The effects of dobutamine on cardiac sympathetic activity in patients with congestive heart failure

OBJECTIVES: The goal of this work was to study the effects of short-term infusion of dobutamine on efferent cardiac sympathetic activity. BACKGROUND: Increased efferent cardiac sympathetic activity is associated with poor outcomes in the setting of congestive heart failure (CHF). Dobutamine is commonly used in the therapy of decompensated CHF. Dobutamine, through its effects on excitatory beta-receptors, may increase cardiac sympathetic activity. METHODS: Seven patients with normal left ventricular (LV) function and 13 patients with CHF were studied. A radiotracer technique was used to measure cardiac norepinephrine spillover (CANESP) before and during an intravenous infusion of dobutamine titrated to increase the rate of rise in LV peak positive pressure (+dP/dt) by 40%. RESULTS: Systemic arterial pulse pressure increased significantly in response to dobutamine in the normal LV function group (74 +/- 3 mm Hg to 85 +/- 3 mm Hg, p = 0.005) but remained unchanged in the CHF group. Dobutamine caused a significant decrease in LV end-diastolic pressure in the CHF group (14 +/- 2 mm Hg to 11 +/- 2 mm Hg, p = 0.02), an effect not observed in the normal LV group. In the normal LV function group, CANESP did not change in response to dobutamine (75 +/- 22 pmol/min vs. 72 +/- 22 pmol/min, p = NS). In contrast, dobutamine infusion was associated with a significant reduction in CANESP in patients with CHF (199 +/- 43 pmol/min to 128 +/- 30 pmol/min, p < 0.0009). CONCLUSIONS: Dobutamine infusion caused a significant sympatholytic response in patients with CHF. This sympathetic withdrawal response is probably related to reduction of LV filling pressures and/or activation of ventricular mechanoreceptors with dobutamine infusion.     

Systemic delivery of β-blockers via transdermal route for hypertension

Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later.     

Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design,characterization, in vitro and in vivo evaluation

Abstract

Naringenin (NRG), predominant flavanone in grapefruits, possesses anti-inflammatory, anti-carcinogenic, hepato-protective and anti-lipid peroxidation effects. Slow dissolution after oral ingestion due to its poor solubility in water, as well as low bioavailability following oral administration, restricts its therapeutic application. The study is an attempt to improve the solubility and bioavailability of NRG by employing self-nanoemulsifying drug delivery technique. Preliminary screening was carried out to select oil, surfactant and co-surfactant, based on solubilization and emulsification efficiency of the components. Pseudo ternary phase diagrams were constructed to identify the area of nanoemulsification. The developed self-nanoemulsifying drug delivery systems (SNEDDS) were evaluated in term of goluble size, globule size distribution, zeta potential, and surface morphology of nanoemulsions so obtained. The TEM analysis proves that nanoemulsion shows a droplet size less than 50?nm. Freeze thaw cycling and centrifugation studies were carried out to confirm the stability of the developed SNEDDS. In vitro drug release from SNEDDS was significantly higher (p?<?0.005) than pure drug. Furthermore, area under the drug concentration time-curve (AUC_0–24) of NRG from SNEDDS formulation revealed a significant increase (p?<?0.005) in NRG absorption compared to NRG alone. The increase in drug release and bioavailability as compared to drug suspension from SNEDDS formulation may be attributed to the nanosized droplets and enhanced solubility of NRG in the SNEDDS.     

Drug induced oral erythema multiforme: Case report

Introduction:Drug induced oral erythema multiforme a rare clinical entity which involves only the lips and oral mucosa without skin involvement. These lesions are difficult in diagnosing with other oral ulcerative lesions with similar clinical manifestations.Patient concerns:This article presents 2 case reports of Oral erythema multiforme in which drugs were the precipitating factor. Its etiopathogenesis, differential diagnosis and treatment modalities of the disease is discussed.Diagnosis:Based on patient''s complaints, drug history and clinical appearance, provisional diagnosis of drug induced erythema multiforme was considered.Intervention:For case 1, patient was instructed to discontinue usage of drug and prescribed systemic steroid (Prednisolone 10 mg/d) for a week along with germicidal drugs to prevent secondary infection. Medication was tapered to 5 mg/d after first week.For case 2, patient was instructed to discontinue the drug and systemic steroid prednisolone 20 mg /d for 1 week with tapering dose of 10 mg/d for the second week was administered.Outcome:For case 1 and case 2 healing of the lesions were evident on third week of follow up.Conclusion:Medications should be taken under medical supervision. Over the counter drugs might lead to allergic reactions like drug induced oral erythema multiforme, which is a rare variant and needs to be differentiate from other oral ulcerative lesion for prompt management and follow-up.     

Pulsed Doppler echocardiography in the diagnosis and estimation of severity of aortic insufficiency

Detection and estimation of the degree of chronic aortic insufficiency with pulsed Doppler echocardiography was attempted in 27 patients documented to have aortic insufficiency on aortography. Twenty-five patients had associated aortic stenosis or mitral valve disease, or both. A disturbed diastolic flow within the left ventricular outflow tract was recorded in all but one patient (Doppler sensitivity 96 percent). Aortic insufficiency was clinically undetected In three patients (clinical sensitivity 89 percent). In a small number of patients Doppler echocardiography also appeared to be highly specific for this disorder. The Doppler technique estimated the degree of aortic Insufficiency by assessing the distribution of diastolic flow within the outflow tract and the body of the left ventricle. A significant correlation between the Doppler method and the angiographic estimation of aortic insufficiency was found (r = 0.88, p < 0.01).     

The Effects of Intravenous Levofloxacin on the QT Interval and QT Dispersion

The QT dispersion (QT_d) is a non-invasive means of identifying those patients at an increased risk of developing sudden cardiac death (SCD). Although levofloxacin has a minimal effect on the QT_c interval, isolated reports of QT prolongation, polymorphic ventricular tachycardia with a normal QT interval and TdP have been reported. The purpose of this study was to examine the effect of intravenous levofloxacin on the QT interval and QT_d. Of the 50 patients who were deemed candidates to receive intravenous levofloxacin, 29 met the eligibility criteria and were enrolled in this study. A 12-lead ECG was performed before the initiation of levofloxacin (baseline), and on days 3 and 5. The QT^c _min, QT^c _max and the QT_d were calculated. Measurements where made by two independent observers blinded to the patients’ clinical status. The QT_d increased significantly on days 3 and 5 following the initiation of therapy [QT_d (baseline) 33.3 ± 20 ms, QT_d (day 3) 64.4 ± 31.3 ms (p = 0.023), QT_d (day 5) 66.8 ± 20.3 ms, (p = 0.008)]. The increase in the QT_d was significantly longer in men than women. Although women had a shorter baseline QT_d compared to men, this did not achieve statistical significance. Intravenous levofloxacin was found to significantly increase the QT_d, which was more pronounced in men compared to women. Its effect on the QT_d may increase the risk of developing a potentially fatal ventricular arrhythmia. Therefore, care must be taken when prescribing this medication to patients with a pre-existing risk of developing SCD.