sodium-oxybate and Hypertension

This study analyzed how glyphosate exposure in the gestational period affects vascular function in their offspring, focusing on the influence of age and whether oxidative stress is involved in this effect. To this, pregnant Wistar rats were exposed through drinking water to 0.2% of a glyphosate commercial formulation, and we analyzed the response to acetylcholine and phenylephrine in the aorta from offspring of glyphosate herbicide-based (O-GHB) and controls (O-CON) rats at 3, 6, and 12 months of age. O-GHB groups showed no changes in arterial blood pressure or aorta histological analysis. Relaxation to acetylcholine was reduced in O-GHB than O-CON. Acute TEMPOL increased relaxation to acetylcholine in O-GHB at 6 and 12 months of age. The aorta from O-GHB was hyperactive to phenylephrine only at 6 months of age. Preincubation with N-nitro-L-arginine methyl ester (L-NAME) increased contraction to phenylephrine more in O-CON than O-GHB. TEMPOL similarly reduced phenylephrine response. This effect was prevented by L-NAME. Results reinforce the concept that oxidative stress during the perinatal period contributes to the development of vascular changes in adulthood. Results also reveal that although no changes in cardiac or histological parameters have been demonstrated, the current levels considered safe for exposure to glyphosate deserve further investigation, especially during pregnancy.

Topics: Acetylcholine; Animals; Blood Pressure; Endothelium, Vascular; Female; Glyphosate; Herbicides; Humans; Hypertension; Maternal Exposure; NG-Nitroarginine Methyl Ester; Phenylephrine; Pregnancy; Rats; Rats, Wistar; Sodium Oxybate

Lower-sodium oxybate (LXB) is a novel formulation that is approved by the US Food and Drug Administration (FDA) to treat cataplexy and excessive daytime sleepiness (EDS) in adult patients and children ≥7 years with narcolepsy. LXB contains 92% less sodium than sodium oxybate (SXB), which adds 550-1640 mg of sodium/day at usual doses of 3-9 g/day. The FDA has declared LXB to be clinically superior to SXB due to greater safety by reducing the chronic sodium load. Narcolepsy patients have high comorbidities for hypertension and cardiovascular disease conditions, which can be adversely affected by high sodium intake.. This drug review discusses narcolepsy, current and upcoming pharmacotherapy, and LXB chemistry, pharmacodynamics, pharmacokinetics, and metabolism. Published results from LXB's phase 1 studies, a phase 3 study, and two post-marketing studies are reviewed. Databases searched included PubMed, Google Scholar, Lexi-Comp, Scopus, Science, and Ovid.. LXB is efficacious in treating daytime sleepiness and cataplexy in adults and children ≥7 years with narcolepsy. Using LXB instead of SXB formulations may benefit narcolepsy patients with cardiovascular comorbidities and hypertension, but long-term studies are needed to prove it.

Topics: Adult; Calcium; Cataplexy; Child; Disorders of Excessive Somnolence; Humans; Hypertension; Magnesium; Narcolepsy; Potassium; Sodium; Sodium Oxybate

Cushing's syndrome results from lengthy and inappropriate exposure to excessive concentrations of either endogenous or exogenous glucocorticoids. This case report describes a patient with a novel type of Cushing's syndrome due to the use of party drugs. A 35-year-old woman had gained 8 kg body weight in 5 months and complained of anxiety. She showed a Cushing-like appearance and mild hypertension (blood pressure, BP 150/95 mmHg). She reported daily use of increasing doses of gamma-hydroxybutyric acid (GHB), a popular party drug. ACTH plasma levels were in the upper normal range (41 ng/l), with normal plasma cortisol (0.36 micromol/l). She showed an abnormal overnight 1 mg dexamethasone suppression test (cortisol 0.38 micromol/l). The urinary excretion of free cortisol in 24 h was also increased (0.47 micromol/24 h). CT scanning of the abdomen showed normal adrenals. After stopping GHB intake she lost 7 kg body weight and her BP normalized (BP 135/80 mmHg). GHB is a popular party drug in the Netherlands, but it is also used as a narcotic and for the treatment of narcolepsy. We hypothesize that GHB may bind to the pituitary gland gamma-aminobutyric acid-B receptors leading to ACTH overproduction.

Topics: Adult; Cushing Syndrome; Female; Humans; Hydrocortisone; Hypertension; Sodium Oxybate; Substance-Related Disorders

Gamma-hydroxybutyrate (GHB) withdrawal syndrome is increasingly encountered in emergency departments among patients presenting for health care after discontinuing frequent GHB use. This report describes the characteristics, course, and symptoms of this syndrome.. A retrospective review of poison center records identified 7 consecutive cases in which patients reporting excessive GHB use were admitted for symptoms consistent with a sedative withdrawal syndrome. One additional case identified by a medical examiner was brought to our attention. These medical records were reviewed extracting demographic information, reason for presentation and use, concurrent drug use, toxicology screenings, and the onset and duration of clinical signs and symptoms.. Eight patients had a prolonged withdrawal course after discontinuing chronic use of GHB. All patients in this series were psychotic and severely agitated, requiring physical restraint and sedation. Cardiovascular effects included mild tachycardia and hypertension. Neurologic effects of prolonged delirium with auditory and visual hallucinations became episodic as the syndrome waned. Diaphoresis, nausea, and vomiting occurred less frequently. The onset of withdrawal symptoms in these patients was rapid (1 to 6 hours after the last dose) and symptoms were prolonged (5 to 15 days). One death occurred on hospital day 13 as withdrawal symptoms were resolving.. In our patients, severe GHB dependence followed frequent ingestion every 1 to 3 hours around-the-clock. The withdrawal syndrome was accompanied initially by symptoms of anxiety, insomnia, and tremor that developed soon after GHB discontinuation. These initial symptoms may progress to severe delirium with autonomic instability.

Topics: Adult; Autonomic Nervous System Diseases; Delirium; Diagnosis, Differential; Doping in Sports; Emergency Treatment; Fatal Outcome; Female; Humans; Hypertension; Male; Psychoses, Substance-Induced; Retrospective Studies; Sodium Oxybate; Substance Abuse Detection; Substance Withdrawal Syndrome; Tachycardia; Time Factors

We report a case of gamma-hydroxybutyrate (GHB) withdrawal resulting in severe agitation, mental status changes, elevated blood pressure, and tachycardia hours after stopping chronic use of GHB. The patient admitted to substantial GHB abuse on a daily basis for 2.5 years. Previous attempts at cessation reportedly resulted in diaphoresis, tremors, and agitation. The patient's symptoms, negative polypharmacy history, and negative urine and blood toxicological analysis for alcohol, benzodiazepines, sedative-hypnotics, or other substances suggested the diagnosis of GHB withdrawal. Later analysis of a patient drug sample confirmed the presence of GHB. The patient required 507 mg of lorazepam and 120 mg of diazepam over 90 h to control agitation. This is one of the few reported cases of GHB withdrawal and one of the most severe. Given the increasing use of GHB, more cases of severe GHB withdrawal should be anticipated.

Topics: Adult; Akathisia, Drug-Induced; Anti-Anxiety Agents; Autonomic Nervous System Diseases; Emergencies; GABA Modulators; Hallucinations; Humans; Hypertension; Lorazepam; Male; Sodium Oxybate; Substance Withdrawal Syndrome; Tachycardia; Tremor

The haemodynamic effects of anaesthesia with gamma-hydroxybutyrate (GHB)/sufentanil for elective coronary artery bypass grafting (CABG) were investigated and compared in patients with unimpaired left ventricular function (ejection fraction > or = 45%, left ventricular end diastolic pressure < or = 16 mmHg) and patients with impaired left ventricular function. In 38 consecutive patients scheduled for CABG (21 with unimpaired and 17 with impaired left ventricular function), anaesthesia was induced with etomidate, sufentanil and pancuronium. After tracheal intubation, the lungs were normoventilated (end tidal Pco2 4.9-5.6 kPa) with an oxygen-air mixture (Fio2 0.5). Total intravenous anaesthesia was maintained with GHB (20 mg kg-1 h-1 after a 'priming dose' of 40 mg kg-1) and sufentanil (2 micrograms kg-1 h-1). Haemodynamic measurements were made after induction of anaesthesia and at various times in the prebypass period. Patients in both groups showed similar haemodynamic trends. Mean arterial pressure showed a maximum reduction of 10%, whereas heart rate and right- and left-sided filling pressures remained unchanged within the groups after the induction of anaesthesia. Cardiac index remained unchanged in both groups, although values differed between the groups. A total of 14 out of 21 patients (67%) with unimpaired and 10 out of 17 patients (59%) with impaired ventricular function required supplementary administration of opioids to control temporary hypertension after sternotomy. No episodes of myocardial ischaemia were detected during the study period using ST segment analysis (leads II and V5). The results of this study suggest that GHB provides adequate haemodynamic conditions in the prebypass period and may be a suitable agent for TIVA also in patients with impaired left ventricular function undergoing CABG.

Topics: Aged; Anesthesia, Intravenous; Anesthetics, Intravenous; Blood Pressure; Cardiac Output; Coronary Artery Bypass; Electrocardiography; Female; Heart Rate; Hemodynamics; Humans; Hypertension; Intubation, Intratracheal; Male; Middle Aged; Myocardial Ischemia; Narcotics; Respiration, Artificial; Sodium Oxybate; Sternum; Stroke Volume; Sufentanil; Thoracotomy; Vascular Resistance; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

A sustained increase in blood pressure was obtained by intraperitoneal (i.p.) or intravenous (i.v.) administration of gammahydroxybutyric acid (GHBA, 1 g/kg) in rats under nitrous oxide anesthesia and in conscious rats with indwelling catheters in the aorta and a jugular vein. Evans blue-albumin and 125I-labeled serum albumin, given i.v. before GHBA, were used to study the function of the blood-barrier in rats killed 60 min after the injection of the drug. Brains from rats subjected to acute hypertension while awake showed less extravasation of albumin than did brains from anesthetized rats. Sectioning of the cervical symphatetic nerves did not increase extravasation in conscious rats. The cerebral blood flow, determined with the 14C-ethanol technique, did not significantly differ in GHBA-treated rats and controls. Because of the sustained increase in blood pressure, GHBA-induced hypertension might be a useful model for the study of long-term effects on the brain of hypertensive opening of the blood-brain barrier.

Topics: Anesthesia, General; Animals; Blood Pressure; Capillary Permeability; Cerebrovascular Circulation; Consciousness; Hydroxybutyrates; Hypertension; Male; Rats; Rats, Inbred Strains; Sodium Oxybate

Topics: Adult; Antihypertensive Agents; Capillaries; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Oxidation-Reduction; Oxygen; Oxygen Consumption; Partial Pressure; Sodium Oxybate; Vascular Resistance

Topics: Anesthesia; Animals; Humans; Hydroxybutyrates; Hypertension; Rats; Sodium Oxybate