Combination Of Nifedipine Research Articles

Effects of olive leaf extract and nifedipine, alone and in combination, on blood pressure, neutrophil gelatinase-associated lipocalin, malondialdehyde, and creatinine levels in an Nω-nitro-L-arginine methyl ester-induced rat model of preeclampsia

Preeclampsia (PE) is a significant health problem in pregnancy, affecting 6–7% of all gestations and leading to fetal growth retardation, infant morbidity and mortality, premature birth, and maternal death. Currently, effective treatment options for PE are limited. This study aimed to evaluate the therapeutic potential of olive leaf extract (OLE) and nifedipine, alone and in combination, in improving pregnancy outcomes in rats induced with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME). Rats were treated with single and combination treatments of nifedipine and OLE for four weeks, after being induced with L-NAME for six weeks. Following gestational day assessment and systolic blood pressure testing, the rats were sacrificed, and blood samples were collected for Neutrophil Gelatinase-Associated Lipocalin (NGAL), Malondialdehyde (MDA), proteinuria and Creatinine (SCr) Levels examinations. The results revealed the combination of nifedipine and OLE significantly improved the results of several biomarker analyses associated with PE, including increased NGAL levels, a significant decrease in MDA levels, decrease in proteinuria and elevated creatinine levels. The combination nifedipine and OLE treatment also exhibited a significant antihypertensive effect compared to either nifedipine or OLE monotherapy, as evidenced by the reduction in systolic and diastolic blood pressure levels. This study provides novel evidence for the potential of olive leaf extract as a nutraceutical adjunct for the prevention and treatment of PE. The significant improvements observed in several pathological features associated with PE, including antihypertensive effects, warrant further investigation. Future research should focus on elucidating the underlying mechanisms of action and exploring the clinical applicability of olive leaf extract in human populations with PE.

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

BackgroundPreterm 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.MethodsFor 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.ResultsSeven 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.ConclusionsGiven 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.

Rationale use of drugs in pregnancy induced hypertension at a tertiary care hospital

Background: Pregnancy induced hypertension known as preeclampsia is considered to be the second cause of death next to anaemia. There are significant sources of maternal and foetal mortality and morbidity. Antihypertensive medication reduces the progression of the course of hypertensive disorders. However, its effect on the outcomes of pregnancy may include development of preeclampsia, preterm delivery, foetal /neonatal demise, IUGR, low birth weight. Whether such associations are casual or confounded is unknown. Hence, we intended to study the rationale use of drugs in pregnancy induced hypertensive patients. Methods: Patients diagnosed with hypertensive disorders in pregnancy were recruited. Pregnant women in the age group of 18-45 years who consented to participate were included. Non pregnant women and women with PCOD, depression and on any medications were excluded. Details on drug treatment, type of drugs, combination, dose, dosage and duration were noted. Results: 105 patients were enrolled. 51% belonged to 18-25 years. 98% mothers received monotherapy and 2% received dual therapy. Labetalol was the most commonly prescribed drug. 50% of the patients received a combination of Nifedipine and Methyldopa while another 50% received Nifedipine with Labetalol. The outcome of new born babies born in mothers receiving antihypertensive drugs had complications of low birth weight and malformations. The dose of the medications prescribed was well within the range. Conclusions: Proper counselling to the patients regarding life style management, regular follow ups and monitoring of blood pressure is important to understand, resolve the burden and complication.

A Comparison of Nifedipine Versus a Combination of Nifedipine and Sildenafil Citrate in the Management of Preterm Labour.

Background Preterm delivery is a significant contributor to neonatal and infant morbidity and mortality. Preventive methods are preferable to treatment protocols for reducing perinatal mortality and morbidity. The calcium channel blocker nifedipine has the potential to be employed as a tocolytic, whereas the phosphodiesterase inhibitor sildenafil citrate promotes smooth muscle relaxation. Objective This study aims to examine the tocolytic effect of nifedipine in combination with sildenafil citrate in managing preterm labour (PTL). Methods After approval from the ethical board, 160 patients fulfilling the selection criteria were enrolled in the study from the outpatient and emergency department of obstetrics and gynaecology, University of Lahore, Pakistan. After taking written informed consent, their demographic profile, i.e., name, age, gestational age at presentation, parity, and expected date of delivery was noted. Patients were randomly assigned in a 1:1 ratio to two study groups (Group A: sildenafil citrate + nifedipine) and (Group B: nifedipine) using a computer-generated random number table to obtain a trial sequence. In group A, each patient was given nifedipine 20 mg orally, followed by 10 mg orally every eight hours for 48 hours and vaginal administration of sildenafil citrate, 25 mg at eight-hour intervals, for 48 hours. In group B, females were given nifedipine 20 mg orally, followed by 10 mg orally every 8 hours for 48 hours. They were kept admitted for 72 hours.SPSS Statistics version 21.0 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.) was used to enter and analyse the collected data. Mean and standard deviation was calculated for quantitative variables like age, gestational age at presentation, gestational age at delivery, and BMI. Frequency and percentage were calculated for parity and preterm delivery. Results The study involved 160 patients, with the average age in Group A being 29.60±4.9 years and in Group B being 30.96±4.98 years. In terms of gestational age at delivery, Group A had an average of 34.16±1.7 weeks, while Group B had an average of 33.5±1.8 weeks (p-value<0.05). Preterm delivery was observed in 68.5% of Group A and 41.3% of Group B, with a significant p-value of 0.001. The study also discovered that the duration of prolonged pregnancy was significantly higher in Group A compared to Group B, with averages of 14.96±10.37 days and 10.24±8.97 days, respectively (p-value=0.002). Conclusion The results of this study suggest that the combination of sildenafil citrate and nifedipine may offer a promising new approach to improving pregnancy outcomes in cases of PTL. In the present study, sildenafil citrate plus nifedipine showed a significant effect in the management of PTL and prolongation in mean gestational age at delivery.

The Value of Injection Therapy with Botulinum Toxin in Pain Treatment of Primary Chronic Anal Fissures Compared to Anal Dilation, and Local Nifedipine in Combination with Lidocaine.

Introduction: Anal fissure is a longitudinal tear of the mucosa of the anal canal extending from the outer anal orifice in the direction of the dentate line of the inner anal opening. Fissures are divided into primary and secondary, and acute or chronic. Besides minimal rectal bleeding, itching and soiling, primary chronic anal fissures (PCAF) manifest with anal pain as theirs main determinant. It is described as the most troubling symptom. Aim: To compare the effect of injection therapy with botulinum toxin A (ITBT) vs. anal dilation (AD), and local nifedipine with lidocaine (LNL) in pain treatment of PCAF. Materials and Methods: This controlled retrospective prospective longitudinal study covered 94 patients, divided in 3 groups. The first was treated with ITBT, the second with AD and third using LNL (31, 33 and 30 patients respectively). Clostridium botulinum toxin A was used, dissolved with saline to concentration of 200 U/ml. The solution was applied to both sides of PCAF at dose of 40U. Modified technique of AD was done using 3 fingers of a single hand, progressively introduced into the anal canal, followed by gradual lateral distraction during 1 min. LNL therapy was conducted using nifedipine (0.3%) with lidocaine (1.5%) ointment, applied twice daily for 3 weeks. To measure pain, a visual analog scale (VAS) was used. The follow-up period was 12 weeks with checkup at week 4. Results: The median age of participants was 46.6±13.9 years (50 males vs. 44 females). The type of therapy had a significantly different effect on pain at week 4 (p=0.0003). Severe pain was present in only 2 ITBT patients, 16 AD, and 6 LNL patients. Post hoc analyses showed different pain disappearance time by week 12 (p <0.0001). The mean time was shortest in ITBT group (6.1±1.5 weeks). Anal pain intensity significantly differed among the 3 groups (Fisher exact, p=0.002). Namely, 71% in ITBT group rated the pain as weakest (VAS score 1) compared to 18.2% in AD and 30% of patients in LNL group. The overall pain reduction significance was in favor of ITBT, due to the differences between the ITBT and AD groups (p=0.00024) and ITBT compared to LNL group (p=0.018). Conclusion: ITBT is superior to AD and LNL in reducing pain in PCAF.

Postpartum medical management of hypertension and risk of readmission for hypertensive complications.

To compare the risk of readmission in those receiving no treatment, labetalol, nifedipine or both at hospital discharge following delivery complicated by presence of hypertension. Retrospective study at a single tertiary care center over a 4-year period (2017-2020). Those with peripartum hypertension (pHTN), defined as any SBP greater than 140 mmHg or DBP greater than 90 mmHg on two occasions 4 h apart during their admission for delivery were included. The primary outcome was postpartum readmission because of hypertensive complications. Analysis was stratified by medication prescribed at discharge (no treatment prescribed, labetalol, nifedipine, or both). The risks of readmission for the management of pHTN were estimated using logistic regression and adjusted for confounding variables. Nineteen thousand, four hundred and twenty-five women gave birth during the study period and 4660 (24.0%) met the described definition of pHTN. Of those, 1232 (26.4%) were discharged on antihypertensive medication (s). There were 217 (4.7%) readmissions for hypertensive complications following discharge. Compared with patients who did not receive antihypertensive medication at discharge, any nifedipine prescription was found to significantly decrease the risk of readmission: monotherapy [aOR 0.27 (0.15-0.48)], nifedipine with labetalol [aOR 0.35 (0.16-0.77)]. Labetalol monotherapy was associated with increased risk of readmission [aOR 1.66 (1.06-2.61)]. The risk of postpartum readmission for hypertensive complication was reduced by 65% when patients were discharged on nifedipine monotherapy and 56% with combined nifedipine and labetalol treatment when compared with no treatment. Patients discharged on labetalol monotherapy were nearly six times as likely to be readmitted for hypertensive complications when compared with patients on nifedipine monotherapy.

Visualization of Food Polyphenols.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is commonly used in food and pharmacological sciences to visualize localization of drugs and food compounds and their metabolites in plant, animal, and human tissues. The localization of compounds obtained by MALDI-MSI images provides useful information for elucidating their physiological and pharmacological properties. Food polyphenols, naturally occurring in tea, coffee, fruits and vegetables, have health benefits owing to their preventative effects against conditions such as cancer, diabetes, and cardiovascular diseases. In order to elucidate the pharmacological properties of polyphenols, their absorption, distribution, metabolism and excretion must be investigated. However, application of MALDI-MS imaging for polyphenols is challenging due to lack of an appropriate matrix reagent to visualize polyphenols in targeted biological tissue. The present work highlights the development of MALDI-MSI for visualization of food polyphenols. Nifedipine, which produces a nitrosophenyl pyridine derivative under laser irradiation, could be a new matrix for MS detection of polyphenols. The combination of nifedipine and phytic acid (a metal-chelating agent) successfully achieved MS visualization of polyphenols in biological tissue. The inhibitor-aided MALDI-MSI has been applied for elucidation of intestinal absorption routes and metabolic behaviors of polyphenols. The MALDI-MSI technique shows great potential for visualizing absorption, distribution and metabolism processes of food polyphenols.

Plausibility of the combination of 17 α hydroxyprogesterone injection and Nifedipine versus Magnesium sulfate in the management of preterm labor, RCT

Background: Preterm birth is the leading cause of neonatal mortality and the most common reason for neonatal admission to the hospital. Although the causes of preterm labor are not well understood, the burden of preterm births is clear—preterm births account for approximately 70% of neonatal deaths and 36% of infant deaths as well as 25–50% of cases of long-term neurologic impairment in children. Objective: To compare the effectiveness of the tocolytic action of the standard protocol of Magnesium sulfate versus the combination of Nifedipine and 17 α hydroxyprogesterone injection in the term of acute tocolysis therapy on the perinatal outcome and to abrupt threatened preterm labor between 24 weeks to 33 weeks and 6 days. Patients and methods: A prospective randomized control trial study conducted at Zagazig Maternity Hospital, included 102 pregnant women who presented with threatened preterm labor at the Emergency Department of Zagazig University Maternity Hospital. The participants were divided into two groups, group (1) included 51 cases who received the standard protocol of Magnesium Sulfate: loading dose 4 g IV; maintenance 2 g/hr for 24 hrs.

Postpartum Readmission for Hypertension After Discharge on Labetalol or Nifedipine.

To assess whether readmission for hypertension by 6 weeks postpartum differed between patients discharged on nifedipine or labetalol. This cohort study included patients with delivery admissions from 2006 to 2017 who were discharged from the hospital on nifedipine or labetalol and were included in a large, national adjudicated claims database. We identified patients' discharge medication based on filled outpatient prescriptions. We compared rates of hospital readmission for hypertension between patients discharged postpartum on labetalol alone, nifedipine alone, or combined nifedipine and labetalol. Patients with chronic hypertension without superimposed preeclampsia were excluded. Comparisons based on medication were performed using logistic regression models with adjustment for prespecified confounders. Comparisons were also stratified by hypertensive disorder of pregnancy severity. Among 1,582,335 patients overall, 14,112 (0.89%) were discharged postpartum on labetalol, 9,001 (0.57%) on nifedipine, and 1,364 (0.09%) on both medications. Postpartum readmissions for hypertension were more frequent for patients discharged on labetalol compared with nifedipine (641 patients vs 185 patients, 4.5% vs 2.1%, adjusted odds ratio [aOR] 1.63, 95% CI 1.43-1.85). Readmissions for hypertension were more frequent for patients discharged on labetalol compared with nifedipine for both mild (4.5% vs 2.7%, aOR 1.57, 95% CI 1.29-1.93) and severe hypertensive disorders of pregnancy (261 patients vs 72 patients, 5.7% vs 3.2%, aOR 1.63, 95% CI 1.43-1.85). Readmissions for hypertension were more frequent on combined nifedipine and labetalol compared with nifedipine (3.1% vs 2.1%), but the odds were lower after confounder adjustment (aOR 0.80, 95% CI 0.64-0.99). Postpartum discharge on labetalol was associated with increased risk of readmission for hypertension compared with discharge on nifedipine.

Hypertensive emergencies crisis and the choice of therapy in prehospital treatments

People with arterial blood pressure &gt;140/90 mmHg (hypertension) have accelerated development of atherosclerosis and changes in blood vessels and other organs of the body, therefore, such arterial blood pressure must be treated. A hypertensive crisis is defined as an extreme increase in arterial blood pressure with a systolic blood pressure over 180 mmHg and diastolic blood pressure over 120 and 130 mmHg, respectively, and poses an immediate danger to the patient's life. At the heart of each hypertensive crisis is severe hypertension. In the Emergency medicine center Zivinice has been carried out a prospective study ehich include four study groups were formed as a sequential sample of 160 participants of both sexes. By administering a combination of furosemide amp. And diazepam amp. The mean systolic blood pressure in all observed groups decreased from 186.25 mmHg to 167.5 mmHg, and the mean diastolic blood pressure decreased from 120.53 mmHg to 97.5 mmHg. By prescribing a combination of nifedipine tab., furosemide amp. and diazepam amp., the average systolic blood pressure all observed groups was reduced from 186.25 mmHg to 152 mmH, and the average diastolic blood pressure was reduced from 120.53 mmHg to 91.2 mmHg.

Fast-Dissolving Nifedipine and Atorvastatin Calcium Electrospun Nanofibers as a Potential Buccal Delivery System.

Geriatric patients are more likely to suffer from multiple chronic diseases that require using several drugs, which are commonly ingested. However, to enhance geriatric patients’ convenience, the electrospun nanofiber system was previously proven to be a successful alternative for the existing oral dosage forms, i.e., tablets and capsules. These nanofibers prepared either as single- or multi-layered fibers could hold at least one active compound in each layer. They might also be fabricated as ultra-disintegrated fibrous films for oral cavity administration, i.e., buccal or sublingual, to improve the bioavailability and intake of the administered drugs. Therefore, in this work, a combination of nifedipine and atorvastatin calcium, which are frequently prescribed for hypertension and hyperlipidemia patients, respectively, was prepared in a coaxial electrospinning system for buccal administration. Scanning electron microscopy image showed the successful preparation of smooth, non-beaded, and non-porous surfaces of the drug-loaded nanofibers with an average fiber diameter of 968 ± 198 nm. In contrast, transmission electron microscopy distinguished the inner and outer layers of those nanofibers. The disintegration of the drug-loaded nanofibers was ≤12 s, allowing the rapid release of nifedipine and atorvastatin calcium to 61% and 47%, respectively, after 10 min, while a complete drug release was achieved after 120 min. In vitro, a drug permeation study using Franz diffusion showed that the permeation of both drugs from the core–shell nanofibers was enhanced significantly (p < 0.05) compared to the drugs in a solution form. In conclusion, the development of drug-loaded nanofibers containing nifedipine and atorvastatin calcium can be a potential buccal delivery system.

Nifedipine Potentiates Susceptibility of Salmonella Typhimurium to Different Classes of Antibiotics.

The calcium channel blocker nifedipine induces cellular iron export, thereby limiting the availability of the essential nutrient iron for intracellular pathogens, resulting in bacteriostatic activity. To study if nifedipine may exert a synergistic anti-microbial activity when combined with antibiotics, we used the mouse macrophage cell line RAW267.4, infected with the intracellular bacterium Salmonella Typhimurium, and exposed the cells to varying concentrations of nifedipine and/or ampicillin, azithromycin and ceftriaxone. We observed a significant additive effect of nifedipine in combination with various antibiotics, which was not observed when using Salmonella, with defects in iron uptake. Of interest, increasing intracellular iron levels increased the bacterial resistance to treatment with antibiotics or nifedipine or their combination. We further showed that nifedipine increases the expression of the siderophore-binding peptide lipocalin-2 and promotes iron storage within ferritin, where the metal is less accessible for bacteria. Our data provide evidence for an additive effect of nifedipine with conventional antibiotics against Salmonella, which is partly linked to reduced bacterial access to iron.

Study on the Clinical Characteristics and Treatment of Obstetric Hypertension with Sequence Pattern Mining Algorithm.

Aiming at the difficulty in setting the support threshold for sequential pattern mining algorithms and improving the effectiveness of the support threshold setting without the guidance of domain experts' experience, an improved SPADE (sequential pattern discovery using equivalence classes) algorithm is proposed. By analyzing the relationship between the number of frequent sequences and the support threshold, the support threshold is dynamically selected. Using the electronic medical record data from a medical centre, the time-series relationship of the drugs taken by hypertension patients was extracted as the drug sequence dataset. By determining the optimal support threshold of the dataset, the frequent sequence set is mined, and the sequence rules are generated from the obtained regular sequences to visualize the sequence rules. The sequence rules of medication for hypertensive patients were combined with the patients' physical indicators for the recommendation. For patients with obstetric hypertension, a combination of nifedipine and captopril is recommended. Through the comparison of the observation group and control group, we study the curative effect of various drugs. The results showed that the total effective rate of the observation group was about 96.6%; compared with the control group, the result indicated that the difference was significant (P < 0.05). The comparison of blood pressure levels between the two groups after treatment also showed that the results of the observation group were ideal (P < 0.05). In addition, the incidence of postpartum haemorrhage and perinatal complications in the observation group was also significantly reduced (P < 0.05). Therefore, the combination of medication for pregnancy hypertension syndrome can effectively improve the treatment effect of the disease and reduce the rate of postpartum haemorrhage and the incidence of perinatal complications.

Comparison between methyldopa and combination of methyldopa and nifedipine in terms of mean change in blood pressure in pregnancy induced hypertension

Objective: Comparison between Methyldopa and combination of Methyldopa and Nifedipine in terms of mean change in blood pressure in pregnancy induced hypertension. Material and methods: This randomized controlled trial was conducted at Department of Obstetrics and Gynecology, Combined Military Hospital Bahawalpur from February 2020 to August 2020 over the period of 6 months. Total 80 patients with pregnancy induced hypertension as per operational definition having age 20-40 years and having gestational age ≥ 20 weeks assessed on LMP were selected. Results: Mean age of the patients was 30.81 ± 5.670 years, mean age of patients of group A was 31.50 ± 5.809 years and mean age of group B was 30.13 ± 5.515 years. Mean gestational age was 30.17 ± 5.981 weeks, mean gestational age of patients of group A was 29.70 ± 6.329 weeks and mean gestational age of patients of group B was 30.65 ± 5.65 weeks. In group A, mean diastolic blood pressure was decrease from 101.2250 ± 4.97938 to 84.5000 ± 3.26599 and in group B from 107.7750 ± 7.18434 to 82.5000 ± 2.25320. Comparison of mean decrease in diastolic blood pressure between group A (High dose Methyldopa) and group B (Low dose Low dose Methyldopa with Nifedipine) was done. Mean decrease in diastolic blood pressure in group A was 16.72 ± 3.935 and in group B was 25.28 ± 6.876. Statistically significant difference of mean decrease in diastolic blood pressure between the both groups was noted with p value 0.000. Conclusion: Results of this study showed that Low dose Methyldopa with Nifedipine combination is more effective as compared to High dose Methyldopa to reduce diastolic blood pressure in pregnant women suffering from pregnancy induced hypertension. Keywords: Diastolic blood pressure, Methyldopa, Nifedipine, Pregnancy induced hypertension, Systolic blood pressure

Comparison of the Effect of Nifedipine Alone and the Combination of Nifedipine and Sildenafil in Delaying Preterm Labor: A Randomized Clinical Trial

Objective: Recently, sildenafil as a drug effective in relaxing smooth muscles can be used as an adjunct to delay the onset of uterine contractions and therefore the occurrence of preterm labor. The aim of this study was to evaluate the effect of nifedipine combination with sildenafil on preterm delivery compared with nifedipine alone. Materials and methods: This randomized double-blinded clinical trial was performed on pregnant women with a gestational age of 26-34 weeks with singleton pregnancy and symptoms of preterm delivery. The mothers were randomly assigned into two groups receiving nifedipine plus sildenafil or those receiving nifedipine alone. The time of delivery, maternal and neonatal complications were compared between the two groups. Results: Mothers who received the combination therapy experienced significantly lower preterm delivery within 72 hours of intervention compared to nifedipine alone (4.5% versus 27.3%, p = 0.002). The rate of delivery during the first 7 days after discharge was 7.6% and 31.8% in nifedipine plus sildenafil and nifedipine alone, respectively (P = 0.001). The prevalence of neonatal respiratory distress syndrome (RDS) as well as mean birth weight was higher in the nifedipine group alone. Treatment protocol with nifedipine and sildenafil compared with nifedipine alone was associated with a significant increase in preterm delivery delay (beta =-5.819, p = 0.001). Conclusion: The use of sildenafil in addition to nifedipine causes more delay in delivery in cases of preterm labor, followed by lower risk for RDS, reduces neonatal intensive care unit (NICU) admission, and preserves neonatal birth weight.

Investigating the interaction between nifedipine- and ritonavir-containing antiviral regimens: A physiologically based pharmacokinetic/pharmacodynamic analysis.

Hypertension is a common comorbidity of patients with COVID-19, SARS or HIV infection. Such patients are often concomitantly treated with antiviral and antihypertensive agents, including ritonavir and nifedipine. Since ritonavir is a strong inhibitor of CYP3A and nifedipine is mainly metabolized via CYP3A, the combination of ritonavir and nifedipine can potentially cause drug-drug interactions. This study provides guidance on nifedipine treatment during and after coadministration with ritonavir-containing regimens, using a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) analysis. The PBPK/PD models for 3 formations of nifedipine were developed based on the Simcyp nifedipine model and the models were verified using published data. The effects of ritonavir on nifedipine exposure and systolic blood pressure (SBP) were assessed for instant-release, sustained-release and controlled-release formulations in patients. Various nifedipine regimens were investigated when coadministered with or without ritonavir. PBPK/PD models for 3 formulations of nifedipine were successfully established. The predicted maximum concentration (Cmax ), area under plasma concentration-time curve (AUC), maximum reduction in SBP and area under effect-time curve were all within 0.5-2.0-fold of the observed data. Model simulations showed that the inhibitory effect of ritonavir on CYP3A4 increased the Cmax of nifedipine 17.92-48.85-fold and the AUC 63.30-84.01-fold at steady state and decreased the SBP by >40mmHg. Thus, the combination of nifedipine and ritonavir could lead to severe hypotension. Ritonavir significantly affects the pharmacokinetics and antihypertensive effect of nifedipine. It is not recommended for patients to take nifedipine- and ritonavir-containing regimens simultaneously.

Nifedipine Alone or Combined With Sildenafil Citrate for Management of Threatened Preterm Labour: A Randomized Trial

(BJOG. 2019;126:729–735) Threatened preterm labor (PTL) (between 20 and 37 wks’ gestation) can be postponed using tocolytic therapy to transfer the patient to a center with a neonatal intensive care unit (NICU) and/or administer corticosteroids for the prevention or management of respiratory morbidity. Nifedipine is a calcium channel blocker that has been shown to be more effective and safer than ritodrine for tocolytic therapy of threatened PTL. This study aimed to compare a combination of nifedipine and sildenafil citrate (SC), a selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase-5, compared with nifedipine alone, in terms of tocolytic effects in PTL cases.

Randomized Controlled Trials of Tianma Gouteng Decoction Combined with Nifedipine in the Treatment of Primary Hypertension: A Systematic Review and Meta-Analysis.

Background Hypertension is a primary risk factor for cardiovascular disease (CVD). Tianma Gouteng decoction (TGD), originating from Zabingzhengzhixinyi, has been used for thousands of years in China to treat hypertension, giddiness, and migraine. This updated meta-analysis aimed at assessing the efficacy and safety of TGD combined with nifedipine in the treatment of primary hypertension. Methods Related research published prior to September 1, 2019, was found in electronic databases without language limitations. Fourteen studies were selected and analyzed for specified criteria, including the quality of the studies. All outcomes were recorded exhaustive. Data management and analysis were performed using RevMan 5.3 software. Results A total of 1,537 (769 cases in the experimental group and 768 cases in the control group) patients were enrolled. The total efficacy rate was improved significantly for the combination of nifedipine with TGD compared to nifedipine treatment alone (I2 = 22%, RR = 1.17, and 95% CI: 1.12 to 1.22). Traditional Chinese medicine (TCM) symptoms of patients were obviously improved in the experimental group than in the control group (I2 = 22%, RR = 1.17, and 95% CI: 1.12 to 1.22). Traditional Chinese medicine (TCM) symptoms of patients were obviously improved in the experimental group than in the control group (I2 = 22%, RR = 1.17, and 95% CI: 1.12 to 1.22). Traditional Chinese medicine (TCM) symptoms of patients were obviously improved in the experimental group than in the control group (I2 = 22%, RR = 1.17, and 95% CI: 1.12 to 1.22). Traditional Chinese medicine (TCM) symptoms of patients were obviously improved in the experimental group than in the control group (I2 = 22%, RR = 1.17, and 95% CI: 1.12 to 1.22). Traditional Chinese medicine (TCM) symptoms of patients were obviously improved in the experimental group than in the control group (P < 0.00001) when two studies (shicaihong 2017 and xiaoyugao 2017) were removed. And the results of DBP showed no heterogeneity (I2 = 22%, RR = 1.17, and 95% CI: 1.12 to 1.22). Traditional Chinese medicine (TCM) symptoms of patients were obviously improved in the experimental group than in the control group (P < 0.00001) when two studies (shicaihong 2017 and xiaoyugao 2017) were removed. And the results of DBP showed no heterogeneity (Conclusion The combination of TGD and nifedipine has a better effect in the treatment of hypertension, including blood pressure lowering and patients' TCMs improving. However, our findings must be handled with care because of the small sample size and low quality of clinic trials cited. Other rigorous and large-scale RCTs are in need to confirm these results.

Antihypertensive and antidiabetic activities of Erythrina senegalensis DC (Fabaceae) stem bark aqueous extract on diabetic hypertensive rats

Erythrina senegalensis is traditionally used in Cameroon for its relaxing and hypoglycemic properties in the treatment of cardiovascular diseases and diabetes. High blood pressure and diabetes mellitus are frequently linked. These pathologies represent major risk factors for cardiovascular and renal diseases. The present study was designed to evaluate the antidiabetic and antihypertensive activity of the stem bark of Erythrina senegalensis aqueous extract in male hypertensive diabetic rats (HDR). Hypertension and diabetes were induced by oral administration of sucrose (15%) and ethanol (40°) at doses of 1.5g/kg and 5g/kg respectively for 30 days, followed by an intravenous injection of streptozotocin (STZ; 40mg/kg). A control group of 5 rats received distilled water (10mL/kg) followed by intravenous injection of 0.9% NaCl (1 mL/100g). HDR were divided into 4 groups of 5 rats each according to their blood glucose level and continued to receive ethanol in association with: distilled water (10mL/kg); group I, metformin (200mg/kg)+nifedipine (10mg/kg); group II, plant extract (100 and 200mg/kg) group IV and V, respectively for 28 days. At the end of the treatment, hemodynamic parameters were recorded by the direct method. Animals were sacrificed; blood and organs (aorta, heart, liver, and kidneys) were collected for biochemical and histological analysis. Phytochemistry and HPLC-DAD-HRESI-MS were used to determine the major compounds of the extract. The administration of sucrose, alcohol, and STZ resulted in a significant increase in blood glucose, hemodynamic parameters, and body weight loss. A significant decrease in pancreatic islets size, nitrite, GSH, SOD and catalase activity was observed in HDR. There was also a significant increase in serum triglycerides, total cholesterol, creatinine, bilirubin, and transaminases activity in HDR. The aqueous extract of E. senegalensis, as well as the metformin+nifedipine combination, significantly improved all these parameters. HPLC coupled to both diode array and mass spectrometry detectors revealed the presence of 15 compounds and 11 of them were identified. These results suggest that the aqueous extract of E. senegalensis possess antihypertensive, hypoglycemic, hypolipidemic, cardiomodulator and antioxidant properties involved in the improvement of the metabolic disorders found in HDR. This may be due at least in part to the presence of Erysenegalensein (D, O, N, E), Warangalone, senegalensin and 6,8-diprenylgenistein identified in the extract.

Development of stability indicating HPTLC method for estimation of antihypertensive drug combination nifedipine and valsartan

ABSTRACTA precise and accurate method for the analysis of antihypertensive drug combination nifedipine and valsartan was developed using the HPTLC method. The stationary phase used was a pre-coated silica gel G60 – F254 aluminium sheet and the mobile phase was acetonitrile: methanol: n-butanol: acetic acid (6:2:2:0.1, v/v/v/v). The detection of spots was carried out densitometrically using a UV detector at 230 nm in the absorbance mode. The Rf values of valsartan and nifedipine were found to be 0.25 and 0.65, respectively. The calibration curve was found to be linear in the range of 120–320 ng/band and 900–2400 ng/band for nifedipine and valsartan, respectively. Forced degradation studies were performed using stress conditions like acid and base hydrolysis, photolytic, thermal and oxidative stress degradation to develop the stability indicating method. The degradation study indicated that nifedipine was susceptible to acid-base hydrolysis, oxidative stress degradation and photolytic degradation, while valsartan was susceptible to acid-base hydrolysis and oxidative stress degradation.