The concept of resistant hypertension may be changed during pregnancy by the physiological hemodynamic changes and the particularities of therapy choices in this period. This review discusses the management of pregnant patients with preexisting resistant hypertension and also of those who develop severe hypertension in gestation and puerperium.

Alpha-adrenergic agonist toxicity is due to a broad group of pharmaceutical agents known as alpha agonists, which can be further broken down into central alpha-2 agonists and peripheral alpha-1 agonists. Central alpha-2 agonists include clonidine, guanfacine, tizanidine, guanabenz, and methyldopa. Peripheral alpha-1 agonists include imidazoline, oxymetazoline, tetrahydrozoline, and naphazoline. Mainly there are 2 alpha receptors of pharmacological significance – central alpha-2 and peripheral alpha-1 adrenergic receptors. Stimulation of central alpha-2 receptors causes decreased secretion of catecholamines through a negative feedback mechanism. Stimulation of peripheral alpha-1 receptors primarily increases blood pressure via induced vasoconstriction. Alpha-adrenergic agonist toxicity is of primary concern with alpha-2 adrenergic agonist xenobiotics through the resulting depletion of catecholamines associated with these agents; however, there are many topical alpha-1 agonists that when misused cause similar toxicity. Toxicity is encountered in various populations, particularly in children and adolescents, due to the growing use of these agents. Toxicity is associated with a compilation of symptoms, including central nervous system depression, bradycardia, and hypotension. Alpha-adrenergic toxicity is often very responsive to supportive care, including intravenous fluid administration, airway monitoring, and repletion of catecholamines as necessary via the use of vasopressor agents. There is no antidote approved for human use, and naloxone has no proven efficacy.

Synedrella nodiflora (SNE) has been used traditionally for many neurological conditions and some of these neuroactive effects have been scientifically substantiated. The usefulness of SNE in depression has however not been investigated despite the availability of data in other disease models indicating it may be useful. The present study therefore examined the effect of SNE in acute murine models of depression and the possible mechanisms mediating its activities in these models. Preliminary qualitative phytochemical and high performance liquid chromatography (HPLC) screening were conducted on SNE. The behavioural effects of SNE (100, 300 and 1000 mg/kg) pre-treated mice were examined in the forced swimming (FST) and tail suspension (TST) tests. Behavioural events such as mobility (swimming, climbing, curling and climbing), and immobility, were scored. The possible involvement of monoamines in the effects of SNE was assessed in the TST by pre-treating mice with α-methyldopa, reserpine and para-chlorophenylalanine (pCPA) in separate experiments. Flavonoids, tannins, saponins, alkaloids, cardiac glycosides, coumarins, triterpenes, sterols, anthraquinones and phenolic compounds were present in SNE. HPLC analysis revealed the presence of two major constituents observed at retention times 42.56 and 46.51 min, with percentage composition of 45.72% and 36.88% respectively. SNE significantly reduced immobility scores in both FST and TST, suggesting antidepressant effects. The antidepressant properties of SNE were reversed by the pre-treatment of α-methyldopa, reserpine and pCPA, suggesting a possible involvement of monoamines (noradrenaline and serotonin) in its mechanism(s) of actions. SNE exhibits antidepressant effects, possibly mediated through an interplay of enhancement of noradrenergic and serotoninergic mechanisms.

Bioactive natural products, habitually ingested with milk or its derivative nutrients, have been studied for their bioavailability. In this study, we investigated the effects of the co-administration of bovine milk-derived lactoferrin (bLF) and bioactive products, with a focus on catechol-O-methyltransferase (COMT), an enzyme in the catechol metabolism. bLF showed inhibitory activity on COMT in vitro, and acidic pretreatment of bLF enhanced its inhibitory activity. Moreover, partially digested products of bLF by pepsin retained inhibitory activity. Based on these results, bLF was co-administered with levodopa (l-DOPA), which is a catechol compound and a precursor of dopamine, and the effect of bLF on l-DOPA absorption and metabolism was investigated in a mouse model. The co-administration of l-DOPA and bLF alone showed no effect on the concentration of l-DOPA in plasma. However, with the additional administration of carbidopa, the concentration of l-DOPA was significantly enhanced. Furthermore, the ratio of l-DOPA/3-O-methyldopa significantly increased. On the other hand, casein, which is a major milk protein, was not effective. In addition, COMT activity in the intestines was lowered with bLF administration. We concluded that the co-administration of bLF and carbidopa enhances the concentration of l-DOPA.

The vegetable kingdom is a wide source of a diverse variety of enzymes with broad biotechnological applications. Among the main classes of plant enzymes, the polyphenol oxidases, which convert phenolic compounds to the related quinones, have been successfully used for biosensor development. The oxidation products from such enzymes can be electrochemically reduced, and the sensing is easily achieved by amperometric transducers. In this work, the polyphenoloxidases were extracted from jurubeba (Solanum paniculatum L.) fruits, and the extract was used to construct a carbon paste-based biosensor for pharmaceutical analysis and applications. The assay optimization was performed using a 0.1 mM catechol probe, taking into account the amount of enzymatic extract (50 or 200 μL) and the optimum pH (3.0 to 9.0) as well as some electrochemical differential pulse voltammetric (DPV) parameters (e.g., pulse amplitude, pulse range, pulse width, scan rate). Under optimized conditions, the biosensor was evaluated for the quantitative determination of acetaminophen, acetylsalicylic acid, methyldopa, and ascorbic acid. The best performance was obtained for acetaminophen, which responded linearly in the range between 5 and 245 μM (R = 0.9994), presenting a limit of detection of 3 μM and suitable repeatability ranging between 1.52% and 1.74% relative standard deviation (RSD).

Major histocompatibility (MHC) class II molecules are strongly associated with many autoimmune disorders. In type 1 diabetes (T1D), the DQ8 molecule is common, confers significant disease risk, and is involved in disease pathogenesis. We hypothesized that blocking DQ8 antigen presentation would provide therapeutic benefit by preventing recognition of self-peptides by pathogenic T cells. We used the crystal structure of DQ8 to select drug-like small molecules predicted to bind structural pockets in the MHC antigen-binding cleft. A limited number of the predicted compounds inhibited DQ8 antigen presentation in vitro, with 1 compound preventing insulin autoantibody production and delaying diabetes onset in an animal model of spontaneous autoimmune diabetes. An existing drug with a similar structure, methyldopa, specifically blocked DQ8 in patients with recent-onset T1D and reduced inflammatory T cell responses to insulin, highlighting the relevance of blocking disease-specific MHC class II antigen presentation to treat autoimmunity.

The indications for lisdexamfetamine (LDX), a central nervous system stimulant, were recently expanded to include treatment of moderate to severe binge eating disorder (BED). Areas covered: This review aims to describe the chemistry and pharmacology of LDX, as well as the clinical trials investigating the efficacy and safety of this medication for the management of BED. Expert opinion: LDX is the first medication with United States Food and Drug Administration approval for the treatment of BED. It is an inactive prodrug of d-amphetamine that extends the half-life of d-amphetamine to allow for once daily dosing. D-amphetamine acts primarily to increase the concentrations of synaptic dopamine and norepinephrine. Metabolism of LDX to d-amphetamine occurs when peptidases in red blood cells cleave the covalent bond between d-amphetamine and l-lysine. D-amphetamine is then further metabolized by CYP2D6. Excretion is primarily through renal mechanisms. In clinical trials, LDX demonstrated statistical and clinical superiority over placebo in reducing binge eating days per week at doses of 50 and 70 mg daily. Commonly reported side effects of LDX include dry mouth, insomnia, weight loss, and headache, and its use should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia or coronary artery disease. As with all CNS stimulants, risk of abuse needs to be assessed prior to prescribing.