Nanotechnological Strategies for Vaginal Administration of Drugs-A Review

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Desenvolvimento de métodos analíticos de desreplicação por RMN, EM e análise multivariada do perfil metabolômico de espécies de Solanaceae com potencial biológico

Pós-graduação em Química - IQ

Sobre a promoção da saúde na contemporaneidade: um desafio ao farmacêutico educador

Pós-graduação em Educação - IBRC

Cytotoxic and genotoxic effects of high concentrations of the immunosuppressive drugs cyclosporine and tacrolimus in MRC-5 cells

Immunosuppressive drugs are used to suppress immune system activity in transplant patients and reduce the risk of organ rejection. The present study evaluated the potential cytotoxic, genotoxic and mutagenic of the immunosuppressive drugs cyclosporine (CsA) and tacrolimus (FK-506) on normal human fibroblasts (MRC-5 cells). Based on plasma concentrations of the immunosuppressive drugs, which were obtained from the records of kidney transplant patients at the Kidney Institute of Londrina, Brazil, 11 concentrations of each immunosuppressive were chosen to evaluate cell viability using the MIT assay. From these results, CsA and FK-506 concentrations of 135, 300, 675, and 1520 ng/ml and 8, 16, 24, and 32 ng/ml, respectively, were evaluated using (i) the comet assay, (ii) the nuclear division index (NDI), (iii) the micronucleus test (CBMN) and (iv) cell proliferation curves generated by quantifying cell numbers and protein levels. In this study, 1520 to 3420 ng/ml CsA decreased cell viability after 48 h of exposure. Genotoxic effects were observed only with a concentration of 1520 ng/ml after 3 h of exposure and with concentrations of 675 and 1520 ng/ml after 24 h of exposure. Mutagenic effects were observed only for the concentration of 1520 ng/ml. FK-506 decreased cell viability after 72 h of exposure for concentrations up to 20 ng/ml; genotoxic effects were observed with concentrations up to 8 ng/ml for both treatment times (3 and 24 h) and mutagenic effects were observed with concentrations of 24 and 32 ng/ml after 24 h of treatment. The cell proliferation curves demonstrated the absence of cytostatic effects of these drugs, and these data were confirmed by the NDI analysis. Our results suggest that concentrations lower than 300 ng/ml of CsA and 16 ng/ml of FK-506 are safe for use, as they did not induce genotoxic and mutagenic damage or affect MRC-5 cell viability and proliferation. (C) 2014 Elsevier GmbH. All rights reserved.

Use of anatomical, chemical, and molecular genetic characteristics in the quality control of medicinal species: a case study of sarsaparilla (Smilax spp.)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Synthesis and total 1H- and 13C-NMR assignment of cephem derivatives for use in ADEPT approaches

We report the synthesis and total NMR characterization of 5-thia-1-azabicyclo-[4.2.0]oct-2-ene-2-carboxylic acid-3-[[[(4″- nitrophenoxy)carbonyl]oxy]-methyl]-8-oxo-7-[(2-thienyloxoacetyl)amino] -diphenylmethyl ester-5-dioxide (5), a new cephalosporin derivative. This compound can be used as the carrier of a wide range of drugs containing an amino group. The preparation of the intermediate product, 5-thia-1-azabicyclo[4.2.0] oct-2-ene-2-carboxylic acid-3-[methyl 4-(6-methoxyquinolin-8-ylamino) pentylcarbamate]-8-oxo-7-[(2-thienyloxoacetyl)amino]-diphenylmethyl ester-5-dioxide (6), as well as the synthesis of the antimalarial primaquine prodrug 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid-3-[methyl 4-(6-methoxyquinolin-8-ylamino)pentylcarbamate]-8-oxo-7-[(2-thienyloxoacetyl) amino]- 5-dioxide (7) are also described, together with their total 1H- and 13C-NMR assignments. © 2008 by MDPI.

Medicamentos inadequados para idosos na estratégia da saúde da família

The ageing process can change the pharmacodynamics and pharmacokinetics parameters. Therefore, some medications are considered potentially inappropriate (PIM) for the elderly people, since they can increase the likelihood of occurrence of adverse drug events. The objectives are to estimate the frequency of use of PIM in the elderly people, with potentially hazardous drug interactions (PHDI) and to evaluate the impact of pharmaceutical intervention (PI) for the prescription of safer therapeutic alternatives. A cross-sectional study was performed in a Health Family Strategy (region of Araraquara, SP), between January and February/2012. The medical records of patients aged ≥60 years, that use at least one drug, were consulted for identification of PIM, according to the Beers criteria. The MPI identified were classified considering the Anatomical Therapeutic Chemical Classification System (ATC) and the essentiality of the drug (safety, effectiveness, quality and cost parameters) The inclusion criteria were met by 358 elderly, being that 93 of them (26%) had taken at least one PIM. Of the 114 different drugs prescribed for elderly, ten were classified as PIM, of which four of them act on the central nervous system, four on cardiovascular system and two on the digestive tract. Seven MPI are essential medicines, belonging to national list of essential drugs (RENAME-2010). Fourteen drug interactions were identified, of which two are PHDI (fluoxetine/amitriptyline and digoxin/hydrochlorothiazide).After the PI, there was no change in medical prescriptions of patients with PIM use or with DI. Medical prescriptions of elderly attended in the Health Family Strategy show pharmacotherapeutic safety problems, of which may be responsible for health hazardous for this age group. Although the intervention carried out by letter had been ineffective for the adherence of doctors in prescribing safe alternatives, wide dissemination of the lists that contain PIM and PHDI is need, as well as the inclusion of safer equivalents in RENAME, in order to contribute for rational use of drugs.

A platform for designing quantitative infrared spectrophotometric method for drugs and pharmaceuticals analysis: a rediscover for an ecological and safer technique in the routine quality control laboratories

This paper describes the importance of an innovative analytical technique for drugs and pharmaceuticals quantification, using Fouriertransform infrared (FTIR) transmission spectroscopy. This method does not use organic solvents, which is one great advantage over the most common analytical methods. This fact contributes to minimize the generation of organic solvent waste by the industry and thereby reduces the impact of its activities on the environment. The method involved absorbance measurements of the band corresponding to one of the chosen group in the molecule. Obviously, the method should be validated according to ICH guidelines, showing linearity, precision, accuracy and robustness, over a concentration range, using small amounts to prepare the analyte. The validated method is able to quantify drugs and pharmaceuticals and can be used as an environmentally friendly alternative for the routine analysis in pharmaceutical industry quality control.

Synergism of crude extracts and essential oils from medicinal plants with antimicrobial drugs

The emergence of resistant strains to conventional antimicrobial drugs has been constant as well as research aimed new alternatives of antibacterial agents. Therefore, considering that natural products have been an important potential source of new antimicrobial drugs, aim to verify the synergism by disk and time kill curve method between antimicrobials (extracts-Ext. and essential oils-EO) from four plant and eight antimicrobial drugs against Staphylococcus aureus and Escherichia coli strains from human specimens. The S. aures strains were highly susceptible with all plant antimicrobials (eg., 1.24 mg/ml with Vernonia polyanthes Ext. and 2.21 mg/ml with Eugenia uniflora EO for the Minimal Inhibitory Concentration-MIC). According disk method, the Bacharis dracunculifolia and V. polyanthes EO had synergism with all eight tested drugs while only Matricaria chamomilla Ext. showed synergism against S. aureus. The synergism was found with V. polyanthes and E. uniflora Ext. while M. chamomilla Ext. had antagonism against E. coli strains. By time kill curve, the bacterial growth inhibition was superior when drugs were tested alone and the synergism effect also was verified. The antagonism effect was detected only for E. coli strains and only with Ext. Results indicated the potential use of these products as coadjutants during treatment of infectious diseases.

Patterns of Ecstasy Use and Associated Harm: Results of a Brazilian Online Survey

The aim of this study was to gather information about ecstasy users in Brazil, particularly on issues related to risks associated to the use of the drug, so as to offer a basis to prevention projects. A total of 1,140 Brazilian ecstasy users answered an online questionnaire from August 2004 to February 2005. Participants were predominantly young single heterosexual well-educated males from upper economical classes. A categorical regression with optimal scaling (CATREG) was performed to identify the risks associated with ecstasy use. ""Pills taken in life"" had a significant correlation with every investigated risk, particularly ecstasy dependence, unsafe sex, and polydrug use. ""Gender,"" ""sexual orientation,"" and ""socioeconomic class"" were not predictive of risk behavior. The Internet proved to be a useful tool for data collection. Given the recent increase in ecstasy availability in Brazil, a first prevention campaign directed toward the drug is urgent. At least in a preliminary Brazilian intervention, the campaign must be conducted at night leisure places, mainly frequented by youngsters from upper socioeconomic classes. The results do not call for information material with specific targets, such as gender or sexual orientation. The study`s limitations have been noted.

Gender parity and drug use: are girls catching up with boys?

Objective: To evaluate the association between gender and use of alcohol, tobacco, and other drugs in adolescents aged 10 to 18 years in the municipalities of Jacare and Diadema, Sao Paulo, Brazil. Methods: A total of 971 adolescents completed the Drug Use Screening Inventory (DUSI). Results: In our sample, 55% of adolescents were male, 33.8% reported having made use in the previous month of alcohol, 13.5% of cigarettes, and 6.4% of illicit drugs. There was no significant difference between genders in the use of alcohol, tobacco, and illicit drugs in any of the analysis (p > 0.05). The use of alcohol, tobacco, and illicit drugs was associated with the city, age, educational level, school failure, and relationship with parents (p < 0.05). Conclusions: Substance abuse among adolescents in our sample seems to follow the recent global trend towards the equalization of drug use between genders. This result should be taken into account by public health professionals in developing policies for this problem. (C) 2012 Elsevier Editora Ltda. All rights reserved.

Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy?

Objective. To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. Methods. A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) epsilon 20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. Results. The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED epsilon 20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED epsilon 20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED epsilon 20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED epsilon 20 mg + IS + CQ (57.4%; P = 0.09). Conclusion. Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity.

The association between low alcohol use and traffic risk behaviors among Brazilian college students

Although there are a large number of studies focused on binge drinking and traffic risk behaviors (TRB), little is known regarding low levels of alcohol consumption and its association to TRB. The aim of this cross-sectional study is to examine the association of low to moderate alcohol intake pattern and TRB in college students in Brazil. 7037 students from a National representative sample were selected under rigorous inclusion criteria. All study participants voluntarily fulfilled a structured, anonymous, and self-questionnaire regarding alcohol and drug use, social-demographic data, and TRB. Alcohol was assessed according to the average number of alcoholic units consumed on standard occasions over the past 12 months. The associations between alcohol intake and TRB were summarized with odds ratio and their confidence interval obtained from logistic regression. Compared with abstainers students who consumed only one alcohol unit had the risk of being a passenger in a car driven by a drunk driver increased by almost four times, students who reported using five or more units were increased by almost five times the risk of being involved in a car crash. Compared with students who consumed one alcohol unit, the risk of driving under the influence of alcohol increased four times in students using three alcohol units. Age group, use of illicit drugs, employment status, gender, and marital status significantly influenced occurrence of TRB among college students. Our study highlights the potential detrimental effects of low and moderate pattern of alcohol consumption and its relation to riding with an intoxicated driver and other TRB. These data suggest that targeted interventions should be implemented in order to prevent negative consequences due to alcohol use in this population. (C) 2012 Elsevier Inc. All rights reserved,

Prescribed use of methylphenidate hydrochloride and its correlates among Brazilian college students

Background: The prevalence of prescribed use of methylphenidate (MPH) and its correlates are not well-known in Brazil. Objective: To estimate the prevalence of prescribed use of MPH and its correlates in a sample of Brazilian college students. Methods: Twelve-thousand seven hundred and eleven college students filled out a drug use questionnaire. They were divided into two groups based on the lifetime use of MPH: MPH users (MPHU) and MPH non-users (MPHNU). Quasi-binomial regression models were carried out in order to evaluate the correlation among MPHU and other variables. Results: A lifetime use of MPH was reported from 0.9% of college students (MPHU). Being from the Midwest (PR = 4.8, p < 0.01) and South (PR = 5.2, p < 0.05), living in students housing (PR = 5.8, p < 0.001), prescribed use of amphetamines (PR = 8.9, p < 0.001) and benzodiazepines (< 3 weeks: PR = 4.4, p < 0.001; >= 3 weeks: PR = 6.7, p < 0.001), and harmful use of alcohol (PR = 4.0, p < 0.05) were correlated with MPHU. Discussion: The association of alcohol and drug use with prescribed use of MPH among college students suggests the importance of screening drinking patterns and use of other drugs among students with ADHD symptoms. Cesar ELR, et al. / Rev Psiq Clin. 2012; 39(6):183-8

Drug use in college students: a 13-year trend

OBJECTIVE: To analyze drug use trends among college students in 1996, 2001 and 2009. METHODS: A cross-sectional epidemiological study with a multistage stratified cluster sample with 9,974 college students was conducted in the city of Sao Paulo, southeastern Brazil. An anonymous self-administered questionnaire was used to collect information on drug use assessed in lifetime, the preceding 12 months and the preceding 30 days. The Bonferroni correction was used for multiple comparisons of drug use rates between surveys. RESULTS: There were changes in the lifetime use of tobacco and some other drugs (hallucinogens [6.1% to 8.8%], amphetamines [4.6% to 8.7%], and tranquilizers [5.7% to 8.2%]) from 1996 to 2009. Differences in the use of other drugs over the 12 months preceding the survey were also seen: reduced use of inhalants [9.0% to 4.8%] and increased use of amphetamines [2.4% to 4.8%]. There was a reduction in alcohol [72.9% to 62.1%], tobacco [21.3% to 17.2%] and marijuana [15.0% to 11.5%] use and an increase in amphetamine use [1.9% to 3.3%] in the preceeding 30 days. CONCLUSIONS: Over the 13-year study period, there was an increase in lifetime use of tobacco, hallucinogens, amphetamines, and tranquilizers. There was an increase in amphetamine use and a reduction in alcohol use during the preceding 12 months. There was an increase in amphetamine use during the preceding 30 days.