Efficient administration of a combination of nifedipine and sildenafil citrate versus only nifedipine on clinical outcomes in women with threatened preterm labor: a systematic review and meta-analysis.

BACKGROUND: Preterm labor (PTL) is a common and serious pregnancy disorder that can cause long-term neurological issues in the infant. There are conflicting studies concerning whether sildenafil citrate (SC) reduces preterm labor complications. Therefore, the meta-analysis aimed to examine the clinical outcomes in women with threatened PTL who received nifedipine plus SC therapy versus only nifedipine. METHODS: For the original articles, six databases were searched using relevant keywords without restriction on time or language until January 13, 2024. The Cochrane risk-of-bias tool for randomized trials (RoB) and the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) were both used to assess the risk of bias in randomized and non-randomized studies, and GRADE determined the quality of our evidence. Meta-analysis of all data was carried out using Review Manager (RevMan) version 5.1. RESULTS: Seven studies with mixed quality were included in the meta-analysis. The study found that combining nifedipine and SC resulted in more prolongation of pregnancy (MD = 6.99, 95% CI: 5.32, 8.65, p < 0.00001), a lower rate of delivery in the 1st to 3rd days after hospitalization (RR = 0.62, 95% CI: 0.50, 0.76, p < 0.00001), a higher birth weight (252.48 g vs. nifedipine alone, p = 0.02), and the risk ratio of admission to the neonatal intensive care unit (NICU) was significantly lower (RR = 0.62, 95% CI: 0.50, 0.76, p < 0.00001) compared to nifidepine alone. The evidence was high for prolongation of pregnancy, delivery rate 24-72 h after admission, and NICU admission, but low for newborn birth weight. CONCLUSIONS: Given the effectiveness of SC plus nifedipine in increased prolongation of pregnancy and birth weight, lower delivery in the 1st to 3rd days after hospitalization, and NICU admission, Gynecologists and obstetricians are suggested to consider this strategy for PTL management, although additional article rigor is required to improve the quality of the evidence.

Seasonal variation in ambulatory blood pressure control in patients on clinic blood pressure-guided antihypertensive treatment.

BACKGROUND: We investigated seasonal variation in ambulatory blood pressure control in hypertensive patients on clinic blood pressure-guided antihypertensive treatment. METHODS: The study participants were hypertensive patients enrolled in an 8-week therapeutic study. Antihypertensive treatment was initiated with long-acting dihydropyridine calcium channel blockers amlodipine 5 mg/day or the gastrointestinal therapeutic system (GITS) formulation of nifedipine 30 mg/day, with the possible up-titration to amlodipine 10 mg/day or nifedipine-GITS 60 mg/day at 4 weeks of follow-up. RESULTS: The proportion of up-titration to higher dosages of antihypertensive drugs at 4 weeks of follow-up was higher in patients who commenced treatment in autumn/winter ( n  = 302) than those who commenced treatment in spring/summer ( n  = 199, 24.5 vs. 12.0%, P  < 0.001). The control rate of clinic blood pressure, however, was lower in autumn/winter than in spring/summer at 4 (56.7 vs. 70.7%, P  = 0.003) and 8 weeks of follow-up (52.5 vs. 74.9%, P  < 0.001). At 8 weeks, patients who commenced treatment in autumn/winter, compared with those who commenced treatment in spring/summer, had a significantly ( P ≤0.03) smaller daytime (mean between-season difference -3.2/-2.8 mmHg) but greater nighttime SBP/DBP reduction (3.6/1.6 mmHg). Accordingly, at 8 weeks, the prevalence of nondippers was significantly ( P  < 0.001) higher in spring/summer than in autumn/winter for both SBP (54.8 vs. 30.0%) and DBP (53.4 vs. 28.8%). CONCLUSION: Clinic blood pressure-guided antihypertensive treatment requires a higher dosage of medication in cold than warm seasons, which may have led to over- and under-treatment of nighttime blood pressure, respectively.

Utility of nifedipine use for Doppler ultrasound early after liver transplantation to predict short-term complications and long-term outcomes.

PURPOSE: To evaluate the response to nifedipine administration measured by changes in hepatic arterial (HA) flow on post-operative Doppler ultrasound (US) to predict short-term complications and long-term outcomes in liver transplant (LT) patients. METHODS: Patients who underwent LT with post-operative Doppler US within 3 days between 1 January 2005 and 31 December 2015 were included in this retrospective single center study. The patients who received and did not receive nifedipine during the Doppler US comprised the study and control groups, respectively. A positive response to nifedipine was defined as the detection of HA flow when none was present initially or a reduction in HA resistive index (RI) ≥ 0.1 after nifedipine administration. The rates of re-transplantation, re-operation, percutaneous intervention (PCI), and overall survival (OS) were recorded. Cox proportional hazards regression was used to evaluate the association of clinic-demographic variables and Doppler findings with the outcome measures. RESULTS: 444 LT patients (305 M/139F, mean age 51.7 ± 17.4 years, mean interval between LT-Doppler US 1.12 ± 0.9 days) are presented. 220 patients comprised the nifedipine study group [n = 157/220 (71.4%) responder, n = 63/220 (28.6%) nonresponder] and 224 patients comprised the control group. There was no difference in re-transplantation or PCI rates between the groups (all p-values ≥ 0.2 and ≥ 0.08, respectively). The responder group had a lower rate of re-operation vs. the control group (15.9% vs. 24.1%, p = 0.03) and nonresponder group (15.9% vs. 31.8%, p = 0.004). 1-year and 2-year OS were similar between the groups (all p-values > 0.37). CONCLUSION: Short-term complication rates and long-term outcomes for patients with liver transplant who responded to nifedipine administration on Doppler US are similar to those who did not require nifedipine administration. A lack of response to nifedipine was associated with a higher re-operation rate.

Biological Activity of a Coumarin Derivative on Heart Failure Using an Ischemia/Reperfusion Injury Model.

Heart failure is a health problem worldwide. There are some drugs for it, including digoxin, spironolactone, captopril, and valsartan, but some of these drugs can produce secondary effects, such as arrhythmia, cough, hyperkalemia, hyponatremia and hypotension. The aim of this research was to evaluate the biological activity of coumarin (2H-chromen-2-one) and its derivatives (3BrAcet-C, 3-4Br-Ph-C, 4-CN-7D-C, 4-Me-7-Ph-C and 6Br-3-D-C) against ischemia/reperfusion injury as a therapeutic alternative for heart failure. In addition, the biological activity of the coumarin derivative 4-Me-7-Ph-C on left ventricular pressure (LVP) was determined in the absence or presence of ouabain and nifedipine at a dose of 1 nM using an isolated rat heart model. The results showed that i) the coumarin derivative 4-Me-7-Ph-C significantly decreased the infarct area (p+=+0.05) compared with 3BrAcet-C, 3-4Br-Ph-C, 4-CN-7D-C, and 6Br-3-D-C; and ii) 4-Me-7-Ph-C increased LVP in a dose-dependent manner, which effect was inhibited by nifedipine. These data suggest that coumarin 4-Me-7-Ph-C may act as a type-L calcium channel activator, so it could be a good agent to treat heart failure.

Slow on the Draw-ED Management of Elevated BP in Older Adults.

PURPOSE OF REVIEW: The purpose of this study is to review data surrounding the emergency department management of elevated blood pressure in older adults, including the management of hypertensive crisis and outpatient management of markedly elevated blood pressure. RECENT FINDINGS: Acute lowering of blood pressure in older adults with markedly elevated blood pressure may lead to serious complications without improvements in hospital length of stay, return visits, or mortality. Older adults presenting with elevated blood pressures without evidence of end-organ damage should be referred for outpatient management of their blood pressure. Treatment of hypertensive emergency should follow standard guidelines with additional considerations for aging physiology. Acute lowering of elevated blood pressure in older adults without evidence of end-organ damage has the potential for harm. If the emergency physician opts to acutely treat, they should consider the increased risk of side effects in older adults and avoid Beers list medications including short-acting nifedipine and clonidine.

Physiologic Treatment of Severe Hypertension in Pregnancy and Postpartum.

We aimed to evaluate physiologic treatment of severe hypertension. This was a retrospective cohort study of pregnant and postpartum patients with severe hypertension (systolic blood pressure [BP] 160 mm Hg or higher or diastolic BP 110 mm Hg or higher) treated with intravenous labetalol or hydralazine at a single tertiary care center between 2013 and 2018. Patients were classified as having physiologic treatment if they had hyperdynamic physiology (pulse pressure 65 mm Hg or higher) and received labetalol or had vasoconstrictive physiology (diastolic BP 100 mm Hg or higher) and received hydralazine. The primary outcome was number of antihypertensive doses to achieve nonsevere BP. Of 1,120 patients included in the analysis, 653 had physiologic treatment and 467 had nonphysiologic treatment, with 16 (1.4%) excluded for inability to classify physiology. Physiologic treatment was associated with fewer antihypertensive doses (1.4±0.9 doses vs 1.6±1.4 doses; adjusted ß -0.28, 95% CI, -0.42 to -0.14) and lower odds of medication conversion (2.5% vs 4.7%; adjusted odds ratio 0.48, 95% CI, 0.24-0.93) but no difference in time to nonsevere BP (31 minutes [interquartile range 16-66 minutes] vs 34 minutes [interquartile range 15-76 minutes]; adjusted hazard ratio 1.0, 95% CI, 0.9-1.2). Physiologic treatment of severe hypertension warrants further evaluation.

Inhibitory effect of Nifedipine on aldose reductase delays cataract progression.

Aldose reductase (ALR2) is a rate-limiting component of the polyol pathway, which is essential for the NADPH-mediated conversion from glucose to sorbitol. ALR2 dysregulation has been linked to α-crystallin aggregation, increased oxidative stress, and calcium inflow, all of which contribute to a diabetic cataract. Given its crucial role in occular pathologies, ALR2 has emerged as a promising target to treat oxidative stress and hyperglycaemic condition which form the underlying cause of diabetic cataracts. However, several of them had issues with sensitivity and specificity to ALR2, despite being screened as effective ALR2 inhibitors from a wide range of structurally varied molecules. The current study investigates the inhibitory potential of Nifedipine, an analog of the dihydro nicotinamide class of compounds against ALR2 activity. The enzyme inhibition studies were supported by in vitro biomolecular interactions, molecular modeling approaches, and in vivo validation in diabetic rat models. Nifedipine demonstrated appreciable inhibitory potential with the purified recombinant hAR (human aldose reductase; with an IC50 value of 2.5 µM), which was further supported by Nifedipine-hAR binding affinity (Kd = 2.91 ± 1.87 × 10-4 M) by ITC and fluorescence quenching assays. In the in vivo models of STZ-induced diabetic rats, Nifedipine delayed the onset progression of cataracts by preserving the antioxidant enzyme activity (SOD, CAT, and GPX GSH, TBARS, and protein carbonyls) and was shown to retain the α-crystallin chaperone activity by reducing the calcium levels in the diabetic rat lens. In conclusion, our results demonstrate effective inhibition of ALR2 by Nifedipine, resulting in amelioration of diabetic cataract conditions by lowering oxidative and osmotic stress while retaining the chaperone activity of α-crystallins. The present study could be envisaged to improve the eye condition in older adults upon Nifedipine treatment.

Comparison of outcomes following intravenous magnesium compared with intravenous labetalol and oral nifedipine in 355 pregnant Han Chinese women with preeclampsia.

As per the American College of Obstetricians and Gynecologists in 2013, magnesium sulfate is the gold standard for the management of preeclampsia, but it has a short action time that does not provide stable maintenance of blood pressure. Labetalol is currently recommended as first-line treatment by the national UK guidance. This study included 355 pregnant Han Chinese women with preeclampsia and aimed to compare outcomes following intravenous magnesium compared with intravenous labetalol and oral nifedipine. Women received 4 g intravenous magnesium sulfate followed by the maintenance dose of 1 g/h intravenous magnesium sulfate (MS cohort, n = 104) or intravenous labetalol (LB cohort, n = 115), or oral nifedipine (NF cohort, n = 136). Therapy success: systolic blood pressure ~140 mm Hg and diastolic blood pressure ~90 mm Hg, therapy failure: persistent systolic blood pressure ≥ 160 or diastolic blood pressure ≥ 110 mm Hg after maximum dosage of therapy (EL). Women of all cohorts successfully decreased systolic and diastolic blood pressures at EL as compared to them before therapy conditions (P < .001, for all). At EL, systolic and diastolic blood pressures of women of the LB cohort decreased more than those of women of the MS and NF cohorts (P < .05, for all). Therapy was more successful in women of the LB cohort than those of the NF cohort (107 [93%] vs 112 [82%], P = .0132). More numbers of women were reduced blood pressure after 1 day of therapy from the LB cohort than those of the NF (75 [65%] vs 21 [15%]) and MS (75 [65%] vs 35 [34%]) cohorts (P < .0001 for both). Labetalol-induced tachycardia, bradycardia, and intracranial hemorrhage in pregnant women and respiratory distress syndrome and hypoglycemia in neonates. Intravenous labetalol provides proper reduction of blood pressure in Han Chinese women with preeclampsia but has the risk of undesirable maternal and neonatal adverse effects (Level of Evidence: IV; Technical Efficacy: Stage 4).

NITROSAMINE CONTAMINATION WITHIN CARDIAC MULTIMEDICATION - SARTANS (VALSARTAN), CALCIUM CHANNEL BLOCKERS (AMLODIPINE AND NIFEDIPINE), AND ANTIARRHYTHMICS (PROPAFENONE) AS A SIGNIFICANT FACTOR IN THE DEVELOPMENT AND PROGRESSION OF MULTIPLE KERATINOCYTIC CANCERS: ADVANCEMENT ROTATION FLAP FOR KERATOACANTHOMA OF THE UPPER LIP AND UNDERMINING SURGERY FOR BCC OF THE SHOULDER AS AN OPTIMAL DERMATOSURGICAL APPROACH.

The data on the polycontamination of multimedication in polymorbid patients with a heterogeneous class of carcinogens/nitrosamines, NDSRIs (classified according to the FDA regulation to the companies of 2023 to those with a carcinogenic potency between 1 and 5), are one of the most important steps to clarify the concept of skin cancer nitrosogenesis/ pathogenesis. The FDA is the first regulatory institution in the world to courageously declare that a problem exists and should be addressed. The main and currently unexplained and somewhat controversial issue lies in 1) the sporadic nature of polycontamination in different geographical regions, and 2) the lack of official data from the established international, but also regional pharmaceutical market regulators on the results of the checks conducted for nitrosamine contamination of the respective batches. It is this that leads scientists to the idea of (albeit seemingly) speculative but entirely possible controlled contamination of the production in certain geographical regions. This (hypo)thesis is supported, albeit indirectly, by the fact that: a recent regional check for possible contamination of sartans in a particular geographical region was not indicative of the presence of any nitrosamines/NDSRIs. But this fact is indicative of several extremely important things: 1) contamination is not ubiquitous, its genesis is heterogeneous; 2) contamination could be completely avoided at production level in certain geographical regions; 3) ˝controlled contamination˝ or carelessness of a heterogeneous nature should be excluded by the relevant regulators. Regular inspection and certification of medicinal products in relevant geographical regions to exclude contamination with nitrosamines/NDSRIs would be the surest method to protect public health globally. The initial parameters of the restrictive processes for the availability of nitrosamines in medicines have been established by the most powerful regulator globally in the face of the FDA, with the hope being that manufacturers will find a short-term solution to the problem. We report another patient who simultaneously developed 2 cutaneous tumors under potentially/actually nitrosamine contaminated drugs such as: beta blockers- atenolol, calcium antagonists- nifedipine/amlodipine, sartans- valsartan and antiarrhythmics- propafenone. One of the tumors was localized in the upper lip area (keratoacanthoma) and the other in the right shoulder area (basal cell carcinoma). Successful surgical treatment of the tumors was performed in the form of upper lip advancement rotation flap and elliptical excision of the second lesion. The evolution/growth rate of the tumors in relation to the potential mutagens/carcinogens heterogeneous in their potency contained in the drugs is commented.

Treatment of acute-onset hypertension in pregnancy: A network meta-analysis of randomized controlled trials comparing anti-hypertensives and route of administration.

BACKGROUND: Consensus on the relative efficacy of available antihypertensive agents used in pregnancy is lacking. OBJECTIVE: To compare treatment success with antihypertensives and categorize by route of administration. SEARCH STRATEGY: MEDLINE, Embase, PubMed, Web of Science, Scopus, CINAHL, and clinicaltrials.gov were searched without date restriction. DATA COLLECTION: Peer-reviewed randomized controlled trials (RCTs) comparing pharmacologic agents used to treat hypertension in parturients were included. Evaluated treatment groups included IV-labetalol (BBIV), IV-hydralazine (DIV), oral-nifedipine (CCBPO), sublingual nifedipine (CCBSL), IV-calcium channel blocker (nonspecific)(CCBIV), IV-nitroglycerine (NTG), epoprostenol infusion (PRO), IV-ketanserin (5HT2B), IV-diazoxide (BZO), oral-nifedipine + methyldopa (CCBAG), oral-methyl-dopa (AAG), and oral prazosin (ABPO). ANALYSIS: Seventy-four studies (8324 patients) were eligible post PRISMA guidelines screening. Results were pooled using a Bayesian-approach for success of treatment (study defined target blood pressure), time to achieve target pressure, and neonatal intensive-care admissions. RESULTS: Treatment success (primary outcome, 55 trials with 5518 patients) was analyzed. Surface under the cumulative ranking curve (SUCRA) was categorized for 13 drugs, CCBPO (0.84) followed by CCBSL (0.78) were most likely to be effective in achieving target blood pressure. After sub-grouping by presence/absence of preeclampsia, CCB-PO ranked highest for both [(0.82) vs. (0.77), respectively]. Serotonin antagonists (0.99) and nitroglycerin (0.88) ranked highest for time to target pressure. NICU admissions were lowest for alpha-2 agonists (0.89), followed by BB PO (0.82) and hydralazine IV (0.49). CONCLUSION: Oral calcium-channel blockers ranked highest for treatment success. Ketanserin achieved target blood pressure fastest, warranting additional research. The results should be interpreted with caution as SUCRA values may not indicate whether the differences between interventions have clinically meaningful effect sizes.

L-type calcium ion channel-mediated activation of autophagy in vascular smooth muscle cells via thonningianin A (TA) alleviates vascular calcification in type 2 diabetes mellitus.

Vascular calcification (VC) is associated with increased morbidity and mortality, especially among people with type 2 diabetes mellitus (T2DM). The pathogenesis of vascular calcification is incompletely understood, and until now, there have been no effective therapeutics for vascular calcification. The L-type calcium ion channel in the cell membrane is vital for Ca2+ influx. The effect of L-type calcium ion channels on autophagy remains to be elucidated. Here, the natural compound thonningianin A (TA) was found to ameliorate vascular calcification in T2DM via the activation of L-type calcium ion channels. The results showed that TA had a concentration-dependent ability to decrease the transcriptional and translational expression of the calcification-related proteins runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2) and osteopontin (OPN) (P < 0.01) via ATG7-dependent autophagy in ß-glycerophosphate (ß-GP)- and high glucose (HG)-stimulated primary mouse aortic smooth muscle cells (MASMCs) and alleviate aortic vascular calcification in VitD3-stimulated T2DM mice. However, nifedipine, an inhibitor of L-type calcium ion channels, reversed TA-induced autophagy and Ca2+ influx in MASMCs. Molecular docking analysis revealed that TA was located in the hydrophobic pocket of Cav1.2 α1C and was mainly composed of the residues Ile, Phe, Ala and Met, which confirmed the efficacy of TA in targeting the L-type calcium channel of Cav1.2 on the cell membrane. Moreover, in an in vivo model of vascular calcification in T2DM mice, nifedipine reversed the protective effects of TA on aortic calcification and the expression of the calcification-related proteins RUNX2, BMP2 and OPN (P < 0.01). Collectively, the present results reveal that the activation of cell membrane L-type calcium ion channels can induce autophagy and ameliorate vascular calcification in T2DM. Thonningianin A (TA) can target and act as a potent activator of L-type calcium ion channels. Thus, this research revealed a novel mechanism for autophagy induction via L-type calcium ion channels and provided a potential therapeutic for vascular calcification in T2DM.

Una paciente con fenómeno de Raynaud del pezón e hipertiroidismo / A patient with Raynaud's phenomenon of the nipple and hyperthyroidism

Introducción: el fenómeno de Raynaud del pezón es una patología poco frecuente. Puede presentarse asociada a hipertiroidismo o enfermedades autoinmunes del tejido conectivo. Presentamos un caso asociado a hipertiroidismo.Caso clínico: mujer, de 39 años, que consulta por dolor en pezón que se agrava con la lactancia 1 mes después del parto. Se diagnosticó fenómeno de Raynaud del pezón, que mejoró con la toma de nifedipino. Tres meses después, la paciente presentó fiebre. El análisis de sangre mostró hormona estimulante del tiroides (TSH) 0,0008 mU/L (normal: 0,55-4,75 mU/L) y T4 libre 48 pg/mL (normal: 2,30-4,20 pg/mL). Los anticuerpos antitiroglobulina fueron > 500 UI/mL. La T3, los anticuerpos antiperoxidasa (TPO) y la inmunoglobulina estimulante del tiroides fueron normales. Se diagnosticó tiroiditis posparto (TPP). Dos meses después, los niveles de TSH y T4 libre volvieron a la normalidad.Conclusión: nuestra paciente presenta una TPP asociada a un fenómeno de Raynaud.(AU)

Introduction: Raynaud's phenomenon of the nipple is a rare pathology. It can occur associated with hyperthyroidism or autoimmune connective tissue diseases.We report a case associated with hyperthyroidism.Case study: a 39-year-old woman consulted for nipple pain, which worsened with breastfeeding, one month after childbirth. Raynaud's phenomenon of the nipple was diagnosed, which improved with nifedipine. Three months later the patient developed fever. Blood test revealed thyroid stimulating hormone (TSH) 0.0008 mU/L (normal 0.55-4.75 mU/L) and free T4 48 pg/mL (normal 2.30-4.20 pg/mL). Antithyroglobulin antibodies were >500 IU/mL. T3, antiperoxidase antibodies (TPO), and thyroid-stimulating immunoglobulin were normal. Postpartum thyroiditis (PPT) was diagnosed. Two months later, TSH and free T4 levels returned to normal.Conclusion: our patient presented PPT associated with Raynaud's phenomenon.(AU)

Assessing the efficacy and safety of Sildenafil vs. Nifedipine in improving endometrial blood flow and thickness in women with recurrent first-trimester miscarriage.

Endometrial thickness and uterine blood flow influence pregnancy continuation until term. Nifedipine, a type II calcium channel blocker, and Sildenafil, a type 5-specific phosphodiesterase inhibitor, have shown the potential to improve these factors. This study aims to compare the safety and efficacy of Nifedipine and Sildenafil in improving endometrial blood flow and thickness in Iraqi women with recurrent first-trimester miscarriages. Women with unexplained recurrent pregnancy loss in the first trimester (non-pregnant during the study) were randomly assigned to two groups. Transvaginal color Doppler ultrasound assessed uterine artery pulsatility, resistance indexes, and endometrial thickness during the second phase of the menstrual cycle (day 15 to day 25). The first group received oral Nifedipine (10 mg) twice daily, while the second group received oral Sildenafil citrate (20 mg) every 8 hours from day 5 to day 25. Baseline measurements showed no significant differences in pulsatility index between the groups (2.02±0.52 for Nifedipine, 2.03±0.49 for Sildenafil, p=0.927). Sildenafil treatment resulted in a more noticeable reduction in the pulsatility index. The resistive index had a significant difference in baseline readings (0.98±0.14 for Nifedipine, 1.06±0.14 for Sildenafil, p=0.033), with Sildenafil showing a more pronounced reduction. Post-treatment, Sildenafil demonstrated a greater improvement in endometrial thickness than Nifedipine (10.09±0.74 mm vs. 9.34±0.50 mm, respectively; p<0.001). Both medications were safe and effective in improving endometrial blood flow and thickness in women with recurrent pregnancy miscarriages, with Sildenafil showing greater efficacy.

Evaluation and Management of Hypertensive Disorders of Pregnancy.

Hypertensive disorders of pregnancy complicate up to 10% of pregnancies and remain the major cause of maternal and neonatal morbidity and mortality. Hypertensive disorders of pregnancy can be classified into four groups depending on the onset of hypertension and the presence of target organ involvement: chronic hypertension, preeclampsia, gestational hypertension, and superimposed preeclampsia on chronic hypertension. Hypertension during pregnancy is associated with a higher risk of cardiovascular disease and kidney failure. Early diagnosis and proper treatment for pregnant women with hypertension remain a priority since this leads to improved maternal and fetal outcomes. Labetalol, nifedipine, methyldopa, and hydralazine are the preferred medications to treat hypertension during pregnancy. In this comprehensive review, we discuss the diagnostic criteria, evaluation, and management of pregnant women with hypertension.

Arrest of mouse preterm labor until term delivery by combination therapy with atosiban and mundulone, a natural product with tocolytic efficacy.

There is a lack of FDA-approved tocolytics for the management of preterm labor (PL). In prior drug discovery efforts, we identified mundulone and mundulone acetate (MA) as inhibitors of in vitro intracellular Ca2+-regulated myometrial contractility. In this study, we probed the tocolytic potential of these compounds using human myometrial samples and a mouse model of preterm birth. In a phenotypic assay, mundulone displayed greater efficacy, while MA showed greater potency and uterine-selectivity in the inhibition of intracellular-Ca2+ mobilization. Cell viability assays revealed that MA was significantly less cytotoxic. Organ bath and vessel myography studies showed that only mundulone exerted inhibition of myometrial contractions and that neither compounds affected vasoreactivity of ductus arteriosus. A high-throughput combination screen identified that mundulone exhibits synergism with two clinical-tocolytics (atosiban and nifedipine), and MA displayed synergistic efficacy with nifedipine. Of these combinations, mundulone+atosiban demonstrated a significant improvement in the in vitro therapeutic index compared to mundulone alone. The ex vivo and in vivo synergism of mundulone+atosiban was substantiated, yielding greater tocolytic efficacy and potency on myometrial tissue and reduced preterm birth rates in a mouse model of PL compared to each single agent. Treatment with mundulone after mifepristone administration dose-dependently delayed the timing of delivery. Importantly, mundulone+atosiban permitted long-term management of PL, allowing 71% dams to deliver viable pups at term (>day 19, 4-5 days post-mifepristone exposure) without visible maternal and fetal consequences. Collectively, these studies provide a strong foundation for the development of mundulone as a single or combination tocolytic for management of PL.

Therapeutic improvements of nifedipine controlled-release tablets combined with sacubitril valsartan on patients with diabetic nephropathy complicated with hypertension.

This study aimed to evaluate the efficacy of nifedipine controlled-release tablets combined with sacubitril valsartan in diabetic nephropathy (DN) patients with hypertension. One hundred and twelve DN patients with hypertension were enrolled. They were randomly divided into the control group (treated with nifedipine controlled-release tablets combined with valsartan) and the observation group (treated with nifedipine controlled-release tablets combined with sacubitril valsartan). Renal function, endothelial function and inflammatory response were examined. After three-months treatment, the levels of clinical indexes (glycosylated hemoglobin, fasting blood glucose, systolic and diastolic blood pressure), renal function indicators (urinary albumin excretion rate, blood urea nitrogen, serum creatinine and cystatin C), endothelial function indicators (microalbumin, angiotensin II, thrombomodulin and cartilage oligomeric matrix protein) and inflammatory response factors (interleukin-6 and tumor necrosis factor-α) in the observation group were significantly lower than those in the control group. Nifedipine controlled-release tablets combined with sacubitril valsartan could effectively alleviate the progression of DN combined with hypertension.

Oral nifedipine may be a preferential option for treating acute severe hypertension during pregnancy: a meta-analysis.

AIM: To compare oral nifedipine and intravenous labetalol in the treatment of acute severe hypertension in pregnancy (SHP). METHODS: The primary outcomes were the required time to achieve target blood pressure (RTATBP), systolic blood pressure (SBP) and diastolic BP (DBP) after treatment, secondary outcomes were the number of doses (NoD) and adverse events (AEs). RESULTS: There was no difference between oral nifedipine and intravenous labetalol in SBP, DBP, and AE. However, oral nifedipine provided less RTATBP and NoD. CONCLUSION: Oral nifedipine was associated with less RTATBP and NoD and otherwise did not differ from intravenous labetalol.

Repurposing drugs to treat trichinellosis: in vitro analysis of the anthelmintic activity of nifedipine and Chrysanthemum coronarium extract.

Albendazole is the most common benzimidazole derivative used for trichinellosis treatment but has many drawbacks. The quest for alternative compounds is, therefore, a target for researchers. This work aims to assess the in vitro anthelmintic effect of nifedipine, a calcium channel blocker, and a methanol extract of the flowers of Chrysanthemum coronarium as therapeutic repurposed drugs for treating different developmental stages of Trichinella spiralis in comparison with the reference drug, albendazole. Adult worms and muscle larvae of Trichinella spiralis were incubated with different concentrations of the studied drugs. Drug effects were evaluated by parasitological and electron microscopic examination.As a result, the effects of these drugs on muscle larvae were time and dose-dependent. Moreover, the LC50 after 48 h incubation was 81.25 µg/ml for albendazole, 1.24 µg/ml for nifedipine, and 229.48 µg/ml for C. coronarium. Also, the effects of the tested drugs were prominent on adult worms as the LC50 was 89.77 µg/ml for albendazole, 1.87 µg/ml for nifedipine, and 124.66 µg/ml for C. coronarium. SEM examination of the tegument of T. spiralis adult worms and larvae showed destruction of the adult worms' tegument in all treated groups. The tegument morphological changes were in the form of marked swellings or whole body collapse with the disappearance of internal contents. Furthermore, in silico studies showed that nifedipine might act as a T. spiralis ß-tubulin polymerization inhibitor.Our results suggest that nifedipine and C. coronarium extract may be useful therapeutic agents for treating trichinellosis and warrant further assessment in animal disease models.

Nifedipine attenuates alveolar bone destruction and improves trabecular microarchitectures in mice with experimental periodontitis.

Studies have shown that nifedipine exerts anti-inflammatory and immunosuppressive actions in addition to being a calcium channel blocker. The present study was performed to explore the influence of nifedipine on alveolar bone destruction in mice with experimental periodontitis by evaluating morphological information acquired from micro-computed tomography analysis. BALB/c mice were randomly assigned into four groups: control (C) group; experimental periodontitis (E) group; experimental periodontitis + 10 mg/kg dose of nifedipine (EN10) group; and experimental periodontitis + 50 mg/kg dose of nifedipine (EN50) group. Periodontitis was induced by oral inoculation with Porphyromonas gingivalis over a 3-week time period. Nifedipine significantly mitigated the loss of alveolar bone height as well as increase of root surface exposure induced by experimental periodontitis. Additionally, the reduction in the bone volume fraction associated with P. gingivalis infection was significantly recovered upon nifedipine treatment. Further, nifedipine attenuated P. gingivalis-induced deteriorations in the trabeculae-associated parameters. Significant difference was evident between Groups EN10 and EN50 in both the extent of alveolar bone loss and microstructural parameters assessed, except trabecular separation and trabecular number. Nifedipine appeared to have good performance in ameliorating bone loss in mice with induced periodontitis. Nifedipine may be utilized in the clinical management of periodontitis, though further research is indicated to verify the therapeutic effect.