Effect of atenolol pre-treatment in heart damage in a model of intestinal ischemia-reperfusion

Abstract Purpose: To investigate the effects of atenolol in inflammatory mediator and oxidative stress in a myocardial injury by intestinal ischemia/reperfusion in rat model. Methods: Adult Wistar male rats were randomly (n=8), anesthetized and divided in: Sham: submitted to operation only; group SS+IR: intravenous saline infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); group AT+IR: intravenous atenolol infusion (2 mg/kg) following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); and group AT+I+AT+R: intravenous atenolol infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and in the time 45 minutes other atenolol doses were administrated and the artery was open for 120 minutes (reperfusion), all animals were submitted to muscular relaxation for mechanical ventilation. In the end of experiment the animals were euthanized and the hearts tissue were morphology analyzed by histology and malondialdehyde by ELISA, and the plasma were analyzed for tumor necrosis factor-alpha by ELISA. Results: The group SS+IR demonstrated the higher malondialdehyde levels when compared with the atenolol treated-groups (p=0.001) in the heart tissue. The tumor necrosis factor-alpha level in plasma decrease in the treated groups when compared with SS+IR group (p=0.001). Histology analyses demonstrate pyknosis, edema, cellular vacuolization, presence of inflammatory infiltrate and band contraction in the heart tissue of the rats. Conclusion: Atenolol significantly reduce the degree of cardiac damage after intestinal ischemia-reperfusion.

Solid lipid nanoparticles of irbesartan: preparation, characterization, optimization and pharmacokinetic studies

ABSTRACT Irbesartan is an antihypertensive with limited bioavailability and solid lipid nanoparticles (SLN) is one of the approaches to improve bioavailability. Solid lipid nanoparticles were prepared using glyceryl monostearate by solvent emulsification method followed by probe sonication. Irbesartan loaded SLNs were characterized and optimized by parameters like particle size, zeta potential, surface morphology entrapment efficiency and in vitro release. The optimized formulation was then further evaluated for the pharmacokinetic studies in Wistar rats. Irbesartan-loaded SLN of particle size 523.7 nm and 73.8% entrapment efficiency showed good bioavailability in Wistar rats and also showed optimum stability in the studies. The SLN prepared using glyceryl monostearate by solvent emulsification method leads to improve bioavailability of the drug.

Metanálise de estudos de bioequivalência: a intercambiabilidade de genéricos e similares que contêm hidroclorotiazida é possível, mas não àqueles com maleato de enalapril / Meta-analysis for bioequivalence studies: interchangeability of generic drugs and similar containing hydrochlorothiazide is possible but not with enalapril maleate

INTRODUÇÃO: O programa de genéricos no Brasil propiciou maior acesso da população a medicamentos. Para garantir a intercambiabilidade entre medicamentos referência e genérico ou similar, é necessário que eles sejam bioequivalentes. Com o crescimento do número de medicamentos genéricos, é comum que pacientes o substituam por outro genérico ou similar. Contudo, essa troca pode não garantir a manutenção da bioequivalência. Para avaliar a segurança na intercambiabilidade entre diferentes genéricos e similares com hidroclorotiazida e maleato de enalapril, foi realizada metanálise de vários estudos de bioequivalência que utilizaram esses medicamentos. MÉTODOS: Foram utilizados dados provenientes de estudos de bioequivalência de genéricos e similares registrados pela Agência Nacional de Vigilância Sanitária (Anvisa). A compatibilidade dos dados de cada um dos estudos foi analisada, e a determinação de um intervalo de confiança para as diferenças entre as médias dos parâmetros farmacocinéticos, área sob a curva (ASC) e concentração plasmática máxima (Cmáx ), foi feita para cada estudo por meio da metanálise. RESULTADOS: A intercambiabilidade entre as combinações dos três produtos com Hidroclorotiazida foi confirmada com base nos intervalos de confiança obtidos. Para os medicamentos com maleato de enalapril, a intercambiabilidade não foi confirmada em 50 por cento das comparações estudadas dos produtos. CONCLUSÃO: A intercambiabilidade foi comprovada entre os três produtos com hidroclorotiazida. No entanto, para o maleato de enalapril, metade dos produtos estudados não é intercambiável, uma vez que não contempla os intervalos preconizados pelos testes de bioequivalência; portanto, a resposta farmacocinética e, por conseguinte, a efetividade do medicamento podem ser alteradas.

INTRODUCTION: The generic drugs program provided a better population's access to medicines. To ensure interchangeability between a brand-name and generic or similar drugs is necessary that they are bioequivalent. With the growing number of generic drugs, it is common for patients to replace a generic to another or one similar. However, this exchange can not guarantee the maintenance of bioequivalence. To evaluate the safety interchangeability between different generic and similar drugs with hydrochlorothiazide and enalapril maleate, a meta-analysis was carried out with several bioequivalence studies with these drugs. METHODS: Data from bioequivalence of generic and similar drugs approved by the National Health Surveillance Agency (Anvisa) (drug regulatory agency in Brazil) were used. The compatibility of data from each study was analyzed and the determination of a confidence interval for the differences between the means of pharmacokinetic parameters, area under the curve (ASC0-t) and maximum plasma concentration (Cmax), was made for each study by meta-analysis. RESULTS: The interchangeability between the combinations of the three products with hydrochlorothiazide was confirmed based on the obtained confidence intervals. For the drugs studied with enalapril maleate interchangeability has not been confirmed for 50 percent of the product comparisons. CONCLUSION: The exchange was established between the three products with hydrochlorothiazide. However, for the enalapril maleate half of the products studied are not interchangeable, considering they do not match the established intervals for bioequivalence tests, so the pharmacokinetics behavior and thus the effectiveness of the product may be changed.

Hipertensão no idoso: tratamento / Hypertension in the elderly: treatment

O tratamento da hipertensão no paciente idoso deve incluir mudanças no estilo de vida, e entre elas a perda de peso e a restrição de sódio são as mais eficazes. Quando houver necessidade de anti-hipertensivo, a dose inicial deve ser metade da utilizada no paciente jovem, e a pressão arterial deve ser gradualmente reduzida. O diurético do tipo tiazídico é recomendado como terapia inicial, embora outras classes de anti-hipertensivos sejam eficazes e seguras, a menos que haja indicação de agente específico para comorbidade associada. No paciente com hipertensão sistólica isolada, o tratamento com diurético tiazídico ou antagonista de canais de cálcio do tipo diidropiridínico mostrou ser eficaz na redução de eventos cardiovasculares. Alfabloqueador pode ser adicionado à terapia inicial, mas não como monoterapia. A efetividade do betabloqueador no idoso hipertenso somente tem sido questionada como tratamento inicial. Poucos pacientes são controlados com monoterapia e a combinação de anti-hipertensivos tem boa aplicação. A recomendação para pressão arterial alvo no idoso hipertenso não difere da do jovem, ou seja, valores menores que 140/90mmHg - a menos que o paciente seja diabético ou renal, casos em que a meta é inferior a 130/80mmHg. O tratamento do paciente com hipertensão sistólica isolada deve-se ter precaução para não se reduzir a diastólica abaixo de 55mmHg. No hipertenso muito idoso, acima de 80 anos, o tratamento anti-hipertensivo reduz eventos cardiovasculares e não deve diferir do daquele entre 60-80 anos, em que a medicação de escolha passa pelo diurético tipo tiazídico. Alguns dados atuais apontam na direção de que o declínio cognitivo pode ser prevenido com o uso de anti-hipertensivos, mas essa área necessita de mais estudos. Apesar de o efeito do tratamento de reposição hormonal sobre os níveis pressônicos ser discreto, há necessidade de monitoração cuidadosa da pressão arterial na mulher na pós-menopausa que utiliza essa terapia. A reposição ...

Therapy in older individuals with hypertension should include lifestyle modifications, wherever weight loss and restriction of sodium is more efficient. When antihypertensive therapy is indicated, the starting dose of medication should be often one half of that used in the younger patients and the blood pressure should be reduced more gradually. Thiazide-type diureticis recommended as initial therapy, when there is no compelling indication for another agent, although other classes of antihypertensives are safe and effective. In the patient with isolated systolic hypertension, initial treatment with thiazide-type diuretic or a dihydropyridine calcium channels blocker has been shown to improve outcomes. Alfa-blocker therapy can be added to the existing therapy, but not be used as monotherapy. Effectiveness of traditional betablockers use as initial therapy in elderly hipertensive patients has been questioned. Few patients are controlled by initial monotherapy and combination therapy is often required. The minimum recomended target for elderly patients with hypertension, the same for younger, is less than 140/90mmHg, whereas in patients with diabetes or renal disease, the goal is lower than 130/80mmHg. Patients with isolated systolic hypertension should be treated to a target lower than 140mmHg, although more data on those with baseline systolic of 140 to 159mmHg are required. When treating isolated systolic hypertension, one should exercise caution in lowering diastolic blood pressure less than 55mmHg. In hypertension in very old, over 80 years, the antihypertensive therapy reduces cardiovascular outcomes and not differ of that between 60-80 years in which the medication of choice still thiazide-type diuretic. Some current data suggest that cognitive decline can be prevented by use antihypertensive tharapy, but this area nees more studies. In spite of the effect of hormone replacement therapy on blood pressure are usually small, it should be monitored...

[Enhancement of eprosartan mesylate dissolution from immediate release tablets in vitro]

Eprosartan mesylate is the latest angiotensin II receptor antagonist approved by FDA. It is used for the treatment of hypertension. It has a low oral bioavailabilty not more than 13%. This study aims to enhance eprosartan mesylate release from immediate release oral tablet by adding solubility enhancers to the formula of the marketed tablet, then comparing dissolution profiles. The formula of the studied tablet was determined by preparing a formula similar to that of the marketed tablet in its physical properties and dissolution profiles. Eprosartan mesylate release from the prepared tablet and the marketed tabled was studied in different dissolution media: HCI acidic medium pH 1.2, phosphate buffer pH 6.8, and phosphate buffer pH 7.5. Results were compared. Spectrophotometer was used to titrate the amount of active ingredient release in the dissolution medium. Titration method by spectrophotometry was validated. Effect of addition of solubility enhancers in various percentages to the formula on eprosartan mesylate release was studied. Tween 80, gypsophila saponin, L-arginin, citric acid, and sodium bicarbonate were used. Statistical study was performed using T-Test and one-way ANOVA Test to compare means of samples at a confidence level of 5%. Consequent Dunnett's Test was used to compare with control sample. The highest release of eprosartan mesylate from the prepared tablet was noted successively in the phosphate buffer pH 7.5, HCI acidic medium pH 1.2, and phosphate buffer pH 6.8. One-way ANOVA Test did not show any statistically significant difference [p>0.05]. Using 6% of Tween 80, 6% of gypsophila saponinin, or L-arginin in a molar ratio 1:3 resulted in minor improvement in dissolution rate 0.05]. Addition of studied solubility enhancers to eprosartan mesylate tablet did not result in statistically significant imrovement of drug release

Pharmacokinetics and bioequivalence study of the two 20-mg quinapril hydrochloride tablet formulations in healthy Thai male volunteers.

OBJECTIVE: To determine the pharmacokinetics and bioequivalence of two 20-mg quinapril hydrochloride tablet preparations; Quinaril (The Biolab Ltd, Bangkok, Thailand) as the test and Accupril as the reference. MATERIAL AND METHOD: The present study was a single dose, randomized two-period crossover design conducted in 24 healthy volunteers under fasting conditions with a 7-day washout period. Serial plasma concentrations of quinapril and its active metabolite quinaprilat up to 24 h after dosing were determined by HPLC with UV detection. The pharmacokinetic parameters were analyzed by noncompartmental analysis and the ANOVA was carried out using logarithmically transformed data of the AUC and C as well as untransformed T(max). RESULTS: There were no significant differences between the two preparations regarding the T(max) of quinapril and quinaprilat and their median T(max) were 0.5 h and 1.4 - 1.5 h, respectively. The half-life of quinapril (1.2 h) was faster than quinaprilat (1.8-1.9 h) although the volume of distribution (Vd/F) of quinapril (1.1 L/kg) was larger than quinaprilat (0.3 L/kg), however, its clearance rate (CL/F) was faster when compared to quinaprilat (20-26 ml/min/kg vs. 1.7 ml/min/kg). The mean (90% CI) for the ratios Reference/Test of quinapril were 0.99 (0.89-1.10), 0.99 (0.90-1.09) and 1.01 (0.90-1.14), respectively for AUC(0-24), AUC(0-infinity) and C(max). Similarly, the corresponding values for quinaprilat were 0.95 (0.90-1.01), 0.95 (0.90-1.01) and 1.03 (1.00-1.07), respectively. These values were within the bioequivalence range of 0.80 - 1.25, thus, demonstrated the bioequivalence of the two preparations. CONCLUSION: The results of the present study indicated that the two quinapril HCL preparations are bioequivalent and it can be assumed that they are therapeutically equivalent and exchangeable in clinical practice.

Bioequivalence study of four different trademarks of enalapril maleate in spontaneously hypertensive rats

INTRODUCTION: High blood pressure is a systemic disease which has major clinical and psycho-social repercussions, involves a high morbidity-mortality rate and generates high costs for the health system. Its treatment involves the use of antihypertensive drugs, which are commercialized as trademark, generic or similar drugs. PURPOSE: To verify the antihypertensive effect produced by a similar dose of different trademarks of enalapril maleate in spontaneously hypertensive rats (SHR). METHODS: Fifteen mg/kg of enalapril maleate were administered by gavage in 50 SHR rats and their blood pressure was verified through tail plethysmography every three days in a period of 16 days. RESULTS: The group treated with reference drug has shown a significant reduction on blood pressure levels when compared to the control group. Thus, treatments with enalapril maleate of generic, similar-A and similar-B brands have also shown significant reduction on animals' blood pressure. CONCLUSION: The use of generic drug and similars (A and B) drugs in the same doses and for the same period of time has not shown significant difference regarding the reference drug, which suggests that the brands tested are bioequivalent.

INTRODUÇÃO: A hipertensão arterial é uma doença sistêmica que traz grandes repercussões clínicas e psico-sociais, cursa com uma elevada morbi-mortalidade e gera elevados gastos para o sistema de saúde. Seu tratamento envolve a utilização de fármacos anti-hipertensivos, os quais são comercializados como remédios de marca, genéricos ou similares. PURPOSE: Verificar o efeito anti-hipertensivo produzido por dose igualitária de diferentes marcas de maleato de enalapril, em ratos naturalmente hipertensos. MÉTODOS: Foram administrados, por meio de gavagem, 15 mg/kg de maleato de enalapril em 50 ratos naturalmente hipertensos e verificada a pressão arterial, através de pletismografia de cauda, a cada três dias, em um período de 16 dias. RESULTADOS: O grupo testado com o fármaco de referência mostrou uma redução significativa dos níveis pressóricos quando comparado ao grupo controle. Da mesma forma, o tratamento com Maleato de Enalapril da marca genérica e das marcas similar-A e similar-B também produziu redução significativa da pressão arterial dos animais. CONCLUSÃO: A utilização do medicamento genérico e os similares A e B nas doses utilizadas e no tempo de experimentação adotado, não indicou diferença significativa em relação ao fármaco de referência, sugerindo que as marcas testadas são bioequivalentes.

Disposition and tissue distribution of ML12 in rats / 华中科技大学学报（医学）（英德文版）

To investigate the disposition and tissue distribution of ML12 after intravenous (iv) administration in rats, the compound in plasma or in tissue was extracted into ethyl acetate under basic condition and was determined by HPLC after extracted by dilute sulfuric acid. Excitation wavelength and emission wavelength of fluorescence detection were 278 nm and 307 nm, respectively. The data were processed with the software 3P97 to calculate the main pharmaceutical parameters of ML12. At dose of 5 and 10 mg/kg, the elimination of the drug from plasma was found to be kinetically linear, but when the dosage was 20 mg/kg, a non-linear feature was observed. The highest level of ML12 was found in the kidney. Distribution of ML12 after iv administration was extensive and the concentration-time profile was found to be fitted to an open two-compartment model.

S-amlodipine--the 2007 clinical review.

S-amlodipine is the only vaso-active enantiomer of amlodipine. This article reviews the published data in nearly 5000 patients. Randomised controlled trials of S-amlodipine at half the dose of racemate in the treatment of hypertension, have shown it to be as effective as racemic amlodipine. The postmarketing surveillance studies (n = 4089) of S-amlodipine confirmed its antihypertensive efficacy and showed that the incidence of peripheral oedema is negligible with S-amlodipine compared to racemic amlodipine. Further, the patients with peripheral oedema who were switched over from racemic amlodipine to S-amlodipine resolved their oedema associated with the racemate, while sustaining the blood pressure control. Subgroup analyses showed S-amlodipine to be effective and safe in elderly hypertensives and isolated systolic hypertension patients. A clinical study in normotensive angina patients confirmed the anti-anginal efficacy of S-amlodipine at half the dose of racemate. Fixed-dose combinations of S-amlodipine with atenolol and S-amlodipine with hydrochlorothiazide have been shown to be effective and well tolerated in clinical practice. In the light of its efficacy and favourable tolerability profile, S-amlodipine used alone or in combination with other antihypertensive or anti-anginal drugs, is a valuable treatment option in the management of hypertension and angina.

The effect of angiotensin II receptor blocker on peritoneal membrane transports in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: The objective of this study was to examine the effects of angiotensin II receptor blocker (ARB), used as an antihypertensive medication, on peritoneal membrane transporters in continuous ambulatory peritoneal dialysis (CAPD) patients. MATERIAL AND METHOD: Prospective and cross-over experimental study of peritoneal membrane transporters was conducted in 7 CAPD patients with hypertension. All previous antihypertensive drugs had been replaced by candesartan at the dose of 8-16 mg/day to control blood pressure below 140/90 mmHg. Hydralazine, which has no effect on peritoneal membrane transports, was added if the target blood pressure was not achieved. All patients had received candesartan for 12 weeks, then, were retreated with the previous antihypertensive drugs for another 6-week period. The modified peritoneal function tests assessing peritoneal membrane transports were performed at 1) baseline, 2) 6 weeks, 3) 12 weeks following candesartan treatment, and 4) 6 weeks after candesartan withdrawal. RESULTS: The blood pressure target was achieved in all patients and was not different among the 4 periods. The albumin clearance and 4-hour albumin loss were significantly decreased following candesartan treatment (p < 0.05). Both values returned to the high baseline levels after 6 weeks of candesartan withdrawal. There were no significant changes in net ultrafiltration and various small and large solute transports. No adverse effects, including hyperkalemia or increased erythropoietin dosage, had been observed. CONCLUSION: In hypertensive CAPD patients, candesartan could provide nutritional benefit by attenuating peritoneal loss of albumin and provides an effective antihypertensive action. Furthermore, candesartan does not impair other solute transports and net ultrafiltration.

Uso clínico de medicamentos anti-hipertensivos / Clinical use of antihipertensive drugs

O tratamento medicamentoso da hipertensão arterial em associação com medidas não-farmacológicas, visa a reduzir as cifras pressóricas e, primordialmente, a morbidade e mortalidade cardiovasculares.Os medicamentos mais utilizados no tratamento da hipertensão arterial pertencem a cinco classes principais: diuréticos, betabloqueadores, antagonistas dos canais de cálcio, inibidores da enzima conversora da angiotensina e antagonistas do receptor ATI da angiotensina II. Menos comumente, empregam-se medicamentos de outras classes, como bloqueadores alfa-2 adrenérgicos centrais e vaso dilatadores diretos.Neste capítulo são descritos os mecanismos de ação anti-hipertensiva, usos clínicos e indicações preferenciais, reações adversas e contra indicações de cada grupo...

Relative bioavailability study of 20-mg enalapril tablets in healthy male volunteers.

The pharmacokinetic and relative bioavailability studies of 20-mg enalapril tablets, the test product manufactured by Biolab, Thailand compared to the reference product (Merck Sharp & Dohme, USA) was conducted in 14 healthy Thai male volunteers following a single dose, two-period, crossover design. Each subject received 20-mg enalapril tablets of both formulations with a 1-week washout period. Plasma samples collected over a 24-h period after administration were analyzed by LC/MS/MS. Pharmacokinetic parameters were determined by using non-compartmental analysis. Regarding bioequivalence testing, the 90 per cent confidence intervals of Cmax and AUC(0-infinity) ratios (test/reference) of enalapril were 101.8-134.9 per cent and 105.9-121.4 per cent and those of enalaprilat were 104.2-122.3 per cent and 104.5-118.1 per cent. Based on the European bioequivalence guideline, the 90 per cent confidence intervals of Cmax and AUC(0-infinity) ratios of both parent and metabolite forms were within the acceptable ranges of 70-143 per cent and 80-125 per cent, respectively. It was concluded that the test formulation was bioequivalent to the reference formulation and both formulations can be used interchangeably in clinical practice.

Efeito de tratamentos anti-hipertensivos no coração de ratos com inibição crônica da síntese do óxido nítrico: biometria, alometria e estereologia / Antihypertensive drugs treatment effects in rats heart with inhibition of nitric oxide synthesis: biometry, allometry and stereology

Alterações estruturais do miocárdio devidas á inibição da síntese de óxido nítrico e concomitante tratamento com três drogras anti-hipertensivas foram estudadas quantitativamente após de 40 dias do tratamento. Cinco grupo de 10 ratos: Controle, L-NAME, espironolactona, enalapril e verapamil foram estudados. L-NAME foi administrado na dose de 50 mg/kg/dia na água do bebedouro. No 41§ dia de experimentação os ratos foram anestesiados, pesados e sacrificados. A pressão arterial da cauda (PAC) aumentou 76 por cento e 16 por cento nos grupos L-NAME e espironolactona, respectivamente, em comparação ao grupo de controle. A espironolactona, o enalapril e o verapamil foram eficientes em reduzir a PAC nos respectivos grupos (a espironolactona foi menos eficiente na redução da PAC). O volume do coração (VC) foi maior no grupo L-NAME que nos outros grupos, mas não foi diferente entre os grupos L-NAME e espironolactona. O ventrículo esquerdo foi o responsável pelas mudanças no VC. A relação entre o VC e a massa corporal (MC) não foi significativa entre os grupos L-NAME e espironolactona. Porém, esta relação foi alométrica nos grupos controle, enalapril e verapamil. No grupo controle o VC teve uma tendência alométrica positiva em relação a MC, mas nos trupos enalapril e verapamil esta tendência foi alométrica negativa. A hipertrofia cardíaca nestes animais foi prevenida mais eficazmente pelo uso do enalapril e do verapamil do que pela espironolactona. A inibição da síntese do ON provocou modificações no miocárdio e as drogas anti-hipertensivas foram eficientes na prevenção das modificações causadas pela hipertensão e a estereologia quantificou estas alteraçoes. Foram determinadas as densidades de volume dos cardiomiócitos (Vv[c]), intertício cardíaco (Vv[i]), densidade de superfície de cardiomiócitos (Sv[c]) e área transversão média dos cardiomiócitos (A[c]). Ocorreu hipertrofia dos cardiomiócitos vista através do aumento da A[c] que foi 30 por centro maior no grupo L-NAME, 13 por cento nos grupos espironolactona e enalapril. Aos 40 dias ocorrei diminuilão do Vv[c] e aumento do Vv[i] nos animais L-NAME (15 por centro e 24 por centro respectivamente)...

Evaluación de estudios clínicos de recuperación de la función endotelial con fármacos hipotensores

El endotelio cumple un papel crucial en el mantenimiento de la integridad del sistema cardiovascular, a través de sus funciones vasodilatadoras, antitrombóticas y antiaterogénicas. La disfunción endotelial ha sido implicada en la génesis de importantes enfermedades como la hipertensión arterial, la aterosclerosis, la enfermedad arterial coronaria, la insuficiencia cardiaca crónica, la diabetes mellitus, etc. Varios métodos clínicos han sido descritos para valorar la función endotelial; entre los mejor estandarizados están el de la respuesta vasomotora coronaria a la infusión de acetilcolina o bradicinina en arterias de conducción evaluada por pletismografía, y la vasodilatación dependiente de flujo (VDF) en arterias de conducción del antebrazo, valorada por el cambio en el diámetro de la arteria braquial de frente a la hiperemia reactiva, determinado por eco-doppler. En el presente artículo revisamos los diferentes estudios dirigidos a investigar el efecto de diferentes drogas hipotensoras en la recuperación de la función endotelial en pacientes con hipertensión esencial, enfermedad arterial coronaria e insuficiencia cardíaca crónica. Los inhibidores de la enzima convertidora de la angiotensina (ECA-I) son los fármacos que con más consistencia ejercen un efecto beneficioso en la recuperación de la función vasodilatadora dependiente de endotelio. Existen diferencias en la capacidad de mejorar la función endotelial entre los diferentes componentes

Pharmacokinetics and pharmacodynamics of propranolol in hypertensive patients after sublingual administration: systemic availability

The bioavailability of propranolol depends on the degree of liver metabolism. Orally but not intravenously administered propranolol is heavily metabolized. In the present study we assessed the pharmacokinetics and pharmacodynamics of sublingual propranolol. Fourteen severely hypertensive patients (diastolic blood pressure (DBP) =115 mmHg), aged 40 to 66 years, were randomly chosen to receive a single dose of 40 mg propranolol hydrochloride by sublingual or peroral administration. Systolic (SBP) and diastolic (DBP) blood pressures, heart rate (HR) for pharmacodynamics and blood samples for noncompartmental pharmacokinetics were obtained at baseline and at 10,20,30,60 and 120 min after the single dose. Significant reductions in BP and HR were obtained, but differences in these parameters were not observed when sublingual and peroral administrations were compared as follows: SBP (17 vs 18 percent, P=NS), DBP (14 vs 8 percent, P=NS) and HR (22 vs 28 percent, P=NS), respectively. The pharmacokinetic parameters obtained after sublingual or peroral drug administration were: peak plasma concentration (CMAX): 147 + 72 vs 41 + 12 nl/ml, P<0.05; time to reach CMAX (TMAX): 34 + 18 vs 52 + 11 min, P<0.05; biological hall-life (t1/2b): 0.91 + 0.54 vs 2.41 + 1.16 h, P<0.05; area under the curve (AUCT): 245 + 134 vs 79 + 54 ng h(-1) ml(-1), P<0.05; total body clearance (CLT/F):44 + 23 vs 26 + 12 ml min(-1) kg(-1), P=NS. Systemic availability measured by the AUCT ratio indicates that extension of bioavailability was increased 3 times by the sublingual route. Mouth paresthesia was the main adverse effect observed after sublingual administration. Sublingual propranolol administration showed a better pharmacokinetic profile and this route of administration may be an alternative for intravenous or oral administration.

Nefropatía hipertensiva, experiencia de siete años del Hospital General de Ticomán, SS / Hypertensive nephropathy. experience of 7 years of the General Hospital of Ticomán, SS

En un estudio retrospectivo se revisaron los expedientes de los pacientes que ingresaron a nuestro servicio con diagnóstico de nefropatía hipertensiva de enero de 1988 a diciembre de 1994, evaluandose la edad y el sexo del paciente, el timpo de evolución de la hipertensión, la terapéutica empleada y las cifras tensionales previas al tratamiento. No se incluyeron pacientes con diabetes mellitus por la incapacidad de precisar la causa primaria del daño renal. En el periodo estudiado ingresaron 29 pacientes con tal diagnóstico; los factores que encontramos como favorecedores del deterioro renal fueron: ausencia de tratamiento (RR 47), manejo con diuréticos (RR 24.4), uso de betabloqueadores (RR 24). Nuestros resultados concuerdan con lo reportado por otros autores acerca de la presentación del daño renal a pesar del control de las cifras tensionales con diuréticos y/o betabloqueadores, y ponen en tela de juicio su papel organoprotector

Lípidos y lipoproteínas de ayuno y postprandiales durante la administración crónica de fármacos antihipertensivos / Fasting and post-prandial lipids and lipoproteins during chronic administration of antihypertensive drugs

Con el objeto de evaluar el efecto de diversos fármacos antihpertensivos sobre los lípidos de ayuno y la lipemia postprandial, se estudiaron 39 pacientes hipertensos normolipidémicos: 28 hombres y 11 mujeres con edades de 52.3 ñ 9.0 y 58.5 ñ 7.1 años, respectivamente. Después de 4 semanas de administración de placebo se midieron los lípidos de ayuno y se administró una carga de grasa estandarizada, que proporcionó 65 g/m² de superficie corporal, y se cuantificaron los lípidos y lipoproteínas postprandiales cada 3 horas durante 9 horas. A continuación, en forma aleatoria, los pacientes fueron asignados uno de 4 grupos de tratamiento activo: Grupo I (n=10) metoprolol, 100 mg/día; Grupo II (n=9) nicardipina, 90 mg/día; Grupo III (n=11) captopril, 75 mg/día; Grupo IV (n=9) clortalidona, 25 mg/día. Cuatro semanas más tarde se repitieron las cuantificaciones de lípidos y lipoproteínas de ayuno y postplandiales. Los valores de tensión arterial sistólica y diastólica descendieron significativamente en los cuatro grupos estudiados (p<0.05). Las concentraciones de lípidos y lipoproteínas en el ayuno y durante el postprandio no tuvieron cambios significativos. Sin embargo, la lipemia postprandial fue ligeramente menor en tres de los cuatro grupos estudiados (metoprolol, nicardipina y captopril), y no se modificó en los pacientes tratados con clortalidona. Estos resultados confirman que en pacientes hipertensos normolipidémicos la administración de estos fármacos antihipertensivos a dosis bajas, no produce efectos desfavorables en los lípidos de ayuno, y señalan por primera vez, que tampoco afectan la lipemia postprandial.