Quality of essential drugs in tropical countries: evaluation of antimalarial drugs in the Brazilian Health System

INTRODUCTION: The emergence of drug resistance is one of the main problems concerning malaria treatment. The use of counterfeit and/or substandard antimalarial drugs can contribute to the development of parasite resistance. Thus, the aim of this study was to evaluate the quality of antimalarial drugs distributed in Brazil. METHODS: Samples containing chloroquine phosphate, mefloquine hydrochloride, primaquine phosphate, and quinine sulfate tablets were delivered to the Rio de Janeiro central storeroom (CENADI), state storerooms (SS), and Basic Health Units (BHUs) in the north region of Brazil - a total of 10 sample sets. After 5 months of storage, the samples were collected, and in vitro quality control analyses according to official and published methods were performed. RESULTS: Inadequate drug storage conditions were found in two SS and in all BHUs evaluated. There were no quality deviations found in the chloroquine samples. The quinine samples exhibited weight variation above the allowed limits. The primaquine samples were found to have packaging deficiency. The release of mefloquine in samples from some regions showed a statistically significant difference when compared with the CENADI samples. CONCLUSIONS: It is important to periodically evaluate the quality and storage conditions of essential drugs. The quality deviations found with the primaquine and quinine samples are not related to storage conditions and must be addressed urgently. The decreased mefloquine release from tablets is related to formulation problems or influenced by inadequate storage conditions, prompting further investigation. Even with the mentioned problems, the samples would probably not contribute to resistant parasite selection.

Evaluation of pharmaceutical assistance in public primary care in Brasília, Brazil

OBJECTIVE: Pharmaceutical assistance is essential in health care and a right of citizens according to Brazilian law and drug policies. The study purpose was to evaluate aspects of pharmaceutical assistance in public primary health care. METHODS: A cross-sectional study using WHO drug indicators was carried out in Brasília in 2001. From a random sample of 15 out of 62 centers thirty exiting patients per center were interviewed. RESULTS: Only 18.7% of the patients fully understood the prescription, 56.3% could read it, 61.2% of the prescribed drugs were actually dispensed, and mean duration of pharmaceutical dispensing was 53.2 seconds. Each visit lasted on average 9.4 minutes. Of prescribed and non-dispensed drugs, 85.3% and 60.6% were on the local essential drug list (EDL) respectively. On average 83.2% of 40 essential drugs were in stock, and only two centers had a pharmacist in charge of the pharmacy. The mean number of drugs per prescription was 2.3, 85.3% of prescribed drugs were on the EDL, 73.2% were prescribed using the generic denomination, 26.4% included antibiotics and 7.5% were injectables. The most prescribed groups were: cardiovascular drugs (26.8%), anti-infective drugs (13.1%), analgesics (8.9%), anti-asthmatic drugs (5.8%), anti-diabetic drugs (5.3%), psychoactive drugs (3.7%), and combination drugs (2.7%). CONCLUSIONS: Essential drugs were only moderately available almost 30 years after the first Brazilian EDL was formulated. While physician use of essential drugs and generic names was fairly high, efficiency was impaired by the poor quality of pharmaceutical care, resulting in very low patient understanding and insufficient guarantee of supply, particularly for chronic diseases.

Combined effect of the essential oil from Chenopodium ambrosioides and antileishmanial drugs on promastigotes of Leishmania amazonensis

To date, there are no vaccines against Leishmania, and chemotherapy remains the mainstay for the control of leishmaniasis. The drugs of choice used for leishmaniasis therapy are significantly toxic, expensive and with a growing frequency of refractory infections. Because of these limitations, a combination therapy is the better hope. This work demonstrates that the essential oil from Chenopodium ambrosioides shows a synergic activity after incubation in conjunction with pentamidine against promastigotes of Leishmania amazonensis. However, an indifferent effect has been found for combinations of meglumine antimoniate or amphotericin B and the essential oil.

Presence of dual diagnosis between users and non-users of licit and illicit drugs in Brazil

ABSTRACT Objective Investigate the occurrence of dual diagnosis in users of legal and illegal drugs. Methods It is an analytical, cross-sectional study with a quantitative approach, non-probabilistic intentional sampling, carried out in two centers for drug addiction treatment, by means of individual interviews. A sociodemographic questionnaire, the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and the Mini-International Neuropsychiatric Interview (MINI) were used. Results One hundred and ten volunteers divided into abstinent users (group 1), alcoholics (group 2) and users of alcohol and illicit drugs (group 3). The substances were alcohol, tobacco, crack and marijuana. A higher presence of dual diagnosis in group 3 (71.8%) was observed, which decreased in group 2 (60%) and 37.1% of drug abstinent users had psychiatric disorder. Dual diagnosis was associated with the risk of suicide, suicide attempts and the practice of infractions. The crack consumption was associated with the occurrence of major depressive episode and antisocial personality disorder. Conclusion It was concluded that the illicit drug users had a higher presence of dual diagnosis showing the severity of this clinical condition. It is considered essential that this clinical reality is included in intervention strategies in order to decrease the negative effects of consumption of these substances and provide better quality of life for these people.

Antibacterial activity of Ocimum gratissimum L. essential oil

The essential oil (EO) of Ocimum gratissimum inhibited Staphylococcus aureus at a concentration of 0.75 mg/ml. The minimal inhibitory concentrations (MICs) for Shigella flexineri, Salmonella enteritidis, Escherichia coli, Klebsiella sp., and Proteus mirabilis were at concentrations ranging from 3 to 12 mg/ml. The endpoint was not reached for Pseudomonas aeruginosa (>=24 mg/ml). The MICs of the reference drugs used in this study were similar to those presented in other reports. The minimum bactericidal concentration of EO was within a twofold dilution of the MIC for this organism. The compound that showed antibacterial activity in the EO of O. gratissimum was identified as eugenol and structural findings were further supported by gas chromatography/mass spectra retention time data. The structure was supported by spectroscopic methods.

Therapeutic switching: from antidermatophytic essential oils to new leishmanicidal products

This study examined whether the antidermatophytic activity of essential oils (EOs) can be used as an indicator for the discovery of active natural products against Leishmania amazonensis. The aerial parts of seven plants were hydrodistilled. Using broth microdilution techniques, the obtained EOs were tested against three strains of dermatophytes (Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis). To compare the EOs antifungal and antiparasitic effects, the EOs activities against axenic amastigotes of L. amazonensis were concurrently evaluated. For the most promising EOs, their antileishmanial activities against parasites infecting peritoneal macrophages of BALB/c mice were measured. The most interesting antifungal candidates were the EOs from Cymbopogon citratus, Otacanthus azureus and Protium heptaphyllum, whereas O. azureus, Piper hispidum and P. heptaphyllum EOs exhibited the lowest 50% inhibitory concentration (IC50) values against axenic amastigotes, thus revealing a certain correspondence between both activities. The P. hispidum EO was identified as the most promising product in the results from the infected macrophages model (IC50: 4.7 µg/mL, safety index: 8). The most abundant compounds found in this EO were sesquiterpenes, notably curzerene and furanodiene. Eventually, the evaluation of the antidermatophytic activity of EOs appears to be an efficient method for identifying new potential drugs for the treatment of L. amazonensis.

Essential oil of Lippia alba and its main constituent citral block the excitability of rat sciatic nerves

Lippia alba is empirically used for infusions, teas, macerates, and hydroalcoholic extracts because of its antispasmodic, analgesic, sedative, and anxiolytic effects. Citral is a mixture of trans-geranial and cis-neral and is the main constituent of L. alba essential oil and possesses analgesic, anxiolytic, anticonvulsant, and sedative effects. The present study evaluated the effects of the essential oil of L. alba (EOLa) and citral on compound action potentials (CAPs) in Wistar rat sciatic nerves. Both drugs inhibited CAP in a concentration-dependent manner. The calculated half-maximal inhibitory concentrations (IC50) of peak-to-peak amplitude were 53.2 µg/mL and 35.00 µg/mL (or 230 µM) for EOLa and citral, respectively. Peak-to-peak amplitude of the CAP was significantly reduced by 30 µg/mL EOLa and 10 µg/mL citral. EOLa and citral (at 60 and 30 µg/mL, values close to their respective IC50 for CAP blockade) significantly increased chronaxy and rheobase. The conduction velocity of the first and second CAP components was statistically reduced to ∼86% of control with 10 µg/mL EOLa and ∼90% of control with 3 µg/mL citral. This study showed that EOLa inhibited nerve excitability and this effect can be explained by the presence of citral in its composition. Both EOLa and citral showed inhibitory actions at lower concentrations compared with other essential oils and constituents with local anesthetic activity. In conclusion, these data demonstrate that EOLa and citral are promising agents in the development of new drugs with local anesthetic activity.

The essential role of democracy in the Bush Doctrine: the invasions of Iraq and Afghanistan

Everyone knows that democracy played a role in the Bush Doctrine. What not everyone knows is that this role was essential for the doctrine to be put into operation under which the Iraq invasion was prepared and launched. We argue moreover that, even if aggressive, the Bush doctrine is compatible with the American Liberal Tradition. To demonstrate these arguments we analyze the links between democracy, security, and the US national interests as expressed in the pillars of the American foreign policy since the end of Cold War. The consequential belief of the Bush Administration on the positive effect of exporting democracy by the use of force to Afghanistan and Iraq to fight terrorism will be remarked. It will be shown, however, that in the first years of the Bush Administration, among the justifications for the military interventions in the two countries, security reasons prevailed over democratic concerns, although the latter was significantly present since the early hours after September 11. It was only when it became clear that WMDs did not exist in Iraq that the exporting of democracy as the ultimate weapon to fight terrorism grew remarkably and prevailed over security reasons to invade those rogue states. The paper uses quantitative and qualitative content analysis of the speeches of President Bush and his Secretaries of State and Defense.

Use of psychoactive drugs and related falls among older people living in a community in Brazil

INTRODUCTION: Population aging in Brazil has increased the prevalence of neurodegenerative diseases (Parkinson's and Alzheimer's disease) and affective disorders (anxiety, depression), all common in old age. A retrospective study was carried out with the purpose of ascertaining if there is an association between falls and psychoactive medication use among older residents of a community in Brazil. METHODS: All residents aged 65+ (n=161) of one neighborhood of Campo Belo, Brazil (population of 48,000) were evaluated regarding the use of psychoactive drugs and the occurrence of falls in the 12 months preceding the study. Vision and hearing screenings were also performed. RESULTS: From the study population, 9.3% were taking prolonged half-life benzodiazepines, 4.4% anticonvulsants (mostly barbiturates), 2.5% antidepressants (all cyclics) and 8.1% alpha-methyldopa. No subject reported use of hypnotics, neuroleptics or drugs to treat Alzheimer's or Parkinson's diseases (except biperiden). As a whole, drugs that increase the risk of falls were used by 1/5 of this population. In the 12-month period preceding the study, 27 residents (16.8%) experienced falls and, of those, 4 (14.8%) had fracture(s). There was an independent association between psychoactive drug use and falls when variables such as age, gender, vision and hearing were controlled (p=0.02). CONCLUSIONS: Although the population of this neighborhood must be considered young (only 4% are 65 years old or more), there are already problems related to the use of psychoactive drugs among people. Prescribed anxiolytics, anticonvulsants, antidepressants and antihypertensives are not appropriate for this age group and their use is associated with falls.

Risk of drug interaction: combination of antidepressants and other drugs

OBJECTIVE: To assess the frequency of combination of antidepressants with other drugs and risk of drug interactions in the setting public hospital units in Brazil. METHODS: Prescriptions of all patients admitted to a public hospital from November 1996 to February 1997 were surveyed from the hospital's data processing center in São Paulo, Brazil. A manual search of case notes of all patients admitted to the psychiatric unit from January 1993 to December 1995 and all patients registered in the affective disorders outpatient clinic in December 1996 was carried out. Patients taking any antidepressant were identified and concomitant use of drugs was checked. By means of a software program (Micromedex®) drug interactions were identified. RESULTS: Out of 6,844 patients admitted to the hospital, 63 (0.9%) used antidepressants and 16 (25.3%) were at risk of drug interaction. Out of 311 patients in the psychiatric unit, 63 (20.2%) used antidepressants and 13 of them (20.6%) were at risk. Out of 87 patients in the affective disorders outpatient clinic, 43 (49.4%) took antidepressants and 7 (16.2%) were at risk. In general, the use of antidepressants was recorded in 169 patients and 36 (21.3%) were at risk of drug interactions. Twenty different forms of combinations at risk of drug interactions were identified: four were classified as mild, 15 moderate and one severe interaction. CONCLUSION: In the hospital general units the number of drug interactions per patient was higher than in the psychiatric unit; and prescription for depression was lower than expected.

Biological drugs for the treatment of psoriasis in a public health system

OBJECTIVE To analyze the access and utilization profile of biological medications for psoriasis provided by the judicial system in Brazil.METHODSThis is a cross-sectional study. We interviewed a total of 203 patients with psoriasis who were on biological medications obtained by the judicial system of the State of Sao Paulo, from 2004 to 2010. Sociodemographics, medical, and political-administrative characteristics were complemented with data obtained from dispensation orders that included biological medications to treat psoriasis and the legal actions involved. The data was analyzed using an electronic data base and shown as simple variable frequencies. The prescriptions contained in the lawsuits were analyzed according to legal provisions.RESULTS A total of 190 lawsuits requesting several biological drugs (adalimumab, efalizumab, etanercept, and infliximab) were analyzed. Patients obtained these medications as a result of injunctions (59.5%) or without having ever demanded biological medication from any health institution (86.2%), i.e., public or private health services. They used the prerogative of free legal aid (72.6%), even though they were represented by private lawyers (91.1%) and treated in private facilities (69.5%). Most of the patients used a biological medication for more than 13 months (66.0%), and some patients were undergoing treatment with this medication when interviewed (44.9%). Approximately one third of the patients discontinued treatment due to worsening of their illness (26.6%), adverse drug reactions (20.5%), lack of efficacy, or because the doctor discontinued this medication (13.8%). None of the analyzed medical prescriptions matched the legal prescribing requirements. Clinical monitoring results showed that 70.3% of the patients had not undergone laboratory examinations (blood work, liver and kidney function tests) for treatment control purposes.CONCLUSIONS The plaintiffs resorted to legal action to get access to biological medications because they were either unaware or had difficulty in accessing them through institutional public health system procedures. Access by means of legal action facilitated long-term use of this type of medication through irregular prescriptions and led to a high rate of adverse drug reactions as well as inappropriate clinical monitoring.

Chronic use of benzodiazepines among older adults

OBJECTIVE To analyze the perception of and motivation for the chronic use of benzodiazepine among older adults. METHODS A qualitative study was conducted on 22 older adults living in Bambuí, MG, Southeastern Brazil, who were taking benzodiazepines and had the clinical and cognitive ability to respond to interview questions. The collected data were analyzed on the basis of the “signs, meanings, and actions” model. RESULTS The main reasons pointed out for the use of benzodiazepines were “nervousness”, “sleep problems”, and “worry” due to family and financial problems, everyday problems, and existential difficulties. None of the interviewees said that they used benzodiazepines in a dose higher than that recommended or had been warned by health professionals about any risks of their continuous use. Different strategies were used to obtain the prescription for the medication, and any physician would prescribe it, indicating that a bond was established with the drug and not with the health professional or healthcare service. Obtaining and consuming the medication turned into a crucial issue because benzodiazepine assumes the status of an essential food, which leads users to not think but sleep. It causes a feeling of relief from their problems such as awareness of human finitude and fragility, existential difficulties, and family problems. CONCLUSIONS Benzodiazepine assumes the characteristics of polyvalence among older adults, which extrapolate specific clinical indications, and of essentiality to deal with life’s problems in old age. Although it relieves the “nerves”, the chronic use of benzodiazepines buffers suffering and prevents older adults from going through the suffering. This shows important difficulties in the organization and planning of strategies that are necessary for minimizing the chronic use in this population.

Problems in the regulatory policy of the drug market

OBJECTIVE Analyze the implementation of drug price regulation policy by the Drug Market Regulation Chamber.METHODS This is an interview-based study, which was undertaken in 2012, using semi-structured questionnaires with social actors from the pharmaceutical market, the pharmaceuticals industry, consumers and the regulatory agency. In addition, drug prices were compiled based on surveys conducted in the state of Sao Paulo, at the point of sale, between February 2009 and May 2012.RESULTS The mean drug prices charged at the point of sale (pharmacies) were well below the maximum price to the consumer, compared with many drugs sold in Brazil. Between 2009 and 2012, 44 of the 129 prices, corresponding to 99 drugs listed in the database of compiled prices, showed a variation of more than 20.0% in the mean prices at the point of sale and the maximum price to the consumer. In addition, many laboratories have refused to apply the price adequacy coefficient in their sales to government agencies.CONCLUSIONS The regulation implemented by the pharmaceutical market regulator was unable to significantly control prices of marketed drugs, without succeeding to push them to levels lower than those determined by the pharmaceutical industry and failing, therefore, in its objective to promote pharmaceutical support for the public. It is necessary reconstruct the regulatory law to allow market prices to be reduced by the regulator as well as institutional strengthen this government body.

Stability of Schistosoma mansoni progeny to antischistosomal drugs

The susceptibility of the MAP Brazilian strain (F1 to F5 progenies) of S. mansoni to four antischistosomal drugs has been reported in a previous study. In the present investigation, progeny F14 of the same strain, was tested for stability to the same 4 drugs. A new medication, Oltipraz (35,972 RP), was added to the study. Five groups of 12 mice infected with cercariae by tail immersion were treated with hycanthone, oxamniquine, niridazole, praziquantel and Oltipraz. An untreated group was used as control. Schistosomal activity was assessed by the localization of worms in the portal vein system, by oogram changes, and percentage of parasite reduction. The stability of the susceptibility of progeny F14 did not change in relation to generations F1 to F5; the progeny was resistant to hycanthone and oxamniquine; but sensitive to niridazole, praziquantel and Oltipraz. We emphasize the importance of the phenomenon of resistance of the worm in view of the fact that oxamniquine has been widely used in Brazilian areas where mansonic schistosomiasis is endemic.

Schistosoma mansoni: effects of anesthetics and antimonial drugs on worm shift in the mouse

Mice experimentally infected with Schistosoma mansoni were injected with sodium thiopental or sodium antimonyl gluconate (Triostib R), or submitted to halothane inhalation, with or without a previous injection of thiopental. Data obtained showed that halothane and thiopental induce worm shift to the liver (99 and 76%, respectively). Sodium gluconate and antimonium (Triostib R) shifted 52% of worms towards the liver. These results seem to indicate that the use of antimonium would be unnecessary, when surgical removal of schistosomules is carried out through the extracorporeal filtration technique, in patients with portal hypertension.