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Clinical Cardiology Sep 1994Amlodipine, a third-generation dihydropyridine calcium antagonist, has a mode of action and pharmacodynamic profile which are comparable to those of conventional... (Review)
Review
Amlodipine, a third-generation dihydropyridine calcium antagonist, has a mode of action and pharmacodynamic profile which are comparable to those of conventional compounds in this series, such as nifedipine. Its physicochemical behavior, however, appears to be somewhat different. A pKa value of 8.7 means that amlodipine is predominantly present in the ionized form at a physiologic pH. It possesses, therefore, a strong affinity for cell membranes. These phenomena apparently contribute to amlodipine's unique pharmacokinetic profile, which is characterized by almost complete absorption, late-peak plasma concentrations, high bioavailability, and slow hepatic biodegradation. This profile translates into potential clinical benefits by virtue of a slow onset of action and long duration of effect. The slow onset of action may explain why there seems to be very little reflex tachycardia and a lower incidence of vasodilator side effects when comparing amlodipine with conventional dihydropyridines. The slow elimination of amlodipine explains the long duration of action, which allows a convenient once-daily dosage schedule.
Topics: Amlodipine; Angina Pectoris; Animals; Humans; Hypertension; In Vitro Techniques
PubMed: 9156957
DOI: No ID Found -
British Journal of Pharmacology May 2022Non-alcoholic fatty liver disease (NAFLD) represents a severe public health problem. It often coexists with hypertension in the context of metabolic syndrome. We...
BACKGROUND AND PURPOSE
Non-alcoholic fatty liver disease (NAFLD) represents a severe public health problem. It often coexists with hypertension in the context of metabolic syndrome. We investigated the effects of amlodipine on NAFLD combined with hypertension and investigated the underlying mechanism/s.
EXPERIMENTAL APPROACH
Mice were fed with high-fat diet (HFD) and 0.05% N-nitro-L-arginine methylester sterile water to induce NAFLD with hypertension. Gut microbiota composition and function were assessed by 16S ribosomal DNA and metagenomic sequencing. Untargeted metabolome profiles were applied to identify differential metabolites in mice caecum.
KEY RESULTS
Amlodipine besylate and amlodipine aspartate significantly decreased liver injury and hepatic steatosis, and improved lipid metabolism with a concomitant reduction in the expression of lipogenic genes in mice with NAFLD and hypertension. Mechanistically, amlodipine besylate and amlodipine aspartate have potential to restore intestinal barrier integrity and improve antimicrobial defence, along with the elevated abundances of Akkermansia, Bacteroides and Lactobacillus. Noteworthily, the gut microbiota in amlodipine besylate- and amlodipine aspartate-treated mice had higher abundance of functional genes involved in taurine and hypotaurine metabolism. Consistently, the strengthened taurine and hypotaurine metabolism was confirmed by untargeted metabolome analysis. Based on the correlation and causal analysis, the altered gut microbiota composition and the enhancement of taurine and hypotaurine metabolism may synergistically decreased alanine aminotransferase, liver triglycerides, lipogenic genes and plasma cholesterol in HFD-fed hypertensive mice.
CONCLUSION AND IMPLICATIONS
Amlodipine besylate and amlodipine aspartate exert multifactorial improvements in NAFLD and hypertension by modulating gut microbiota. They may serve as promising therapeutic agents for treating these diseases.
Topics: Amlodipine; Animals; Antihypertensive Agents; Diet, High-Fat; Gastrointestinal Microbiome; Mice; Non-alcoholic Fatty Liver Disease
PubMed: 34862599
DOI: 10.1111/bph.15768 -
Profiles of Drug Substances,... 2012
Review
Topics: Amlodipine; Animals; Calcium Channel Blockers; Crystallization; Drug Contamination; Drug Stability; Humans; X-Ray Diffraction
PubMed: 22469316
DOI: 10.1016/B978-0-12-397220-0.00002-7 -
Clinical Medicine (London, England) Jul 2022
Topics: Amlodipine; Humans; Hyponatremia; Risk Factors
PubMed: 36220214
DOI: 10.7861/clinmed.22-4-s41 -
Journal of Medical Economics Mar 2009To review the pharmacoeconomic impact of the use of amlodipine in coronary artery disease (CAD) patients. (Review)
Review
OBJECTIVES
To review the pharmacoeconomic impact of the use of amlodipine in coronary artery disease (CAD) patients.
METHODS
A review of the available outcome trials evaluating the clinical effectiveness of amlodipine in hypertensive patients or in patients with CAD or diabetic nephropathy was carried out to identify pharmacoeconomic studies that quantified the economic impact of using amlodipine instead of another treatment.
RESULTS
A combined analysis of two trials comparing angiotensin receptor blockers (ARBs) with a calcium channel blocker amlodipine suggested that amlodipine provided more protection against stroke and myocardial infarction than ARBs. In addition, in keeping with previous meta-analyses, calcium channel blockade with amlodipine also prevented more stroke than angiotensin-converting enzyme inhibitors and old drug classes. Pharmacoeconomic analysis conducted in the US and Europe demonstrated that the use of amlodipine resulted in fewer hospitalisations and the need for fewer invasive surgical procedures in the short and long term and at a modest incremental cost. The use of amlodipine resulted in improved clinical outcomes as well as slight savings in cost.
CONCLUSIONS
Amlodipine is not only cost effective, but predicted to be cost saving when compared with usual care, warranting its consideration as an agent of choice in patients with CAD.
Topics: Amlodipine; Antihypertensive Agents; Coronary Artery Disease; Economics, Pharmaceutical; Humans
PubMed: 19450066
DOI: 10.3111/13696990802525266 -
American Journal of Cardiovascular... Oct 2015Perindopril, an ACE inhibitor, and amlodipine, a dihydropyridine calcium channel blocker, are established antihypertensive agents with complementary mechanisms of... (Review)
Review
Perindopril, an ACE inhibitor, and amlodipine, a dihydropyridine calcium channel blocker, are established antihypertensive agents with complementary mechanisms of action. Recently, a once-daily, orally-administered, fixed-dose combination (FDC) of perindopril arginine plus amlodipine besylate (Prestalia(®); hereafter referred to as perindopril/amlodipine FDC) was approved in the USA for the treatment of hypertension. This article reviews the efficacy and tolerability of perindopril/amlodipine FDC and briefly summarizes the agent's pharmacologic properties. As demonstrated in short-term randomized controlled trials, perindopril/amlodipine FDC was significantly more effective in reducing blood pressure (BP) than monotherapy with either of the component drugs, and it appeared to be more effective than an up-titration scheme using valsartan and valsartan/amlodipine. The FDC agent was generally well tolerated, with the most common adverse events (peripheral edema, cough, headache, and dizziness) being consistent with the well-defined tolerability profiles of the individual component drugs. Furthermore, perindopril/amlodipine FDC was associated with a numerically lower incidence of peripheral edema compared with amlodipine monotherapy. Thus, perindopril/amlodipine FDC represents a useful option for the treatment of hypertension, including as initial therapy for patients likely to require multiple drugs to achieve their BP targets.
Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Drug Combinations; Drug Interactions; Humans; Hypertension; Perindopril; Randomized Controlled Trials as Topic
PubMed: 26341621
DOI: 10.1007/s40256-015-0144-1 -
Drugs 2009black triangle Olmesartan medoxomil/amlodipine is a fixed-dose combination of olmesartan medoxomil and amlodipine, both established antihypertensive agents. Dose... (Review)
Review
black triangle Olmesartan medoxomil/amlodipine is a fixed-dose combination of olmesartan medoxomil and amlodipine, both established antihypertensive agents. Dose titration with the individual constituent drugs is recommended before switching to the equivalent fixed-dose combination. black triangle In a randomized, double-blind, factorial trial in patients with mild to severe hypertension, 8 weeks of olmesartan medoxomil/amlodipine was more effective in reducing diastolic BP (DBP) and systolic BP (SBP) than placebo or equivalent dosages of olmesartan medoxomil or amlodipine as monotherapy. black triangle In two randomized, double-blind trials in patients with moderate to severe hypertension not adequately treated with amlodipine or olmesartan medoxomil monotherapy, 8 weeks of olmesartan medoxomil/amlodipine 20 mg/5 mg, 40 mg/5 mg or 40 mg/10 mg per day was more effective in reducing DBP and SBP than continuing treatment with olmesartan medoxomil 20 mg/day or amlodipine 5 mg/day monotherapy. black triangle More patients receiving olmesartan medoxomil/amlodipine at approved dosages than monotherapy recipients at equivalent dosages reached BP goals (42.5-51.0% vs 21.1-36.3% in the factorial trial and 44.5-54% vs 28.5-30% in the monotherapy comparisons). black triangle In the comparison with amlodipine monotherapy, >70% of olmesartan medoxomil/amlodipine recipients, some requiring upwards dosage adjustment, met BP goals. black triangle Olmesartan medoxomil/amlodipine was generally well tolerated in clinical trials. Peripheral oedema was significantly less common in olmesartan medoxomil/amlodipine 40 mg/10 mg per day than amlodipine monotherapy 10 mg/day recipients.
Topics: Amlodipine; Antihypertensive Agents; Drug Combinations; Humans; Hypertension; Imidazoles; Olmesartan Medoxomil; Randomized Controlled Trials as Topic; Tetrazoles; Treatment Outcome
PubMed: 19405551
DOI: 10.2165/00003495-200969060-00005 -
Journal of Hypertension Jul 2023SBP and blood pressure variability are independent risk factors for cerebral small vessel disease, a leading cause for stroke and dementia. Calcium-channel blockers are...
BACKGROUND
SBP and blood pressure variability are independent risk factors for cerebral small vessel disease, a leading cause for stroke and dementia. Calcium-channel blockers are known to reduce blood pressure variability and may thus offer benefit against dementia. Beyond this effect, the impact of calcium-channel blockers on hypertension-induced neuroinflammation, and especially, microglial phenotype remains unknown. We aimed to study the ability of amlopidine to alleviate microglia inflammation, and slow down cognitive dysfunction in aged hypertensive mice.
METHODS
Hypertensive BPH/2J and normotensive BPN/3J mice were studied until 12 months of age. Hypertensive mice were untreated or received amlodipine (10 mg/kg per day). Blood pressure parameters were measured by telemetry and tail cuff plethysmography. Mice underwent repeated series of cognitive tasks. Brain immunohistochemistry was performed to study blood-brain barrier dysfunction and microglial pro-inflammatory phenotype (CD68 + Iba1 + cells; morphological analysis).
RESULTS
Amlodipine normalized SBP over the entire life span and decreased blood pressure variability. BPH/2J mice exhibited impaired short-term memory that was prevented by amlodipine at 12 months (discrimination index 0.41 ± 0.25 in amlodipine-treated vs. 0.14 ± 0.15 in untreated BPH/2J mice, P = 0.02). Amlopidine treatment of BPH/2J did not prevent blood-brain barrier leakage, a measure of cerebral small vessel disease, but limited its size. Microglia's inflammatory phenotype in BPH/2J, characterized by an increased number of Iba1 + CD68 + cells, increased soma size and shortened processes, was partly reduced by amlodipine.
CONCLUSION
Amlodipine attenuated the short-term memory impairment in aged hypertensive mice. Beyond its blood pressure lowering capacity, amlodipine may be cerebroprotective by modulating neuroinflammation.
Topics: Animals; Mice; Amlodipine; Antihypertensive Agents; Blood Pressure; Calcium; Calcium Channel Blockers; Dementia; Hypertension; Microglia; Neuroinflammatory Diseases
PubMed: 37071429
DOI: 10.1097/HJH.0000000000003445 -
The Medical Letter on Drugs and... Oct 1992
Clinical Trial Review
Topics: Amlodipine; Angina Pectoris; Angina Pectoris, Variant; Humans; Hypertension
PubMed: 1406450
DOI: No ID Found -
American Journal of Hospital Pharmacy Jan 1994The chemistry, pharmacology, pharmacokinetics, efficacy, and adverse effects of amlodipine are reviewed. Amlodipine belongs to the dihydropyridine subclass of calcium... (Review)
Review
The chemistry, pharmacology, pharmacokinetics, efficacy, and adverse effects of amlodipine are reviewed. Amlodipine belongs to the dihydropyridine subclass of calcium antagonists. Amlodipine is a potent peripheral and coronary vasodilator with high selectivity for vascular smooth muscle and minimal effect on myocardial contractility or cardiac conduction. Absorption after oral administration is slow, and the duration of action is long, with a half-life of 36-45 hours. Amlodipine has FDA-approved labeling for use in the treatment of hypertension, chronic stable angina, and vasospastic angina. The agent is also indicated for use in hypertensive or anginal patients who also have congestive heart failure due to systolic dysfunction (New York Heart Association classes II and III). Clinical trials suggest that effective 24-hour control of hypertension and angina is provided by once-daily administration of amlodipine 5-10 mg alone or in combination with other drugs. No clinically important drug interactions have been observed to date. Amlodipine has not shown any unfavorable effects on serum glucose or lipid levels. The most common adverse effect is peripheral edema. Amlodipine is effective and well tolerated when given alone or in combination with other drugs for the treatment of hypertension and angina. Amlodipine may offer advantages over verapamil, diltiazem, and nifedipine in patients with hypertension or angina with associated congestive heart failure due to systolic dysfunction.
Topics: Amlodipine; Animals; Calcium Channel Blockers; Cardiovascular Diseases; Humans
PubMed: 8135260
DOI: No ID Found