Patients with hypertension often require a combination of three antihypertensive agents to achieve blood pressure control, but very few single-pill triple combinations are available. The aim of this study was to determine whether a single-pill triple combination of perindopril, indapamide, and amlodipine was as effective as a dual-pill combination of perindopril/indapamide plus separate amlodipine at reducing blood pressure in patients with uncontrolled, essential hypertension.
Calcium channel blockers are commonly prescribed medications; calcium channel blocker overdose is becoming increasingly prevalent. The typical presentation of a calcium channel blocker overdose is hypotension and decreased level of consciousness. We describe a case of a calcium channel blocker overdose that led to bilateral cortical blindness, a presentation that has not previously been reported.
BackgroundWe examined whether the level of highsensitivity C-reactive protein (hsCRP), a marker of low-grade inflammation, predicted the response of clinic and ambulatory blood pressure (BP) to antihypertensive treatment.MethodsA randomized, open-label, multicenter trial was performed in 88 hypertensive patients (mean age = 63.4 years) allocated to receive losartan 50 mg or amlodipine 5 mg for 4 weeks, and each treatment was changed to losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg in combination or amlodipine 10 mg for a further 4 weeks. Clinic and ambulatory BP were measured before and after 8 weeks of treatment, and hsCRP was measured at baseline.ResultsThe patients were divided into groups with hsCRP levels above and below the median (0.47 mg/L) for the study population. In the total population, 24-hour systolic BP (SBP) (P = 0.03) and daytime SBP (P = 0.01) were significantly higher in the above-median hsCRP group after 8 weeks of treatment. In multivariable regression analysis, baseline hsCRP was a significant determinant of the percentage change in daytime SBP (β = 0.29; P = 0.02) in the total population. In the losartan/HCTZ treatment group, changes in 24-hour SBP, daytime SBP, and diastolic BP were significantly smaller in the above-median hsCRP group than the below-median hsCRP group, whereas the amlodipine group did not show these differences.ConclusionsBaseline low-grade inflammation in patients with hypertension was associated with a poor ambulatory BP response, especially with losartan/HCTZ treatment. Initial measurement of hsCRP could be useful for selection of an appropriate antihypertensive drug.Clinical Trials REGISTRATIONTrial Number UMIN000002438.
We present a case of a 31 year-old patient, who required pharmacological treatment for stage 1 hypertension. He received amlodipine 10 mg once daily in combination with lisinopril 20 mg daily. Three months after beginning treatment asymptomatic, rust-colored spots developed which were located on the tibia from the ankles to the knees. The amlodipine treatment was discontinued and after seven months skin lesions completely disappeared. Six month after withdrawal of lisinopril the patient started taking amlodipine again, with the result that identical skin symptoms re-appeared after one month. Schamberg’s disease was diagnosed and confirmed by a skin biopsy. Early drug discontinuation was necessary in order to prevent progression of the lesions. This article is protected by copyright. All rights reserved.
Ca(2+) antagonist drugs are widely used in therapy of cardiovascular disorders. Three chemical classes of drugs bind to three separate, but allosterically interacting, receptor sites on CaV1.2 channels, the most prominent voltage-gated Ca(2+) (CaV) channel type in myocytes in cardiac and vascular smooth muscle. The 1,4-dihydropyridines are used primarily for treatment of hypertension and angina pectoris and are thought to act as allosteric modulators of voltage-dependent Ca(2+) channel activation, whereas phenylalkylamines and benzothiazepines are used primarily for treatment of cardiac arrhythmias and are thought to physically block the pore. The structural basis for the different binding, action, and therapeutic uses of these drugs remains unknown. Here we present crystallographic and functional analyses of drug binding to the bacterial homotetrameric model CaV channel CaVAb, which is inhibited by dihydropyridines and phenylalkylamines with nanomolar affinity in a state-dependent manner. The binding site for amlodipine and other dihydropyridines is located on the external, lipid-facing surface of the pore module, positioned at the interface of two subunits. Dihydropyridine binding allosterically induces an asymmetric conformation of the selectivity filter, in which partially dehydrated Ca(2+) interacts directly with one subunit and blocks the pore. In contrast, the phenylalkylamine Br-verapamil binds in the central cavity of the pore on the intracellular side of the selectivity filter, physically blocking the ion-conducting pathway. Structure-based mutations of key amino-acid residues confirm drug binding at both sites. Our results define the structural basis for binding of dihydropyridines and phenylalkylamines at their distinct receptor sites on CaV channels and offer key insights into their fundamental mechanisms of action and differential therapeutic uses in cardiovascular diseases.
Practical relevance: Feline hypertension is a common disease in older cats that is frequently diagnosed in association with other diseases such as chronic kidney disease and hyperthyroidism (so-called secondary hypertension), although some cases of apparent primary hypertension are also reported. The clinical consequences of hypertension can be severe, related to ‘target organ damage’ (eye, heart and vasculature, brain and kidneys), and early diagnosis followed by appropriate therapeutic management should help reduce the morbidity associated with this condition. Clinical challenges: Despite being a common disease, routine blood pressure (BP) monitoring is generally performed infrequently, probably leading to underdiagnosis of feline hypertension in clinical practice. There is a need to: (i) ensure BP is measured as accurately as possible with a reproducible technique; (ii) identify and monitor patients at risk of developing hypertension; (iii) establish appropriate criteria for therapeutic intervention; and (iv) establish appropriate therapeutic targets. Based on current data, amlodipine besylate is the treatment of choice to manage feline hypertension and is effective in the majority of cats, but the dose needed to successfully manage hypertension varies between individuals. Some cats require long-term adjuvant therapy and, occasionally, additional therapy is necessary for emergency management of hypertensive crises. Evidence base: These Guidelines from the International Society of Feline Medicine (ISFM) are based on a comprehensive review of the currently available literature, and are aimed at providing practical recommendations to address the challenges of feline hypertension for veterinarians. There are many areas where more data is required which, in the future, will serve to confirm or modify some of the recommendations in these Guidelines.
Calcium channel blockers (CCBs) are widely used for reducing blood pressure of hypertensive patients. Recent reports document the beneficial effects of CCB for preventing dementia; however, the results are controversial. We aim to evaluate the risk of developing dementia among elderly hypertensive patients treated with CCB.We designed a retrospective population-based cohort study using the records of the National Health Insurance Research Database of Taiwan dated from 2000 to 2010. The study cohort comprised 82,107 hypertensive patients of more than 60 years of age, and 4004 propensity score (PS)-matched pairs were selected according to age, sex, year of hypertension diagnosis, and baseline comorbidities. We employed a robust Cox proportional hazard model to estimate the hazard ratio (HR) of developing dementia in the PS-matched cohort.The annual incidence of dementia in the CCB-exposure group was significantly lower than that in the comparator group (3.9 vs 6.9 per 1000 person-years, P < 0.01) during the follow-up period (4.4 ± 2.5 years). Based on the PS-matched cohort, the adjusted HR of dementia in the CCB-exposure group was significantly lower than that in comparator group (HR = 0.53, 95% confidence interval: 0.39-0.72, P < 0.01). Sensitivity and subgroup analyses also confirmed similar findings.Our results provided evidence for an association between CCB use and a lower risk of developing dementia among the elderly hypertensive patients. Further studies are required to explore the causal relationship between CCB use and dementia.
Context. Calcium channel blocker poisoning is a common and sometimes life-threatening ingestion. Objective. To evaluate the reported effects of treatments for calcium channel blocker poisoning. The primary outcomes of interest were mortality and hemodynamic parameters. The secondary outcomes included length of stay in hospital, length of stay in intensive care unit, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. Methods. Medline/Ovid, PubMed, EMBASE, Cochrane Library, TOXLINE, International pharmaceutical abstracts, Google Scholar, and the gray literature up to December 31, 2013 were searched without time restriction to identify all types of studies that examined effects of various treatments for calcium channel blocker poisoning for the outcomes of interest. The search strategy included the following Keywords: [calcium channel blockers OR calcium channel antagonist OR calcium channel blocking agent OR (amlodipine or bencyclane or bepridil or cinnarizine or felodipine or fendiline or flunarizine or gallopamil or isradipine or lidoflazine or mibefradil or nicardipine or nifedipine or nimodipine or nisoldipine or nitrendipine or prenylamine or verapamil or diltiazem)] AND [overdose OR medication errors OR poisoning OR intoxication OR toxicity OR adverse effect]. Two reviewers independently selected studies and a group of reviewers abstracted all relevant data using a pilot-tested form. A second group analyzed the risk of bias and overall quality using the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) checklist and the Thomas tool for observational studies, the Institute of Health Economics tool for Quality of Case Series, the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines, and the modified NRCNA (National Research Council for the National Academies) list for animal studies. Qualitative synthesis was used to summarize the evidence. Of 15,5577 citations identified in the initial search, 216 were selected for analysis, including 117 case reports. The kappa on the quality analysis tools was greater than 0.80 for all study types. Results. The only observational study in humans examined high-dose insulin and extracorporeal life support. The risk of bias across studies was high for all interventions and moderate to high for extracorporeal life support. High-dose insulin. High-dose insulin (bolus of 1 unit/kg followed by an infusion of 0.5-2.0 units/kg/h) was associated with improved hemodynamic parameters and lower mortality, at the risks of hypoglycemia and hypokalemia (low quality of evidence). Extracorporeal life support. Extracorporeal life support was associated with improved survival in patients with severe shock or cardiac arrest at the cost of limb ischemia, thrombosis, and bleeding (low quality of evidence). Calcium, dopamine, and norepinephrine. These agents improved hemodynamic parameters and survival without documented severe side effects (very low quality of evidence). 4-Aminopyridine. Use of 4-aminopyridine was associated with improved hemodynamic parameters and survival in animal studies, at the risk of seizures. Lipid emulsion therapy. Lipid emulsion was associated with improved hemodynamic parameters and survival in animal models of intravenous verapamil poisoning, but not in models of oral verapamil poisoning. Other studies. Studies on decontamination, atropine, glucagon, pacemakers, levosimendan, and plasma exchange reported variable results, and the methodologies used limit their interpretation. No trial was documented in humans poisoned with calcium channel blockers for Bay K8644, CGP 28932, digoxin, cyclodextrin, liposomes, bicarbonate, carnitine, fructose 1,6-diphosphate, PK 11195, or triiodothyronine. Case reports were only found for charcoal hemoperfusion, dialysis, intra-aortic balloon pump, Impella device and methylene blue. Conclusions. The treatment for calcium channel blocker poisoning is supported by low-quality evidence drawn from a heterogeneous and heavily biased literature. High-dose insulin and extracorporeal life support were the interventions supported by the strongest evidence, although the evidence is of low quality.
The aim of the current study was to assess the association between 3 different calcium channel blockers (CCBs) (nifedipine, amlodipine and felodipine) and gingival overgrowth in patients with a diagnosis of severe refractory hypertension.
Nifedipine is a generic, well-known and commonly-prescribed dihydropyridine calcium channel blocker used in the treatment of hypertension and Prinzmetal’s angina. A known but very rare and serious adverse effect of nifedipine is clinically-apparent hepatitis which can take months to resolve.