Warfarin: pharmacological profile and drug interactions with antidepressants / Varfarina: perfil farmacológico e interações medicamentosas com antidepressivos

Oral anticoagulants are among the drugs with the greatest number of drug interactions. The concomitant use of several medications is a common practice in patients with cardiovascular problems, who often also present with depression; therefore, the probability of an interaction occurring between warfarin and the antidepressants is high, and may result in increased or decreased anticoagulant activity. Since the possible interactions between these two classes of drugs have been poorly explored in literature, with a risk to the patients who use them, we reviewed the pharmacology of warfarin and its possible interactions with antidepressants. Of the antidepressants analyzed, those that showed relevant effects on the interaction with warfarin were, in decreasing order: paroxetine, venlafaxine, fluoxetine, and duloxetine.

Os anticoagulantes orais estão entre as drogas com maior número de interações medicamentosas. O uso concomitante de vários medicamentos é uma prática comum em pacientes com problemas cardiovasculares, os quais frequentemente também apresentam depressão; assim, a probabilidade de ocorrer alguma interação entre a varfarina e os antidepressivos é bem expressiva, podendo resultar em um aumento ou uma diminuição da atividade anticoagulante. Como as possíveis interações entre essas duas classes de medicamentos se mostraram pouco exploradas na literatura, com risco aos pacientes que fazem uso delas, revisamos a farmacologia da varfarina e suas possíveis interações com antidepressivos. Dos antidepressivos analisados, os que apresentaram efeitos relevantes na interação com a varfarina foram, em ordem decrescente: paroxetina, venlafaxina, fluoxetina e duloxetina.

The effects of antidepressants and pilocarpine on rat parotid glands: an immunohistochemical study

OBJECTIVES: To evaluate the effects of antidepressants and pilocarpine on the quantity of myoepithelial cells and on the proliferation index of the epithelial cells of rat parotid glands. INTRODUCTION: Hyposalivation, xerostomia, and alterations in saliva composition are important clinical side effects related to the use of antidepressants. METHODS: Ninety male Wistar rats were allocated to nine groups. The control groups received saline for 30 (group C30) or 60 days (group C60) or pilocarpine for 60 days (group Pilo). The experimental groups were administered fluoxetine (group F30) or venlafaxine for 30 days (group V30); fluoxetine (group FS60) or venlafaxine (group VS60) with saline for 60 days; or fluoxetine (group FP60) or venlafaxine (group VP60) with pilocarpine for 60 days. Parotid gland specimens were processed, and the immunohistochemical expression of calponin and proliferating cell nuclear anti-antigen on the myoepithelial and parenchymal cells, respectively, was evaluated. Analysis of variance (ANOVA), Tukey HSD and Games-Howell tests were applied to detect differences among groups (p<0.05). RESULTS: Compared with the controls, chronic exposure to antidepressants was associated with an increase in the number of positively stained cells for calponin. In addition, venlafaxine administration for 30 days was associated with an increase in the number of positively stained cells for proliferating cell nuclear anti-antigen. Fluoxetine and pilocarpine (group FP60) induced a significant decrease in the number of positively stained cells for calponin compared with all other groups. CONCLUSIONS: The number of positively stained cells for calponin increased after chronic administration of antidepressants. The proliferation index of the epithelial cells of rat parotid glands was not altered by the use of antidepressants for 60 days.

Effectiveness of three solvents and two associations of solvents on gutta-percha and resilon

This study evaluated the effectiveness of 3 solvents (Citrol orange oil, Eucalyptol and Tetrachloroethylene) and 2 associations of solvents (Citrol orange oil+Tetrachloroethylene and Eucalyptol+Tetrachloroethylene) on 3 types of gutta-percha (conventional, thermoplastic and EndoREZ) and Resilon. Ten discs (10 mm diameter x 1 mm thick) from each material were prepared using standard metallic molds. Each specimen was weighed to determinate its initial mass. The specimens were immersed in the solvents for 10 min, followed by immersion in distilled water for 20 min, and were then reweighed to obtain the final mass. The mean weight loss determined the solvent capacity. Data were analyzed by ANOVA and Tukey's test at 5 percent significance level. Tetrachloroethylene was the most effective on conventional gutta-percha (p<0.05). Tetrachloroethylene was also the most effective on thermoplastic gutta-percha, but it was not significantly different (p>0.05) from Eucalyptol+Tetrachloroethylene, Citrol+Tetrachloroethylene, and Citrol. All solvents and associations presented little effectiveness on Resilon. The association Eucalyptol+Tetrachloroethylene was the most effective on EndoREZ, but it did not differ significantly (p>0.05) from Citrol+Tetrachloroethylene and Tetrachloroethylene. All evaluated substances presented solvent action. Tetrachloroethylene improved the effectiveness of both Citrol and Eucalyptol.

Este estudo avaliou a efetividade de 3 solventes (Citrol, Eucaliptol e Tetracloroetileno) e 2 associações (Citrol+Tetracloroetileno e Eucaliptol+Tetracloroetileno) sobre 3 tipos de guta-percha (convencional, termoplástica e EndoREZ) e Resilon. Dez discos (10 mm x 1 mm) de cada material foram preparados utilizando moldes metálicos. Cada espécime foi pesado para determinar a massa inicial. Os mesmos foram imersos nas soluções testadas por 10 min e em água destilada por 20 min. Os espécimes foram novamente pesados, agora para determinar a massa final. A perda média de peso determinou a capacidade solvente. Os dados foram analisados pelos testes ANOVA e Tukey. O tetracloroetileno foi o mais efetivo sobre a guta-percha convencional (p<0,05). Ele também foi o mais efetivo sobre a guta-percha termoplástica, mas sem diferença significativa para o Eucaliptol+Tetracloroetileno, Citrol+Tetracloroetileno e o Citrol (p>0,05). Todos os solventes e associações apresentaram pequena ação sobre o Resilon. A associação Eucaliptol+Tetracloroetileno obteve o melhor resultado sobre o EndoREZ, mas sem diferença significativa para o Citrol+Tetracloroetileno e o Tetracloroetileno (p>0,05). Todas as soluções apresentam ação solvente. O Tetracloroetileno melhorou a efetividade do Citrol e do Eucaliptol.

1.8 cineole decreases gastric compliance in anesthetized rats

PURPOSE: To study the effect of 1,8 cineoleee components of the essencial oil of Croton nepetaefolius - plant of North-East of Brasil, used in the popular medicine for riots of the gastrointestinal tract - on the motor behavior of the gut of Wistar rats. METHODS: Used 16 male animals under jejun of 24h weighing 300-350g. The effect of 1.8 cineoleee (1 or 3mg/Kg) on gastric compliance had been lead in anaesthetized rats. The variations of the gastric volume (GV), had been measured by plethysmography, while AP, HR and CVP had been monitored continuously by a digital system of data acquisition. RESULTS: Observe reduction of the GV, which was significant on 30, 40, 50 and 60min after treatment (2.0±0.1; 1.9±0.1; 1.8±0.1 and 1.7±0.1mL, versus 2.1±0.2mL). The AP presented significant fall after the administration of 1.8 cineoleee, remaining thus during 60min of monitorization (87.9±7.7; 87.6±7.1; 87.9±6.4; 87.8±5.7; 86.0±5.5 and 87.7±6.0mmHg, respectively versus 94.4±6.2 mmHg), as well as the HR (366.3±13.4; 361.7±11.5; 357.3±10.4; 353.0±10.4; 348.3±11.1 and 350.4±13.7bpm, respectively versus 395.2±11.1bpm). The CVP did not suffer significant variations after treatment. CONCLUSION: Observe the 1.8 cineoleee reduces the gastric compliance in anaesthetized rats besides presenting effect hipotensor and bradicardic; probably for direct action on the gastrointestinal and vascular smooth muscel and moduling the autonomic nervous system.

OBJETIVO: Estudar o efeito do 1.8 cineol, componente do Cróton nepetaefolius (planta do Nordeste) comumente usada na medicina popular para distúrbios do trato gastrintestinal (TGI), sobre o comportamento motor do TGI de ratos Wistar anestesiados. MÉTODOS: Utilizamos 16 animais machos, pesando entre 300 a 350g. Os estudos de complacência gástrica foram conduzidos em animais sob jejum de 24h. As variações do volume gástrico (VG), foram medidas por pletismografia, enquanto a PA, FC e PVC foram monitoradas continuamente por um sistema digital de aquisição de dados. RESULTADOS: Observamos diminuição do VG, o qual foi significativo aos 30, 40, 50 e 60min após o tratamento com 1.8 cineol quando comparado ao perído basal (2,0±0,1; 1,9±0,1; 1,8±0,1 e 1,7±0,1mL, vs 2,1±0,2mL). A PA apresentou queda significativa após a administração de 1.8 cineol, mantendo-se assim durante os 60min de monitoração (87,9±7,7; 87,6±7,1; 87,9±6,4; 87,8±5,7; 86,0±5,5 e 87,7±6,0mmHg, respectivamente vs 94,4±6,2; mmHg), bem como a FC (366,3±13,4; 361,7±11,5; 357,3±10,4; 353,0±10,4; 348,3±11,1 e 350,4±13,7bpm respectivamente vs 395,2±11,1bpm). Já a PVC não sofreu variações significativas durante após o tratamento. CONCLUSÃO: O 1.8 cineol diminui a complacência gástrica em ratos anestesiados além de apresentar efeitos hipotensor e bradicárdico; provavelmente por ação direta sobre a musculatura lisa gastrintestinal e vascular e modulação do sistema nervoso autônomo.

Effect of escitalopram and venlafaxine on seizure score and lipid peroxidation in mice receiving carbamazepine antiepileptic therapy

The frequent co-existence of depression in epileptic patients raises the issue of simultaneous use of antidepressants along with anti-epileptic drugs in management of such cases. However, it is necessary to evaluate the safety of these antiepileptic/antidepressant drug combinations. The present study investigates the effect of either antidepressant; escitalopram [selective serotonin reuptake inhibitor, SSRI] or venlafaxine [serotonin/noradrenaline reuptake inhibitor, SNRI], administered alone or in combination, with the conventional antiepileptic drug carbamazepine on chemo-convulsions induced by picrotoxin. In addition, the effect of both antidepressants on lipid peroxidation, as an assumable cause of neuro-degenration in epilepsy, was studied in a model of chronic restraint in mice. The results show enhancement of seizure severity with significant increase in lipid peroxidation upon escitalopram treatment whether alone or in combination with carbamzepine. On the other hand, venlafaxine, administered alone or in combination with carbamazepine, provided significant protection against picrotoxin-induced convulsions as well as lipid peroxidation favoring its application in management of epilepsy-depression co-morbidities

Eucalyptol, an essential oil, reduces contractile activity in rat cardiac muscle

Eucalyptol is an essential oil that relaxes bronchial and vascular smooth muscle although its direct actions on isolated myocardium have not been reported. We investigated a putative negative inotropic effect of the oil on left ventricular papillary muscles from male Wistar rats weighing 250 to 300 g, as well as its effects on isometric force, rate of force development, time parameters, post-rest potentiation, positive inotropic interventions produced by Ca2+ and isoproterenol, and on tetanic tension. The effects of 0.3 mM eucalyptol on myosin ATPase activity were also investigated. Eucalyptol (0.003 to 0.3 mM) reduced isometric tension, the rate of force development and time parameters. The oil reduced the force developed by steady-state contractions (50 percent at 0.3 mM) but did not alter sarcoplasmic reticulum function or post-rest contractions and produced a progressive increase in relative potentiation. Increased extracellular Ca2+ concentration (0.62 to 5 mM) and isoproterenol (20 nM) administration counteracted the negative inotropic effects of the oil. The activity of the contractile machinery evaluated by tetanic force development was reduced by 30 to 50 percent but myosin ATPase activity was not affected by eucalyptol (0.3 mM), supporting the idea of a reduction of sarcolemmal Ca2+ influx. The present results suggest that eucalyptol depresses force development, probably acting as a calcium channel blocker.

Reversible chemical sterilization: effects of cyclohexanol administration on the testes and epididymides of male rabbit.

Cyclohexanol administration (25 mg/kg/day orally for 40 days) produced a brief period of infertility in rabbits by inhibiting the process of spermatogenesis at the spermatocyte and spermatid levels. Seminiferous tubule and Leydig cell nuclear dimensions were reduced. The lumen of epididymides and ductus deferens were devoid of spermatozoa. Cyclohexanol administration reduced the concentrations of RNA, protein, sialic acid and glycogen in the testes and epididymides, whereas the total cholesterol concentration of the testes was elevated. Depletion of adrenal ascorbic acid was conspicuous. Moderate elevation of serum cholesterol, phospholipids, triglycerides, bilirubin, and pyruvate transaminase were recorded. Histopathological examination of liver did not show any damage. Leydig cell impairment and decreased production of RNA and sialic acid in the testes returned to subnormal values after cessation of cyclohexanol treatment for 70 days. Normal spermatogenesis was seen after 10 weeks of recovery period.