado civil, índice de massa corpórea ou história familiar de câncer de mama. O percentual de casos diagnosticados em estádio tardio ainda é elevado, quando comparado com o encontrado em países desenvolvidos, o que aponta para necessidade de políticas que facilitem a detecção precoce da doença na região.

The aim of the study was to evaluate the possible association between sociodemographic characteristics and the clinical stage of breast cancer in women admitted for care at an oncology reference center. The medical records of 257 patients treated between November 2009 and November 2010 were reviewed. The data of interest were extracted onto a database and analyzed using logistic regression to identify the variables associated with the clinical stage. The patients were on average 54.5 years of age, primarily Caucasian (62.8%), with no family history of breast cancer (78.2%) and above the ideal body mass index (57.7%). Cancer diagnosis was late (stage II and IV) in 32.7% of patients. There was no significant relationship between the initial or early stages and age, skin color, marital status, body mass index and family history of breast cancer. The percentage of cases diagnosed in a late stage is still high when compared to what is found in developed countries, which points to the need for policies that facilitate the early detection of the disease in the region.

Natural Diterpenes from Coffee, Cafestol, and Kahweol Induce Peripheral Antinoceception by Adrenergic System Interaction.

Cafestol and kahweol are diterpenes found only in the non-saponified lipid fraction of coffee. They are released during boiling and retained in the filtration process. Previous studies have shown peripheral antinociception induced by endogenous opioid peptides released by these diterpenes. Considering that the activation of the opioid system leads to a noradrenaline release, the aim of this study was to verify the participation of the noradrenergic system in the peripheral antinociception induced by cafestol and kahweol. Hyperalgesia was induced by an intraplantar injection of prostaglandin E2 (2 µg). Cafestol or kahweol (80 µg/paw) were administered locally into the right hindpaw alone, and after the agents α 2-adrenoceptor antagonist yohimbine (5, 10 and 20 µg/paw), α 2 A-adrenoceptor antagonist BRL 44 408 (40 µg/paw), α 2B-adrenoceptor antagonist imiloxan (40 µg/paw), α 2 C-adrenoceptor antagonist rauwolscine (10, 15 and 20 µg/paw), α 2D-adrenoceptor antagonist RX 821 002 (40 µg/paw), α 1-adrenoceptor antagonist prazosin (0.5, 1 and 2 µg/paw), or ß-adrenoceptor antagonist propranolol (150, 300 and 600 ng/paw), respectively. Noradrenaline reuptake inhibitor reboxetine (30 µg/paw) was administered prior to cafestol or kahweol low dose (40 µg/paw) and guanetidine 3 days prior to the experiment (30 mg/kg, once a day), depleting the noradrenaline storage. Intraplantar injection of cafestol or kahweol (80 µg/paw) induced a peripheral antinociception against hyperalgesia induced by PGE2. This effect was reversed by intraplantar injections of yohimbine, rauwolscine, prazosin and propranolol. Reboxetine injection intensified the antinociceptive effect of cafestol or kahweol low-dose, and guanethidine reversed almost 70 % of the cafestol or kahweol-induced peripheral antinociception. This study gives evidence that the noradrenergic system participates in cafestol and kahweol-induced peripheral antinociception with the release of endogenous noradrenaline.

Involvement of endogenous opioid peptides in the peripheral antinociceptive effect induced by the coffee specific diterpene kahweol.

BACKGROUND: Kahweol is a diterpene present in the oil derived from coffee beans. Although several pharmacological activities of kahweol are already well described in the literature, no study was done in order to assess the analgesic activity of this substance. Thus, the aim of this study was to investigate the possible peripheral antinociceptive effect of kahweol. Considering that the opioid peptides have been implicated in peripheral antinociception induced by non-opioidergic compounds, the present study also evaluated the endogenous opioids involvement in this effect. METHODS: The rat paw pressure test was used, and hyperalgesia was induced by intraplantar injection of prostaglandin E2 (2µg/paw). All drugs were administered subcutaneously in the hindpaws of male Wistar rats. The expression of ß-endorphin was examined by immunohistochemistry in the skin tissue samples of the plantar surface of rat right hindpaws. RESULTS: Intraplantar injection of kahweol (40 and 80µg) induced significant peripheral antinociception. The antinociceptive effect of kahweol was due to a local peripheral action because the higher dose (80µg/paw) did not produce any effect in the contralateral paw. The opioid receptor antagonist naloxone (50 and 100µg/paw) prevented action of kahweol (80µg/paw) and the aminopeptidases inhibitor bestatin (400µg/paw) potentiated the antinociceptive effect of kahweol (40µg/paw). Furthermore, kahweol treatment increased the intensity of ß-endorphin immunoreactivity in the epithelium of rat paws. CONCLUSIONS: The results discussed here provide evidence that kahweol treatment has peripheral antinociceptive effect and suggest that this effect is mediated by the release of endogenous opioids.

CB1 and CB2 cannabinoid receptor agonists induce peripheral antinociception by activation of the endogenous noradrenergic system.

BACKGROUND: Cannabinoid agonists induce norepinephrine release in central, spinal, and peripheral sites. Previous studies suggest an interaction between the cannabinoid and adrenergic systems on antinociception. In this study, we sought to verify whether the CB1 and CB2 cannabinoid receptor agonists anandamide and N-palmitoyl-ethanolamine (PEA), respectively, are able to induce peripheral antinociception via an adrenergic mechanism. METHODS: All drugs were administered locally into the right hindpaw of male Wistar rats. The rat paw pressure test was used, with hyperalgesia induced by intraplantar injection of prostaglandin E2 (2 µg). RESULTS: Anandamide, 12.5 ng/paw, 25 ng/paw, and 50 ng/paw elicited a local peripheral antinociceptive effect that was antagonized by CB1 cannabinoid receptor antagonist AM251, 20 µg/paw, 40 µg/paw, and 80 µg/paw, but not by CB2 cannabinoid receptor antagonist AM630, 100 µg/paw. PEA, 5 µg/paw, 10 µg/paw, and 20 µg/paw, elicited a local peripheral antinociceptive effect that was antagonized by AM630, 25 µg/paw, 50 µg/paw, and 100 µg/paw, but not by AM251, 80 µg/paw. Antinociception induced by anandamide or PEA was antagonized by the nonselective α2 adrenoceptor antagonist yohimbine, 05 µg/paw, 10 µg/paw, and 20 µg/paw, and by the selective α2C adrenoceptor antagonist rauwolscine, 10 µg/paw, 15 µg/paw, and 20 µg/paw, but not by the selective antagonists for α2A, α2B, and α2D adrenoceptor subtypes, 20 µg/paw. The antinociceptive effect of the cannabinoids was also antagonized by the nonselective α1 adrenoceptor antagonist prazosin, 0.5 µg/paw, 1 µg/paw, and 2 µg/paw, and by the nonselective ß adrenoceptor antagonist propranolol, 150 ng/paw, 300 ng/paw, and 600 ng/paw. Guanethidine, which depletes peripheral sympathomimetic amines (30 mg/kg/animal, once a day for 3 days), restored approximately 70% the anandamide-induced and PEA-induced peripheral antinociception. Furthermore, acute injection of the norepinephrine reuptake inhibitor reboxetine, 30 µg/paw, intensified the antinociceptive effects of low-dose anandamide, 12.5 ng/paw, and PEA, 5 µg/paw. CONCLUSIONS: This study provides evidence that anandamide and PEA induce peripheral antinociception activating CB1 and CB2 cannabinoid receptors, respectively, stimulating an endogenous norepinephrine release that activates peripheral adrenoceptors inducing antinociception.

Mu, delta, and kappa opioid receptor agonists induce peripheral antinociception by activation of endogenous noradrenergic system.

Opioid receptor agonists induce noradrenaline release in the supraspinal, spinal, and peripheral sites. Endogenous noradrenaline release can induce an antinociceptive effect by activation of the α(2) adrenoceptor. This interaction between the opioid and the adrenergic systems could be the alternative mechanism by which opioid receptor agonists mediate peripheral antinociception. Therefore, the aim of the present study was to verify whether peripheral antinociception induced by the µ, δ, and κ opioid receptor agonists DAMGO, SNC80, and bremazocine, respectively, through the endogenous noradrenergic system. All drugs were administered locally into the right hind paw of male Wistar rats. The rat paw pressure test was used, with hyperalgesia induced by intraplantar injection of prostaglandin E(2). DAMGO, SNC80, or bremazocine elicited local dose-dependent peripheral antinociception. This peripheral effect was antagonized by the nonselective α(2) adrenoceptor antagonist yohimbine and by the selective α(2C) adrenoceptor antagonist rauwolscine but not by the selective antagonists for α(2A), α(2B), and α(2D) adrenoceptor subtypes (BRL 44 480, imiloxan, and RX 821002, respectively). The opioid-induced effect was antagonized by the nonselective α(1) adrenoceptor antagonist prazosin and by the nonselective ß adrenoceptor antagonist propranolol. Guanethidine, a depletor of peripheral sympathomimetic amines, restored approximately 50-60% of the opioid-induced peripheral antinociception. Furthermore, acute injection of the noradrenaline reuptake inhibitor reboxetine intensified the antinociceptive effects of low-dose DAMGO, SNC80, or bremazocine. This study provides evidence that DAMGO, SNC80, or bremazocine induces peripheral antinociception by noradrenaline release and interaction with adrenoceptors.

Angiotensin-(1-7) induces peripheral antinociception through mas receptor activation in an opioid-independent pathway.

The G protein-coupled receptor Mas was recently described as an angiotensin-(1-7) [Ang-(1-7)] receptor. In the present study, we demonstrate an antinociceptive effect of Ang-(1-7) for the first time. Additionally, we evaluated the anatomical localization of Mas in the dorsal root ganglia using immunofluorescence. This is the first evidence indicating that this receptor is present in sensitive neurons. The antinociceptive effect was demonstrated using the rat paw pressure test. For this test, sensitivity is increased by intraplantar injection of prostaglandin E(2). Ang-(1-7) administered locally into the right hind paw elicited a dose-dependent antinociceptive effect. Because the higher dose of Ang-(1-7) did not produce an effect when injected into the contralateral paw, this effect was considered local. The specific antagonist for the Mas receptor, A-779, inhibited the peripheral antinociception induced by exposure to 4 µg/paw Ang-(1-7) in a dose-dependent manner. The highest dose completely reversed the antinociceptive effect induced by Ang-(1-7), suggesting that the Mas receptor is an obligatory component in this process and that other angiotensin receptors may not be involved. When injected alone, the antagonist was unable to induce hyperalgesia or antinociception. Alternatively, naloxone was unable to inhibit the antinociceptive effect induced by Ang-(1-7), suggesting that endogenous opioid peptides may not be involved in this response. These data provide the first anatomical basis for the physiological role of Ang-(1-7) in the modulation of pain perception via Mas receptor activation in an opioid-independent pathway. Taken together, these results provide new perspectives for the development of a new class of analgesic drugs.

Cafestol, a coffee-specific diterpene, induces peripheral antinociception mediated by endogenous opioid peptides.

The opioid peptides have been implicated in peripheral antinociception induced by non-opioidergic compounds, including non-steroidal anti-inflammatory drugs and α(2) -adrenoceptor agonists. The aims of the present study were to investigate the possible peripheral antinociceptive effect of cafestol, a diterpene present in the oil derived from coffee beans, and to evaluate the involvement of opioid peptides in its effect. The rat paw pressure test was used to assess antinocipeptive effects. Hyperalgesia was induced by intraplantar injection of prostaglandin E(2) (2 µg/paw). All drugs were locally administered into the hind-paws of male Wistar rats. Intraplantar injection of cafestol (20, 40 and 80 µg) induced peripheral antinociception. The antinociceptive effect of cafestol was due to a local action because the higher dose (80 µg/paw) did not produce any effect in the contralateral paw. The opioid receptor antagonist naloxone (25, 50 and 100 µg/paw) prevented the action of cafestol (80 µg/paw), whereas the aminopeptidase inhibitor bestatin (400 µg/paw) potentiated the antinociceptive effect of cafestol (40 µg/paw). The results of the present study provide evidence that cafestol treatment has a peripheral antinociceptive effect and suggest that this effect is mediated by the release of endogenous opioids.

Noradrenaline activates the NO/cGMP/ATP-sensitive K(+) channels pathway to induce peripheral antinociception in rats.

Despite the classical peripheral pronociceptive effect of noradrenaline (NA), recently studies showed the involvement of NA in antinociceptive effect under immune system interaction. In addition, the participation of the NO/cGMP/KATP pathway in the peripheral antinociception has been established by our group as the molecular mechanism of another adrenoceptor agonist xylazine. Thus the aim of this study was to obtain pharmacological evidences for the involvement of the NO/cGMP/KATP pathway in the peripheral antinociceptive effect induced by exogenous noradrenaline. The rat paw pressure test was used, with hyperalgesia induced by intraplantar injection of prostaglandin E(2) (2µg/paw). All drugs were locally administered into the right hind paw of male Wistar rats. NA (5, 20 and 80ng/paw) elicited a local inhibition of hyperalgesia. The non-selective NO synthase inhibitor l-NOarg (12, 18 and 24µg/paw) antagonized the antinociception effect induced by the highest dose of NA. The soluble guanylyl cyclase inhibitor ODQ (25, 50 and 100µg/paw) antagonized the NA-induced effect; and cGMP-phosphodiesterase inhibitor zaprinast (50µg/paw) potentiated the antinociceptive effect of NA low dose (5ng/paw). In addition, the local effect of NA was antagonized by a selective blocker of an ATP-sensitive K(+) channel, glibenclamide (20, 40 and 80µg/paw). On the other hand, the specifically voltage-dependent K(+) channel blocker, tetraethylammonium (30µg/paw), Ca(2+)-activated K(+) channel blockers of small and large conductance types dequalinium (50µg/paw) and paxilline (20µg/paw), respectively, were not able to block local antinociceptive effect of NA. The results provide evidences that NA probably induces peripheral antinociceptive effects by activation of the NO/cGMP/KATP pathway.

Perfil epidemiológico da hanseníase num município superendêmico do interior do sudeste brasileiro / Epidemiological profile of leprosy in the hyperendemic municipality in the inner of brazilian southeastern

A hanseníase é uma doença infecto-contagiosa de evolução crônica que se manifesta principalmente através de sinais e sintomas dermatoneurológicos. O objetivo deste trabalho foi avaliar a situação epidemiológica da hanseníase no município de Teófilo Otoni (TO)-MG, no período de 2001 a 2010 de forma descritiva e retrospectiva.Os altos coeficientes de detecção geral e em menores de 15 anos encontrados, mantêm o município como hiperendêmico para hanseníase, sinalizando a necessidade de intensificar as ações de vigilância epidemiológica.O percentual médio de grau 2 de incapacidade,entre os casos novos estudados no momento do diagnóstico foi considerado alto (10,1%) segundo Ministério da Saúde (MS). O percentual médio de casos novos avaliados, no momento da alta por cura, apresentando grau 2 de incapacidade física foi de 4,3%. O coeficiente de prevalência no município de TO foi considerado médio (1- 4,9/10.000hab) no período de 2001 a 2010 com exceção dos anos de 2003, 2004 e 2005 quando foi considerado muito alto (12,7; 14,1 e 12,6/10.000 habitantes)respectivamente. Com relação a variável prevalência oculta, verificou-se que 526 casos de hanseníase não foram diagnosticados no município, significando que 40,3% dos doentes permaneceram sem diagnóstico naquele período, podendo atuar como fontes de contágio contribuindo para a cadeia de transmissão da doença.É necessário que o município promova e intensifique a descentralização das ações de controle da doença,desenvolva programas de capacitação para as equipes multiprofissionais da Estratégia de Saúde da Família(ESF) e estimule a busca ativa de novos casos.

Leprosy is an infectious disease manifested primarily bysigns and symptoms dermato-neurological. The objectiveof this study was to evaluate the epidemiological situation of leprosy in the city of Teofilo Otoni (TO), MGstate in the period 2001-2010 as a descriptive and retrospective study. The high detection rates in general and in children under 15 years found in TO, keep this municipality as hyper-endemic for leprosy, signaling the need to strengthen the epidemiological surveillance. The average percentage of grade 2 disability among new cases studied at diagnosis was considered high (10.1 %) according to the Ministry of Health in Brazil. The average percentage of new cases assessed at the time of discharge after cure, with grade 2 disability was 4.3 %. The prevalence rate in the city of TO was considered medium (1 to 4.9 /10.000 hab ) in the period from 2001 to 2010 except for the years 2003 , 2004 and 2005 when it was considered very high ( 12.7 , 14.1 and 12.6 / 10.000 hab) respectively. Regarding the prevalence hidden variable, it was found that 526 cases of leprosy were not diagnosed in the city,meaning that 40.3 % of patients remained undiagnosed at that time and may act as sources of infection contributing to the chain of disease transmission. It is necessary for the municipality to promote and intensify the decentralization of control of the disease, and also develop training programs for the multidisciplinary teams at family health strategy (ESF) and encourage active search for new cases.