Comparison of Blood Pressure Control With Amlodipine and Controlled‐Release Isradipine: An Open‐Label, Drug Substitution Study

Abstract

An open-label drug substitution study showed that controlled-release isradipine (Dynacirc-CR) can be safely substituted for amlodipine on a mg-for-mg basis in patients with mild-to-moderate hypertension. When controlled-release isradipine was substituted for amlodipine, blood pressure was more effectively controlled, and edema rates were reduced. When subjects resumed amlodipine therapy, the previous gain in blood pressure reduction and lessening of edema vanished. The basis for this more favorable pattern of efficacy and side-effects with controlled-release isradipine, although mechanistically unresolved, may relate to a lesser degree of sympathetic nervous system activation.

The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson's disease

“…Neuroprotection was dose-dependent, with an estimated plasma isradipine IC50 of 13 nM for cell bodies and 19 nM for terminals. These plasma concentrations are in the range achieved in humans with doses of isradipine within those approved for the treatment of hypertension (Ganz et al, 2005; Shenfield et al, 1990), suggesting that isradipine could be a viable neuroprotective agent in early stage PD.…”

Pharmacologic and Therapeutic Considerations in Hypertension Therapy With Calcium Channel Blockers: Focus on Verapamil

“…An additional option in certain instances (where the glomerular filtration rate decrease is not excessive) is to consider CCB therapy together with an ACE inhibitor (or ARB). [160][161][162] Resolution of peripheral edema by drug switching (at least with the older CCBs) is unlikely to reflect fundamental biologic differences between drugs. 158 The chronic use of CCBs has also been shown to be a cause of bilateral symmetric false-positive captopril renography in patients with established renal artery stenosis.…”

“…Preliminary data have shown that among elderly patients receiving ACE inhibitors, the use of CCBs is associated with a reduced risk of worsening renal function-presumably because of CCB-related afferent arteriolar vasodilation. 162 If there is a relevant difference in the biology of these compounds, it would have to be ascribed to differences in vascular permeability and/or differing effects on precapillary and postcapillary vascular resistance. 159 Peripheral Edema.…”

“…Among the several dihydropyridine CCBs, there have been inconsistent findings when switching from one dihydropyridine CCB to another or when converting to different formulations of the same drug to lessen or resolve the peripheral edema. [160][161][162] Resolution of peripheral edema by drug switching (at least with the older CCBs) is unlikely to reflect fundamental biologic differences between drugs. 162 If there is a relevant difference in the biology of these compounds, it would have to be ascribed to differences in vascular permeability and/or differing effects on precapillary and postcapillary vascular resistance.…”

“…[160][161][162] Resolution of peripheral edema by drug switching (at least with the older CCBs) is unlikely to reflect fundamental biologic differences between drugs. 162 If there is a relevant difference in the biology of these compounds, it would have to be ascribed to differences in vascular permeability and/or differing effects on precapillary and postcapillary vascular resistance. There are 2 exceptions, however, to this issue of drug switching: (1) edema will diminish upon conversion from a dihydropyridine CCB to a nondihydropyridine CCB, such as verapamil or diltiazem; and (2) the newer dihydropyridine CCBs, such as lacidipine, 66 manidipine 163,164 and lercanidipine, 66,165 are reported to cause less peripheral edema.…”