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Pregnancy Hypertension Mar 2023To evaluate the major congenital malformation (MCM) risk of first-trimester antihypertensive exposure, specifically of amlodipine and methyldopa.
OBJECTIVES
To evaluate the major congenital malformation (MCM) risk of first-trimester antihypertensive exposure, specifically of amlodipine and methyldopa.
STUDY DESIGN
A large administrative claims database was used.
MAIN OUTCOME MEASURES
The prevalence of antihypertensive prescriptions during pregnancy was described in 91,390 women giving birth between 2010 and 2019. The MCM risk of first-trimester antihypertensives was evaluated in 1,185 women diagnosed with hypertensive disorders in the first trimester. The MCM risk of first-trimester amlodipine and methyldopa was evaluated in 178 women who were prescribed antihypertensives in the first trimester.
RESULTS
Antihypertensives were prescribed to 278 (0.30%) women during their first trimester. The prescription prevalence in the first trimester was highest for methyldopa (115, 0.13%), followed by amlodipine (55, 0.06%). Antihypertensives were prescribed to 2,955 (3.23%) women during pregnancy. Nifedipine (903, 0.99%) and nicardipine (758, 0.83%) were the most frequently prescribed oral and injectable antihypertensives during pregnancy, both with a significant increase in annual prevalence. Of the 1,185 women diagnosed with hypertensive disorders in the first trimester, antihypertensives were prescribed to 178 women. The adjusted odds ratio (aOR) of MCMs in the first-trimester prescription of any antihypertensive medication was 1.124 (95% confidence interval [CI], 0.618-2.045). Amlodipine and methyldopa were prescribed to 44 and 93 of the 178 women, respectively. The aORs of MCMs in the first-trimester prescription of amlodipine and methyldopa were 1.219 (95% CI, 0.400-3.721) and 0.921 (0.331-2.564), respectively.
CONCLUSIONS
The MCM risk of first-trimester exposure to antihypertensives, including amlodipine and methyldopa, was not suggested.
Topics: Pregnancy; Female; Humans; Male; Antihypertensive Agents; Methyldopa; Pregnancy Trimester, First; Amlodipine; Hypertension, Pregnancy-Induced; Pre-Eclampsia
PubMed: 36646019
DOI: 10.1016/j.preghy.2023.01.001 -
Future Microbiology May 2023This study was designed to evaluate the antimicrobial activity of amlodipine against strains. The antimicrobial activity of amlodipine was evaluated by the broth...
This study was designed to evaluate the antimicrobial activity of amlodipine against strains. The antimicrobial activity of amlodipine was evaluated by the broth microdilution method and its interaction with oxacillin was evaluated by checkerboard assay. The possible mechanism of action was evaluated by flow cytometry and molecular docking techniques. Amlodipine showed activity against between 64 and 128 μg/ml, in addition to showing synergism in approximately 58% of the strains used. Amlodipine also showed good activity against forming and mature biofilms. The possible mechanism of action may be attributed to its ability to lead to cell death. Amlodipine has antibacterial activity against .
Topics: Humans; Oxacillin; Staphylococcus aureus; Amlodipine; Molecular Docking Simulation; Drug Synergism; Anti-Bacterial Agents; Staphylococcal Infections; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests
PubMed: 37204289
DOI: 10.2217/fmb-2022-0230 -
International Journal of Clinical... Feb 2022To describe a case of angioedema associated with increasing the dose of HMG-CoA reductase inhibitor (atorvastatin) from 20 to 40 mg daily in a patient previously stable...
PURPOSE
To describe a case of angioedema associated with increasing the dose of HMG-CoA reductase inhibitor (atorvastatin) from 20 to 40 mg daily in a patient previously stable on angiotensin II receptor blocker (losartan) and calcium channel blocker (amlodipine) as antihypertensive agents.
SUMMARY
A 79-year-old woman with no known drug allergies and a history of multiple clinical conditions presented to the emergency department with facial and periorbital swelling, edema of the lower extremities, shortness of breath, and generalized itching and skin rash, that started 2 days after increasing her atorvastatin dose from 20 to 40 mg daily. She was concurrently on losartan 50 mg and amlodipine 5 mg daily for the management of hypertension. Atorvastatin was discontinued, and the symptoms resolved during hospitalization.
CONCLUSION
While atorvastatin use is not commonly associated with angioedema, the prescriber should be mindful of this possible adverse effect, especially when increasing the dose, or when prescribing together with medications known to cause angioedema (e.g., angiotensin II receptor blockers and calcium channel blockers), which may increase the risk of this adverse event.
Topics: Aged; Amlodipine; Angioedema; Antihypertensive Agents; Atorvastatin; Calcium Channel Blockers; Female; Humans; Hypertension; Losartan
PubMed: 34779391
DOI: 10.5414/CP204025 -
Circulation Jan 2024Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of coronary flow reserve (CFR) allows identification of patients with angina with nonobstructive coronary arteries who would benefit from anti-ischemic therapy.
METHODS
Patients with angina with nonobstructive coronary arteries underwent blinded invasive CFR measurement and were randomly assigned to receive 4 weeks of amlodipine or ranolazine. After a 1-week washout, they crossed over to the other drug for 4 weeks; final assessment was after the cessation of study medication for another 4 weeks. The primary outcome was change in treadmill exercise time, and the secondary outcome was change in Seattle Angina Questionnaire summary score in response to anti-ischemic therapy. Analysis was on a per protocol basis according to the following classification: coronary microvascular disease (CMD group) if CFR<2.5 and reference group if CFR≥2.5. The study protocol was registered before the first patient was enrolled (International Standard Randomised Controlled Trial Number: ISRCTN94728379).
RESULTS
Eighty-seven patients (61±8 years of age; 62% women) underwent random assignment (57 CMD group and 30 reference group). Baseline exercise time and Seattle Angina Questionnaire summary scores were similar between groups. The CMD group had a greater increment (delta) in exercise time than the reference group in response to both amlodipine (difference in delta, 82 s [95% CI, 37-126 s]; <0.001) and ranolazine (difference in delta, 68 s [95% CI, 21-115 s]; =0.005). The CMD group reported a greater increment (delta) in Seattle Angina Questionnaire summary score than the reference group in response to ranolazine (difference in delta, 7 points [95% CI, 0-15]; =0.048), but not to amlodipine (difference in delta, 2 points [95% CI, -5 to 8]; =0.549).
CONCLUSIONS
Among phenotypically similar patients with angina with nonobstructive coronary arteries, only those with an impaired CFR derive benefit from anti-ischemic therapy. These findings support measurement of CFR to diagnose and guide management of this otherwise heterogeneous patient group.
Topics: Female; Humans; Male; Amlodipine; Coronary Artery Disease; Coronary Circulation; Cross-Over Studies; Microcirculation; Microvascular Angina; Myocardial Ischemia; Phenotype; Ranolazine; Middle Aged; Aged
PubMed: 37905403
DOI: 10.1161/CIRCULATIONAHA.123.066680 -
Chemosphere Sep 2022For the quantifiable amounts of Telmisartan (TLM) and Hydrochlorothiazide (HYD) in the presence of Amlodipine (AML) in a ternary mixture of synthetic laboratory mixture,...
For the quantifiable amounts of Telmisartan (TLM) and Hydrochlorothiazide (HYD) in the presence of Amlodipine (AML) in a ternary mixture of synthetic laboratory mixture, a novel, sensitive, quick, and practical reversed-phase high-performance liquid chromatography (RP-HPLC) method was given. In order to separate, a Waters Spherisorb ODS-2 C18 column was used. For HYD, TLM, and AML, these techniques were viable over linearity ranges of 4-12 μg/mL, 4-25 μg/mL, and 5-40 μg/mL, respectively. The mobile phase system was acetonitrile:methanol: phosphate buffer at pH 2.5 (65:5:30 v/v/v), and the flow rate was 1.5 mL/min. Novel spectrophotometric methods were applied for active substances to determine simultaneously. The first method is absorptivity centering using factorized spectrum, and the second method is dual amplitude difference coupled with absorbance subtraction. These approaches have been effectively applied to bulk, laboratory synthetic mixtures to employ active components quantitatively. Correlation coefficients were found to be higher than 0.99 and the limit of detection values lower than 0.49 μg/mL in both spectrophotometric methods. The methodologies were validated following ICH recommendations. In the developed HPLC method, the limit of detection values was found to be 0.01 μg/mL for HYD and 0.02 μg/mL for AML and TLM. The correlation coefficients for the HPLC method were found to be 0.9971 for HYD, 0.9990 for AML, and 0.9983 for TLM. The suggested HPLC technique is a simple, effective, sensitive, environmentally friendly, and time-saving approach for determining TLM and HYD in the presence of AML.
Topics: Amlodipine; Chromatography, High Pressure Liquid; Humans; Hydrochlorothiazide; Leukemia, Myeloid, Acute; Telmisartan
PubMed: 35667505
DOI: 10.1016/j.chemosphere.2022.135074 -
Clinical Pharmacology in Drug... Jun 2022This study aimed to evaluate the bioequivalence of 2 amlodipine besylate tablet formulations, a generic formulation and an original formulation, and to investigate their... (Randomized Controlled Trial)
Randomized Controlled Trial
This study aimed to evaluate the bioequivalence of 2 amlodipine besylate tablet formulations, a generic formulation and an original formulation, and to investigate their pharmacokinetic and safety profiles. This study was designed as a randomized, open-label, single-dose, crossover, dual-period study and was divided into fasting and postprandial human bioequivalence trials. In the first trial after overnight fasting, 28 subjects were given 5-mg amlodipine besylate tablets via oral administration, and blood specimens were obtained up to 144 hours after dosing; another 28 subjects had a high-fat meal 1 hour before drug administration and proceeded the same as the fasting trial. Bioequivalence was evaluated using 90%CIs for the ratio test/reference of log area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration, log AUC from time 0 to infinity, and log peak concentration. The plasma concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. The safety was assessed throughout the study. The results show that no significant differences were observed between the pharmacokinetic profiles of the test and reference amlodipine besylate tablets in the fasting and postprandial trials. The 90%CIs of the peak concentration, AUC from time 0 to the last quantifiable concentration and AUC from time 0 to infinity of amlodipine in the 2 trials were within the commonly accepted bioequivalence criteria of 80% to 125%. Compared with the pharmacokinetic parameters of the fasting and postprandial trials, food had no significant effect on exposure of amlodipine besylate. There was no significant difference in safety statistical results between the 2 groups. The results suggest that generic and original amlodipine besylate tablets are bioequivalent with similar safety profiles.
Topics: Amlodipine; Area Under Curve; Cross-Over Studies; Drugs, Generic; Healthy Volunteers; Humans; Tablets; Therapeutic Equivalency
PubMed: 34981666
DOI: 10.1002/cpdd.1064 -
High Blood Pressure & Cardiovascular... Sep 2023Azelnidipine is one of the newer Calcium Channel Blockers (CCB) approved in China, Japan, and India. Some studies have found that the blood pressure-lowering effect of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Azelnidipine is one of the newer Calcium Channel Blockers (CCB) approved in China, Japan, and India. Some studies have found that the blood pressure-lowering effect of azelnidipine is more than amlodipine, and others found the effect similar.
AIM
This meta-analysis was conducted to evaluate the efficacy of azelnidipine in managing hypertensive patients by lowering Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) as compared to amlodipine.
METHODS
PubMed/MEDLINE, Google Scholar, PROQUEST, and International Clinical Trial Registry Platform (ICTRP) were searched for published articles to evaluate the clinical efficacy of azelnidipine in the management of hypertension patients. Data were extracted from the selected 11 randomized clinical trials (RCTs). The risk of bias 2 (RoB2) tool was used for the quality assessment of the included studies, and the random-effects model was used to estimate the effect size.
RESULTS
There were no statistically significant differences in the reduction of SBP (Mean Difference, MD: - 1.07; 95% CI: - 4.10, 1.95, p-value: 0.49) and DBP (MD: 0.27; 95% CI: - 2.66, 3.20, p-value: 0.86) between both the drugs. In terms of HR reduction, there was a statistically significant difference (MD: - 3.63; 95% CI: - 5.27, - 2.00, p-value: < 0.0001) between both drugs. Egger's test excluded any publication bias for the included studies (p = 0.21). Meta-regression excluded the effect of the duration of treatment on outcome parameters.
CONCLUSION
Though no significant difference between azelnidipine and amlodipine was found, in terms of reduction in SBP and DBP, azelnidipine reduced heart rate significantly compared to amlodipine.
PROSPERO REGISTRATION
CRD42023390361.
Topics: Humans; Amlodipine; Antihypertensive Agents; Dihydropyridines; Calcium Channel Blockers; Hypertension; Blood Pressure
PubMed: 37768510
DOI: 10.1007/s40292-023-00601-5 -
Basic & Clinical Pharmacology &... Oct 2019The combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) for the treatment of hypertension showed improved efficacy and safety.... (Clinical Trial)
Clinical Trial
The combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) for the treatment of hypertension showed improved efficacy and safety. Amlodipine is mainly metabolized by cytochrome P450 (CYP) 3A4, whereas losartan is metabolized by CYP2C9 and CYP3A4. The potential pharmacokinetic interactions between amlodipine and losartan were assessed. An open-label, three-period, fixed-sequence trial was conducted. Amlodipine, losartan and combined amlodipine and losartan were administered to 24 healthy male participants during periods 1, 2 and 3, respectively, for 9 days each. The pharmacokinetics of amlodipine, losartan and EXP-3174, an active metabolite of losartan, were assessed at steady-state. Twenty participants completed the study without serious adverse events. Losartan did not influence the exposure of amlodipine at steady-state (AUC , 165.15 ng h/mL [amlodipine alone] vs 172.36 ng h/mL [combination], P = 0.389) [geometric mean ratio (GMR) (90% confidence interval [CI]), 1.060 (0.954-1.178)]. In addition, the exposure of EXP-3174 was not affected by amlodipine (AUC , 1159.46 ng h/mL vs 1105.10 ng h/mL, P = 0.295) (GMR [90% CI], 0.957 [0.891-1.027]). However, amlodipine significantly decreased the exposure of losartan at steady-state (AUC , 1241.50 ng h/mL vs 1082.02 ng h/mL, P = 0.006) (GMR [90% CI], 0.875 [0.813-0.942]) and increased oral clearance of losartan (84.65 L/h vs 97.26 L/h, P = 0.002). Combination use of two drugs caused additive haemodynamic changes compared to treatment of amlodipine or losartan alone. The co-administration of amlodipine and losartan was tolerable and did not cause substantial pharmacokinetic interaction, even though losartan disposition was affected. Combination use of the two drugs caused additive haemodynamic changes compared to monotherapy of amlodipine or losartan.
Topics: Administration, Oral; Adult; Amlodipine; Angiotensin Receptor Antagonists; Antihypertensive Agents; Calcium Channel Blockers; Drug Interactions; Drug Therapy, Combination; Healthy Volunteers; Hemodynamics; Humans; Hypertension; Losartan; Male; Middle Aged; Republic of Korea; Young Adult
PubMed: 31058419
DOI: 10.1111/bcpt.13244 -
Open Heart Jan 2023Coronary artery vasospasm is an abnormal spasm of coronary arteries that cause transient or complete occlusion without exertion. It causes stable angina to ACS. However,...
BACKGROUND
Coronary artery vasospasm is an abnormal spasm of coronary arteries that cause transient or complete occlusion without exertion. It causes stable angina to ACS. However, this can be prevented by calcium channel blockers (CCBs) which suppress Ca influx into the vascular muscle cells. Nevertheless, several CCBs adverse effects are harmful for these patients. Selecting the right CCBs would give the best clinical practice.
METHOD
The studies were obtained from four major medical databases by various keywords. Inclusion and exclusion criteria were implemented as adult >18 years, observational study, English language and drug of interest. Duplicates were eliminated, and the remaining studies were reviewed. Final full-texts assessment was conducted independently by Newcastle-Ottawa Scale and Revised Cochrane.
RESULTS
The search found 1378 articles. However, six studies were selected after implementing the study criteria. Diltiazem was found to decrease angina and increase quality of life until 12th week of treatment; however, some adverse effects include atrioventricular block and recurrent angina up till 4th week were found. Meanwhile, nifedipine was found to decrease vasospastic angina (VSA) by the fourth and eighth weeks of treatment. Nevertheless, it caused excessive drop in BP and increase heart rate by eighth week. In addition, slow-release preparation of both CCBs were found to increase efficacy and compliance. Lastly amlodipine was also found to decrease VSA by 17%±140% and 33% after 6 weeks, but further studies needed.
CONCLUSION
Diltiazem, nifedipine and amlodipine are potent in decreasing VSA, however, tailoring specific CCBs adverse reactions to patient condition and the drug preparation would be substantially beneficial for the outcome.
Topics: Adult; Humans; Calcium Channel Blockers; Diltiazem; Coronary Vasospasm; Nifedipine; Calcium; Quality of Life; Amlodipine; Observational Studies as Topic
PubMed: 36634997
DOI: 10.1136/openhrt-2022-002179 -
Hypertension (Dallas, Tex. : 1979) Jun 2023Renal denervation (RDN) lowers blood pressure (BP) in patients with uncontrolled hypertension. Limited data exist on the effectiveness of different antihypertensive...
BACKGROUND
Renal denervation (RDN) lowers blood pressure (BP) in patients with uncontrolled hypertension. Limited data exist on the effectiveness of different antihypertensive medications following RDN on BP and maladaptive cardiac phenotypes.
METHODS
Eighty-nine male spontaneously hypertensive rats with continuous BP recording underwent RDN or sham operation. Ten days postsurgery, spontaneously hypertensive rats were randomized to receive no antihypertensive medication, amlodipine, olmesartan, hydrochlorothiazide, bisoprolol, doxazosin, or moxonidine for 28 days. Cardiac remodeling was determined histologically, and activation of the renin-angiotensin-aldosterone system was explored.
RESULTS
Before initiation of antihypertensive drugs, RDN reduced mean arterial pressure (-12.6 mm Hg [95% CI, -14.4 to -10.8]; <0.001). At study end, mean arterial pressure was lower in RDN compared with sham operation in drug-naïve controls (=0.006), olmesartan (=0.002), amlodipine (=0.0004), hydrochlorothiazide (=0.006), doxazosin (0.001), and bisoprolol (=0.039) but not in animals receiving moxonidine (=0.122). Compared with pooled BP change of all other drug classes, mean arterial pressure change was largest for olmesartan (-15.9 mm Hg [95% CI, -18.6 to -13.2]; <0.001) and amlodipine (-12.0 mm Hg [95% CI, -14.7 to -9.3]; <0.001). In drug-naïve controls, RDN reduced plasma renin activity (-5.6%¸ =0.03) and aldosterone concentration (-53.0%; =0.005). In the presence of antihypertensive medication, plasma renin activity and aldosterone remained unchanged after RDN. Cardiac remodeling was not affected by RDN alone. In animals receiving olmesartan after RDN, cardiac perivascular fibrosis was attenuated. Amlodipine and bisoprolol following RDN reduced cardiomyocyte diameter.
CONCLUSIONS
Following RDN, treatment with amlodipine and olmesartan resulted in the largest BP reduction. Antihypertensive medications mediated heterogeneous effects on renin-angiotensin-aldosterone system activity and cardiac remodeling.
Topics: Animals; Male; Rats; Aldosterone; Amlodipine; Antihypertensive Agents; Bisoprolol; Blood Pressure; Cardiomyopathies; Denervation; Doxazosin; Hydrochlorothiazide; Hypertension; Kidney; Rats, Inbred SHR; Renin; Sympathectomy
PubMed: 36999443
DOI: 10.1161/HYPERTENSIONAHA.122.20756