Evaluation of amlodipine dosing for conversion of nifedipine extended-release to amlodipine in the treatment of hypertension.

OBJECTIVE: To evaluate the appropriate dosing of amlodipine when converting patients from nifedipine extended-release (nifedipine ER) to amlodipine in the treatment of hypertension. METHODS: Patients of the Outpatient Clinic of Cheyenne Veterans Affairs Medical Center, Wyoming, receiving nifedipine ER for the management of hypertension (systolic BP or SBP > 140 mm Hg and diastolic BP or DBP > 90 mm Hg), participated in this study. Nifedipine ER was changed to amlodipine on entry into this study. An inclusion criterion was the BP had to be under control (SBP < 140 mm Hg and DBP < 90 mm Hg) before the switch. The BP in each study patient was monitored once weekly (once every 2 wk in some patients) for a total of six clinic visits or until BP was under control. Dosing titration of amlodipine was required in 16 of 27 patients after the switch. To assess the adequacy of the conversion, the statistical significance of the difference of the mean BP values before and at the end of the monitoring period was estimated by using the t-test for paired data. RESULTS: Twenty-seven male patients completed this study. BP in all study patients was adequately controlled after nifedipine ER was switched to amlodipine. The SBP and DBP values before and after the switch were similar (SBP: 124 +/- 12 vs. 126 +/- 9 mm Hg, CI of the mean difference -6.10 to 1.80; DBP: 76 +/- 8 vs. 76 +/- 7 mm Hg, CI of the mean difference -2.45 to 3.63). Initial amlodipine dose of 5 or 10 mg once daily was used in our study. No serious adverse effects were observed in any of the study patients after the drug switch. CONCLUSIONS: This study indicates the amlodipine dosage of 5 or 10 mg once daily can be used when nifedipine ER is converted to amlodipine in the treatment of hypertension. Dosage titration of amlodipine may be required to obtain adequate control of BP.

Agonist versus antagonist binding to alpha-adrenergic receptors.

The binding properties of two alpha-adrenergic radioligands, [3H]epinephrine (an agonist) and [3H]dihydroergocryptine (an antagonist), were compared in two model systems--membranes derived from human platelets and membranes from rat liver. The platelet contains exclusively alpha 2 and the liver mostly (approximately 80%) alpha 1 receptors. Agonists induce the formation of a guanine nucleotide-sensitive high-affinity state of alpha 2 but not alpha 1 receptors. [3H]Dihydroergocryptine labels all the alpha receptors, whereas [3H]epinephrine at low concentrations labels predominantly the high-affinity form of the alpha 2 receptor in both platelet and liver. However, in the liver, alpha-adrenergic effects such as glycogen phosphorylase activation are shown to be mediated via alpha 1 receptors. Thus, in liver membranes the endogenous "physiological" agonist may not label the physiologically relevant alpha 1 receptors in typical radioligand binding assays using low concentrations of [3H]epinephrine.