Sympathetic Neurofunction Testing in Gestational Hypertension and Relationship with Developing Preeclampsia and Eclampsia: Real-world Evidences from Clinical Pharmacology Clinics.

BACKGROUND: Gestational hypertension carries a high-risk for adverse maternal and fetal outcomes, and it can also develop into preeclampsia. A relative decrease in parasympathetic and increase in sympathetic activity has been seen in normal pregnancy which returns to baseline after delivery. The present study aimed to detect any abnormality in sympathetic neurofunction in gestational hypertension and to identify its possible association with the development of preeclampsia/eclampsia. METHODS: A prospective, observational study was carried out among gestational hypertensive patients between 24 and 26 weeks of gestation, who were sent to clinical pharmacology clinics for autonomic neurofunction testing, along with their 24-hour urinary protein testing reports. Preisometric handgrip (IHG) and post-IHG differences in diastolic blood pressure (DBP) were noted. The association between Δ DBP and the development of eclampsia/preeclampsia was probed. RESULTS: A total of 52 pregnancy-induced hypertension (PIH) participants, both multigravida (n = 15) and primigravida (n = 37) were included in one arm (PIH arm), and 52 matched (age and gravida) pregnant women, those do not have PIH included in another arm for comparative analysis. On comparing the PIH arm and normal arm, prehand grip DBP (p ≤ 0.0001), posthand grip DBP, and Δ DBP were significantly higher in the PIH arm. Correlation between Δ DBP and 24 hours' proteinuria was observed in the PIH arm, with a significant positive correlation. CONCLUSION: A high-rise in DBP post-IHG exercise is associated with gestational hypertensive mothers and this rise is strongly correlated with the development of preeclampsia and eclampsia, which suggests that addressing sympathetic hyperactivity could be a potential area to target therapeutics while managing gestational hypertension.

Efficacy and Safety of Patiromer in Hyperkalemia: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients at the highest risk of hyperkalemia are those with chronic kidney disease (CKD) stages 3 and 4. OBJECTIVE: To evaluate the efficacy and safety of patiromer in hyperkalemia in patients with heart failure or CKD. METHODS: The Cochrane Renal Group's Specialized Register was searched through contact with the Trials' Search Coordinator. We aimed at including randomized controlled trials with patiromer in patients with developed or risks of developing hyperkalemia, comparing against an active comparator or placebo. Three studies matched our inclusion and exclusion criteria, which we included in the meta-analysis. All-cause mortality, reduction in hospitalization, episodes of hypokalemia or hyperkalemia, and cardiovascular and gastrointestinal adverse events during the treatment period were our primary outcomes. Serial change in serum potassium (K+) until end of treatment or follow-up during the trial period and all other reported adverse reactions during the treatment period were our secondary outcomes. Meta-analysis (RevMan version 5.3.5) and descriptive statistics were used. RESULTS: There was a non-significant improvement in all-cause mortality and serious cardiovascular events with patiromer than placebo. Hospitalization data were unavailable. Although serious gastrointestinal events were more common with placebo, there was a significant reduction ( P = .02) in the risk of non-serious gastrointestinal events with placebo. Patiromer lowered serum K+ more than placebo, and there were more patients developing hyperkalemia with placebo. High-dose patiromer was associated with better efficacy in some parameters but with more adverse events. CONCLUSION: Although patiromer seems promising, more trials with active comparator are essential to finalize its indication and use in hyperkalemia.

Lysergic acid diethylamide: a drug of 'use'?

Lysergic acid diethylamide (LSD), described as a classical hallucinogen, began its journey from the middle of the last century following an accidental discovery. Since then, it was used as a popular and notorious substance of abuse in various parts of the world. Its beneficial role as an adjunct to psychotherapy was much unknown, until some 'benevolent' experiments were carried out over time to explore some of its potential uses. But, many of its effects were unclear and seemed to be a psychedelic enigma. In this review article, we have described the receptor pharmacology, mechanism of action, effects and adverse effects of LSD on the normal body system. We have also highlighted its addictive potentials and the chances of developing tolerance. We have assimilated some of the interesting therapeutic uses of this drug, such as an antianxiety agent, a creativity enhancer, a suggestibility enhancer, and a performance enhancer. We have also described LSD to be successfully used in drug and alcohol dependence, and as a part of psychedelic peak therapy in terminally ill patients. The relevant chronological history and literature in the light of present knowledge and scenarios have been discussed. Based on available evidence, LSD could be tried therapeutically in certain specific conditions under controlled settings. But as we mention, due to all the safety concerns, the use of this nonaddictive 'entheogen' in actual practice warrants a lot of expertise, caution, cooperation and ethical considerations.

Inhibition by tadalafil of contractility of isolated nonpregnant human myometrium.

OBJECTIVE: To investigate the inhibitory effect of tadalafil on the contractility of isolated nonpregnant human myometrium. MATERIALS AND METHODS: The ability of tadalafil (25, 40, and 63 µM) to inhibit 55 mM KCl-induced contractility of isolated nonpregnant human myometrium was studied. The ability of the ATP-sensitive potassium channel blocker glibenclamide (10 µM) and the calcium-sensitive potassium channel (BKCa) blocker iberiotoxin (100 nM) to reverse the inhibitory effect of 40 µM tadalafil on 55 mM KCl-induced myometrial contractility was also studied. RESULTS: Tadalafil produced a concentration-dependent inhibition of myometrial contractility that was statistically significant at 40 and 63 µM concentrations of tadalafil. The inhibition by tadalafil of myometrial contractility was statistically significantly reversed by the concurrent administration of glibenclamide and iberiotoxin. CONCLUSIONS: These results suggest that tadalafil inhibits human myometrial contractility by opening ATP-sensitive potassium channels and BKCa channels. The opening of these channels could have been due to the action of raised intracellular levels of cGMP due to inhibition of PDE-5 by tadalafil. The results suggest that tadalafil could be investigated for use in clinical conditions requiring relaxation of the myometrium.

Inhibition by sildenafil of contractility of isolated non-pregnant human myometrium.

OBJECTIVE: To investigate the ability of sildenafil to inhibit the contractility of isolated non pregnant human myometrium. MATERIALS AND METHODS: The inhibitory effect of three concentrations (3, 10, and 30 µM) of sildenafil on 55 mM KCl-induced contractility of isolated non-pregnant human myometrium was studied. The ability of the guanylyl cyclase inhibitor ODQ (10 µM), the adenylyl cyclase inhibitor MDL-12,330A (10 µM), the non-specific potassium channel blocker TEA (2 mM), and the calcium-sensitive potassium (BKCa) channel blocker iberiotoxin (100 nM) to reverse the inhibition of 10 µM sildenafil on KCl-induced myometrial contractility was also studied. RESULTS: Sildenafil produced a concentration-dependent inhibition of KCl-induced myometrial contractility that was statistically significant at all three concentrations of sildenafil used. The inhibition by 10 µM sildenafil of KCl-induced myometrial contractility was not reversed by the concurrent administration of ODQ or MDL-12,330A. The inhibition of 10 µM sildenafil of myometrial contractility was partially reversed by concurrent administration of TEA and totally and significantly reversed by the concurrent administration of iberiotoxin. CONCLUSIONS: These results suggest that sildenafil inhibits the contractility of isolated non-pregnant human myometrium. The results suggest that sildenafil does so by opening BKCa channels.