Effects of intraoperative diltiazem infusion on flow changes in arterial and venous grafts in coronary artery bypass graft surgery / Efeitos da infusão intraoperatória de diltiazem sobre as mudanças do fluxo em enxertos arteriais e venosos em cirurgia de revascularização do miocárdio

AbstractObjective:This study aimed to show the effects of intra-operative diltiazem infusion on flow in arterial and venous grafts in coronary artery bypass graft surgery.Methods:Hundred fourty patients with a total of 361 grafts [205 (57%) arterial and 156 (43%) venous] underwent isolated coronary surgery. All the grafts were measured by intraoperative transit time flow meter intra-operatively. Group A (n=70) consisted of patients who received diltiazem infusion (dose of 2.5 microgram/kg/min), and Group B (n=70) didn't receive diltiazem infusion.Results:Mean graft flow values of left internal mammary artery were 53 ml/min in Group A and 40 ml/min in Group B (P<0.001). Pulsatility index (PI) values of left internal mammary artery for Group A and Group B were 2.6 and 3.0 respectively (P<0.001). No statistically significant difference was found between venous graft parameters.Conclusion:We recommend an effect of diltiazem infusion in increasing graft flows in coronary artery bypass graft operations.

ResumoObjetivo:Este estudo teve como objetivo mostrar os efeitos da infusão de diltiazem intraoperatória no fluxo arterial e enxertos venosos em cirurgia de revascularização do miocárdio.Métodos:Cento e quarenta pacientes com um total de 361 enxertos [205 (57%) arteriais e 156 (43%) venosos] passaram por uma cirurgia coronária isolada. Todos os enxertos foram medidos pelo medidor de fluxo de tempo de trânsito intraoperatório. Grupo A (n=70), formado por pacientes que receberam infusão de diltiazem (dose de 2,5 micrograma/kg/min), e Grupo B (n=70), por aqueles que não receberam infusão de diltiazem.Resultados:Os valores médios de fluxo de enxerto de artéria mamária interna esquerda foram 53 ml/min no grupo A e 40 ml/min no Grupo B (P<0,001). Valores do índice de pulsatilidade da artéria mamária interna esquerda para o Grupo A e do Grupo B foram de 2,6 e 3,0, respectivamente (P<0,001). Não houve diferença estatisticamente significativa entre os parâmetros do enxerto venoso.Conclusão:Sugerimos um efeito da infusão de diltiazem em aumentar os fluxos de enxerto em operações de bypass de artéria coronária.

Efficacy of diltiazem as an adjunct to lignocaine in intravenous regional anesthesia

Various adjuncts have been used with lignocaine to decrease tourniquet pain and prolong post-operative analgesia during intravenous regional anesthesia [IVRA]. Calcium-channel blockers potentiate the analgesic effect of local anesthetics. This study was designed to evaluate the efficacy of diltiazem as an adjunct to lignocaine in IVRA with respect to tourniquet tolerance, perioperative analgesia, and quality of anesthesia. In this prospective, randomized, and double-blind study, 40 patients [American Society for Anesthesiologists grade I/II] undergoing elective hand surgery under IVRA were assigned into two groups of 20 each and administered IVRA either with lignocaine 3 mg/kg [group Lignocaine [L]] or lignocaine 3 mg/kg plus diltiazem 0.2 mg/kg [group Lignocaine-Diltiazem [LD]] with normal saline [total volume-40 ml]. Hemodynamic parameters, onset of the complete sensory blockade, motor blockade, and intraoperative [tourniquet pain] and post-operative Visual Analogue Scale scores, total intraoperative and consumption of post-operative fentanyl intraoperative were recorded. Sensory block was established in 2.5 +/- 0.688 min in group LD verses 5.60 +/- 0.851 min in group L. Motor blockade was established in 8.65 +/- 0.933 min in group LD and 13.46 +/- 0.604 min in group L. The mean VAS scores >3 were attained early at 30 min [3.1 +/- 0.912] in group L. Patients in group L requested early rescue analgesic at 30 +/- 8.633 min compared with 49.64 +/- 7.958 min in group LD. Diltiazem as an adjunct to lignocaine provided enhanced intraoperative and post-operative analgesia without any significant side effects

Pre - emptive epidural analgesia with bupivacaine, deltiazem and ketamine singly or in combination - A Randomised Trial.

Background: A randomized control study was designed to compare postoperative epidural analgesia by preemptive use of epidural administration of local anesthetic- bupivacaine alone and in combination with NMDA blocker- ketamine or calcium channel blocker- diltiazem singly or both in combination . Medhods: Sixty female patients in age group 35-50 yrs with ASA grade I and II, posted for open abdominal hysterectomy were randomly distributed in four groups after ethical committee approval and written consent. They were given epidurally 0.4 ml /kg of 0.5 % Bupivacaine in Control group, 0.4 ml /kg of 0.5 % Bupivacaine + Ketamine 5mg in BK group , 0.4 ml /kg of 0.5 % Bupivacaine + Diltiazem 10 mg in BD group and 0.4 ml /kg of 0.5 % Bupivacaine + Ketamine 5 mg + Diltiazem 10 mg in BKD group. Results: BK group had significant pain free period (8.8 ± 1.37) post operatively as compared to rest three groups (P < 0.01). BD group (5.8 ± 0.94) also had comparable pain relief.BKgroup needed three to four number of top-up's in first 24 hours (3.37 ± 0.46) where as BD group needed five to seven number of top-up's in next 24 hours (5.93 ± 0.70) (P < 0.01). BK group and BKD group patients were sedated resulting in reduced number of top-ups required in first 24 hours. Conclusion: Ketamine and diltiazem were found to be synergetic with bupivacaine for preemptive epidural analgesia. Diltiazem was better option over ketamine when sedation is not desirable.

Comparison of the efficacy and safety of topical diltiazem and nitroglycerine for pain relief during transrectal ultrasound guided biopsy of the prostate

INTRODUCTION AND OBJECTIVE: Transrectal ultrasound biopsy of prostate is a painful procedure. The introduction of the rectal probe is one of the major contributors to the pain associated with this procedure. Drugs that relax the anal sphincter should theoretically decrease this pain. This study was done to compare the efficacy and safety of two topical medications that relax the anal sphincter, diltiazem and nitroglycerine, in decreasing the pain associated with transrectal ultrasound guided prostate biopsy. MATERIALS AND METHODS: 66 patients who were to undergo their first prostate biopsy were randomized to receive either 2 mL of 2% topical diltiazem or 2 mL of 0.2% topical nitroglycerine or placebo 20 minutes before prostate biopsy. All patients also received 15 mL of intrarectal lignocaine. A 10-point visual analogue score was used to record the pain immediately after the insertion of the probe, during biopsy and at the end of the procedure. RESULTS: The pain scores due to probe insertion, during biopsy and at the end of the procedure in patients who received topical diltiazem or nitroglycerine were significantly lower compared to the placebo group (p < 0.001). There were no significant differences in the pain scores between the patients receiving diltiazem compared to those receiving nitroglycerine. Higher incidence of headache and fall in blood pressure was noted in patients who received nitroglycerine compared to those receiving diltiazem. CONCLUSION:Topical diltiazem and nitroglycerine are equally effective in reducing the pain associated with transrectal prostatic biopsy. Diltiazem is safer compared to nitroglycerine.

Topical diltiazem hydrochloride and glyceryl trinitrate in the treatment of chronic anal fissure

To compare the symptomatic relief, healing and side-effects of topical diltiazem [DTZ] and glyceryl trinitrate in the treatment of chronic anal fissure. Randomized controlled trial. The Surgical Outpatient Department of Civil Hospital, Karachi, from March 2006 to February 2007. Patients with chronic anal fissure were included in the study and randomized to two groups. One group was administered topical 2% diltiazem hydrochloride and other was given 0.2% glyceryl trinitrate [GTN], perianally twice daily for 8 weeks. Patients with anal fissure due to other diseases like inflammatory bowel disease, malignancy, sexually transmitted diseases, previous treatment with local ointment or surgery; patients who required anal surgery for any concurrent disease like hemorrhoids, pregnant women and patients with significant cardiovascular conditions were excluded. There were four follow-up sessions during the course of treatment. Healing and side-effects were recorded. Analysis was done by SPSS version 10 on intention-to-treat basis. Chi-square was used where appropriate. Eighty patients with symptomatic chronic anal fissure were included in the study and equally divided into two groups. After 8 weeks of treatment healing occurred in 31 of 40 patients treated with diltiazem and 33 of 40 patients treated with GTN [p = 0.576]. There were less side-effects with DTZ [n=13] than with GTN [n=29, p < 0.001]. In particular, headache occurred more commonly with GTN [n=27] than with DTZ [n=9, p < 0.0001]. Diltiazem hydrochloride and glyceryl trinitrate were equally effective in healing chronic anal fissure. Diltiazem caused fewer side-effects particularly headache than glyceryl trinitrate ointment. Diltiazem may be the first-line treatment for chemical sphincterotomy for the chronic anal fissure

Diltiazem [2%] versus glyceryl trinitrate cream [0.2%] in the management of chronic anal fissure

To assess and compare the effectiveness of topical 0.2% glycerl trinitrate [GTN] and topical 2% diltiazem [DTZ], in the management of chronic anal fissure. Comparative, descriptive study. Department of Surgery, Liaquat University of Medical and Health Sciences, Jamshoro/Hyderabad from September 2004 to August 2005. Patients with chronic anal fissure were treated with topical 0.2% GTN [50 patients] and 2% DTZ [47 patients] application for 8 weeks, three times a day at peri anal area. Symtoms, recurrence, wound healing and side effects were compared. Data was analyzed using SPSS version 10 employing X[2] test. A p-value below 0.05 were considered statistically significant. There were 53 females and 44 males with a mean age of 30 years. Patients who received topical diltiazem [DTZ] showed statistically significant difference than those who were prescribed topical glycerl trinitrate terms of wound healing and side effects mainly the headaches [p=0.02 and 0.003 respectively]. Improvement in symptoms [p=0.345] and recurrence rates [p=0.612] turned to be statistically insignificant although recurrence rate was lower with DTZ. Chemical sphincterotomy is an effective first line management for chronic anal fissure. Both GTN and DTZ are equally effective in managing the chronic anal fissure. DTZ has fewer side effects, a better healing response and low recurrence rates

Comparison between the therapeutic effects of internal sphincterotomy and diltiazem gel in chronic anal fissure

Surgery is now the [treatment of choice] for chronic anal fissure. However, considering the pathogenesis of this disease and the tendency for noninvasive and economical procedures, more attention is growing towards the non surgical treatments. Oral or topical nitroglycerin, isosorbide, bethanechol, L-Arginine, nifedipine, diltiazem, adrenergic -antagonists and botulinum toxin have been used to treat chronic anal fissure. In this study, we compared the surgical sphincterotomy and topical diltiazem gel for the treatment of anal fissure. This clinical trial study was performed on two groups of 35 patients. The first group was treated by surgical sphincterotomy and the second group received the topical diltiazem gel. Both groups were examined 2, 4 and 6 weeks after the onset of the treatment and, the findings were recorded and statistically analyzed by SPSS, t-test and X to determine the relation between parameters and p<0.05 was considered to be significant. Two weeks after the onset of treatment, the rate of complete pain relief in the sphincterotomy group and in the diltiazem group was 75% and 45% respectively [p<0.005]. Although this value was the same in both groups 4 weeks after treatment [p=0.357], the wound healing process observed in the first group was significantly higher than the second group [85% VS 40%, p<0.0001]. Both groups had a similar wound healing rate in the 6th week [p=0.0351]. According to our findings, both the surgical sphinctorotomy and the topical diltiazem gel had a similar therapeutic effect on the chronic anal fissure. However, the topical diltiazem gel has shown to have several advantages such as lower complication rates, greater convenience, noninvassivess, [no hospitalization] and lower cost. Therefore this type of treatment considered to be more appropriate for chronic anal fissure, and the surgery should be used as an alternative option for special cases

Efecto del diltiazem sobre los lípidos séricos y lesiones ateroscleróticas en conejos hipercolesterolemicos / Effect of the diltiazem on the seric lipids and atherosclerotics lesions in hypercholesterolemics rabbits

El propósito de este estudio fue evaluar si la administración de diltiazem (30mg/día(vía oral), disminuye la hipercolesterolemia e inhibe la aterosclerosis en 38 conejos machos hipercolesterolemicos. Control: Conejarina por doce semanas, A: dieta rica con 0,3 por ciento de colesterol (DH) por doce semanas. B: DH por doce semanas y desde la tercera semana hasta la dodécima diltiazem, Grupo C: DH por dos semanas y Conejarina + diltiazem desde la tercera semana hasta la duodécima y D: DH por dos semanas y Conejaría desde la tercera hasta la duodécima semana. Se determinaron Colesterol Total (CT), LDL-colesterol (LDLc) y Triglicéridos (Tg) por métodos enzimáticos. A la duodécima semana, se sacrificaron los conejos y el estudio histológico fue realizado por los siguientes métodos: 1. Hematoxilina Eosina evaluó la presencia de lesiones, 2. Gomori's: evaluó la profundidad de las lesiones 3. Computarizado: midió la extensión de las lesiones. En el grupo A y B aumentaron significativamente el CT, LDLc y Tg en relación al control en todos los periodos, a excepción de los Tg a la duodécima semana. Respectoa las lesiones ateroscleróticas, los grupos A y B presentaron lesiones tipo II, III, IV y V, el porcentaje promedio de área lesionada fue: Grupo A: 47,20 por ciento, Grupo B: 57, 60 por ciento. Estos resultados permiten concluir que el diltiazem ejerce un efecto hipolipidemiante cuando se administra junto con una dieta rica en 0,3 por ciento colesterol, se confirma que una dieta adecuada es una buena estrategia para prevenir las displidemías y que el diltiazem no previno, ni indujo regresión de las lesiones ateroscleróticas.

Co-administration of diltiazem and cyclosporine for kidney transplant recipients: a four year follow-up study.

BACKGROUND: Diltiazem and cyclosporin A (CsA) share a similar metabolism and degradation via the hepatic cytochrome p 450 subfamily 3A4. Co-administration of diltiazem with CsA may lead to CsA dosage reduction, blood pressure control and renal protection. OBJECTIVES: To study the four year outcome of kidney transplant recipients who received diltiazem administration with CsA. This was compared to the outcomes of patients who received CsA without diltiazem and were matched for blood pressure control and other baseline characteristics. MATERIAL AND METHOD: Forty eight patients were included in the diltiazem group and seventy patients in the non-diltiazem group. CsA monitoring was done by using trough level (monoclonal fluorescent polarization immunoassay). RESULTS: The results showed that both groups has similar 4-year graft survival (92 and 95 %) with a similar mean final serum creatinine (1.3 mg/dl). Mean dose of CsA during the first month was 30 % lower in the diltiazem than non-diltiazem group. At one year CsA dose was 11% lower in the diltiazem than non-diltiazem group. However the diltiazem group was associated with significantly higher probability to have chronic allograft nephropathy than the non-diltiazem group (31% VS 19%) (RR 2.93; p = 0.03; Multivariate Cox regression). CONCLUSION: Co administration of diltiazem with trough level adjusted CsA is associated with benefits in terms of CsA dose reduction and good graft survival and function. However there appeared to be no protective effect of diltiazem on the progression to chronic allograft nephropathy.

Effect of diltiazem on the pharmacokinetics of microemulsion cyclosporine A in renal transplantation.

OBJECTIVE: Diltiazem might be used as a cyclosporine A (CsA)-sparing agent. There is evidence that CsA (C2) level is the best single point blood sampling for monitoring the CsA level. The authors, therefore, studied the effect of diltiazem on the pharmacokinetics (PK) of CsA, including C2, in renal transplant patients. MATERIAL AND METHOD: Twenty-five CsA-treated renal transplant patients, with neither diseases nor agents that alter the PK of CsA, were enrolled in the present study. The PK of CsA was studied in all patients before and 2 weeks after taking diltiazem. RESULTS: The area under the concentration-time curve (AUC) of CsA was obtained by 2 methods, AUC0-4 and AUC0-12. Before taking diltiazem, the correlation (r) between C0 with AUC0-4 and C0 with AUC0-12 were 0.799 and 0.871, respectively (p = 0.01), r between C2 with AUC0-4 and C2 with AUC0-12 were 0.988 and 0.956, respectively (p = 0.01). Time to maximum concentration (Tmax) of CsA was at 1.5 hr (1.5-4.0 hr) [median (range)]. After two weeks of taking diltiazem, r between C0 with AUC0-4 and C0 with AUC0-12 were 0.577 and 0.784, respectively (p = 0.01), r between C2 with AUC0-4 and C2 with AUC0-12 were 0.988 and 0.896, respectively (p = 0.01). Tmax of CsA was at 1.5 hr (1.5-4.0 hr) [median (range)]. The dosage of CsA could be reduced by 25.8% to maintain the same levels of C0 and C2 in the same patients after taking diltiazem. CONCLUSION: Diltiazem slightly altered the correlation between C2 with AUC of CsA. This indicates that C2 is the best single point blood sampling to monitor the therapeutic levels of CsA in renal transplant patients who are taking diltiazem.

Estudo comparativo randomizado da evolução imediata dos pacientes com artéria radial anastomosada proximalmente na aorta ou como enxerto composto / Comparative randomized study of the immediate outcomes of patients with radial arteries proximally anastomosed to the aorta or as a composite graft

OBJETIVO: A artéria radial (AR) tem sido largamente empregada na revascularização do miocárdio (RM), porém a diferença da anastomose proximal na aorta ou em enxerto composto com a artéria torácica interna esquerda (ATIE) ainda é controversa. Avaliamos os resultados clínicos imediatos do uso da artéria radial (AR) anastomosada proximalmente na aorta ou como enxerto composto em "Y" com a ATIE. MÉTODO: Cem pacientes foram randomizados e submetidos à RM no Hospital Beneficência Portuguesa de São Paulo, no período de novembro de 1999 a março de 2001. Nos pacientes do Grupo I (GI), a AR foi anastomosada proximalmente na aorta e, nos pacientes do Grupo II (GII), a AR foi anastomosada na ATIE. A veia safena (VS) autógena foi usada quando necessário. RESULTADOS: Os grupos I e II mostraram-se homogêneos quanto às características pré-operatórias. A mortalidade imediata total foi de 1,0 por cento (GI 2,0 por cento e GII 0,0 por cento) - p =1,00. O número de artérias coronárias anastomosadas por paciente foi de 3,0+0,12, no GI e de 2,82+0,12, no GII (p=0,29). Os pacientes do GII apresentaram tempo de circulação extracorpórea (CEC) menor do que do GI (p=0,0001). Não houve diferença significativa entre as outras variáveis peri-operatórias estudadas. CONCLUSAO: Os pacientes apresentaram resultados clínicos semelhantes quando a AR foi anastomosada proximalmente na aorta ou como enxerto composto em "Y" na ATIE, e a anastomose proximal na ATIE não aumenta os riscos de complicações imediatas.

Tratamiento de la fisura anal / Treatment of the anal fissure

La fisura anal es una lesión que aparece en la porción epidérmica del canal anal, con sintomatología muy florida de dolor y sangrado defecatorio. Existen dos formas típicas, la primaria o idiopática, relacionada con la isquemia relativa del anodermo debida al incremento del tono basal esfintérico interno, y la secundaria a patologías infecciosas o del tubo digestivo. Objetivo y diseño: En los últimos años surgió el concepto de esfinterotomía química. El motivo de este trabajo es la comparación entre estas técnicas incruentas y la esfinterotomía quirúrgica, evaluando en forma prospectiva randomizada los pacientes tratados con diltiazem al 2 por ciento en vaselina sólida, trinitrato de glicerilo aplicados tópicamente y la esfinterotomía lateral interna.Material y Métodos: Durante el período comprendido entre el 31 de diciembre de 2002 y el 31 de diciembre de 2004 se trataron 174 pacientes; 56 con diltiazem al 2 por ciento, 60 con trinitrato de glicerilo y 58 por medio de esfinterotomía lateral interna 10 abierta y 48 cerrada, (Nottaras). La ubicación de la fisura fue en el 76.8 por ciento o 134 pacientes en hora VI, y en el 23.2 por ciento o 40 en hora XII. La distribución según sexo fue 96 (55.3 por ciento) varones y 78 ( 44.7 por ciento) mujeres. Resultados: Luego de una media de seguimiento de 87 días (7 a 330 días), en el grupo tratado con diltiazem, 33 pacientes presentaron la desaparición de los síntomas en la primer semana, con una curación y epitelización, sin recidiva, en 38 pacientes a las 6 semanas. 7 pacientes evolucionaron mal y necesitaron cirugía, y 9 no se presentaron al control y seguimiento.En el grupo tratado con trinitrato de glicerilo, 36 pacientes tuvieron una buena evolución, 5 necesitaron cirugía, 10 no volvieron a control y 9 suspendieron el tratamiento por reacciones adversas. El grupo de 58 pacientes tratado quirúrgicamente evolucionó favorablemente excepto 2 de ellos que necesitaron una anoplastía con deslizamiento de colgajo. Conclu...

release behavior and kinetic evaluation of diltizem HCI from various hydrophilic and plastic based matrics

In this study, the effects of various hydrophilic [HPMC and Carbopol 971] and plastic [Ethylcellulose and Eudragit RL100] polymers on the release profile of diltiazem HCl from matrix tablets were evaluated in-vitro. For this purpose, tablets containing 60 mg of diltiazem HCl along with various amounts of the aforementioned polymers were prepared using the wet granulation technique. Tablets prepared were placed in a USP apparatus I dissolution tester containing a pH-1.5 HCl solution for the first 2 h and a pH-6.8 phosphate buffer for the next 10 h of the study. The amount of drug released was determined at 237 nm by a UV-visible spectrophotometer. The results showed that all the polymers used in this study could slow down the release of diltiazem HCl from the matrices prepared. This effect, except for HPMC, generally increased proportionately with the amount of polymer. HPMC imparted the best control over drug release and could sustain it for approximately 6 h. All the matrices prepared had a burst release initially; however, it was minimum with HPMC-containing formulations. Fitting of release data to different kinetic models showed that HPMC-matrices conformed best to Hixson-Crowell model, ethylcellulose-matrices to Higuchi and both Eudragit RL100 and Carbopol 971-formulations to either of Hixson-Crowell, Higuchi and first-order kinetics. Release exponent [n] derived from Korsmeyer-Peppas equation for the studied formulations implied that the release of diltiazem HCl from HPMC-matrices was non-Fickian [0.62-0.66] and that of ethylcellulose-formulations was Fickian [n tilde 0.4]. The values of n for Eudragit RL100 and Carbopol 971-matrices ranged from 0.46-0.59, indicating that the drug release was mainly governed by diffusion. Briefly, HPMC was found to be suitable for sustaining the release of diltiazem HCl from matrix-type tablets. Nevertheless, to achieve better results with this polymer, further investigations seem to be necessary

Control of rate versus rhythm in rheumatic atrial fibrillation: a randomized study.

BACKGROUND: Patients with rheumatic heart disease and atrial fibrillation incur significant morbidity and mortality. It is not known which approach, rate control or maintenance of sinus rhythm might be most appropriate. The present study was undertaken to compare the strategy of ventricular rate control versus maintenance of sinus rhythm in rheumatic atrial fibrillation, and to evaluate the role of amiodarone in this patient population. METHODS AND RESULTS: We prospectively studied 144 patients with chronic rheumatic atrial fibrillation in a double-blind protocol-rhythm control (group I: 48 patients each with amiodarone -group Ia; and placebo -group Ib) and compared the effects with the ventricular rate control (group II) by diltiazem (n=48, open-label). Direct current cardioversion was attempted in group I. The mean age of the study population was 38.6+/-10.3 years, left atrial size was 4.7+/-0.6 cm, atrial fibrillation duration was 6.1+/-5.4 years, and 72.9% patients had undergone valvular interventions. At 1 year, 45 patients with sinus rhythm in group I compared to 48 patients in group II demonstrated significant increase in exercise to sinus rhythm time, had improvement in functional class and quality of life score. There was no difference in hospitalization rates, systemic bleeds or incidence of thromboembolism. Five patients died in group II but none in group I (p=0.02). In group I, 73/87 (83.9%) patients converted, and 45/86 (52.3%) patients maintained sinus rhythm at 1 year. Conversion rates were 38/43 (88.4%) with amiodarone versus 34/44 (77.3%) with placebo (p=0.49): corresponding rate for maintaining sinus rhythm was 29/42 (69.1%) versus 16/44 (36.4%), p=0.008 respectively. CONCLUSIONS: Maintenance of sinus rhythm appeared to be superior to ventricular rate control in patients with rheumatic atrial fibrillation in terms of an effect on mortality and morbidity. Sinus rhythm could be restored in the majority and amiodarone was superior to placebo in this regard.

Influence of honey on orally and intravenously administered diltiazem kinetics in rabbits.

Effect of honey on plasma concentration of diltiazem after oral and intravenous administration in rabbits, has been studied. For oral study, single dose of diltiazem (5 mg/kg, p.o.) along with saline was administered to New Zealand white rabbits (n=8). Blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6 and 8 hr after drug administration from marginal ear vein. After a washout period of one week, diltiazem was administered with honey (2.34 ml/kg; p.o.) and the blood samples were collected as above. To the same animals honey (2.34 ml/kg; p.o.) was continued once daily for 7 days. On 8th day, honey and diltiazem were administered simultaneously and blood samples were collected at similar time intervals as mentioned above. For intravenous study the pharmacokinetic was done in each animal on two occasions. The first study was done after single dose administration of diltiazem (5 mg/kg; i.v.) along with saline (2.34 ml/kg; p.o.). Blood samples were collected at 0, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4 and 6 hr after i.v. diltiazem administration. The same animals were treated with honey (2.34 ml/kg; p.o.) for seven days. On day 8, the second study was carried out with single dose i.v. administration of diltiazem along with honey (2.34 ml/kg; p.o.) and blood samples were collected. In the oral study, single dose administration of honey decreased the AUC and Cmax of diltiazem associated with significant increase in clearance and volume of distribution when compared to saline treated group. After one week administration of honey, diltiazem kinetic data showed further reduction in AUC and Cmax and increase in clearance and volume of distribution. In the i.v. study also, multiple dose administration of honey significantly reduced the AUC and increased the clearance value of diltiazem. The results suggest that honey may decrease the plasma concentration of diltiazem after its oral or i.v. administration in rabbits.

Antihypertensive efficacy and tolerability of once-daily sustained-release diltiazem alone and in combination with ramipril in hypertension.

This study assessed once-daily (OD), sustained-release (SR) diltiazem alone and in combination with ramipril in essential hypertension. Fifty patients with supine diastolic blood pressure (DBP) > or = 95-< or = 114 mm Hg were entered into the active treatment phase of the study after 2 weeks of placebo run-in. Sustained-release diltiazem 180 mg OD was administered for 2 weeks, then optimally titrated, at 2 week intervals, to SR diltiazem 240 mg OD and then SR diltiazem 180 mg + ramipril 2.5 mg OD to achieve supine DBP < or = 90 mm Hg. After 4 weeks of diltiazem monotherapy (SR diltiazem 180 mg or 240 mg OD) mean supine DBP was reduced from 102.84 +/- 3.81 mm Hg to 90.15 +/- 5.02 mm Hg (P < 0.01) and mean supine heart rate was reduced from 85.15 +/- 11.02 bpm to 77.62 +/- 11.45 bpm (p < 0.01). Diltiazem monotherapy reduced supine DBP to < or = 90 mm Hg in 35/45 (77.77%) patients. Combination therapy (SR diltiazem 180 mg + ramipril 2.5 mg OD), received by non-responders to diltiazem monotherapy, reduced supine DBP to < or = 90 mm Hg in 3/10 (30%) patients. Sinus bradycardia was observed in one patient. Sustained-release diltiazem alone and in combination with ramipril reduce blood pressure in a dose related manner and is well tolerated.

Comparison of efficacy of intravenous diltiazem and esmolol in terminating supraventricular tachycardia.

OBJECTIVE: Paroxysmal supraventricular tachycardia (PSVT) can be effectively terminated by the intravenous administration of adenosine or verapamil. However adenosine is expensive and injectable verapamil currently is scarcely available. While intravenous diltiazem has been shown to be useful for terminating PSVT, the efficacy of esmolol in this regard has not been evaluated previously. Hence these latter two drugs were studied for their efficacy in terminating PSVT. METHODS: A prospective, randomised, crossover study was undertaken in patients presenting with hemodynamically tolerated PSVT to the ICCU. While 50 patients had been planned for the trial, the study had to be prematurely terminated after 32 patients had been enrolled due to the marked superiority of diltiazem. Two sequential doses with a 5 minute interval of either drug were administered before crossover. Diltiazem was given in a dose of 0.25 mg/kg while the esmolol dose was 0.5 mg/kg. RESULTS: Diltiazem terminated PSVT in all the 16 patients in whom it was given as the first drug. The 12 patients who did not respond to esmolol were also effectively treated with diltiazem. Thus totally 28/28 patients responded to diltiazem while only 4/16 patients responded to esmolol (p < 0.001). Of the 28 patients who responded to diltiazem, in 13 patients the second bolus of diltiazem worked after the first one had failed. No significant adverse effects were seen. CONCLUSION: Intravenous diltiazem is highly effective and safe for terminating PSVT. When the first bolus is ineffective, the second bolus given after 5 minutes usually succeeds. Esmolol in the dose of 0.5 mg/kg has poor efficacy for terminating PSVT, even when 2 boluses are administered.

Antagonistas dos canais de cálcio na insuficiência cardíaca congestiva / Calcium channel blockers in heart failure

A utilizaçäo dos antagonistas dos canais de cálcio no tratamento da disfunçäo ventricular esquerda e da insuficiência cardíaca congestiva tem sido proposta, principalmente, por seu potente efeito vasodilatador.Entretanto, a despeito da base teórica, os resultados dos estudos que exploram seu benefício nessas circunstância clínicas näo têm sido animadores.Talvez, porque os antagonistas dos canais de cálcio podem promover depressäo da contralidade, ativaçäo do sistema neuro-hormonal e alteraçäo desfavorável nos marcadores autonômicos.Os diidropiridínicos de primeira geraçäo demonstram efeitos deletérios sobre as condições hemodinâmicas e o estado clínico.O diltiazem acrescentou prejuízo, quando utilizado em disfunçäo sistólica devida a doença arterial coronária.O verapamil, que näo é utilizado em insuficiência cardíaca congestiva sistólica, monstrou ser benéfico na disfunçäo diastólica ventricular esquerda, como a nisoldipina.Esta última e a nicardipina näo foram consideradas seguras para uso em pacientes com insuficiência cardíaca congestiva moderada a grave.A felopidina näo apresentou diferença de resultados, em relaçäo à mortalidade e a tolerância ao esforço, quando comparada ao grupo placebo.Entretanto, a amlodipina demonstrou uma reduçäo significativa da mortalidade, em pacientes com insuficiência cardíaca congestiva secundária à cardiomiopatia näo isquêmica.Portanto, há que ser cauteloso na utilizaçäo dos antagonistas dos canais de cálcio de primeira geraçäo e considerar o benefício terapêutico demonstrado pela amlodipina, quando adicionada ao tratamento padräo da insuficiência cardíaca congestiva.

Low-dose intravenous diltiazem--efficacy and safety in supraventricular tachyarrhythmias.

Intravenous diltiazem has been used to rapidly reduce ventricular rate in patients with supraventricular tachyarrhythmias (SVTs). This study assesses the efficacy and safety of a low-dose (0.1 mg/kg) intravenous bolus of diltiazem on the heart rate and blood pressure. Fifteen consecutive patients were treated for 21 episodes of atrial fibrillation, sinus tachycardia or ectopic atrial tachycardia. The bolus dose reduced the heart rate significantly in all patients with atrial fibrillation within 5 min (173 +/- 21 to 144 +/- 27 beats/min, p < 0.05) with the maximum response seen at 10 min (128 +/- 26.7 beats/min, p < 0.05). However, patients with sinus tachycardia showed a significant decrease in heart rate only at 15 min (147 +/- 12 to 123 +/- 15 beats/min, p < 0.05). One patient with ectopic atrial tachycardia required maintenance infusion of diltiazem. Conversion to sinus rhythm was observed in another patient with atrial fibrillation. The drug was well tolerated with no significant hypotension, bradyarrhythmia or aggravation of pre-existing congestive heart failure. It is concluded that Indian patients require a lower dose of intravenous diltiazem as compared to Western ones (0.1 mg/kg versus 0.25-0.33 mg/kg) which gives a prompt, effective and safe response in patients with SVTs.