Design and in vitro evaluation of effervescent gastric floating drug delivery systems of propanolol HCl / Diseño y evaluación in vitro de sistemas de administración de tabletas flotantes gástricas everfescentes de HCl propanolol

The purpose of this research was to develop and evaluate effervescent gastric floating tablets of propranolol HCl. The oral delivery of antihypertensive propranolol HCl was facilitated by preparing an effervescent floating dosage form which could increase its absorption in the stomach by increasing the drug’s gastric residence time. In the present work, effervescent floating tablets were prepared with a hydrophilic carrier such as polyethylene oxide (PEO WSR N 60K and PEO WSR 303) as a release retarding agent and sodium bicarbonate as a gas generating agent. The prepared tablets were evaluated for all their physicochemical properties, in vitro buoyancy, drug release and rate order kinetics. From the results, P9 was selected as an optimized formulation based on their 12 h drug release, minimal floating lag time and maximum total floating time. The optimized formulation followed first order rate kinetics with erosion mechanism. The optimized formulation was characterized with FTIR studies and no interaction between the drug and the polymers were observed.

El propósito de la presente investigación fue desarrollar y evaluar tabletas flotantes, efervescentes de HCL propranolol. La administración oral del antihipertensivo HCL propranolol se facilitó mediante la preparación de una forma de dosificación flotante y efervescente que permitiría su absorción en el estómago, mediante el aumento del tiempo de residencia gástrico de la droga. En el presente trabajo, las tabletas flotantes efervescentes fueron preparadas con un portador hidrofílico, tal como el óxido de polietileno (PEO WSR N 60K and PEO WSR 303), como agente retardador y bicarbonato de sodio como un agente generador de gas. Se evaluaron todas las propiedades fisicoquímicas de las tabletas preparadas, su flotación in vitro y su tasa de orden cinético. Se seleccionó el P9 a partir de los resultados obtenidos, como una fórmula óptima, basados en la liberación de la droga a las 12 h, tiempo mínimo de retraso para flotación y máximo tiempo total de flotación. La formulación optimizada siguió una tasa cinética de primer orden con mecanismo de erosión. Esta fórmula óptima se caracterizó mediante estudios FITR y no se observó ninguna interacción entre la droga y los polímeros utilizados.

An HPLC-UV method for the measurement of permeability of marker drugs in the Caco-2 cell assay

The Caco-2 cell line has been used as a model to predict the in vitro permeability of the human intestinal barrier. The predictive potential of the assay relies on an appropriate in-house validation of the method. The objective of the present study was to develop a single HPLC-UV method for the identification and quantitation of marker drugs and to determine the suitability of the Caco-2 cell permeability assay. A simple chromatographic method was developed for the simultaneous determination of both passively (propranolol, carbamazepine, acyclovir, and hydrochlorothiazide) and actively transported drugs (vinblastine and verapamil). Separation was achieved on a C18 column with step-gradient elution (acetonitrile and aqueous solution of ammonium acetate, pH 3.0) at a flow rate of 1.0 mL/min and UV detection at 275 nm during the total run time of 35 min. The method was validated and found to be specific, linear, precise, and accurate. This chromatographic system can be readily used on a routine basis and its utilization can be extended to other permeability models. The results obtained in the Caco-2 bi-directional transport experiments confirmed the validity of the assay, given that high and low permeability profiles were identified, and P-glycoprotein functionality was established.

Effect of cardiopulmonary bypass on the pharmacokinetics of propranolol and atenolol

The pharmacokinetics of some β-blockers are altered by cardiopulmonary bypass (CPB). The objective of this study was to compare the effect of coronary artery bypass graft (CABG) surgery employing CPB on the pharmacokinetics of propranolol and atenolol. We studied patients receiving oral propranolol with doses ranging from 80 to 240 mg (N = 11) or atenolol with doses ranging from 25 to 100 mg (N = 8) in the pre- and postoperative period of CABG with moderately hypothermic CPB (32°C). On the day before and on the first day after surgery, blood samples were collected before β-blocker administration and every 2 h thereafter. Plasma levels were determined using high-performance liquid chromatography and data were treated by pharmacokinetics-modelling. Statistical analysis was performed using ANOVA or the Friedman test, as appropriate, and P < 0.05 was considered to be significant. A prolongation of propranolol biological half-life from 5.41 ± 0.75 to 11.46 ± 1.66 h (P = 0.0028) and an increase in propranolol volume of distribution from 8.70 ± 2.83 to 19.33 ± 6.52 L/kg (P = 0.0032) were observed after CABG with CPB. No significant changes were observed in either atenolol biological half-life (from 11.20 ± 1.60 to 11.44 ± 2.89 h) or atenolol volume of distribution (from 2.90 ± 0.36 to 3.83 ± 0.72 L/kg). Total clearance was not changed by surgery. These CPB-induced alterations in propranolol pharmacokinetics may promote unexpected long-lasting effects in the postoperative period while the effects of atenolol were not modified by CPB surgery.

pH-independent release of propranolol hydrochloride from HPMC-based matrices using organic acids

Propranolol HC1, a widely used drug in the treatment of cardiac arrhythmias and hypertension, is a weak basic drug with pH-dependent solubility that may show release problems from sustained release dosage forms at higher pH of small intestine. This might decrease drug bioavailability and cause variable oral absorption. Preparation of a sustained release matrix system with a pH-independent release profile was the aim of the present study. Three types of organic acids namely tartaric, citric and fumaric acid in the concentrations of 5, 10 and 15% were added to the matrices prepared by hydroxypropyl methylcellulose [HPMC] and dicalcium phosphate. The drug release studies were carried out at pH 1.2 and pH 6.8 separately and mean dissolution time [MDT] as well as similarity factor [f[2]] were calculated for all formulations. It was found that incorporation of 5 and 10% tartaric acid in tablet formulations with 30% HPMC resulted in a suitable pH-independent release profiles with significant higher f[2] values [89.9 and 87.6 respectively] compared to acid free tablet [58.03]. The other two acids did not show the desirable effects. It seems that lower pK[a] of tartaric acid accompanied by its higher solubility were the main factors in the achievement of pH-independent release profiles

Propranolol plasma monitoring in children submitted to surgery of tetralogy of Fallot by a micromethod using high performance liquid chromatography

OBJECTIVE: To evaluate the analytical micromethod using liquid chromatography for the quantification of propranolol in children submitted to surgery of tetralogy of Fallot (TLF). Methods: Only 0.2 mL of plasma is required for the assay. Peaks eluted at 8.4 (Propranolol) and 17.5 min (verapamil, internal standard) from a C18 column, with a mobile phase 0.1 M acetate buffer, pH 5.0, and acetonitrile (60:40, v/v) at flow rate 0.7 mL/min, detected at 290 nm (excitation) and 358 nm (emission). Surgery was started 776 min of drug administration (8.7mg, mean); seven blood samples were collected from six patients (4M/2F; 2.1yrs;11.5kg; 0.80m; 18.9kg/m²). RESULTS: Confidence limits of the method showed high selectivity and recovery, sensitivity of 0.02ng/mL, good linearity (0.05-1000ng/mL), precision of 8.6 percent and accuracy of 3.1 percent. The mean duration of surgery was 283.2min, with the patients remaining under cardiopulmonary bypass (CPB) for 114min. A declining curve of propranolol plasma concentration was obtained after the last dose in the night that preceded the day of surgery. Plasma concentration also was normalized with hematocrit due to the hemodilution caused by the CPB procedure. On the other hand a decrease on drug plasma concentration was obtained between periods, the beginning of surgery to the postoperative day 2 (7.09 ng/mL and 0.05 ng/mL, p<0.05 respectively) and from the end of CPB to the postoperative day 2 (2.79ng/mL e 0.05ng/mL, p<0.05). CONCLUSION: Propranolol monitoring of plasma concentrations of children (TLF) normalized after the last preoperative dose revealed a decline from the beginning of surgery to the second postoperative day, suggesting that, once redistribution was restored, propranolol washout was complete.

OBJETIVO: Avaliar o micrométodo analítico empregando a cromatografia líquida para quantificação de propranolol em crianças operadas de tetralogia de Fallot (TLF). MÉTODO: Requereu-se apenas volumes de 0,2mL de plasma para a realização do ensaio. Os picos foram eluídos em 8.4 (Propranolol) e 17.5 min (verapamil, padrão interno) de uma coluna C18, com fase móvel (tampão acetato 0,1 M pH 5,0 e acetonitrila, 60:40, v/v) em fluxo de 0,7 mL/min, sendo detectados em 290 nm (excitação) e em 358 nm (emissão). A cirurgia iniciou-se 776 min depois da dose administrada (8,7mg, média) e sete amostras de sangue foram coletadas de seis pacientes (4M/2F; 2,1 anos;11,5kg; 0,80m;18,9kg/m²). RESULTADOS: Os limites de confiança do método analítico evidenciaram alta seletividade e recuperação, sensibilidade (0,02ng/mL), boa linearidade (0,05-1000ng/mL), precisão de 8,6 por cento e exatidão de 3,1 por cento. A duração média da cirurgia foi de 283,2min, com os pacientes em circulação extracorpórea (CEC) durante 114min. Uma curva de declínio do propranolol no plasma foi obtida após a última dose na noite que precedeu o dia da intervenção. A concentração plasmática foi normalizada com o hematócrito devido à hemodiluição causada pela CEC. Por outro lado obteve-se decréscimo nas concentrações plasmáticas entre os períodos início da cirurgia para o 2° dia de pós-operatório (7,09 ng/mL e0,05 ng/mL, p<0,05 respectivamente) e do final da CEC para o 2° dia de pós-operatório (2,79ng/mL e 0,05ng/mL, p<0,05). CONCLUSÃO: O monitoramento das concentrações plasmáticas normalizadas do propranolol, em crianças com TLF, após a última dose pré-operatória revelou decaimento do início da cirurgia para o segundo pós-operatório, sugerindo que após a correção cirúrgica, uma vez restaurada a distribuição, a eliminação do fármaco foi completa.

Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery

The pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass (CPB), resulting in unpredictable postoperative hemodynamic responses to usual doses. The objective of the present study was to investigate the pharmacokinetics of propranolol in patients undergoing coronary artery bypass grafting (CABG) by CPB under moderate hypothermia. We evaluated 11 patients, 4 women and 7 men (mean age 57 ± 8 years, mean weight 75.4 ± 11.9 kg and mean body surface area 1.83 ± 0.19 m²), receiving propranolol before surgery (80-240 mg a day) and postoperatively (10 mg a day). Plasma propranolol levels were measured before and after CPB by high-performance liquid chromatography. Pharmacokinetic Solutions 2.0 software was used to estimate the pharmacokinetic parameters after administration of the drug pre- and postoperatively. There was an increase of biological half-life from 4.5 (95 percent CI = 3.9-6.9) to 10.6 h (95 percent CI = 8.2-14.7; P < 0.01) and an increase in volume of distribution from 4.9 (95 percent CI = 3.2-14.3) to 8.3 l/kg (95 percent CI = 6.5-32.1; P < 0.05), while total clearance remained unchanged 9.2 (95 percent CI = 7.7-24.6) vs 10.7 ml min-1 kg-1 (95 percent CI = 7.7-26.6; NS) after surgery. In conclusion, increases in drug distribution could be explained in part by hemodilution during CPB. On the other hand, the increase of biological half-life can be attributed to changes in hepatic metabolism induced by CPB under moderate hypothermia. These alterations in the pharmacokinetics of propranolol after CABG with hypothermic CPB might induce a greater myocardial depression in response to propranolol than would be expected with an equivalent dose during the postoperative period.

Influência da cirurgia de revascularização miocárdica com circulação extracorpórea sobre a farmacocinética do propranolol e do atenolol / Influence of Coronary Artery Bypass Grafting Surgery Employing Cardiopulmonary Bypass in the Pharmacokinetics of Propranolol and Atenolol

Níveis plasmáticos e farmacocinética de beta-bloqueadores podem ser alterados por hipotermia e circulação extracorpórea (H-CEC). Avaliou-se, em pacientes submetidos a revascularização miocárdica (RM) com H-CEC, a farmacocinética do propranolol (n=11) e do atenolol (n=8) nos períodos pré e pós-operatório. Observou-se aumento da meia vida biológica e volume de distribuição apenas para o propranolol. O clearance total permaneceu inalterado para os dois fármacos e ocorreu aumento da concentração plasmática de propranolol do início até o final da H-CEC. Os resultados mostram que a RM com H-CEC induz alterações farmacocinéticas diferentes para o propranolol e o atenolol / Plasma levels and pharmacokinetics of betablockers may be altered by hypothermic cardiopulmonary bypass (H-CPB). We evaluated the pharmacokinetics of propranolol (n=11) and atenolol (n=8) pre and postoperatively in patients submitted to coronary artery bypass grafting surgery (CABG) employing H-CPB. Increase of biological half-life and volume of distribution was observed only for propranolol. The total clearance remained unchanged for both drugs and an increase in plasma propranolol was observed from the beginning to the end of H-CPB. Data obtained show that CABG employing H-CPB influences the propranolol and atenolol pharmacokinetics in distinct ways.

Relationship of Propranolol Pharmacokinetic Parameters with Portosystemic Shunt in CCl4-induced cirrhotic Rats / 대한간학회지

BACKGROUND: This study was designed to determine the relationship of propranolol pharmacokinetic parameters with portosystemic shunt in CCl4-induced cirrhotic rats. METHODS: Cirrhotic rats(n=6) were induced by intramuscular injection of CCl4 in olive oil(two time per weeks) for 12 weeks. Controls (n=6) were injected intramuscularly with the same dose of olive oil for 12 weeks. We evaluated the amount of portosystemic shunt by thallium-201 per rectal scintigraphy. After intravenous bolus injection of propranolol (2mg/kg) to rats, the serum propranolol concentrations were analyzed by a HPLC-fluorimetric detector system. Pharmacokinetic parameters such as C0, AUC, t(1/2(beta)), and CLp were determined in each group. Then, a small amount of heptic tissue was obtained and subjected to determination of the hepatic collagen content by quantitating 4-hydroxyproline and were inspected by microscope after hematoxylin and eosin stain. RESULTS: In liver biopsy, liver fibrosis progressed in CCl4-induced cirrhotic rats. The serum concentrations of propranolol were significantly (p < 0.01) elevated in CCl4-induced cirrhotic rats. Mean amount of 4-hydroxyproline, mean H/L ratio, and mean AUC in CCl4-induced cirrhotic rats was significantly (p < 0.01) higher than that in control rats. There was a relationship between AUC, H/L ratio, and amount of 4-hydroxyproline. CONCLUSION: H/L ratio may help in the selection of drug dosage (especially blood flow dependent drug) in pre-clinical studies for chronic liver disease during the drug development process.

High performance liquid chromatography to determine propranolol in plasma. Drug accumulation in post-surgical patients

An improved, simple and sensitive micromethod based on HPLC-fluorescence is described for quantification of propranolol in plasma. Only 200µL of biological sample were required. The drug and its internal standard (verapamil) are eluted after 3.6 and 8.5 min, respectively, from a 4-micron `C IND. 18ï reverse-phase column using a mobile phase consisting of 0.38 M acetate buffer, pH 5.0 and acetonitrile (65:35, v/v, isocratically) with detection at `lâmbda IND. exï- 290 nm and `lâmbda IND. emï - 358 nm. This method, validated on basis of parameters evaluated for the confidence limits of propranolol measurements in spiked blank plasma, presented 1 ng/mL sensitivity, 1-1000 ng/mL linearity, 6.2 per cent and 7.6 per cent for intra- and inter-assay precision respectively, good accuracy and high selectivity...

Comparison of skin permeability of drugs in mice and human cadaver skin.

In vitro percutaneous absorption of four antihypertensive drugs were carried out across the mice and human cavader skin in order to compare their skin permeability. An interesting trend was noticed in these experiments. Poorly water soluble drug prazosin hydrochloride showed 13 times enhanced flux in the mice skin whereas the steady-state flux of the water soluble drug propranolol hydrochloride was almost same in both human cadaver and mice skin. The permeation rate of prazosin hydrochloride and propranolol hydrochloride through the human cadaver skin fluctuated widely over time, but in mice skin, distinct trends were noticed. The study indicates that the overall permeation rate in mice skin is higher than that in the cadaver skin and the meeting of the target-flux in mice skin does not guarantee its good permeability in human skin.

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.

Variantes de butirilcolinesterasa sérica en población de Santiago oriente / Serum butyrylcholinesterase variants in eastern Santiago

Succinylcholine causes prolonged apneas in a proportion if subjects that have genetical defect of butyrylcholinesterase, due to the presence of unusual alleles in the locus BCHE. To estimate allele frequences of 3 variants of serum butyrylcholinesterase, BCHE*U, BCHE*A and BCHE*F in an urban population of Santiago, Chile, different phenotypes for the locus BCHE were determined in 300 blood samples coming from patients of a private clinical laboratory. The population was formed by an admixture of Amerindian and European (mostly spanich) people. The frequency of BCHE*A was similar to the expected for this population, but BCHE*F frequency was greater than predicted. Eight subjects had a genotype BCHE AK. The higher frequency found for BCHE*F is probably due to the use of more precise detection techniques. Although the used method cannot distinguish BCHE UK from BCHE UU, the findings of individuals with BCHE AK, must lead to the suspicion that the frequency of the allel BCHE K is not negligible in Santiago

Estudio comparativo de la cinética de disolución del clorhidrato de propanolol en forma de tabletas de 40 mg. para cuatro marcas del mercado nacional / Comparative study of the kinetics propanol hydrochloride dissolution in form of tablets form 40 mg. for four brands in the national market

Mediante un diseño experimental de bloques al azar se realizó el estudio cinético de disolución del clorhidrato de propanolol; empleando el equipo No. 1 de la USP XXII-XXXIII, a 100 ñ 1 rpm, temperatura de 37 ñ 1ºC y ácido clorhídrico diluido (1:100) como medio de disolución. Los datos obtenidos se analizaron con base en los modelos comúnmente reportados para este tipo de procesos (orden cero, uno, dos y de la raíz cúbica). Se puede afirmar con error de 1 por ciento y 5 por ciento que el modelo cinético más probable que explica el proceso de disolución del clorhidrato de propanolol es de orden cero para el producto C y de orden uno para los productos A y D. El producto B se ajusta al modelo cinético de orden de la raiz cúbica y presenta el menor tiempo de disolución 50 por ciento (t sub50 por ciento), por lo cual libera más rápidamente el principio activo

El droperidol interactúa con receptores serotonérgicos y adrenoceptores Ó- cardiovasculares / Droperidol interactions with serotonergic and cardiovascular Ó adrenoceptors

En este trabajo se investigó si los receptores cardiovasculares de la serotonina (5-HT) son antagonizados por el droperidol. Los efectos de este fármaco sobre la vasopresión y el cronotropismo positivo obtenidos con la infusión intravenosa de noradrenalina (NA; 1 µg.kg-1.min-1), angiotensina II (1 µg.kg-1.min-1) y quipazina (100 µg.kg-1.min-1) se estudiaron en ratas desmeduladas. El droperidol (0.01 - 1 mg.kg-1,i.v.) revirtió los efectos presores de la NA y la quipazina en forma dependiente de la dosis. El pretratamiento con propranolol, bromefeniramina o atropina (1 mg.kg-1, i.v.; cada uno), no previno los efectos del neuroléptico. Por otra parte, el droperidol no modificó la respuesta presora de la angiotensina II, ni el cronotropismo de las drogas estudiadas. Se observó que los efectos inhibitorios del droperidol (DI50 141 µg/kg; LC 105-191) y de la ketanserina (Di50 110 µg/kg; LC 91-132) sobre la vasopresión de la quipazina, son similares; sin embargo, esta última no fue modificada por la prazosina. Estos resultados indican una interacción del droperidol con los reeptores vasculares 5-HT y confirman su capacidad para bloquear Ó-adrenoceptores

Studies on psychomotor performance in healthy volunteers after diazepam, propranolol and alcohol given alone or in combination.

The effects of diazepam, propranolol or alcohol alone or in combination with each other were examined in ten normal healthy volunteers on tests of psychomotor function. Results showed impaired psychomotor performance persisting upto 4-5 h when the aforementioned agents given singly were tested on simple reaction time (SRT), multiple choice reaction time (MCRT) and critical flicker fusion frequency (CFFF) tasks. Digit cancellation task (DCT) was similarly affected by diazepam and alcohol only. No summation of adverse effects on psychomotor performance was noted when a combination of diazepam and alcohol, diazepam-propranol or alcohol plus propranolol were tested on SRT and MCRT. An additive impairment of CFFF was observed with alcohol - propranolol combination only. No summation of pharmacodynamic effects on DCT were noted when different combinations were used.

Effect of gugulipid on bioavailability of diltiazem and propranolol.

The effect of single oral dose of 1 gm gugulipid was studied on bioavailability of single oral dose of propranolol (40 mg) and diltiazem (60 mg) in 10 and 7 normal healthy male volunteers respectively. It was a randomised within group crossover study. Blood samples were collected at hourly intervals upto 8 hrs. Gugulipid significantly reduced (P < .01) peak plasma concentration (Cmax) and area under curve (AUC 0-8 hrs) of both the drugs in normal volunteers. Such interaction in patients receiving propanolol or diltiazem with gugulipid may lead to diminished efficacy or nonresponsiveness due to significant reduction in bioavailability.

Análisis de las propiedades antihipertensivas del ácido-3-nitropropionico: un compuesto proveniente de plantas del género Astragalus / Antihypertensive properties of 3-nitropropionic acid: a compound derived from the astragalus plant

El ácido 3-nitropropiónico (ANP) es un compuesto proveniente de plantas del género Astragalus que ocasionó relajación dependiente de la concentración en anillos precontraídos de aorta de conejo. La remoción del endotelio o la presencia de atropina, propranolol o bromofeniramina no afectaron el efecto vasodilatador del ANP, el cual fue claramente inhibido por el azul de metileno. Por otra parte, la administración i.v. aguda de ANP en ratas normotensas o crónica por vía oral en perros hipertensos renales, provocó disminución en la presión sanguínea y bradicardia. Finalmente, el ANP ocasionó efectos inotrópicos negativos en aurículas aisladas de cobayos que no fueron bloqueados por atropina e inhibió los incrementos en fuerza y frecuencia de contracción cardíaca provocados por el isoproterenol. Los resultados indican que el ANP posee propiedades vasodilatadoras y antihipertensivas. La actividad vasodilatadora parece ser consecuencia de activación de la guanilato ciclasa, ya que se inhibió con azul de metileno. El efecto hipotensor del ANP fue independiente de la especie del animal o ruta de administración empleada. La bradicardia apreciada en ratas y perros y los efectos inotrópicos y cronotrópico negativos observados en aurículas aisladas, sugieren que el efecto hipotensor del ANP es una mezcla de acciones vasodilatadoras y cardiodepresoras. Los efectos cardíacos del ANP parecen relacionarse con inhibición de las respuestas mediadas por receptores ß-adrenérgicos

Estudo comparativo dos efeitos hemodinâmicos agudos do pindolol e do propanolol em pacientes portadores de cardiopatia isquêmica / Compartive study of the acute hemodynamic effects of pindolol and propranolol in patients with ischemic heart disease

Os efeitos agudos do Propranolol usado na dose de 3mg em 22 pacientes, e do Pindolol, na dose de 0,5mg em 24 pacientes foram estudados em situaçäo basal e 5 minutos após sua administraçäo. A análise comparativa das variáveis demonstrou näo ter havido diferença significativa no efeito de ambas as drogas sobre a pressäo máxima e a pressäo diastólica final de ventrículo esquerdo, as pressöes máxima, mínima e média de aorta, sobre o índice sistólico, e diastólico finais de ventrículo esquerdo, dp/dt máxima e mínima de ventrículo esquerdo e resistência vascular sistêmica (P > 0,05). O Propranolol elevou a pressäo diastólica final de ventrículo direito, reduziu o índice e a freqüência cardíaca, a fraçäo de ejeçäo e a velocidade de encurtamento circunferencial do ventrículo esquerdo (P < 0,05), alteraçöes näo observadas após o Pindolol. O Pindolol determinou elevaçöes significativas nas pressöes máximas de ventrículo direito, máxima, mínima e média de artéria pulmonar (P < 0,05), alteraçöes näo observadas após o Propranolol. A presssäo média do átrio direito aumentou significativamente após uso dos dois medicamentos (P < 0,05). As propriedades simpaticomiméticas do pindolol foram identificadas no presente trabalho, pela tendência que este demonstrou para aumentar o débito cardíaco, reduzir a resistência periférica e melhorar a motilidade segmentar do miocárdio isquêmico