Calcium channel blockers: pharmacology and place in therapy of pediatric hypertension

Flynn, Joseph T.; Pasko, Deborah A.

doi:10.1007/s004670000480

Cited by 105 publications

(110 citation statements)

References 126 publications

(180 reference statements)

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“…The adverse effects of calcium channel blockers are generally minor and include peripheral edema and headache. These are due to the peripheral vasodilation caused by these agents [35,36]. If a primary care physician is uncertain how to proceed with hypertension workup, but needs to start therapy (e.g.…”

Section: Indications and Contraindicationsmentioning

confidence: 99%

“…Amlodipine is dosed once daily; full effect is commonly not seen until the after steady state is reached, often after 5-6 days of therapy, due to its long half-life of 36-45 hours [36]. A multicenter pharmacokinetics study showed that weight-adjusted clearances and volume of distribution were significantly greater in younger children, suggesting a need for higher amlodipine mg/kg/day doses in children less than 6 years of age [37].…”

Section: Relevant Within Class Differencesmentioning

confidence: 99%

“…Nifedipine is a short-acting calcium channel blocker which is available in an extended release formulation; dosing recommendations are available for children 6 years of age and older. The short-acting form, however, should be used with some caution as it has the potential to cause overly rapid drops in blood pressure [36]. Nifedipine's extended release formulation is available in tablet form only, but is sometimes preferable to amlodipine as it reaches steady state faster than amlodipine due to nifedipine's short half-life of 2-4 hours [36].…”

Section: Relevant Within Class Differencesmentioning

confidence: 99%

“…The short-acting form, however, should be used with some caution as it has the potential to cause overly rapid drops in blood pressure [36]. Nifedipine's extended release formulation is available in tablet form only, but is sometimes preferable to amlodipine as it reaches steady state faster than amlodipine due to nifedipine's short half-life of 2-4 hours [36]. Felodipine is only available as an extended-release formulation for which the dosage form must be swallowed whole, limiting utility in younger children.…”

Section: Relevant Within Class Differencesmentioning

confidence: 99%

“…Isradipine must be dosed 3-4 times daily and there is less experience with its use in children. Non-dihydropyridines, such as verapamil and diltiazem, have a negative inotropic effect and are therefore more commonly used for angina and rate control of atrial fibrillation than for hypertension [36]. Additionally, there are little data or experience available on the use of non-dihydropyridines for hypertension in children.…”

Section: Relevant Within Class Differencesmentioning

confidence: 99%

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Pharmacologic Management of Pediatric Hypertension

2015

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Section: Indications and Contraindicationsmentioning

confidence: 99%

Section: Relevant Within Class Differencesmentioning

confidence: 99%

Section: Relevant Within Class Differencesmentioning

confidence: 99%

Section: Relevant Within Class Differencesmentioning

confidence: 99%

Section: Relevant Within Class Differencesmentioning

confidence: 99%

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Pharmacologic Management of Pediatric Hypertension

2015

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Effect of Verapamil on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes

Forlenza

McVean

Beck

et al. 2023

JAMA

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ImportanceIn preclinical studies, thioredoxin-interacting protein overexpression induces pancreatic beta cell apoptosis and is involved in glucotoxicity-induced beta cell death. Calcium channel blockers reduce these effects and may be beneficial to beta cell preservation in type 1 diabetes.ObjectiveTo determine the effect of verapamil on pancreatic beta cell function in children and adolescents with newly diagnosed type 1 diabetes.Design, Setting, and ParticipantsThis double-blind, randomized clinical trial including children and adolescents aged 7 to 17 years with newly diagnosed type 1 diabetes who weighed 30 kg or greater was conducted at 6 centers in the US (randomized participants between July 20, 2020, and October 13, 2021) and follow-up was completed on September 15, 2022.InterventionsParticipants were randomly assigned 1:1 to once-daily oral verapamil (n = 47) or placebo (n = 41) as part of a factorial design in which participants also were assigned to receive either intensive diabetes management or standard diabetes care.Main Outcomes and MeasuresThe primary outcome was area under the curve values for C-peptide level (a measure of pancreatic beta cell function) stimulated by a mixed-meal tolerance test at 52 weeks from diagnosis of type 1 diabetes.ResultsAmong 88 participants (mean age, 12.7 [SD, 2.4] years; 36 were female [41%]; and the mean time from diagnosis to randomization was 24 [SD, 4] days), 83 (94%) completed the trial. In the verapamil group, the mean C-peptide area under the curve was 0.66 pmol/mL at baseline and 0.65 pmol/mL at 52 weeks compared with 0.60 pmol/mL at baseline and 0.44 pmol/mL at 52 weeks in the placebo group (adjusted between-group difference, 0.14 pmol/mL [95% CI, 0.01 to 0.27 pmol/mL]; P = .04). This equates to a 30% higher C-peptide level at 52 weeks with verapamil. The percentage of participants with a 52-week peak C-peptide level of 0.2 pmol/mL or greater was 95% (41 of 43 participants) in the verapamil group vs 71% (27 of 38 participants) in the placebo group. At 52 weeks, hemoglobin A1c was 6.6% in the verapamil group vs 6.9% in the placebo group (adjusted between-group difference, −0.3% [95% CI, −1.0% to 0.4%]). Eight participants (17%) in the verapamil group and 8 participants (20%) in the placebo group had a nonserious adverse event considered to be related to treatment.Conclusions and RelevanceIn children and adolescents with newly diagnosed type 1 diabetes, verapamil partially preserved stimulated C-peptide secretion at 52 weeks from diagnosis compared with placebo. Further studies are needed to determine the longitudinal durability of C-peptide improvement and the optimal length of therapy.Trial RegistrationClinicalTrials.gov Identifier: NCT04233034

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