RESUMO
OBJECTIVE: To assess through a systematic review of the literature if the practice of splitting tablets containing psychoactive/psychotropic medications for medical or economic reasons would result in the expected doses. DATA SOURCES: A MEDLINE and PsycInfo comprehensive search of English-language publications from January 1999 to December 2015 was conducted using the terms describing tablet splitting (tablet splitting, split tablets, tablet subdivision, divided tablets, and half tablets) and psychoactive substances (psychoactive medicines, psychotropic medicines, antidepressants, anxiolytics, anticonvulsants, antipsychotics, and antiparkinsonian agents). An additional supplementary search included the references from the articles found. STUDY SELECTION/DATA EXTRACTION: Studies were included if splitting content was directly related to psychoactive medications and examined the effect of tablet splitting on drug uniformity, weight uniformity, and adherence of psychoactive drugs. Articles were systematically reviewed and examined regarding the study design, methodology, and results of the study. A total of 125 articles were screened, and 13 were selected. RESULTS: Tablet splitting implications are extensive, yet substantial deviations from the ideal weight, potency, and dose uniformity are more prone to be important to patient safety. The uneven division of tablets might result in the administration of different doses than what was prescribed, causing under- or overdosing, which might be relevant depending on the drug. In 55% of the cases, splitting psychoactive drugs was satisfactory. CONCLUSIONS: It cannot be generalized that splitting psychoactive drugs compromises dose accuracy, thus tablet splitting might still be employed in cases in which the advantages outweigh the disadvantages. It is recommended that alternatives be adopted to prevent the disadvantages related to tablet splitting.
Assuntos
Psicotrópicos/administração & dosagem , Humanos , Psicotrópicos/efeitos adversos , Psicotrópicos/economia , ComprimidosRESUMO
Obstructive sleep apnea (OSA) is a multifactorial sleep disorder associated with an increased risk of cardiovascular mortality and morbidity. Several mechanisms have been proposed to explain the association between OSA and cardiovascular dysfunction. One of the proposed mechanisms is an inflammatory response to OSA mediated by tumor necrosis factor (TNF-α). Patients with OSA have higher plasma, serum, and intracellular levels of TNF-α, which may be reduced after apnea treatment with continuous positive airway pressure (CPAP). Because TNF-α plays an important role in OSA related cardiovascular morbidity, the present review aims to identify other preventive measures, in addition to CPAP, that may minimize the inflammatory process in OSA and consequently the risk of premature death due to cardiovascular dysfunction. Thus, we hypothesized that a nutritional immunology profile, i.e., supplementation with omega-3 fatty acids, may be valuable for individuals with OSA.
RESUMO
Cocaine addiction is a public health issue in many countries, stressing the need for more effective treatments. As all drugs of abuse, cocaine acts on the brain reward system, increasing dopamine (DA) levels. Other neurotransmitters such as acetylcholine (ACh) are involved in the mechanisms underlying the development and the maintenance of cocaine addiction. ACh plays an important role in learning and memory processes and also regulates DA in some specific regions of the central nervous system. The present study investigated the effects of biperiden, a muscarinic cholinergic (mACh) antagonist in two animal models: conditioned place preference (CPP) and behavioral sensitization. Male C57BL/6J mice were used in both studies. The CPP protocol was unbiased and carried out in three phases: habituation, conditioning and testing. For conditioning, cocaine was injected at a dose of 10mg/kg in eight 15 min-sessions. The treatment with biperiden (doses of 0.1, 1 and 10 mg/kg) was made 30 min prior to the testing session. For behavioral sensitization development, cocaine was administered at the dose of 10 mg/kg for 10 days. After sensitization, two challenges were performed: saline and cocaine (5 mg/kg). Biperiden (10 mg/kg) was administered 30 min before the cocaine challenge. At the dose of 10 mg/kg, biperiden blocked the cocaine-CPP expression, suggesting an effect on conditioned memory retrieval. However, the same dose potentiated the expression of behavioral sensitization, suggesting an increase in DA release, probably in the NAc. Biperiden, as other mACh antagonists, may be a promising drug for the pharmacologic treatment of cocaine addiction.
Assuntos
Biperideno/farmacologia , Cocaína/farmacologia , Condicionamento Operante/efeitos dos fármacos , Inibidores da Captação de Dopamina/farmacologia , Antagonistas Muscarínicos/farmacologia , Receptor Muscarínico M1/antagonistas & inibidores , Animais , Aprendizagem por Associação/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Masculino , CamundongosRESUMO
Cocaine is a psychotropic drug with a high potential for abuse due to its euphoric effects. Efforts to develop medications for the treatment of cocaine dependence have not been clinically successful. Some studies using animal models have shown positive effects of dopaminergic agents such as partial agonists of the dopamine D1 receptor. Thus, this study aimed to examine the effect of the dopamine D1 receptor partial agonist SKF 38393 on cocaine craving. Adult male C57BL/6J mice were injected with cocaine for 10 days in a conditioned place preference apparatus using a biased procedure and subsequently treated for three consecutive days with SKF 38393. The results showed that SKF 38393 was able to block the preference of cocaine-conditioned animals for the compartment paired with the drug without showing effects on locomotor activity. The results of this study suggest that partial activation of D1 dopamine receptors may be necessary for the development of pharmacotherapies for cocaine addiction.
Assuntos
2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/farmacologia , Aprendizagem por Associação/efeitos dos fármacos , Cocaína/farmacologia , Condicionamento Psicológico/efeitos dos fármacos , Agonistas de Dopamina/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Receptores de Dopamina D1/agonistasRESUMO
It is well-known that cocaine dependence is a public health issue, and several studies stress the need to look for new and more effective treatments. Although the mesolimbic dopamine (DA) system, which originates in the ventral tegmental area (VTA) and projects to several forebrain structures, is known to be critically involved in the neurobiology of cocaine dependence, acetylcholine (ACh) has also been shown to play an important role in cocaine dependence via its action on this reward system. ACh is also important in the formation of hippocampal memory associated with appetitive behavior. Thus, the aim of this study was to evaluate the effect of biperiden, an ACh antagonist with high affinity for muscarinic M1 type receptors, on the acquisition of cocaine-conditioned place preference (CPP) in mice. The cocaine and biperiden were dissolved in sterile saline and were administered intraperitoneally at a dose of 10mg/kg. The conditioning regime was 8 days long, and the cholinergic antagonist was given immediately at the end of each conditioning session. The test for CPP occurred 24h after the last session. The results showed that animals treated with biperiden spent significantly less time in the cocaine-paired compartment than did the ones treated with saline. This finding represents a reduction in the consolidation of cocaine-induced CPP. One hypothesis that could explain this outcome focuses on the action of cholinergic antagonists on the consolidation of contextual memories. The amnesic effect of M1 antagonists on aversive tasks and on morphine CPP has been demonstrated when administered before the training or the conditioning session. The present study highlights the possibility of impairment in the acquisition of an appetitive memory, even when the cholinergic drug is administered after the conditioning session. This protocol also rejects the possibility of performance disturbance and suggests a possible pharmacological tool in the treatment of cocaine dependence.
Assuntos
Aprendizagem por Associação/efeitos dos fármacos , Biperideno/farmacologia , Cocaína/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Memória/efeitos dos fármacos , Antagonistas Muscarínicos/farmacologia , Receptor Muscarínico M1/antagonistas & inibidores , Animais , Condicionamento Operante/efeitos dos fármacos , Masculino , CamundongosRESUMO
Recent data have shown an association between polyunsaturated fatty acid and depression. This study examined the effect of the supplementation with n-6 fatty acid on the behavior of rats treated with imipramine and submitted to the Forced Swimming Test (FST). Non-supplemented imipramine-treated rats presented a significant reduction of immobility time in the FST whereas n-6 fatty acid-supplemented rats showed a significantly higher immobility time. Imipramine significantly increased norepinephrine plasma concentrations in the two groups. These results show that the diet supplemented with n-6 fatty acid altered the behavior of the animals in the FST, inhibiting the imipramine effect.