Hydralazine Research Articles

Formulation and evaluation of sublingual film of hydralazine hydrochloride

The objective of this research was to formulate fast dissolving sublingual film of Hydralazine hydrochloride for rapid action. Hydralazine hydrochloride is a direct acting smooth muscle relaxant used to treat hypertension. It belongs to the hydrazinophthalazine class of drugs. Solvent casting method was adapted to prepare the sublingual films by using a 32 full factorial design. of their components or with individual components 1. FT-IR and Dissolution studies revealed that there was no physico-chemical interaction between Hydralazine hydrochloride and other polymer. All formulations are evaluated for tensile strength, weight variations, moisture content, mucoadhesion strength, in-vitro disintegration study, in-vitro dissolution study, uniformity of drug content, surface pH, % elongation break ,folding endurance. F6 batch contain Hydralazine hydrochloride (Drug), PVA, PVPK-30 and PEG-400. F9 batch was the optimized batch since it showed of Disintegration time (59 sec), surface PH (6.80) and %Drug release (98.55%).

Synthesis, Molecular Structure and Anti-Onchocercal Studies of 1-(Phthalazin-1(2H)-one)[(Pyridin-2-yl)ethylidene]hydrazone

The novel ligand, 1-(phthalazin-1(2H)-one)[(pyridin-2-yl)ethylidene]hydrazone,(APN), derived from the antihypertensive drug, hydralazine hydrochloride, was synthesized and characterized by spectroscopic methods (IR, 1H NMR). The X-ray crystallographic data indicates that APN has an exocyclic C=N bond on the hydralazine moiety. APN revealed significant anti-onchocercal activity with IC50 values of 0.3125 μg/mL on microfilaria and 10 μg/mL on adult worms compared to the standard drug, ivermectin.

Pharmacologic activation of tumor hypoxia: a means to increase tumor 2-deoxy-2-[18F]fluoro-D-glucose uptake?

Tumor hypoxia and tumor metabolism are linked through the activation of metabolic genes following hypoxia-inducible factor 1 (HIF-1) activation. This raises the question of whether this relationship can be exploited to improve 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography ([(18)F]FDG-PET). To do this, [(18)F]FDG uptake was investigated after chemical induction of hypoxia and chemical activation of HIF-1 in an in vitro and an in vivo model of a human colorectal carcinoma. [(18)F]FDG uptake, HIF-1α protein levels, and messenger ribonucleic acid expression of glucose transporter 1 (GLUT1), hexokinase 2, HIF-1α, and carbonic anhydrase IX (CA IX) were determined in HT29 cells after treatment with 200 μM CoCl(2) and 500 μM dimethyloxalylglycine (DMOG). In an HT29 xenograft, the distribution of endogenous and exogenous markers of hypoxia was investigated using immunohistochemistry, and tumor [(18)F]FDG uptake was determined after treatment with a single dose of 5 mg/kg hydralazine and 8 mg DMOG. Treatment of HT29 cells with CoCl(2) and DMOG induced functional HIF-1 and resulted in increased [(18)F]FDG uptake. In an HT29 xenograft, a similar spatial distribution of pimonidazole, CA IX, and GLUT1 was found, and treatment with DMOG resulted in significant increases in maximum and mean standardized uptake values using [(18)F]FDG-PET. Chemical activation of HIF-1 can increase in vitro and in vivo [(18)F]FDG uptake. Imaging after pharmacologic HIF-1 activation might increase tumor [(18)F]FDG uptake when using [(18)F]FDG-PET.

Hydralazine prn, should we really use it?

Hydralazine prn, should we really use it?

Hydralazine prn, should we really use it?

Hydralazine prn, should we really use it?

The Serine Protease Inhibitor Camostat Mesilate Attenuates the Progression of Chronic Kidney Disease through its Antioxidant Effects

Background/Aims: We have so far demonstrated the renoprotective effect of camostat mesilate (CM) in 5/6 nephrectomized rats at least partly through its antioxidant effect. However, precise mechanisms were not fully clarified. Therefore, we now examined the renoprotective and antioxidant mechanisms of CM by using the adenine-induced chronic kidney disease (CKD) rat model. Methods: In protocol 1, we analyzed the effect of CM on CKD. Rats were fed on a 0.75% adenine diet for 3 weeks to induce CKD followed by the experimental period with vehicle, CM, or hydralazine (HYD) treatment for 5 weeks. In protocol 2, we examined the safety of CM and HYD on the normal rats. In addition, we explored free radical scavenging activities of CM and its metabolites in vitro using electron paramagnetic resonance (EPR) spectroscopy. Results: CM, but not HYD, significantly reduced the serum creatinine levels, although both treatments showed similar reduction in the blood pressure. CM decreased mRNA expression and protein levels of fibrotic markers, the severity of renal fibrosis, the accumulation of oxidative stress, and the expression of NADPH oxidase components in the kidney. In the protocol 2, there were no statistically significant differences in general parameters except for the systolic blood pressure in HYD group. EPR study revealed that CM and its metabolites have potent hydroxyl radical scavenging activities in vitro. Conclusion: Our findings indicate that CM significantly ameliorates the progression of CKD partly through its antioxidant effect independently from its blood pressure-lowering effect. Our results suggest the possibility that CM could be a new therapeutic agent that could arrest the progression of CKD.

Simultaneous Equation Method and Absorption Correction Method for the Estimation of Isosorbide Dinitrate and Hydalazine Hydrochloride in Bulk and Their Combined Tablet Dosage Form using UV Spectrophotometry.

In the present work a simple, accurate and precise method has been developed and validated for the simultaneous estimation of isosorbide di nitrate (ISD), hydralazine hydrochloride(HYD)in bulk and their combined dosage form by UV spectrophotometric methods. The method employes estimation of drugs by simultaneous equation method (SEM) using 208.28nm and 232nm i.e λmax values of ISD and HYD respectively. Method B employs the estimation of drugs by absorption correction method (ACM) at 232nm for HYD where absorbance of ISD is very low. Absorbance correction method was based on the property of additively of absorbance. At 232nm, Hydralazine hydrochoride showed absorbance while Isosorbide dinitrate showed very low absorbance. The method involved measurement of absorbance at wavelength 232 nm. For estimation of HYD, corrected absorbance was calculated at 208 nm due to the interference of HYD at this wavelength. Calibration curves were linear with correlation coefficient 0.999 over the concentration range of 2–10μg/mL and 2–10 μg/mL for ISD and HYD respectively. The percent recoveries of the drugs were found nearly 100% representing the accuracy of the both methods. Validation of the proposed methods was carried out for its accuracy, precision, specificity, linearity and limit of detection according to ICH guidelines. The proposed methods can be successfully applied in routine work for the determination of isosorbide dinitrate and hydralazine hydrochloride in combined dosage form.

Brain Angiotensin II Type 1 Receptor Blockade Improves Dairy Blood Pressure Variability via Sympathoinhibition in Hypertensive Rats.

Abnormal blood pressure (BP) elevation in early morning is known to cause cardiovascular events. Previous studies have suggested that one of the reasons in abnormal dairy BP variability is sympathoexcitation. We have demonstrated that brain angiotensin II type 1 receptor (AT1R) causes sympathoexcitation. The aim of the present study was to investigate whether central AT1R blockade attenuates the excess BP elevation in rest-to-active phase in hypertensive rats or not. Stroke-prone spontaneously hypertensive rats (SHRSP) were treated with intracerebroventricular infusion (ICV) of AT1R receptor blocker (ARB), oral administration of hydralazine (HYD), or ICV of vehicle (VEH). Telemetric averaged mean BP (MBP) was measured at early morning (EM), after morning (AM), and night (NT). At EM, MBP was significantly lower in ARB to a greater extent than in HYD compared to VEH, though MBP at AM was the same in ARB and HYD. At NT, MBP was also significantly lower in ARB than in HYD. These results in MBP were compatible to those in sympathoexcitation and suggest that central AT1R blockade attenuates excess BP elevation in early active phase and continuous BP elevation during rest phase independent of depressor response in hypertensive rats.

Managing pre-eclampsia and eclampsia in Dar es Salaam public health facilities: A focus on equipment, supplies, drugs and knowledge of healthcare workers

Introduction: Severe pre-eclampsia and eclampsia (PE/E) is associated with high maternal and neonatal morbidity and mortality. Early detection and treatment of pre-eclampsia may prevent progression to severe PE/E. When severe PE/E occurs, timely use of anticonvulsants and antihypertensives (as part of emergency obstetric and neonatal care) are needed to reduce morbidity and mortality. This study is aimed at assessing the capacity in managing PE/E in public health facilities in Dar-es-Salaam, Tanzania. Methods: A descriptive cross-sectional study was conducted in selected public health facilities in Dar-es-Salaam city that offer reproductive and child services. The health facilities included four hospitals, three health centres and 23 dispensaries. A checklist was used to assess availability of equipment, supplies and drugs, and a structured questionnaire administered by an interviewer was used to assess healthcare workers’ knowledge on risks, symptoms, and drugs used to manage for PE/E. The results are presented as proportions. Results: Guidelines for management of PE/E were available in all hospitals and health centres while 39% of the dispensaries had no the guidelines. Functioning blood pressure machines and stethoscopes were available in all facilities but urine test strips for detecting protein in the urine were available in only one hospital (25%) and 9 (39%) dispensaries. Anticonvulsant drugs were available in all health facilities. Magnesium sulphate, the first-line recommended anticonvulsant, was available in only a quarter of the dispensaries. A quarter of the dispensaries had nifedipine or methyldopa available as antihypertensives, with availability for both drugs being 75% and 100% in the hospitals and health centres respectively. The antihypertensive hydralazine was available in 50%, 33% and 8% of the hospitals, health centres and dispensaries respectively. Calcium gluconate was available in one hospital and one health centre only. Healthcare workers were knowledgeable regarding most risk factors, symptoms and drugs for treatment of hypertension and convulsions in PE/E. A higher proportion of doctors were knowledgeable of the risk factors, symptoms and drugs than the nurses and clinical officers. The majority of the healthcare workers mentioned magnesium sulphate as the drug for treatment of convulsions in PE/E. Conclusions: There is insufficient screening and management of PE/E due to lack of equipment, supplies and drugs. Healthcare workers are relatively knowledgeable regarding risk factors, symptoms and drugs for managing PE/E. This calls for an increase in availability of equipment, supplies and drugs for managing women with PE/E. Healthcare workers need to receive ongoing education to sustain quality care for women with PE/E. Keywords: Pre-eclampsia; Eclampsia; Equipment and supplies; Drugs; Knowledge

Simultaneous Estimation of Hydrochlorothiazide, Hydralazine Hydrochloride, and Reserpine Using PCA, NAS, and NAS-PCA

In this study, new and feasible UV-visible spectrophotometric and multivariate spectrophotometric methods were described for the simultaneous determination of hydrochlorothiazide (HCTZ), hydralazine hydrochloride (H.HCl), and reserpine (RES) in combined pharmaceutical tablets. Methanol was used as a solvent for analysis and the whole UV region was scanned from 200–400 nm. The resolution was obtained by using multivariate methods such as the net analyte signal method (NAS), principal component analysis (PCA), and net analyte signal-principal component analysis (NAS-PCA) applied to the UV spectra of the mixture. The results obtained from all of the three methods were compared. NAS-PCA showed a lot of resolved data as compared to NAS and PCA. Thus, the NAS-PCA technique is a combination of NAS and PCA methods which is advantageous to obtain the information from overlapping results.

High-Salt Intake Induces Cardiomyocyte Hypertrophy in Rats in Response to Local Angiotensin II Type 1 Receptor Activation

Many studies have shown that risk factors that are independent of blood pressure (BP) can contribute to the development of cardiac hypertrophy (CH). Among these factors, high-salt (HS) intake was prominent. Although some studies have attempted to elucidate the role of salt in the development of this disease, the mechanisms by which salt acts are not yet fully understood. Thus, the aim of this study was to better understand the mechanisms of CH and interstitial fibrosis (IF) caused by HS intake. Male Wistar rats were divided into 5 groups according to diet [normal salt (NS; 1.27% NaCl) or HS (8% NaCl)] and treatment [losartan (LOS) (HS+LOS group), hydralazine (HZ) (HS+HZ group), or N-acetylcysteine (NAC) (HS+NAC group)], which was given in the drinking water. Tail-cuff BP, transverse diameter of the cardiomyocyte, IF, angiotensin II type 1 receptor (AT1) gene and protein expression, serum aldosterone, cardiac angiotensin II, cardiac thiobarbituric acid-reactive substances, and binding of conformation-specific anti-AT1 and anti-angiotensin II type 2 receptor (AT2) antibodies in the 2 ventricles were measured. Based on the left ventricle transverse diameter data, the primary finding was the occurrence of significant BP-independent CH in the HS+HZ group (96% of the HS group) and a partial or total prevention of such hypertrophy via treatment with NAC or LOS (81% and 67% of the HS group, respectively). The significant total or partial prevention of IF using all 3 treatments (HS+HZ, 27%; HS+LOS, 27%; and HS+NAC, 58% of the HS group, respectively), and an increase in the AT1 gene and protein expression and activity in groups that developed CH, confirmed that CH occurred via the AT1 in this experimental model. Thus, this study unveiled some relevant previously unknown mechanisms of CH induced by chronic HS intake in Wistar rats. The link of oxidative stress with CH in our experimental model is very interesting and stimulates further evaluation for its full comprehension.

English

English

Biomimetic Microfluidic Device for in Vitro Antihypertensive Drug Evaluation

Microfluidic devices have emerged as revolutionary, novel platforms for in vitro drug evaluation. In this work, we developed a facile method for evaluating antihypertensive drugs using a microfluidic chip. This microfluidic chip was generated using the elastic material poly(dimethylsiloxane) (PDMS) and a microchannel structure that simulated a blood vessel as fabricated on the chip. We then cultured human umbilical vein endothelial cells (HUVECs) inside the channel. Different pressures and shear stresses could be applied on the cells. The generated vessel mimics can be used for evaluating the safety and effects of antihypertensive drugs. Here, we used hydralazine hydrochloride as a model drug. The results indicated that hydralazine hydrochloride effectively decreased the pressure-induced dysfunction of endothelial cells. This work demonstrates that our microfluidic system provides a convenient and cost-effective platform for studying cellular responses to drugs under mechanical pressure.

Development of attenuated baroreflexes in obese Zucker rats coincides with impaired activation of nucleus tractus solitarius

Adult obese Zucker rats (OZR; >12 wk) develop elevated sympathetic nerve activity (SNA) and mean arterial pressure (MAP) with impaired baroreflexes compared with adult lean Zucker rats (LZR) and juvenile OZR (6-7 wk). In adult OZR, baroreceptor afferent nerves respond normally to changes in MAP, whereas electrical stimulation of baroreceptor afferent fibers produces smaller reductions in SNA and MAP compared with LZR. We hypothesized that impaired baroreflexes in OZR are linked to reduced activation of brain stem sites that mediate baroreflexes. In conscious adult rats, a hydralazine (HDZ)-induced reduction in MAP evoked tachycardia that was initially blunted in OZR, but equivalent to LZR within 5 min. In agreement, HDZ-induced expression of c-Fos in the rostral ventrolateral medulla (RVLM) was comparable between groups. In contrast, phenylephrine (PE)-induced rise in MAP evoked markedly attenuated bradycardia with dramatically reduced c-Fos expression in the nucleus tractus solitarius (NTS) of adult OZR compared with LZR. However, in juvenile rats, PE-induced hypertension evoked comparable bradycardia in OZR and LZR with similar or augmented c-Fos expression in NTS of the OZR. In urethane-anesthetized rats, microinjections of glutamate into NTS evoked equivalent decreases in SNA, heart rate (HR), and MAP in juvenile OZR and LZR, but attenuated decreases in SNA and MAP in adult OZR. In contrast, microinjections of glutamate into the caudal ventrolateral medulla, a target of barosensitive NTS neurons, evoked comparable decreases in SNA, HR, and MAP in adult OZR and LZR. These data suggest that OZR develop impaired glutamatergic activation of the NTS, which likely contributes to attenuated baroreflexes in adult OZR.

Pre-Clinical Evolutionary Study of Alpha-Pinene in L-Arginine Induced Acute Pancreatitis in Rat.

Abstract: The purpose of this study was to design matrix tablets of hydralazine hydrochloride to overcome its side effects and to increase its bioavailability. Hydroxypropyl methylcellulose, carbomer, glyceryl dibehenate and cetyl alcohol were used in matrix tablets at various concentrations for sustained drug delivery. Compression and flow properties of powder mixtures were tested before tablets were compressed by direct compression method. Weight variation, diameter and thickness, hardness, tensile strength, friability % and disintegration time of tablets were tested for their physical characterization. Drug:excipient compatibility in tablets was investigated by Fourier Transform Infrared Spectroscopy and Differential Scanning Calorimetry. Determination method of drug in dissolution mediums was validated through following performance criteria: linearity, intra- and inter-day precision, accuracy, specifity and recovery. All formulations met compendial requirements and any chemical interaction between drug and tablet excipients was not detected. It was observed that waxy tablets released drug faster than polymer based tablets. The slowest drug release rate was obtained with carbomer matrix tablets followed by hydroxypropyl methylcellulose, glyceryl dibehenate and cetyl alcohol. Drug release met Higuchi kinetic model in general. While the mechanism of drug release from polymer based tablets was non-Fickian, waxy tablets generally displayed diffusionally controlled drug release. Keywords: Hydralazine HCl, Controlled release, Matrix tablets, Polymers, Lipids

Electrochemical determination of selected antihypertensive and antituberculosis drugs at a tyrosine-modified electrode

A simple and sensitive electrochemical method was proposed for the determination of hydralazine hydrochloride (HDH), isoniazid (ISN), ethambutol hydrochloride (EBH) and pyrazinamide (PZM).

Floating tablets of hydralazine hydrochloride: optimization and evaluation

Hydralazine hydrochloride has a half-life of 2 to 4 hours with an oral bioavailability of 26-50%. Since hydralazine has a demethylating effect on various suppressor genes, it can be used in various types of cancer to support chemotherapy. The purpose of this study was to optimize and evaluate floating tablets of hydralazine hydrochloride designed to prolong the gastric residence time and to provide controlled release of the drug for 14 h. The floating tablets of hydralazine hydrochloride were prepared by the wet granulation method. Semi-synthetic polymers of hydroxy propyl methyl cellulose (HPMC K100M) and ethyl cellulose were used as the release retarding agents. A 2² factorial design was applied to systematically optimize the drug release profile. The concentrations of HPMC K100M and ethyl cellulose were optimized to provide controlled release of hydralazine for 14h. Non-Fickian diffusion release transport was confirmed as the release mechanism for the optimized formulation and the predicted values agreed well with the experimental values. Drug excipient compatibility studies were investigated by FTIR, DSC and XRD. These data indicate that there were no chemical interactions between the drug and the polymer. In vivo X-ray imaging showed floating tablet performance in rabbits.

What Agent Is Best for Managing Acute Hypertensive Emergency in Pregnancy

Hypertensive disorders affect as many as 10% of pregnancies worldwide. Largely because of safety concerns, hydralazine use has declined whereas

A High-Temperature, High-Throughput Method for Monitoring Residual Formaldehyde in Vaccine Formulations

Formaldehyde has long been used in the chemical inactivation of viral material during vaccine production. Viral inactivation is required so that the vaccine does not infect the patient. Formaldehyde is diluted during the vaccine manufacturing process, but residual quantities of formaldehyde are still present in some current vaccines. Although formaldehyde is considered safe for use in vaccines by the Food and Drug Administration, excessive exposure to this chemical may lead to cancer or other health-related issues. An assay was developed that is capable of detecting levels of residual formaldehyde in influenza vaccine samples. The assay employs incubation of dosage formulation suspensions with hydralazine hydrochloride under mildly acidic conditions and elevated temperatures, where formaldehyde is derivatized to yield fluorescent s-triazolo-[3,4-a]-phthalazine. The assay has been traditionally run by high-performance liquid chromatography, where runtimes of 15 minutes per sample can be expected. Our laboratory has developed a plate-based version that drastically improved the throughput to a runtime of 96 samples per minute. The assay was characterized and validated with respect to reaction temperature, evaporation, stability, and selectivity to monitor residual formaldehyde in various influenza vaccine samples, including in-process samples. Heat transfer and evaporation will be especially considered in this work. Since the assay is plate based, it is automation friendly. The new assay format has attained detection limits of 0.01 µg/mL residual formaldehyde, which is easily able to detect and quantify formaldehyde at levels used in many current vaccine formulations (<5 µg/0.5-mL dose).

Synthesis, crystal structure and antifungal activity of a Ni(II) complex of a new hydrazone derived from antihypertensive drug hydralazine hydrochloride

A new complex of nickel(II) with 1-(2-[(5-methylfuran-2yl)methylene)] hydrazono) phthalazine HL (1) has been synthesized and characterized by elemental analysis, IR, electronic spectra, TGA, 1H and 13C NMR spectroscopy. The crystal structures of the free ligand and its complex have been determined by single crystal X-ray diffraction techniques. In the complex the hydrazone ligand chelates to the nickel(II) through nitrogen atoms in a bidentate manner. The antifungal activity of the ligand and its nickel(II) complex 3 was studied against Aspergillus niger, Aspergillus flavus and Candida albicans. The results revealed modest activity of the complex (3) against the tested organisms with inhibition zones of 14, 14 and 13mm, compared to the free ligand 1 with inhibition zones of 11mm each for A. niger, A. flavus and C. albicans respectively.