Doses Of Nifedipine Research Articles

FETO-MATERNAL OUTCOME OF INTRAVENOUS LABETALOLAND ORAL NIFEDIPINE IN SEVERE PRE-ECLAMPSIA- A COMPARATIVE STUDY

Introduction: Pre-eclampsia (PE) is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. Aims and objectives: 1. to determine the efficacy and safety of oral nifedipine for treatment of severe hypertension of pregnancy compared with intravenous labetalol. 2. To compare the time taken to reach the therapeutic goal blood pressure after using intravenous labetalol & oral nifedipine in severe pregnancy induced hypertension. 3. The time taken to achieve a blood pressure of less than 150/100 mmHg. 4. To compare the maternal and perinatal outcome among the subjects using nifedepine over labetalo. Material and method: PROSPECTIVE RANDOMISED INTERVENTIONAL COMPARITIVE TRAIL. One and half year. Conclusion: Our present study compares the efficacy of oral Nifedipine and IV Labetalol in reaching the therapeutic goal. From the results of our study we can conclude that nifedipine required less time for reaching target BP as compare to labetalol. Less no of dose of nifedipine was used for the rapid control of blood pressure in severe hypertension in pregnancy. So, Nifedipine may be preferable as it is a simple, less time and is an oral regimen.

Electrochemical reduction of Procardia drug with aid of silver phosphate/strontium phosphate nanoparticles (AgP/SrP NPs) modified glassy carbon electrode

Procardia drug nifedipine (NFD) belongs to a class of 2-nitrophenyl derivative known as calcium channel blocker which is used for the treatment of high blood pressure, cardiovascular disease, angina pectoris and migraine after oral eat. Over dosages of NFD will causes severe health issues such as pounding heartbeat and swollen ankles for that detection of NFD is very important. In this study, Silver phosphate/Strontium phosphate nanoparticles (AgP/SrP NPs) were synthesized through a facile co-precipitation method in order to modify a glassy carbon electrode (GCE) and applied for the electrochemical detection of NFD. As-synthesized nanoparticles were confirmed using various characterization techniques such as X-ray diffraction (XRD), Fourier transform infrared (FT-IR), Raman spectroscopy, High-resolution transmission electron microscopy (HR-TEM), Field Emission Scanning electron microscopy (FE-SEM), Energy dispersive X-ray (EDAX) and elemental mapping studies. These outcomes revealed that as-synthesized AgP/SrP NPs were formed by homogeneous morphology with the defined crystal structure and functional groups without any filth. The electrochemical activities of AgP/SrP NPs were explored via cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. These results suggested that AgP/SrP NPs exhibit excellent electrocatalytic activity than other modified GCE under optimized conditions. The developed AgP/SrP NPs modified GCE demonstrates that excellent electrochemical activity towards NFD which exhibits a lower detection limit with wide linear range (0.003 µM, 0.01 – 89.69 µM), better selectivity, repeatability, reproducibility and storage stability. Furthermore, real samples analyses were achieved in lake water and commercial NFD tablet which outcomes good recovery results, and these suggested that AgP/SrP NPs modified GCE considered as a promising candidate for electrochemical sensing of Procardia drug NFD.

Drug Treatment of Raynaud's Phenomenon of the Nipple.

Drug Treatment of Raynaud's Phenomenon of the Nipple.

Maternal and fetal parameters in pregnant woman undergoing tocolysis with nifedipine

Abstract Objectives: to evaluate the effects of nifedipine with tocolysis under maternal and fetal parameters. Methods: a cohort study with 40 pregnant women admitted at a high-risk pregnancy ward to inhibit premature labor between September/2010 to May/2012. Nifedipine was used as a 20mg sublingual attack dose and maintained 20mg every six and eight hours orally. The variables of the analysis were fetal heart rate (FHR), maternal heart rate (MHR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), and amniotic fluid index (AFI). All the variables were evaluated prior to administrating nifedipine and approximately after 6 hours and every 24 hours, until hospital discharge. Results: there were no modification of the FHR (p=0.48) and the SBP (p=0.29). The MHR increased after 24 hours, but with no statistical difference (p=0.08), returning to similar levels as at admission within 48 hours. The DBP decreased at 6 (p=0.04) to 72 hours, being stable afterwards. The AFI decreased significantly at 24, 48 and 72 hours. Conclusions: the use of high doses of nifedipine with tocolysis causes a decrease of the maternal’s diastolic blood pressure and consequently decreases the amniotic fluid index, but probably without any clinical repercussions.

EVALUATION OF ANTI-ANXIETY EFFECT OF NIFEDIPINE COMPARED TO DIAZEPAM IN SWISS ALBINO MICE USING BEHAVIOURAL MODELS

Objective: The present study was undertaken to evaluate the acute and chronic anxiolytic effects of nifedipine in comparison to diazepam using in Swiss Albino mice using two behavioral models.
 Methods: 30 Swiss albino mice were divided into 5 groups with 6 mice in each group. The study was conducted in two phases to evaluate acute and chronic effects. The groups consisted of diazepam (1 mg/kg), 3 doses of nifedipine (2.6 mg/kg, 5.2 mg/kg and 10.4 mg/kg) and vehicle control. The Elevated Plus Maze (EPM) and Light and Dark box were used to evaluate the anti-anxiety effects. The number of entries and time spent in the open arm of the elevated plus-maze and in the light area of light and dark box model were noted and compared among the 5 groups. Observations were analyzed using ANOVA and post hoc Tukey's test.
 Results: Nifedipine (5.2 mg/kg and 10.4 mg/kg) significantly increased the number of entries and time spent in the open arm compared to vehicle control in the EPM test (p<0.001). Similarly, in the light and dark box test, nifedipine (5.2 mg/kg and 10.4 mg/kg) increased the number of entries and time spent in the light area compared to vehicle control (p<0.05). However, the low dose of nifedipine (2.6 mg/kg) did not exhibit significant findings.
 Conclusion: Two doses of nifedipine (5.2 mg/kg and 10.4 mg/kg) possess anti-anxiety effects both on acute and chronic administration in both elevated plus maze and light and dark box model.

Effectiveness of an oral versus sublingual loading dose of nifedipine for tocolysis.

To determine the effectiveness of an oral versus sublingual loading dose of nifedipine for tocolysis. An open, randomized clinical trial conducted between March 1, 2013, and April 31, 2014. Participants were pregnant women with a diagnosis of premature labor, single live fetus, topical pregnancy, gestational age 24-36weeks, normal fetal vitality, cervical dilatation less than or equal to 4cm, cervical effacement less than or equal to 80%, and intact amniotic membranes. They were randomized into two groups, oral and sublingual nifedipine, 20mg loading dose, repeated every 30minutes (maximum dose of 60mg). The primary endpoint was the time until tocolysis and the secondary endpoints were the effectiveness of tocolysis within 90minutes, 12hours, and 48hours; premature delivery within 48hours; and maternal hemodynamic parameters and side effects. There were 80 patients randomized to oral (n=40) and sublingual (n=40) nifedipine. The time required for tocolysis was significantly less with sublingual nifedipine (160minutes vs 340minutes; P=0.0003). Sublingual nifedipine was also more successful than oral nifedipine at inhibiting premature labor within 90minutes (n=8 [20.0%] vs n=1 [2.5%], P=0.014). There was no statistically significant difference between the groups for the other secondary endpoints. Compared with oral administration, a sublingual loading dose of nifedipine resulted in faster tocolysis in patients with premature labor. Brazilian Clinical Trials Registry (ReBEC): U1111-11566186.

Differential effects on out-of-hospital cardiac arrest of dihydropyridines: real-world data from population-based cohorts across two European countries.

AimsVarious drugs increase the risk of out-of-hospital cardiac arrest (OHCA) in the general population by impacting cardiac ion channels, thereby causing ventricular tachycardia/fibrillation (VT/VF). Dihydropyridines block L-type calcium channels, but their association with OHCA risk is unknown. We aimed to study whether nifedipine and/or amlodipine, often-used dihydropyridines, are associated with increased OHCA risk, and how these drugs impact on cardiac electrophysiology.Methods and resultsWe conducted a case–control study with VT/VF-documented OHCA cases with presumed cardiac cause from ongoing population-based OHCA registries in the Netherlands and Denmark, and age/sex/index date-matched non-OHCA controls (Netherlands: PHARMO Database Network, Denmark: Danish Civil Registration System). We included 2503 OHCA cases, 10 543 non-OHCA controls in Netherlands, and 8101 OHCA cases, 40 505 non-OHCA controls in Denmark. To examine drug effects on cardiac electrophysiology, we performed single-cell patch-clamp studies in human-induced pluripotent stem cell-derived cardiomyocytes. Use of high-dose nifedipine (≥60 mg/day), but not low-dose nifedipine (<60 mg/day) or amlodipine (any-dose), was associated with higher OHCA risk than non-use of dihydropyridines [Netherlands: adjusted odds ratios (ORadj) 1.45 (95% confidence interval 1.02–2.07), Denmark: 1.96 (1.18–3.25)] or use of amlodipine [Netherlands: 2.31 (1.54–3.47), Denmark: 2.20 (1.32–3.67)]. Out-of-hospital cardiac arrest risk of (high-dose) nifedipine use was not further increased in patients using nitrates, or with a history of ischaemic heart disease. Nifedipine and amlodipine blocked L-type calcium channels at similar concentrations, but, at clinically used concentrations, nifedipine caused more L-type calcium current block, resulting in more action potential shortening.ConclusionHigh-dose nifedipine, but not low-dose nifedipine or any-dose amlodipine, is associated with increased OHCA risk in the general population. Careful titration of nifedipine dose should be considered.

Efficacy and safety of low dose sublingual nifedipine dripping pills (5 mg) in the acute treatment of moderate and severe hypertension: a randomized, double-blind, positive-drug parallel-controlled, multi-center clinical study

Objective: To evaluate the efficacy and safety of low dose sublingual nifedipine dripping pills (5 mg) in treating moderate and severe hypertension in comparison with normal dose (10 mg) of sublingual nifedipine dripping pills. Methods: This study was designed as a randomized, double-blind, positive drug parallel controlled, multi-center, non-inferiority clinical trial. Patients with moderate and severe hypertension were enrolled by 14 clinical trial centers, randomly divided into the trial group (sublingual 5 mg nifedipine dripping pills) and the control group (sublingual 10 mg nifedipine dripping pills). The changes in blood pressure were monitored continuously within 2 hours after the initial administration, repeated the dose in 20 minutes interval after the initial administration for up to additional 3 doses (maximum 4 doses) if the antihypertensive efficacy was not satisfactory. The efficacy of antihypertensive therapy between the two groups was evaluated by repeated administration rates and blood pressure changes at 60 minutes post the initial administration, and the safety of treatment was evaluated by recording adverse event rate of the two groups. Results: The anti-hypertensive effective rates at 60 minutes after sublingual administration were 83.5% (202/242) and 86.7% (208/240) respectively between the trial group and control group (χ(2)=1.307, P=0.253) . On the aspect of antihypertensive effectiveness at 60 minutes after single dose of sublingual administration, the anti-hypertension effective rates of the trial group and the control group were 85.6% (154/180) and 87.2% (164/188) respectively (χ(2)=0.221, P=0.639). Prevalence of the repeated administration was also similar between the two groups (25.6%(62/242) in the trial group and 21.7% (52/240) in the control group, χ(2)=1.043, P=0.307). On the safety aspect, there was no adverse events/reactions in the trial group, but there were 15 cases of adverse events/reactions occurred in control group (6.25%, χ(2)=15.611, P<0.001). Conclusions: In the treatment of moderate to severe hypertension, the antihypertensive efficacy of low dose nifedipine dripping pills is similar to that of conventional dosage, and the safety profile of low dose nifedipine dripping pills is better than that of the conventional dose.

Coadministration of the prostaglandin F2α receptor antagonist preterm labour drug candidate OBE022 with magnesium sulfate, atosiban, nifedipine and betamethasone.

To investigate presence or absence of clinically relevant drug interactions (pharmacokinetic and safety/tolerability) of OBE022 with standard-of-care medicines for preterm labour, enabling coadministration and further clinical development. Part A: open-label, randomized, 3-period crossover assessing coadministration of single doses of OBE022 (1100mg) and MgSO4 . Part B: open-label, single-sequence crossover assessing the interactions following administration of OBE022 (1000mg/day) at steady state coadministered with single doses of atosiban, nifedipine and betamethasone. Twenty-five healthy nonpregnant women of reproductive age were enrolled (Part A: n=12; Part B: n=13). OBE022, alone or in combination with standard-of-care medications, was well tolerated. Headache and dizziness were the most frequently reported adverse events; dizziness occurred more often with the nifedipine/OBE022 combination. There were no clinically significant pharmacokinetic interactions when coadministered with MgSO4 . Co-administration had no notable effect on atosiban exposure. Atosiban reduced exposure to OBE002 (peak concentration [Cmax ] 22%, area under the concentration-time curve [AUC] 19%). Coadministration with betamethasone slightly increased betamethasone exposure (Cmax +18%, AUC +27%) and OBE002 exposure (Cmax +35%, AUC +15%). These changes were not considered clinically significant. Coadministration with nifedipine slightly increased OBE002 exposure (Cmax +29%, AUC +24%) and markedly increased nifedipine exposure (Cmax by 2-fold and AUC by 2-fold), which may be clinically significant. The use of OBE022, a PGF2α antagonist prodrug, in combination with standard-of-care medicines may provide new treatment alternatives for preterm labour. All tested combinations were well tolerated. Nifedipine doses could potentially be reduced or staggered when coadministered with OBE022.

Nifedipine induced gingival enlargement in an edentulous patient: a case report with one year follow up

BackgroundGingival enlargement due to calcium channel blockers is a common complaint reported by patients. It can be localized or generalized and can range from mild to severe, affecting patients appearance and function. Nifedipine induced gingival enlargement is noticed only in 10 % of patients and very few cases of Nifedipine induced gingival enlargement in an edentulous patient have been documented in the literature.Case presentationHere in, we report a case of gingival enlargement in a 70 year old hypertensive edentulous patient who was on low dose Nifedipine therapy. Patient wanted complete dentures. We planned to excise the overgrowth and followed up for 1 year.ConclusionNifedipine induced gingival enlargement noticed only in 10 % of patients. Hence, there is a need for physicians and dentist to make a coordinated treatment plan and practice care while prescribing these drugs which are associated with gingival overgrowth.

Effects of cyclosporin, nifedipine and phenytoin on gingival myofibroblast transdifferentiation in monkeys

Objective:Myofibroblasts have been associated with the development of several pathologic fibrotic conditions. This longitudinal study aims to assess the proliferative and antiapoptotic effects of cyclosporin, nifedipine and phenytoin on gingival connective tissue cells of nonhuman primate, as well as to analyze a possible role of myofibroblasts in gingival overgrowth.Materials and Methods:Gingival samples from the right superior canine area were obtained from 12 male monkeys ( Sapajus spp ) to comprise the control group. After one week, the animals were randomly assigned to three groups, which received daily oral doses of cyclosporin, nifedipine or phenytoin for 120 days. Gingival samples were collected from the left superior canine area of two animals of each group at 52 and 120 days. Histological sections were stained with hematoxylin and eosin, and immunoreacted against α-SMA, Ki- 67 and bcl-2.Results:α-SMA immunoreaction was negative in the control and experimental groups. Similarly, no difference between groups concerning immunostaining against Ki-67 and bcl-2 was observed in connective tissue cells.Conclusion:Based on this methodology, it may be concluded that gingival overgrowths induced by cyclosporin, nifedipine and phenytoin are not associated with neither myofibroblast transdifferentiation, proliferation nor apoptosis of gingival connective cells in monkeys.

Intracellular emetic signaling evoked by the L-type Ca2+ channel agonist FPL64176 in the least shrew (Cryptotis parva)

Ca2+ plays a major role in maintaining cellular homeostasis and regulates processes including apoptotic cell death and side-effects of cancer chemotherapy including vomiting. Currently we explored the emetic mechanisms of FPL64176, an L-type Ca2+ channel (LTCC) agonist with maximal emetogenic effect at its 10 mg/kg dose. FPL64176 evoked c-Fos immunoreactivity in shrew brainstem sections containing the vomit-associated nuclei, nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus. FPL64176 also increased phosphorylation of proteins ERK1/2, PKCα/βII and Akt in the brainstem. Moreover, their corresponding inhibitors (PD98059, GF 109203X and LY294002, respectively) reduced FPL64176-evoked vomiting. A 30 min subcutaneous (s.c.) pretreatment with the LTCC antagonist nifedipine (10 mg/kg) abolished FPL64176-elicited vomiting, c-Fos expression, and emetic effector phosphorylation. Ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs) mediate intracellular Ca2+ release from the sarcoplasmic/endoplasmic reticulum. The RyR antagonist dantrolene (i.p.), or a combination of low doses of nifedipine and dantrolene, but not the IP3R antagonist 2-APB, significantly attenuated FPL64176-induced vomiting. The serotonin type 3 receptor (5-HT3R) antagonist palonosetron (s.c.), the neurokinin 1 receptor (NK1R) antagonist netupitant (i.p.) or a combination of non-effective doses of netupitant and palonosetron showed antiemetic potential against FPL64176-evoked vomiting. Serotonin (5-HT) and substance P immunostaining revealed FPL64176-induced emesis was accompanied by an increase in 5-HT but not SP-immunoreactivity in the dorsomedial subdivision of the NTS. These findings demonstrate that Ca2+ mobilization through LTCCs and RyRs, and subsequent emetic effector phosphorylation and 5-HT release play important roles in FPL64176-induced emesis which can be prevented by 5-HT3R and NK1R antagonists.

The Effect of Tocolysis by Oral Nefidipine on Doppler Velocimetry of Umbilical, Middle Cerebral Arteries and Ductus Venosus

AbstractAim of Work: To assess effect of nifedipine administration as a tocolytic agent on placental and fetal cerebral blood flow as well as on fetal cardiac function by measuring Pulsatility Index (PI) of the umbilical artery, Middle Cerebral Arteries (MCA) and Ductus Venosus (DV) twice, immediately before initial nifedipine dose and 24 hours after the therapy.Methods: Prospective, observational, analytic cohort, clinical trial involved 70 women with single viable fetus between 24-35 weeks undergoing tocolysis by nifedipine. Pulsatility Index (PI) of the umbilical artery, Middle Cerebral Arteries (MCA) and Ductus Venosus (DV) was assessed twice, immediately before initial nifedipine dose and 24 hours after the therapy.Results: The mean age of pregnant participants was (28.6± 3.1), mean Body Mass Index (BMI) was (22.2±1.3). There was no significant effect of nifedipine on Hemodynamic parameters (maternal heart rate, systolic blood pressure and diastolic blood pressure). There was no statistically significant difference of Pulsatility Index (PI) of the umbilical artery, Middle Cerebral Arteries (MCA) and Ductus Venosus (DV) before and after treatment.Conclusion: Oral nifedipine is a safe tocolytic agent on placental and fetal cerebral blood flow as well as on fetal cardiac function when used in pregnant women at risk of preterm delivery during the first 24 hours.

BLOOD PRESSURE CONTROL OF NIFEDIPINE GITS 60MG TREATMENT IN PREVIOUSLY UNCONTROLLED HYPERTENSIVE PATIENTS

Objective: Post-marketing surveillance data has confirmed the efficacy and tolerability of 30 and 60 mg Nifedipine GITS in the management of hypertension. However, role of high dose Nifedipine GITS in controlling blood pressure (BP) in patients with uncontrolled BP levels with prior antihypertensive therapy is not studied. This 2nd analysis of ADEPT study aimed to evaluate the effect of Nifedipine GITS 60 mg treatment on 24 hours BP control in uncontrolled hypertensive patients using Ambulatory Blood Pressure Monitoring (ABPM). Design and method: Men and women (18–65 years) whose BP was uncontrolled with prior antihypertensive monotherapy were included in a prospective, open-label, multicenter, single-arm study. Patients received oral Nifedipine GITS 60 mg for 8 weeks, OD. BP data was obtained at baseline, week 2, 4, and 8. Mean 24-h systolic (SBP) and diastolic blood pressure (DBP) data was obtained through 24-h ABPM at baseline and after Week 8. BP reduction at each hour and throughout 8-week study period was analyzed along with heart rate (HR). Results: Patients who started both baseline and week 8 ABPM between 8:00 and 11:59AM were included in the analyses (n = 138, age = 55.6 ± 8.1 years, 58% men, 42% women). Hourly variation in SBP and DBP at baseline and week 8 is represented in Fig.1. Mean 24-h SBP decreased from 129.1 ± 16.1 mmHg to 121.6 ± 12.7 mmHg and DBP decreased from 79.1 ± 10.1 mmHg to 76.0 ± 9.2 mmHg. T/P ratio for SBP was 0.71 and 0.63 for DBP. Mean change in SBP and DBP for last 4-h at baseline and week 8 was 133.4 ± 15.0 mmHg and 126.3 ± 12.6 mmHg, 82.9 ± 9.1 mmHg and 80.0 ± 8.8 mmHg respectively. Mean change in SBP and DBP for last 6-h at baseline and week 8 was 131.9 ± 14.9 mmHg and 124.6 ± 11.9 mmHg, 81.6 ± 9.0 mmHg and 78.4 ± 8.8 mmHg respectively. 24-h variation in HR was 1.5 bpm.Conclusions: Nifedipine GITS showed good efficacy in the last dosing time along with good BP control for 24-h in patients with uncontrolled BP with prior antihypertensive monotherapy.

Fatal cerebral hemorrhage in a tetraplegic patient due to autonomic dysreflexia triggered by delay in emptying urinary bladder after unsuccessful intermittent catheterization by carer: lessons learned

IntroductionOver-distension of urinary bladder in a high spinal cord injury patient is a triggering factor for autonomic dysreflexia. Removing triggering factors is vital to prevent autonomic dysreflexia.Case presentationA 36-year-old tetraplegic patient, who was managed by intermittent catheterizations performed by caregivers, developed recurrent autonomic dysreflexia during a week due to: 1) carers not performing intermittent catheterizations every night; 2) infrequent catheterizations during the day, leading to distension of urinary bladder. A day before his demise, carer attempted routine catheterization; but was unable to insert the catheter; blood pressure rose to 192/109 mmHg. Nifedipine 10 mg was administered. Thirty minutes later, blood pressure was 181/113 mmHg; second dose of Nifedipine was not given. Forty minutes elapsed before a senior carer came and catheterized successfully. Meanwhile, patient developed pounding headache; became drowsy; was talking incoherently. Four and half hours after unsuccessful catheterization, carers contacted emergency services and the patient was taken to Accident and Emergency; CT of head revealed very large acute intracranial hemorrhage in the right frontal and parietal lobes. The patient expired a day later. The Coroner’s verdict: “Patient died of massive intracranial hemorrhage caused by autonomic dysreflexia, a known complication of high spinal cord injury. Emergency protocols to manage autonomic dysreflexia were not followed in the days leading up to his death.”ConclusionFailed urethral catheterization is a potentially life-threatening emergency; every patient should have a care plan explicitly describing what should be done when catheterization is not successful. Preventive measures rather than episodic treatment of autonomic dysreflexia should be the guiding principle.

Anticonvulsant effect of nifedipine, dizepam and in combination on pentylenetetrazol induced experimental models of epilepsy on albino rats

Background: In many patients, the presently available antiepileptic drugs such as phenobarbital, phenytoin, benzodiazepines, sodium valproate, etc., are unable to control seizures efficiently and the problem of adverse effects has also not been circumvented completely and approximately 30% of the patients continue to have seizures with current antiepileptic drugs therapy. Hence, search should continue to develop newer, more effective, and safer neuro-protective agents for treatment of epilepsy. Aim of the study was to investigate the activity of nifedipine, the dihydropyridine calcium channel blocker, diazepam, the benzodiazepine anti- convulsant of established efficacy and their combinations against rat models of pentylenetetrazol (PTZ) induced convulsions. Method: Wister albino rats of either sex, weighing between 150-220gm were used. Rats were divided into 10 groups, in each group n=6 total N=60.Methods: PTZ was administration 30 min after test drug administration. Intraperitoneal injection of PTZ at the dose of 80mg/Kg body weight were administered to the rats to produce chemically-induced seizure. The effect of nifedipine and diazepam were assessed on such seizure model. The onset and duration of clonic convulsion were recorded.Results: The onset time of PTZ-induced clonic convulsion was significantly prolonged with the Nifedipine in the doses of 4mg and 8mg per Kg. in comparison to nifedipine in dose of 2mg per Kg. The interesting observation was that while Diazepam in 1mg/Kg. dose significantly (P&lt;0.05) prolonged the onset time, there was significant decrease (P &lt;0.001) in the onset time of PTZ-induced clonic convulsion with diazepam in doses of 2 and 4mg per Kg. in comparison to Diazepam 1mg per Kg. But the combination of diazepam 2.5 mg and Nifedipine 2.6mg and 5.3mg exhibited significant prolongation of the onset time. Diazepam 1 and 2mg per Kg was found to be equally effective in reduction of convulsion time, while 4mg dose showed more reduction of convulsion time. The combination of diazepam and nifedipine showed no better reduction in the convulsion time and also valproic acid in doses of 135mg. Kg.Conclusions: Nifedipine (3-5mg/Kg) and diazepam (2.5mg/Kg.) combination delayed the onset of convulsion. Diazepam 2mg / Kg. alone was effective in reduction of duration of convulsion. The combination dose having 2.6mg of nifedipine showed comparable protection with valproic acid 135mg per Kg. while the combination having 5.3mg of nifedipine showed significantly better protection.

O22-4 - Nifedipine Attenuates Doxorubicin-induced Cardiomyopathy by Suppressing CaMKII-NF-kB Pathway

Background: Activation of CaMKII induces cardiomyocyte death in doxorubicin (DOX)-induced cardiomyopathy. Nifedipine, L-type calcium channel blocker, has been shown to inhibit CaMKII activity in hypertrophic heart. The purpose of this study was to determine whether nifedipine could attenuate DOX-induced cardiomyopathy by inhibiting CaMKII activity and to elucidate its downstream signaling. Methods and Results: Mice were treated with DOX (18 mg/kg via 3 intravenous injections over 1 week) with or without subpressor dose of nifedipine (10 mg/kg/day). Two weeks after DOX treatment, nifedipine prevented DOX-induced decrease in left ventricular fractional shortening (25.7 ± 1.5% vs. 32.9 ± 0.3%, P < .05). Nifedipine decreased Dox-induced cardiomyocyte death as assessed by Billingham score (2.88 ± 0.25 vs. 1.88 ± 0.48 P < .05). It also inhibited DOX-induced phosphorylation of CaMKII and NF-kB, their active forms, by 42% and 30%, respectively (P < .05), in the heart. In cultured neonatal rat ventricular myocytes (NRVMs), DOX (10 µM, 24h) increased phosphorylated CaMKII and NF-kB and cleaved caspase-3, and LDH release, a marker of cell death. Treatment with nifedipine (10 µM, 24h) or autocamtide 2-related inhibitory peptide (AIP, 10 µM, 24h), a selective inhibitor of CaMKII, significantly suppressed DOX-induced increases in phosphorylated CaMKII, cleaved caspase-3 and LDH release in NRVMs, which was accompanied by a decrease in phosphorylated NF-kB. Conclusions: Nifedipine attenuated DOX-induced cardiomyopathy by suppressing CaMKII-NF-kB pathway. Therapeutic strategy designed to interfere with this pathway might be beneficial in its prevention.

ANTI CONVULSANT EFFECT OF NIFEDIPINE, DIAZEPAM AND IN COMBINATION ON MES INDUCED EPILEPSY IN RATS

Background: The role of calcium in the process of epileptogenesis and neurotoxicity and excitotoxicity during status epilepticus is involved. In fact, epileptiform bursts are often associated with influx of calcium ion into the nerve cells and a decrease in the extracellular concentration of calcium precedes the onset of seizures. Aim: To investigate the activity of nifedipine, the dihydropyridine calcium channel blocker, diazepam, the benzodiazepine anti- convulsant of established efficacy and their combinations against rat models of MES induced tonic seizure. Method: Wister albino rats of either sex, weighing between 150-220 gm were used for maximal electroshock method. Rats were divided into 10 groups, in each group n=6 total N=60.Group 1: Control, Group 2-4:Nifedipine 2, 4 and 8 mg/kg accordingly, Group 5-7: Diazepam 1,2 and 4 mg/kg accordingly, Group 8:Nifedipine (3.3mg) + Diazepam (3mg), Group 9:Nifedipine (6.6mg) + Diazepam (3mg), Group 10: Phenytoin (25mg/kg). The Controls in the central panel was set at 120 mA current. The Start-Reset knob was switched in the reset position with time of 0.2 seconds was set. The following parameters were observed. Latent period of convulsions, duration of flexion, tonic hind limb extension, posttictal sleep. Results: Nifedipine in doses of 4 and 8 mg / Kg., diazepam in all doses (1, 2 and 4 mg / Kg.) and their combinations were significantly reducing the duration of tonic hind limb extension (THLE). Only Nifedipine in doses of 2 mg / Kg. had no significant change in duration of THLE in comparison to Normal saline. The effect of Nifedipine 8 mg / Kg. on reducing the duration of THLE, indicative its anti-seizure activity on MES seizure was comparable to Diazepam in the dose of 1 mg / Kg. The MES-induced anti-seizure activity of Diazepam in doses of 1 mg / Kg. It was significantly less than Diazepam in doses of 2 and 4 mg / Kg or from the combination doses. Diazepam in 4 mg / Kg. dose was equally effective as the combination. But its effect was also equi-effective with Phenytoin. Conclusion: Nifedipine alone is inferior to diazepam in generalized tonic-clonic seizure and their combination is not having superadditive effect. Key words: Calcium channel blockers; Diazepam; Epilepsy; Maximum electrical shock.

74 Relationship between plasma concentration of nifedipine and pressure control in hypertensive pregnant women

Introduction Nifedipine is a calcium channel blocker used in treatment of hypertension in pregnant women. Objective The objective of the present study was to investigate the relation between the plasma concentration of nifedipine and pressure control in hypertensive pregnant women. Methods Twenty-two hypertensive pregnant women taking oral slow-release nifedipine 20 mg every 12 h were evaluated. Serial blood samples were collected at times 0–12 h after administration of the last nifedipine dose during the third trimester of pregnancy. The blood pressure of the patients was measured 4 in 4 hours from the time 0 to 12 h. Concentrations of nifedipine were determined by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The plasma concentration and the mean arterial pressure were reported as mean and standard deviation. Results The maximum fall in the measurement of mean arterial pressure after 4 h (95.4 ± 10.2 mmHg) was observed right after the mean maximum plasma concentration (27.5 ± 10.6 ng/mL) at time of maximum concentration (1.5 ± 0.5 h). As well as the values of mean arterial pressure at time 12 h (102.0 ± 11.1 mmHg) was similar to the values from time zero (106.8 ± 11.5 mmHg). Conclusion The study demonstrate the action of the drug during the dose interval used, as well as its efficacy. Acknowledgement Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq).

Effect of antihypertensive agents - captopril and nifedipine - on the functional properties of rat heart mitochondria.

Investigation of acute effect on cellular bioenergetics provides the opportunity to characterize the possible adverse effects of drugs more comprehensively. This study aimed to investigate the changes in biochemical and biophysical properties of heart mitochondria induced by captopril and nifedipine antihypertensive treatment. Male, 12-week-old Wistar rats in two experimental models (in vivo and in vitro) were used. In four groups, the effects of escalating doses of captopril, nifedipine and combination of captopril + nifedipine added to the incubation medium (in vitro) or administered per os to rat (in vivo) on mitochondrial ATP synthase activity and membrane fluidity were monitored. In the in vitro model we observed a significant inhibitory effect of treatment on the ATP synthase activity (P<0.05) with nonsignificant differences in membrane fluidity. Decrease in the value of maximum reaction rate Vmax (P<0.05) without any change in the value of Michaelis-Menten constant Km, indicative of a noncompetitive inhibition, was presented. At the in vivo level, we did not demonstrate any significant changes in the ATP synthase activity and the membrane fluidity in rats receiving captopril, nifedipine, and combined therapy. In vitro kinetics study revealed that antihypertensive drugs (captopril and nifedipine) directly interact with mitochondrial ATP synthase. In vivo experiment did not prove any acute effect on myocardial bioenergetics and suggest that drugs do not enter cardiomyocyte and have no direct effect on mitochondria.