Self-Nanoemulsifying Drug Delivery System Loaded with Psiadia punctulata Major Metabolites for Hypertensive Emergencies: Effect on Hemodynamics and Cardiac Conductance

Vasodilators are an important class of antihypertensive agents. However, they have limited clinical use due to the reflex tachycardia associated with their use which masks most of its antihypertensive effect and raises cardiac risk. Chemical investigation of Psiadia punctulata afforded five major methoxylated flavonoids (1–5) three of which (1, 4, and 5) showed vasodilator activity. Linoleic acid-based self-nanoemulsifying drug delivery system (SNEDDS) was utilized to develop intravenous (IV) formulations that contain compounds 1, 4, or 5. The antihypertensive effect of the prepared SNEDDS formulations, loaded with each of the vasodilator compounds, was tested in the angiotensin-induced rat model of hypertension. Rats were subjected to real-time recording of blood hemodynamics and surface Electrocardiogram (ECG) while the pharmaceutical formulations were individually slowly injected in cumulative doses. Among the tested formulations, only that contains umuhengerin (1) and 5,3′-dihydroxy-6,7,4′,5′-tetramethoxyflavone (5) showed potent antihypertensive effects. Low IV doses, from the prepared SNEDDS, containing either compound 1 or 5 showed a marked reduction in the elevated systolic blood pressure by 10 mmHg at 12 μg/kg and by more than 20 mmHg at 36 μg/kg. The developed SNEDDS formulation containing either compound 1 or 5 significantly reduced the elevated diastolic, pulse pressure, dicrotic notch pressure, and the systolic–dicrotic notch pressure difference. Moreover, both formulations decreased the ejection duration and increased the non-ejection duration while they did not affect the time to peak. Both formulations did not affect the AV conduction as appear from the lack of effect on p duration and PR intervals. Similarly, they did not affect the ventricular repolarization as no effect on QTc or JT interval. Both formulations decreased the R wave amplitude but increased the T wave amplitude. In conclusion, the careful selection of linoleic acid for the development of SNEDDS formulation rescues the vasodilating effect of P. punctulata compounds from being masked by the reflex tachycardia that is commonly associated with the decrease in peripheral resistance by most vasodilators. The prepared SNEDDS formulation could be suggested as an effective medication in the treatment of hypertensive emergencies, after clinical evaluation.

MODERN EMERGENCY CARE STRATEGY FOR HYPERTONIC CRISIS

The article is devoted to discussing modern approaches todiagnosis andtreatment in complicated anduncomplicated hypertensive crises.The options for antihypertensive drugs are considereddepending on thenature of target organ damage ina hypertensive crisis.The data on themost frequently prescribed drugs for complicated anduncomplicated hypertensive crisis increases the volumetric velocity of coronary andcerebral blood flowand reduces the pressure inthe pulmonary artery system.It is usually used to relieve the mild uncomplicated hypertensive crisis. Still, a wide range of side effects, including reflex tachycardia, periorbital andperipheral edema, skin redness, pruritus,limits its use.Keywords: cerebral blood flow, routine clinical, hypertension, medical associations, hypertensive crisis

Reevaluation of Lung Injury in TNF-Induced Shock: The Role of the Acid Sphingomyelinase

Tumor necrosis factor (TNF) is a well-known mediator of sepsis. In many cases, sepsis results in multiple organ injury including the lung with acute respiratory distress syndrome (ARDS). More than 20-year-old studies have suggested that TNF may be directly responsible for organ injury during sepsis. However, these old studies are inconclusive, because they relied on human rather than conspecific TNF, which was contaminated with endotoxin in most studies. In this study, we characterized the direct effects of intravenous murine endotoxin-free TNF on cardiovascular functions and organ injury in mice with a particular focus on the lungs. Because of the relevance of the acid sphingomyelinase in sepsis, ARDS, and caspase-independent cell death, we also included acid sphingomyelinase-deficient (ASM-/-) mice. ASM-/- and wild-type (WT) mice received 50 μg endotoxin-free murine TNF intravenously alone or in combination with the pan-caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (zVAD) and were ventilated at low tidal volume while lung mechanics were followed. Blood pressure was stabilized by intra-arterial fluid support, and body temperature was kept at 37°C to delay lethal shock and to allow investigation of blood gases, lung histopathology, proinflammatory mediators, and microvascular permeability 6 hours after TNF application. Besides the lungs, also the kidneys and liver were examined. TNF elicited the release of inflammatory mediators and a high mortality rate, but failed to injure the lungs, kidneys, or liver of healthy mice significantly within 6 hours. Mortality in WT mice was most likely due to sepsis-like shock, as indicated by metabolic acidosis, high procalcitonin levels, and cardiovascular failure. ASM-/- mice were protected from TNF-induced hypotension and reflex tachycardia and also from mortality. In WT mice, intravenous exogenous TNF does not cause organ injury but induces a systemic inflammatory response with cardiovascular failure, in which the ASM plays a role.

What is New in New Generation Calcium Channel Blocker

Hypertension is a multifactorial and multisystem disease in which elevated blood pressure is only one sign of multiple underlying physiological abnormalities. It affects approximately 26% of the population worldwide. Hypertension is one of the leading cause of death as a "silent killer". Several classes of antihypertensive agents have been in clinical use, but CCBs exert most potent antihypertensive action and are widely used as a first line antihypertensive drug in elderly with very few contraindication.Four generations of dihydropyridines CCBs are now available.The fourth-generation highly lipophilic dihydropyridines, lercanidipine, cilnidipine and lacidipine are now available which provide a real degree of therapeutic comfort in terms of stable activity, a reduction in adverse effects and a broad therapeutic spectrum. Cilnidipine is a recently developed CCB, and possesses both L- and N-type calcium channel blocking activity.Cilnidipine causing less reflex tachycardia, less pedal edema, better control of proteinuria, suppressing podocyte damage, increasing insulin sensitivity.This article reviews the current understanding of the pharmacological profile and clinical utility of cilnidipine as a unique antihypertensive drug. Anwer Khan Modern Medical College Journal Vol. 10, No. 1: Jan 2019, P 77-83

A Prospective Study on Surgeries Under General Anaesthesia

The demonstration of laryngoscopy and intubation evokes reflex tachycardia and hypertension and dysrhythmias. Even though this weight rejoinder is fleeting, it is sufficiently significant to reason undesired results on a cardiovascular machine-like dysrhythmia and myocardial ischemia. These cardiovascular variations are dangerous in matured, hypertensive, and ischemic coronary illness victims fundamental legitimately to myocardial localized necrosis or dysrhythmias. This forthcoming, randomized, twofold blinded, study assessed the adequacy of the unmarried oral portion of 150mg Pregabalin and 100mcg Clonidine given an hour before acceptance on the constriction of hemodynamic reaction to tracheal and laryngoscopy intubation. Sixty ASA1 and two or three patient of 15 to 65 year age establishment of together genders experiencing surgery have been randomized into organizations Group-C – a hundred mcg Clonidine Group-P – 150mg Pregabalin General sedative strategies have been normalized. Heart charge, systolic, diastolic, and propose blood strain had been chronicled at standard and 1min, 3min, and 5 minutes subsequently laryngoscopy and intubation. Results have been arranged, and measurable examination transformed into accomplished the utilization of Microsoft exceed expectations and SPSS programming program. Understudy t-test was utilized for measurable factors and chi-square test for subjective factors. With the victims coordinated for segment contours, the outcomes affirmed that there was no impressive distinction in pattern hemodynamic factors among the two gatherings. There become inherently less height in blood strain subsequent laryngoscopy and intubation in pregabalin gathering. Even though tachycardia happened in the two associations subsequent intubation, the expansion heart cost was less in pregabalin foundation.

Cardiogenic shock after nifedipine administration in a pregnant patient: A case report and review of the literature

We present a case of a 21-year-old Caucasian woman at 27 weeks of pregnancy who was admitted to the obstetric department for pre-term labor. She received 10 mg of nifedipine 4 times in 1 h, according to the internal protocol. Shortly after, she brutally deteriorated with pulmonary edema and hypoxemia requiring transfer to the intensive care unit (ICU) for mechanical ventilation. She finally improved and was successfully extubated after undergoing a percutaneous valvuloplasty of the mitral valve. This case illustrates a severe cardiogenic shock after administration of nifedipine for premature labor in a context of unknown rheumatic mitral stenosis. Nifedipine induces a reflex tachycardia that reduces the diastolic period and thereby precipitates pulmonary edema in case of mitral stenosis. This case emphasizes the fact that this drug may be severely harmful and should never be used before a careful physical examination and echocardiography if valvular heart disease is suspected.

Management of Tizanidine Withdrawal Syndrome: A Case Report

Most drugs that act on the central nervous system (CNS) require dose titration to avoid withdrawal syndrome. Tizanidine withdrawal syndrome is caused by adrenergic discharge due to its α2-agonist mechanism and is characterized by hypertension, reflex tachycardia, hypertonicity, and anxiety. Although tizanidine withdrawal syndrome is mentioned as a potential side effect of cessation, it is not common and there have been few reports. We present the case of a 31-year-old woman with tizanidine withdrawal syndrome after discontinuing medication prescribed for a muscle contracture (tizanidine). She showed high adrenergic activity with nausea, vomiting, generalized tremor, dysthermia, hypertension, and tachycardia. Symptoms were reversed and successful reweaning was achieved by restarting tizanidine followed by slow downward titration. Withdrawal syndrome should be considered when drugs targeting the CNS are suddenly stopped. Weaning regimens should be closely monitored for acute withdrawal reactions.

Comparison of the effects of L-type calcium channel antagonist Amlodipine with L/N-type calcium channel antagonist Cilnidipine on blood pressure, heart rate, proteinuria and lipid profile in hypertensive patients

Background: Cilnidipine is a novel and unique 1,4-dydropyridine derivative calcium antagonist that exerts potent inhibitory actions not only on L-type but also on N-type voltage dependent calcium channels. Blockade of the neural N-type calcium channel inhibits the secretion of norepinephrine from peripheral neural terminals and depresses sympathetic nervous system activity.Objective and methods: The purpose of this study was to assess the effect of Cilnidipine and Amlodipine on blood pressure (BP) levels. We did BP monitoring before and after once-daily use of Cilnidipine and Amlodipine in 100 hypertensive patients.Results: Both drugs significantly reduced systolic BP (SBP) and diastolic BP (DBP). However, the reductions in pulse rate (PR) were significantly greater in the Cilnidipine group than the Amlodipine group. N-type calcium channel blockade by Cilnidipine may not cause reflex tachycardia, and may be useful for hypertensive treatment.Conclusion: There was significant reduction in proteinuria with Clindipine as compared to Amlodipine. However, there were no significant change in total cholesterol level in diabetes and non-diabetics in both the group.Bangladesh Journal of Medical Science Vol.15(3) 2016 p.460-465

Squamous Carcinoma of the Lung Presenting as Migraine-Type Headache: A Case Report

Introduction: Orthostatic hypotension has long been recognised as a paraneoplastic effect of lung cancer. Lung cancer presenting with orthostatic hypotension and migraine-type headaches has not been previously described in the literature. Case Report: A 62-year-old Caucasian male presented with headaches, typical of his migraine, after a 30-year migraine-free period. An examination revealed a significant postural drop in BP with reflex tachycardia and no other features of dysautonomia. Investigations showed a metastatic squamous cell lung cancer. Pharmacological treatment of orthostatic hypotension resolved the migraine-type headaches. Discussion: Orthostatic hypotension is associated with lung cancer. Prompt pharmacological treatment in patients not responding to non-pharmacological therapy can provide relief from disabling symptoms of orthostatic hypotension. In this patient, this included symptoms consistent with migraine-type headaches.