Optimization of Diltiazem hydrochloride osmotic formulation using QBD approach

Abstract Diltiazem hydrochloride (DLH) is a calcium channel blocker useful for the treatment of angina pectoris, arrhythmia, and hypertension. DLH having a short half-life needs frequent administration for successful treatment but this poses a problem of poor patient compliance. These requirements are served by elementary osmotic pump tablets (EOP) based controlled-release (CR) systems. Quality by design (QbD) approach assists in screening various factors with subsequent assessment of critical parameters that can have a major impact on the scalability of EOP. Tablets were formulated using wet granulation method followed by osmotic coating. Factorial design based QbD strategy aided in defining the risk assessment of influential variables such as hydrophilic polymers and osmotic coat component on the in-vitro release kinetics of the designed EOP tablets. These formulated EOP systems followed zero-order kinetics, a characteristic feature of EOPs. EOP tablets were formulated applying a systematic QbD statistical approach. The formulated DLH EOP systems with improved concentration-independent behavior helped to address the challenges of IR formulation. Application of QbD strategy in ascertaining the scalability of DLH EOP formulation would help pharmaceutical industries in the translation of EOP based drug delivery systems from R&D to market.

Comparison of the apoptotic effects of topically applied papaverine, diltiazem, and nitroprusside to internal thoracic artery

Abstract Objective: To detect and to compare the apoptotic effects of intraoperatively topically applied diltiazem, papaverine, and nitroprusside. Methods: Internal thoracic artery segments of ten patients were obtained during coronary bypass grafting surgery. Each internal thoracic artery segment was divided into four pieces and immersed into four different solutions containing separately saline (Group S), diltiazem (Group D), papaverine (Group P), and nitroprusside (Group N). Each segment was examined with both hematoxylin-eosin and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in order to determine and quantify apoptosis. Results: Apoptotic cells were counted in 50 microscopic areas of each segment. No significant difference was observed among the four groups according to hematoxylin-eosin staining. However, the TUNEL method revealed a significant increase in mean apoptotic cells in the diltiazem group when compared with the other three groups (Group S=4.25±1.4; Group D=13.31±2.8; Group N=9.48±2.09; Group P=10.75±2.37). The differences between groups were significant (P=0.0001). No difference was observed between the samples of the diabetic and non-diabetic patients in any of the study groups. Conclusion: The benefit of topically applied vasodilator drugs must outweigh the potential adverse effects. In terms of apoptosis, diltiazem was found to have the most deleterious effects on internal thoracic artery graft segments. Of the analyzed medical agents, nitroprusside was found to have the least apoptotic activity, followed by papaverine. Diabetes did not have significant effect on the occurrence of apoptosis in left internal thoracic artery grafts.

Calcium channel blocker diltizem transiently inhibits migration and up-regulates metadherin expression in hepatocellular carcinoma cells / 南方医科大学学报

OBJECTIVE@#To investigate the effect of calcium channel blocker diltizem in reversing multi-drug resistance (MDR) and on metadherin expression in hepatocellular carcinoma cells and explore the molecular mechanism.@*METHODS@#Hepatocellular carcinoma MHCC97H and 7402 cells were treated with diltiazem hydrochloride, a calcium channel blocker (0, 25, 50, 100, 200, and 400 μmol/L), for 12, 24, or 48 h. Wound healing assay was employed to assess the changes in the mobility and migration of the cells following the treatments, and the changes in the expression levels of metadherin mRNA and protein and P-gp protein were determined using RT-PCR and immunocytochemistry.@*RESULTS@#Diltiazem hydrochloride could transiently inhibit the migration and movement of MHCC97H and 7402 cells in a time-and concentration-dependent manner ( < 0.05). Diltiazem hydrochloride at different concentrations also transiently up-regulated the expressions of metadherin mRNA and protein but did not inhibit the expression of P-gp protein in MHCC97H and 7402 cells.@*CONCLUSIONS@#Calcium channel blocker can transiently inhibit the migration of hepatocellular carcinoma cells and up-regulate the expression of metadherin mRNA and protein through a feedback mechanism, suggesting the potential risk of calcium channel blockers for promoting tumor progression during the treatment of malignant tumors.

Cost-Effectiveness of Rate- and Rhythm-Control Drugs for Treating Atrial Fibrillation in Korea

PURPOSE: Although the economic and mortality burden of atrial fibrillation (AF) is substantial, it remains unclear which treatment strategies for rate and rhythm control are most cost-effective. Consequently, economic factors can play an adjunctive role in guiding treatment selection. MATERIALS AND METHODS: We built a Markov chain Monte Carlo model using the Korean Health Insurance Review & Assessment Service database. Drugs for rate control and rhythm control in AF were analyzed. Cost-effective therapies were selected using a cost-effectiveness ratio, calculated by net cost and quality-adjusted life years (QALY). RESULTS: In the National Health Insurance Service data, 268149 patients with prevalent AF (age ≥18 years) were identified between January 1, 2013 and December 31, 2015. Among them, 212459 and 55690 patients were taking drugs for rate and rhythm control, respectively. Atenolol cost $714/QALY. Among the rate-control medications, the cost of propranolol was lowest at $487/QALY, while that of carvedilol was highest at $1363/QALY. Among the rhythm-control medications, the cost of pilsicainide was lowest at $638/QALY, while that of amiodarone was highest at $986/QALY. Flecainide and propafenone cost $834 and $830/QALY, respectively. The cost-effectiveness threshold of all drugs was lower than $30000/QALY. Compared with atenolol, the rate-control drugs propranolol, betaxolol, bevantolol, bisoprolol, diltiazem, and verapamil, as well as the rhythm-control drugs sotalol, pilsicainide, flecainide, propafenone, and dronedarone, showed better incremental cost-effectiveness ratios. CONCLUSION: Propranolol and pilsicainide appear to be cost-effective in patients with AF in Korea assuming that drug usage or compliance is the same.

TeleCondutas: fissura anal / TeleGuides: anal fissure

A fissura anal é uma laceração do revestimento do canal anal inferior. É uma das patologias benignas anorretais mais comuns e, em muitos casos, resolve-se espontaneamente. Sua prevalência é igual entre os sexos e é mais comum em adultos jovens. A grande maioria das fissuras são primárias e causadas por trauma local, como constipação, diarreia ou sexo anal. Fissuras secundárias são encontradas em pacientes com Doença de Crohn, malignidades (neoplasia epidermoide do canal anal, leucemia), tuberculose ou doenças sexualmente transmissíveis (HIV, sífilis, clamídia). Esta guia apresenta informação que orienta a conduta para casos de fissura anal no contexto da Atenção Primária à Saúde, incluindo: classificação, avaliação clínica, diagnóstico, tratamento clínico, tratamento cirúrgico e encaminhamento para especialista.

Development and validation of a stability indicating HPLC method to determine diltiazem hydrochloride in tablets and compounded capsules

ABSTRACT A stability indicating HPLC method to determine diltiazem hydrochloride (DTZ) in tablets and compounded capsules was developed and validated according to Brazilian and the International Conference on Harmonization (ICH) guidelines. The separation was carried out on a Purospher Star® C18 (150 x 4.6 mm i.d., 5 µm particle size, Merck Millipore) analytical column. The mobile phase consisted of a 0.05% (v/v) trifluoroacetic acid aqueous solution and a 0.05% trifluoroacetic acid methanolic solution (44:56, v/v). The flow rate was 1.0 mL.min-1 with a run time of 14 minutes. The detection of DTZ and degradation products (DP) was performed at 240 nm, using a diode array detector. The method proved to be linear, precise, accurate, selective, and robust, and was adequate for stability studies and routine quality control analyses of DTZ in tablets and compounded capsules.

Impact of Diltiazem Alone versus Diltiazem with Nitrate on Five-Year Clinical Outcomes in Patients with Significant Coronary Artery Spasm

PURPOSE: Calcium channel blockers diltiazem and nitrate have been used as selective coronary vasodilators for patients with significant coronary artery spasm (CAS). However, no study has compared the efficacy of diltiazem alone versus diltiazem with nitrate for long-term clinical outcomes in patients with CAS. MATERIALS AND METHODS: A total of 2741 consecutive patients without significant coronary artery disease with positive CAS by acetylcholine (Ach) provocation test between November 2004 and May 2014 were enrolled. Significant CAS was defined as a narrowing of >70% by incremental intracoronary injection of 20, 50, and 100 µg of Ach into the left coronary artery. Patients were assigned to either the diltiazem group (n=842) or the dual group (diltiazem with nitrate, n=1899) at physician discretion. To adjust for potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. After PSM analysis, two well-balanced groups (811 pairs, n=1622, C-statistic=0.708) were generated. RESULTS: At 5 years, there were similar incidences in primary endpoints, including mortality, myocardial infarction, revascularization, and recurrent angina requiring repeat coronary angiography between the two groups. Diltiazem alone was not an independent predictor for major adverse cardiovascular events or recurrent angina requiring repeat coronary angiography. CONCLUSION: Despite the expected improvement of endothelial function and the relief of CAS, the combination of diltiazem and nitrate treatment was not superior to diltiazem alone in reducing mortality and cardiovascular events up to 5 years in patients with significant CAS.

Supraventricular Tachycardia by Concealed Bypass Tract

Concealed bypass tract (CBT) results from incomplete development of the atrioventricular (AV) annulus. CBT conducts only in a retrograde direction, and therefore does not cause pre-excitation on standard electrocardiograms. The most common tachycardia associated with CBT is an orthodromic atrioventricular reentrant tachycardia (AVRT): a pathway involving anterograde circuitry through the AV node and His Purkinje system and retrograde conduction over the accessory pathway. Orthodromic AVRT accounts for approximately 90%-95% cases of AVRT. Most incidences of CBT occur at the left free wall. Vagal maneuvers and/or intravenous (IV) adenosine are recommended for first line acute management of AVRT. However, pharmacological therapy with IV diltiazem, verapamil, or beta blockers can also be effective for acute treatment for orthodromic AVRT in patients who do not show pre-excitation on their resting ECG during sinus rhythm. The first-line ongoing therapy for AVRT is catheter ablation of CBT; when catheter ablation is not indicated or preferred, oral beta blockers, diltiazem, verapamil, flecainide, propafenone, or amiodarone are recommended.

Preventive effects of imperatorin on perfluorohexanesulfonate-induced neuronal apoptosis via inhibition of intracellular calcium-mediated ERK pathway

Early life neuronal exposure to environmental toxicants has been suggested to be an important etiology of neurodegenerative disease development. Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds, is widely distributed environmental contaminants. We have reported that PFHxS induces neuronal apoptosis via ERK-mediated pathway. Imperatorin is a furanocoumarin found in various edible plants and has a wide range of pharmacological effects including neuroprotection. In this study, the effects of imperatorin on PFHxS-induced neuronal apoptosis and the underlying mechanisms are examined using cerebellar granule cells (CGC). CGC were isolated from seven-day old rats and were grown in culture for seven days. Caspase-3 activity and TUNEL staining were used to determine neuronal apoptosis. PFHxS-induced apoptosis of CGC was significantly reduced by imperatorin and PD98059, an ERK pathway inhibitor. PFHxS induced a persistent increase in intracellular calcium, which was significantly blocked by imperatorin, NMDA receptor antagonist, MK801 and the L-type voltage-dependent calcium channel blockers, diltiazem and nifedipine. The activation of caspase-3 by PFHxS was also inhibited by MK801, diltiazem and nifedipine. PFHxS-increased ERK activation was inhibited by imperatorin, MK801, diltiazem and nifedipine. Taken together, imperatorin protects CGC against PFHxS-induced apoptosis via inhibition of NMDA receptor/intracellular calcium-mediated ERK pathway.

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.

Clinical and Histopathological Study of 84 Cases of Pigmented Purpuric Dermatosis / 대한피부과학회지

BACKGROUND: Pigmented purpuric dermatosis (PPD) comprises a group of dermatoses characterized clinically by pinpoint petechiae and purpura with a brown, red, or yellow patchy pigmented base. Histopathologically, extravasation of erythrocytes with hemosiderin deposition, a perivascular lymphocytic infiltrate on the superficial capillaries, and endothelial cell swelling are observed; however, their etiology remains obscure. There have been few reports regarding the clinical and histopathological characteristics of PPD in Korea. OBJECTIVE: To investigate the epidemiology, etiology, clinical manifestations, and histopathological features of PPD in Korea. METHODS: We retrospectively evaluated the clinical manifestations and histopathological features of 84 patients with PPD diagnosed at our center between January 2003 and December 2013. RESULTS: Of the 84 patients, 44 were male and 40 were female. The mean age of occurrence was 44.6 years and, the most commonly involved sites were the lower extremities (95.2%). Most of the PPD patients were asymptomatic (65.5%), however, others complained of itching (25%), pain (3.6%), heat sensations (3.6%), or tingling sensations (2.3%). The majority (63.1%) had Schamberg's disease, 15.5% had Majocchi's disease, 10.7% had eczematid-like purpura of Doucas and Kapetanakis, 7.1% had Gougerot-Blum syndrome, and 3.6% had lichen aureus. Of the 84 patients, 35.7% of patients had medical problems and 32.1% had etiologic factors including orthostatic hypertension (13.2%), trauma (7.2%), contact dermatitis (4.8%), sex hormones (4.8%), postpartum (1.2%), and diltiazem (1.2%). Histopathologically, extravasation of erythrocytes with or without hemosiderin deposit and a mild-to-dense perivascular or lichenoid lymphocytic infiltrate in the upper dermis were common features. A review of the prognoses of 72 patients revealed that 52.8% were clinically improved and that the most common treatment modality was a topical steroid (79.2%). CONCLUSION: Study results suggested variable clinical manifestations with common histologic features of PPD, and that variable etiologic factors could trigger the occurrence of PPD. We recommend the addition of both trauma and sex hormones as etiologic factors. There was no significant difference between the treatment modalities and the level of clinical improvement.

Sphincter-Preserving Therapy for Treating a Chronic Anal Fissure: Long-term Outcomes

PURPOSE: To estimate the risk of recurrent fissure in ano after sphincter preserving treatments. METHODS: A retrospective case note review, combined with a telephone survey was conducted for all patients treated for a chronic anal fissure between 1998 and 2008. RESULTS: Six hundred and twelve patients (303 women: mean age, 39 years; range, 16-86 years) were treated for chronic anal fissure between 1998 and 2008. Topical diltiazem 2% was initially prescribed for 8 weeks. The fissure did not heal in 141 patients. These patients (61 women: mean age, 30 years; range, 15-86 years) were treated with 100 IU botulinum A toxin (Botox) injection combined with a fissurectomy under general anaesthesia. Thirty eight patients suffered a recurrence of their fissure within two years. Thirty-four healed with further medical or sphincter conserving surgical therapy while four required a lateral internal sphincterotomy. CONCLUSION: The vast majority of patients with chronic anal fissure can be treated with sphincter conserving treatments. This may require several interventions before healing can be achieved. Assessment for recurrence after 'conservative' treatments requires a minimum of two-year follow-up.

Cardiotonic activity of methanolic extract of Saussurea lappa Linn roots

The cardiac activity of Saussurea lappa roots was evaluated in isolated perfused rabbit heart by the Langendorff's technique. Heart rate, contractility and coronary flow were determined in the presence of different concentrations of methanolic extract of Saussurea lappa, digoxin and diltiazem. The extract exhibited significant [p<0.01] positive inotropic effect at the first three doses [0.5/ Micro g, 2.5/ Micro g and 5.0/ Micro g] while a significant negative chronotropic effect and coronary flow rates were observed at all the doses tested. These effects were comparable to the effects of digoxin and diltiazem. The increase in force of contraction with decrease in heart rate and coronary flow rates were also observed to be dose dependent as increase in the dose of test extract further enhanced the effects except contractility that started decreasing at higher doses. It is conceivable therefore, that Saussurea lappa roots contain certain pharmacologically active compounds that could be involved in the cardiotonic activity of the extract

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

Pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers

The pharmacokinetics (PK) of ordinary tablets and sustained release capsules of diltiazem hydrochloride in human clinical trials had been studied. The PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules, a new dosage form, has not been reported, although it is very important to clinical use. In this paper, we investigated the PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules and the food influence in Chinese healthy volunteers. The PK parameters indicated that the diltiazem hydrochloride delay-onset sustained-release pellet capsules appeared marked characteristics of delayed and controlled release. An opened-label, randomized and parallel clinical trial was conducted in 36 Chinese healthy volunteers with single oral dose (90 mg, 180 mg or 270 mg) and a multiple oral dose (90 mg d-1×6 d) administration. The effect of food on the PK of one single oral dose (360 mg) was investigated in 24 healthy Chinese volunteers. Plasma diltiazem concentration was determined by reversed-phase high-performance liquid chromatography (RP-HPLC) and the main pharmacokinetic parameters were analyzed by PKSolver (Ver 2.0). All clinical studies were conducted in the Clinical Pharmacological Center (No. JDX1999064) of Xiangya Hospital Affiliated Central South University, China. The PK parameters suggested that the new formulation had marked characteristics of delayed and controlled release of diltiazem, and food intake did not alter significantly diltiazem pharmacokinetic parameters.

Embora a farmacocinética (PK) do cloridrato de diltiazem nas formas de comprimidos de liberação imediata e cápsulas de liberação modificada em ensaios clínicos já tenha sido relatada, a pesquisa da PK do cloridrato de diltiazem na forma de cápsulas com peletes de liberação retardada e sustentada ainda é muito importante. Neste trabalho, propusemos avaliar a farmacocinética do cloridrato de diltiazem administrado através desta nova forma farmacêutica em voluntários chineses sadios, assim como a influência da ingestão de alimentos neste perfil farmacocinético. Foi realizado um ensaio clínico aberto, randomizado e paralelo em 36 voluntários, que receberam dose oral única de 90 mg, 180 mg ou 270 mg e dose múltiplas (90 mg/d × 6 d) pela mesma via de administração. Para avaliar o efeito da ingestão de alimentos sobre a PK do diltiazem foi realizada a administração de dose única (360 mg) em 24 voluntários chineses sadios. A concentração plasmática do diltiazem foi determinada por Cromatografia Liquida de Alta Eficiência em fase reversa (CLAE-FR) e os principais parâmetros farmacocinéticos foram analisados através do emprego do software PKSolver (Ver 2.0). O ensaio de farmacocinética clínica foi conduzido na clínica Pharmacological Center (No.JDX1999064) do Hospital de Xiangya, Central South University, China. Os parâmetros PK obtidos indicaram que a nova formulação de cápsulas de liberação retardada e sustentada de cloridrato de diltiazem possue marcantes características de liberação retardada e controlada do fármaco.

Hypertensive Crisis during Removal of Retroperitoneal Mass in a Patient with Undiagnosed Paraganglioma - A Case Report - / 대한구급학회지

Paragangliomas have been reported on multiple locations. A diagnosis of a catecholamine-secreting tumor was considered only after induction of anesthesia, when BP (blood pressure) increased. A 61-year-old male patient was referred for removal of a retroperitoneal mass suspected hemangiopericytoma. He was on medications for hypertension. There was a surge of ABP (arterial blood pressure) to 186/117 mmHg when the tumor was manipulated at the beginning of the surgery, and this was treated by bolus of diltiazem. After resection of the tumor, ABP dropped to 57/36 mmHg. In order to improve the patient's hemodynamic parameters, crystalloid fluid was given, and ephedrine was administered intravenously. Persistent hypotension was treated with titrated vasopressors (epinephrine and norepinephrine). When paraganglioma is suspected due to a sudden hypertensive crisis during surgery, the surgeon must decide whether to proceed with the surgical procedure or to stop and restart the surgery after proper management of the crisis.

Clinical trial of diltiazem on dystrophic calcinosis cutis in a dog / 대한수의학회지

Dystrophic calcinosis cutis associated with spontaneous hyperadrenocorticism was diagnosed in a 8-year-old female Chihuahua dog with erythematous, erosive, numerous papules, plaques, and crusts on the bilateral trunk, and inguinal region. Serum biochemical abnormalities included increases in alkaline phosphatase (ALP), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), and cholesterol. Radiographs showed mild hepatomegaly and subcutaneous lobulated calcific deposits. Histopathologic examination demonstrated diffuse deposition of basophilic calcified material in the dermis. Von Kossa's stain confirmed calcium deposition. Therapy with diltiazem was useful in resolving calcinosis.

Diltiazem como alternativa ao betabloqueador na angiotomografia de artérias coronárias / Diltiazem as an alternative to beta-blocker in coronary artery computed tomography angiography

FUNDAMENTO: A redução da frequência cardíaca (FC) na angiografia por tomografia das artérias coronarianas (ATCCor) é fundamental para a qualidade de imagem. A eficácia dos bloqueadores de cálcio como alternativas para pacientes com contraindicações aos betabloqueadores não foi definida. OBJETIVOS: Comparar a eficácia na redução da FC e variabilidade RR do metoprolol e diltiazem na ATCCor. MÉTODOS: Estudo prospectivo, randomizado, aberto, incluiu pacientes com indicação clínica de ATCCor, em ritmo sinusal, com FC>70bpm e sem uso de agentes que interferissem com a FC. Cinquenta pacientes foram randomizados para grupos: metoprolol IV 5-15 mg ou até FC≤60 bpm(M), e diltiazem IV 0,25-0,60mg/kg ou até FC≤60 bpm (D). Pressão arterial (PA) e FC foram aferidas na condição basal, 1min, 3min e 5min após agentes, na aquisição e após ATCCor. RESULTADOS: A redução da FC em valores absolutos foi maior no grupo M que no grupo D (1, 3, 5min, aquisição e pós-exame). A redução percentual da FC foi significativamente maior no grupo M apenas no 1 min e 3 min após início dos agentes. Não houve diferença no 5 min, durante a aquisição e após exame. A variabilidade RR percentual do grupo D foi estatisticamente menor do que a do grupo M durante a aquisição (variabilidade RR/ FC média da aquisição). Um único caso de BAV, 2:1 Mobitz I, revertido espontaneamente ocorreu (grupo D). CONCLUSÃO: Concluímos que o diltiazem é uma alternativa eficaz e segura aos betabloqueadores na redução da FC na realização de angiografia por tomografia computadorizada das artérias coronarianas. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).

BACKGROUND: Reducing heart rate (HR) in CT angiography of the coronary arteries (CTACor) is critical to image quality. The effectiveness of calcium channel blockers as alternatives for patients with contraindications to beta-blockers has not been established. OBJECTIVES: To compare the efficacy in the reduction of HR and RR variability of metoprolol and diltiazem in CTACor. METHODS: Prospective, randomized, open study that included patients with clinical indication of CTACor in sinus rhythm with HR > 70 bpm and no use of agents that could interfere with HR. Fifty patients were randomized to the groups: metoprolol IV 5-15 mg or up to HR ≤ 60 bpm (M), and diltiazem IV 0.25 to 0.60 mg/kg or up to HR ≤ 60 bpm (D). Blood pressure (BP) and HR were measured at baseline, 1 minute, 3 minutes and 5 minutes after the agents, at the acquisition and after CTACor. RESULTS: HR reduction in absolute values was higher in group M than in group D (1, 3, 5 min, acquisition and post-test). The percentage reduction of HR was significantly higher in group M only 1 min and 3 min after the start of the agents. There was no difference in 5 min at acquisition and after examination. The percentage RR variability in group D was lower than that in group M during acquisition (RR variability/mean HR of acquisition). A single case of AVB, 2:1 Mobitz I occurred, which was spontaneously reverted (group D). CONCLUSION: We conclude that diltiazem is an effective and safe alternative to beta-blockers in the reduction of HR when performing computed tomography angiography of coronary arteries. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).

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.