OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

This study aims to investigate the mechanism of acacetin in protecting rats from cerebral ischemia-reperfusion injury via the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. Wistar rats were randomized into sham, model, low-and high-dose acacetin, and nimodipine groups, with 10 rats in each group. The rat model of middle cerebral artery occlusion(MCAO) was established with the improved suture method in other groups except the sham group. The neurological deficit score and cerebral infarction volume of each group were evaluated 24 h after modeling. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1β(IL-1β), IL-6, tumor necrosis factor-α(TNF-α), malondialdehyde(MDA), supe-roxide dismutase(SOD), and glutathione(GSH). Western blot was employed to determine the expression levels of B-cell lymphonoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and TLR4/NLRP3 signaling pathway-related proteins(TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β) in the rat brain tissue. Hematoxylin-eosin(HE) staining was employed to reveal the histopathological changes in the ischemic area. Compared with the sham group, the modeling of MCAO increased the neurological deficit score and cerebral infarction volume, elevated the IL-1β, IL-6, TNF-α, and MDA levels and lowered the SOD and GSH levels in the brain tissue(P<0.05). Compared with the MCAO model group, low-and high-dose acacetin and nimodipine decreased the neurological deficit score and cerebral infarction volume, lowered the IL-1β, IL-6, TNF-α, and MDA levels and elevated the SOD and GSH levels in the brain tissue(P<0.05). Compared with the sham group, the model group showed up-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β and down-regulated protein level of Bcl-2 in the brain tissue(P<0.05). Compared with the MCAO model group, the acacetin and nimodipine groups showed down-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1β, and cleaved IL-1β and up-regulated protein level of Bcl-2 in the brain tissue(P<0.05). In conclusion, acacetin regulates the TLR4/NLRP3 signaling pathway to inhibit neuroinflammatory response and oxidative stress, thus exerting the protective effect on cerebral ischemia-reperfusion injury in rats.
Rats ; Animals ; NF-kappa B/metabolism* ; bcl-2-Associated X Protein ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Rats, Sprague-Dawley ; Caspase 1/metabolism* ; Toll-Like Receptor 4/metabolism* ; Nimodipine/pharmacology* ; Interleukin-6 ; Rats, Wistar ; Signal Transduction ; Infarction, Middle Cerebral Artery ; Reperfusion Injury/prevention & control* ; Superoxide Dismutase/metabolism*

OBJECTIVES: The use of anticholinergic drugs in the elderly may lead to negative events such as falls, delirium, urinary retention and cognitive decline, and the higher the number of anticholinergic drugs use, the more such negative events occur. This study aims to analyze the risk factors associated with the prescription of total anticholinergic drugs in elderly outpatients and evaluate the rationality of anticholinergic drugs, and to provide a reference for reducing the adverse effects of anticholinergic drugs. METHODS: A list of drugs with anticholinergic activity based on the Beers criteria was established. The basic information (such as age and gender), clinical diagnosis, and medications of elderly outpatient were extracted from hospital electronic medical records, and the Anticholinergic Cognitive Burden (ACB) Scale was used to calculate the anticholinergic burden for each patient. Logistic regression analysis was used to identify the potential risk factors for the occurrence of problems such as multiple medication and insomnia. RESULTS: A total of 1 840 prescriptions for elderly patients were reviewed. Of these patients, ACB score was more than or equal to 1 in 648 (35.22%) patients. Number of prescription medication (95% CI: 1.221 to 1.336) and insomnia (95% CI: 3.538 to 6.089) were independent factors affecting ACB scores (both P<0.01). Medications for patients of ACB scores were most commonly treated with the central nervous system drugs (such as alprazolam and eszopiclone) and for the cardiovascular system drugs (such as metoprolol and nifedipine). CONCLUSIONS There is a high rate of ACB drugs use in geriatric patients, and the clinical focus should be on multiple medication prescriptions, especially on the central nervous system drugs (such as alprazolam and eszopiclone) and cardiovascular system drugs (such as metoprolol and nifedipine). The prescription review should be emphasized to reduce adverse reactions to anticholinergic drugs in elderly patients.
Humans ; Aged ; Cholinergic Antagonists/adverse effects* ; Outpatients ; Metoprolol ; Alprazolam ; Eszopiclone ; Nifedipine ; Sleep Initiation and Maintenance Disorders ; Risk Factors

To study the protective effect of Ershiwuwei Zhenzhu Pills on ischemic stroke rats. Ninety 4-weeks-old SPF male SD rats were randomly divided into 6 groups(n=15):sham operation group, model group, nimodipine group(12 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills high-dose group(400 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills medium-dose group(200 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills low-dose group(100 mg·kg~(-1)).The permanent middle cerebral artery occlusion model(PMCAO) was established in the model group, nimodipine group, and Ershiwuwei Zhenzhu Pills groups by the improved thread plug method, while the sham operation group did not insert the thread plug.Nimodipine group and Ershiwuwei Zhenzhu Pills groups were given intragastric administration once a day for 24 days before the modeling operation, and once 1 hour before the modeling operation, while sham operation group and model group were given equal volumes of distilled water.The neuroethology of the surviving rats was measured; The volume of cerebral infarction in rats was measured by TTC method; The histopathology of rat brain was observed by HE method; The expression levels of tumor necrosis factor α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),malondialdehyde(MDA),superoxide dismutase(SOD) and catalase(CAT) in serum were detected by ELISA;The mRNA expressions of Notch 1,Jagged 1,Hes 1 and Bcl-2 in rat brain were detected by RT-PCR;Western blot was used to detect the expression levels of caspase-3 protein in rat brain; the expression levels of vascular endothelial growth factor(VEGF) and CD34 positive cells in rat brain were detected by immunofluorescence.The low, medium and high dose groups of Ershiwuwei Zhenzhu Pills and nimodipine group could significantly reduce the neurobehavioral score and cerebral infarction volume of rats with permanent middle cerebral artery occlusion, reduce the morphological changes of nerve cells, decrease the expression of TNF-α,IL-1β and IL-6 in rat serum, increase the activity of SOD and CAT,and reduce the level of MDA.Furthermore, the expression levels of Notch l, Jagged l, Hes l and Bcl-2 mRNA were significantly increased, and the expression level of caspase-3 protein was decreased.Meanwhile, the number of VEGF and CD34 positive cells increased in the treatment group.The differences were statistically significant. Ershiwuwei Zhenzhu Pills has a protective effect on ischemic stroke rats, and its mechanism may be related to anti-inflammation, anti-oxidation, promotion of nerve cell proliferation, inhibition nerve cell apoptosis and promotion of angiogenesis.
Animals ; Caspase 3/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Infarction, Middle Cerebral Artery/drug therapy* ; Interleukin-6/metabolism* ; Ischemic Stroke/drug therapy* ; Male ; Nimodipine/pharmacology* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Vascular Endothelial Growth Factor A/metabolism*

No abstract available.
Amlodipine

Objective To explore the pharmacokinetics of nimodipine in plasma of rats after intraocular administration.Methods Totally 135 SD rats were randomly divided into three groups according to drug administration routes:intraocular(io group),intravenous (iv group),and intragastric (ig group). The doses were 5.0 mg/kg for IO and IV groups and 10.0 mg/kg for IG group. The serum nimodipine level was analyzed by high performance liquid chromatography. The main pharmacokinetic parameters were calculated and compared.Results The pharmacokinetic parameters in io group were as follows:C:0.52 mg/ml;t:5.0 min;and AUC:21.10 mg/(ml·min). The main pharmacokinetic parameters in iv group were as follows:C:3.62 mg/ml;and AUC:52.58 mg/(ml·min). The main pharmacokinetic parameters in ig group were as follows:C:0.20 mg/ml;t:5.0 min;and AUC:5.98 mg/(ml·min).Conclusions Nimodipine is rapidly absorbed after io administration,and the ophthalmic formulation has a higher bioavailability than the oral solution. Therefore,the io route may help to improve the treatment effectiveness of cardiovascular diseases.
Administration, Intravenous ; Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Chromatography, High Pressure Liquid ; Nimodipine ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Vasoplegic syndrome is an increasingly recognized disease in perioperative medicine and is characterized by severe hypotension, normal or elevated cardiac output, and decreased systemic vascular resistance. It occurs commonly after cardiopulmonary bypass but may also occur after other types of surgery.CASE: Vasoplegic syndrome developed in our patient during posterior lumbar interbody fusion because of administering nicardipine after phenylephrine. However, the blood pressure did not increase as expected despite simultaneous use of norepinephrine and vasopressin to increase the reduced systemic vascular resistance.CONCLUSIONS: We present a case of vasoplegic syndrome that developed during posterior lumbar interbody fusion and was treated successfully with methylene blue.
Blood Pressure ; Cardiac Output ; Cardiopulmonary Bypass ; Humans ; Hypotension ; Methylene Blue ; Nicardipine ; Norepinephrine ; Phenylephrine ; Vascular Resistance ; Vasoplegia ; Vasopressins

BACKGROUND: Nicardipine, a calcium channel blocker, is used to treat hypertension in pregnancy or preterm labor. The current study was conducted to investigate the relaxant effects of nicardipine on the isolated uterine smooth muscle of the pregnant rat.METHODS: We obtained uterine smooth muscle strips from pregnant female SD rats. After uterine contraction with oxytocin 10 mU/ml, we added nicardipine (10⁻¹² to 10⁻⁸ M) accumulatively every 20 min. We recorded active tension and frequency of contraction, and calculated EC₅ (effective concentration of 5% reduction), EC₂₅, EC₅₀, EC₇₅, and EC₉₅ of active tension and frequency of contraction using a probit model.RESULTS: Nicardipine (10⁻¹² to 10⁻⁸ M) decreased active tension and frequency of contraction in a concentration-dependent manner. The EC₅₀ and EC₉₅ of nicardipine in the inhibition of active tension of the uterine smooth muscle were 2.41 × 10⁻¹⁰ M and 3.06 × 10⁻⁷ M, respectively. The EC₅₀ and EC₉₅ of nicardipine in the inhibition of frequency of contraction of the uterine smooth muscle were 9.04 × 10⁻¹¹ and 4.18 × 10⁻⁷ M, respectively.CONCLUSIONS: Nicardipine relaxed and decreased the frequency of contraction of the uterine smooth muscle in a concentration-dependent pattern. It might be possible to adjust the clinical dosage of nicardipine in the obstetric field based on our results, but further clinical studies are needed to confirm them.
Animals ; Calcium Channels ; Female ; Humans ; Hypertension ; Muscle, Smooth ; Nicardipine ; Obstetric Labor, Premature ; Oxytocin ; Pregnancy ; Rats ; Relaxation ; Uterine Contraction ; Uterus

Combination therapies of antihypertensive drugs are recommended in cases where hypertension is not controlled by monotherapy. This study aimed to compare the pharmacokinetics (PKs) between fixed-dose combination (FDC) of fimasartan/amlodipine 60/10 mg and the corresponding loose combination. Because of the high intra-subject variability for maximum plasma concentration (C(max)) of fimasartan, a randomized, open-label, 3×3 partial replicated crossover design was adopted. Subjects received a single dose of FDC of fimasartan/amlodipine 60/10 mg or the corresponding loose combination in each period. Blood samples for PK analysis were collected up to 48 hours for fimasartan and 144 hours for amlodipine, respectively. Geometric mean ratios (GMRs) and its 90% confidence intervals (CIs) of the FDC to the loose combination for C(max) and area under the concentration-time curve from time 0 to the last quantifiable time point (AUC(last)) were calculated. Sixty healthy subjects were randomized, and 57 subjects completed the study. The concentration-time profiles of fimasartan and amlodipine were similar between the FDC and loose combination. The GMRs (90% CIs) of the FDC to the loose combination for C(max) and AUC(last) were 1.0440 (0.9202–1.1844) and 1.0412 (0.9775–1.1090) for fimasartan, and 1.0430 (1.0156–1.0711) and 1.0339 (1.0055–1.0631) for amlodipine, respectively. The GMRs and its 90% CIs for C(max) and AUC(last) of fimasartan and amlodipine were included not only in the scaled bioequivalence criteria but also in the conventional bioequivalence criteria. In conclusion, FDC of fimasartan/amlodipine 60/10 mg showed comparable PK profiles with the corresponding loose combination, which suggests their bioequivalence.
Amlodipine ; Antihypertensive Agents ; Cross-Over Studies ; Healthy Volunteers ; Hypertension ; Pharmacokinetics ; Plasma ; Therapeutic Equivalency

OBJECTIVEBased on the western medication, to evaluate the advantages in the morning blood pressure treated with acupuncture at Fengchi (GB 20) and Neck-Jiaji (EX-B 2) combined with acupuncture technique for activating blood circulation, eliminating wind and regulating the liver and spleen in the patients with essential hypertension.

METHODSA total of 90 patients of essential hypertension of the mild and moderate degrees were randomized into a medication group (30 cases, 3 dropping), No.1 acupuncture group (30 cases, 2 dropping) and No.2 acupuncture group (30 cases, 1 dropping). In the medication group, adalat was prescribed for oral administration, 30 mg at 7 am every day, continuously for 6 weeks. In the No.1 acupuncture group, on the basis of the treatment as the medication group, the acupuncture technique for activating blood circulation, eliminating wind and regulating the liver and spleen was applied and the acupoints were Renying (ST 9), Hegu (LI 4), Taichong (LR 3), Quchi (LI 11) and Zusanli (ST 36). In the No.2 acupuncture group, on the basis of the treatment as the No.1 acupuncture group, Fengchi (GB 20) and Neck-Jiaji (EX-B 2) were added in acupuncture. Acupuncture was given in the time zone from 8 am through 10 am every day, once a day, 5 times a week, totally for 6 weeks. Separately, before treatment and in 2, 4 and 6 weeks of treatment, the morning blood pressure, the control rate and the symptom score were observed in the patients of the three groups. The morning blood pressure was followed up in 3 and 6 months separately.

RESULTSCompared with those before treatment, in 2, 4 and 6 weeks of treatment, the levels of blood pressure reduced in the patients of the three groups (<0.05, <0.01). After 2-week treatment, the differences were not significant in the morning blood pressure and its control rate in the patients of the three groups (all >0.05). In 4 and 6 weeks of treatment, the levels of the morning blood pressure in the No.2 acupuncture group were lower than those in the No.1 acupuncture group, and the results in the No.1 and No.2 acupuncture groups were all lower than those in the medication group (all <0.05). In the follow-up visit for 3 and 6 months separately, the differences were not significant in the morning blood pressure among the three groups (all >0.05). In 2, 4 and 6 weeks of treatment, the symptom scores reduced as compared with those before treatment in the three groups (all <0.05). The symptom scores in the No.1 and No.2 acupuncture groups were all lower than those in the medication group (all <0.05). The differences were not significant between the No.1 acupuncture group and the No.2 acupuncture group (all >0.05).

CONCLUSIONThe comprehensive treatment of acupuncture at Fengchi (GB 20) and Neck-Jiaji (EX-B 2) combined with acupuncture technique for activating blood circulation, eliminating wind and regulating the liver and spleen achieve the effects of reducing the morning blood pressure in the patients with essential hypertension, relieving the symptoms of hypertension such as headache, vertigo and tinnitus and the effects are better than those of the acupuncture technique for activating blood circulation, eliminating wind and regulating the liver and spleen.

Acupuncture Points ; Acupuncture Therapy ; Blood Pressure ; Combined Modality Therapy ; Essential Hypertension ; therapy ; Humans ; Nifedipine ; therapeutic use ; Treatment Outcome