A clinical study of the effects of cilnidipine and amlodipine in hypertensive patient focusing on pedal edema

Nidhi Uniyal, Vikaram Singh


Introduction: Many Calcium channel blocker drugs for control of hypertension are available. New drug Cilinidipine is available and approved for treatment of hypertension. It acts by blocking both L-type and N-type voltage-dependent calcium channels. The neural N-type blockade leads to stoppage of the secretion of norepinephrine and it also depresses sympathetic nervous system activity. The aim of the study is to assess the effect of cilnidipine and amlodipine on hypertensive patient. Method: Clinidipine (n=50) and Amolodipine (n=50) were given once daily and BP was measured daily before and after the medicine in 100 hypertensive patients on OPD basis in GDMC, Dehradun. Result: Only 4 patients (n=50; 8%) in cilnidipine group developed edema within 10 days of therapy, while 32 patients (n=50, 64%) developed with edema within 10 days of treatment in amlodipine group. Conclusion: Cilnidipine is also associated with less incidences of pedal edema which is main complaint of patient. It controls BP better with less reflex tachycardia and decrease in morning surge.

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Fukuo K, Yang J, Suzuki T, et al: Nifedipine upregulates manganese superoxide dismutase expression in vascular smooth muscle cells via endothelial cell-dependent pathways. Hypertens Res 2003; 26: 503−508.

Yao K, Sato H, Sonoda R, Ina Y, Suzuki K, Ohno T. Effects of benidipine and candesartan on kidney and vascular function in hypertensive Dahl rats. Hypertens Res. 2003 Jul;26(7):569-76.

Umemoto S, Tanaka M, Kawahara S, et al: Calcium antagonist reduces oxidative stress by upregulating Cu/Zn superoxide dismutase in stroke-prone spontaneously hypertensive rats. Hypertens Res 2004; 27: 877−885.

Yamagata K, Ichinose S, Tagami M. Amlodipine and carvedilol prevent cytotoxicity in cortical neurons isolated from stroke-prone spontaneously hypertensive rats. Hypertens Res. 2004 Apr;27(4):271-82.

Yui Y, Sumiyoshi T, Kodama K, Hirayama A, Nonogi H, Kanmatsuse K, Origasa H, Iimura O, Ishii M, Saruta T, Arakawa K, Hosoda S, Kawai C; Japan Multicenter Investigation for Cardiovascular Diseases-B Study Group. Comparison of nifedipine retard with angiotensin converting enzyme inhibitors in Japanese hypertensive patients with coronary artery disease: the Japan Multicenter Investigation for Cardiovascular Diseases-B (JMIC-B) randomized trial. Hypertens Res. 2004 Mar;27(3):181-91.

Yui Y, Sumiyoshi T, Kodama K, et al: Nifedipine retard was as effective as angiotensin converting enzyme inhibitors in preventing cardiac events in high-risk hypertensive patients with diabetes and coronary artery disease: the Japan Multicenter Investigation for Cardiovascular Diseases-B (JMIC-B) subgroup analysis. Hypertens Res 2004; 27: 449− 456.

Saruta T. Current status of calcium antagonists in Japan. Am J Cardiol. 1998 Nov 12;82(9B):32R-34R.

Hirose H, Saito I. Trends in blood pressure control in hypertensive patients with diabetes mellitus in Japan. Hypertens Res. 2003 Sep;26(9):717-22.

Grossman E, Messerli FH. Effect of calcium antagonists on sympathetic activity. Eur Heart J. 1998 Jun;19 Suppl F:F27-31.

Kario K, Shimada K: Differential effects of amlodipine on ambulatory blood pressure in elderly hypertensive patients with different nocturnal reductions in blood pressure. Am J Hypertens 1997; 10: 261−268.

Kuramoto K, Ichikawa S, Hirai A, Kanada S, Nakachi T, Ogihara T. Azelnidipine and amlodipine: a comparison of their pharmacokinetics and effects on ambulatory blood pressure. Hypertens Res. 2003 Mar;26(3):201-8.

Fujii S, Kameyama K, Hosono M, Hayashi Y, Kitamura K. Effect of cilnidipine, a novel dihydropyridine Ca++-channel antagonist, on N-type Ca++ channel in rat dorsal root ganglion neurons. J Pharmacol Exp Ther. 1997 Mar;280(3):1184-91.

Hirning LD, Fox AP, McCleskey EW, Olivera BM, Thayer SA, Miller RJ, Tsien RW. Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons. Science. 1988 Jan 1;239(4835):57-61.

Minami J, Ishimitsu T, Kawano Y, Numabe A, Matsuoka H. Comparison of 24-hour blood pressure, heart rate, and autonomic nerve activity in hypertensive patients treated with cilnidipine or nifedipine retard. J Cardiovasc Pharmacol. 1998 Aug;32(2):331-6.

Minami J, Ishimitsu T, Higashi T, Numabe A, Matsuoka H: Comparison between cilnidipine and nisoldipine with respect to effects on blood pressure and heart rate in hypertensive patients. Hypertens Res 1998; 21: 215−219.

Kario K, Pickering TG, Umeda Y, Hoshide S, Hoshide Y, Morinari M, Murata M, Kuroda T, Schwartz JE, Shimada K. Morning surge in blood pressure as a predictor of silent and clinical cerebrovascular disease in elderly hypertensives: a prospective study. Circulation. 2003 Mar 18;107(10):1401-6.

Panza JA, Epstein SE, Quyyumi AA. Circadian variation in vascular tone and its relation to alpha-sympathetic vasoconstrictor activity. N Engl J Med. 1991 Oct 3;325(14):986-90.

Sakata K, Shirotani M, Yoshida H, et al: Effects of amlodipine and cilnidipine on cardiac sympathetic nervous system and neurohormonal status in essential hypertension. Hypertension 1999; 33: 1447−1452.

Tomiyama H, Kimura Y, Kuwabara Y, et al: Cilnidipine more highly attenuates cold pressor stress-induced platelet activation in hypertension than does amlodipine. Hypertens Res 2001; 24: 679−684.

Gillman MW, Kannel WB, Belanger A, D'Agostino RB. Influence of heart rate on mortality among persons with hypertension: the Framingham Study. Am Heart J. 1993 Apr;125(4):1148-54.

Furberg CD, Psaty BM, Meyer JV. Nifedipine. Dose-related increase in mortality in patients with coronary heart disease. Circulation. 1995 Sep 1;92(5):1326-31.

Psaty BM, Heckbert SR, Koepsell TD, Siscovick DS, Raghunathan TE, Weiss NS, Rosendaal FR, Lemaitre RN, Smith NL, Wahl PW, et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA. 1995 Aug 23-30;274(8):620-5.

Ruzicka M, Leenen FH. Relevance of 24 H blood pressure profile and sympathetic activity for outcome on short- versus long-acting 1,4-dihydropyridines. Am J Hypertens. 1996 Jan;9(1):86-94.

Chobanian AV, Bakris GL, Black HR, et al: The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289: 2560−2571.

Faulkner JK, McGibney D, Chasseaud LF, Perry JL, Taylor IW: The pharmacokinetics of amlodipine in healthy volunteers after single intravenous and oral doses and after 14 repeated oral doses given once daily. Br J Clin Pharmacol 1986; 22: 21−25.

Minami J, Ishimitsu T, Kawano Y, Matsuoka H. Effects of amlodipine and nifedipine retard on autonomic nerve activity in hypertensive patients. Clin Exp Pharmacol Physiol. 1998 Jul-Aug;25(7-8):572-6.

Lefrandt JD, Heitmann J, Sevre K, et al: The effects of dihydropyridine and phenylalkylamine calcium antagonist classes on autonomic function in hypertension: the VAMPHYRE study. Am J Hypertens 2001; 14: 1083−1089.

Struck J, Muck P, Trubger D, et al: Effects of selective angiotensin II receptor blockade on sympathetic nerve activity in primary hypertensive subjects. J Hypertens 2002; 20: 1143−1149.

ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group: Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288: 2981− 2997.

Ishii M, Kakuo M, Shishido R, Okuno T, Itida S, Matsumoto M: Phase 1 clinical study of FRC-8635 (cilnidipine): single-dose study. Jpn Pharmacol Ther 1993; 21 (Suppl 1): S7−S22.

Morimoto S, Takeda K, Oguni A, Kido H, Harada S, Moriguchi J, Itoh H, Nakata T, Sasaki S, Nakagawa M. Reduction of white coat effect by cilnidipine in essential hypertension. Am J Hypertens. 2001 Oct;14(10):1053-7.

Kojima S, Shida M, Yokoyama H: Comparison between cilnidipine and amlodipine besilate with respect to proteinuria in hypertensive patients with renal diseases. Hypertens Res 2004; 27: 379−385.

Ikeda T, Gomi T, Shibuya Y, et al: Morning rise in blood pressure is a predictor of left ventricular hypertrophy in treated hypertensive patients. Hypertens Res 2004; 27: 939− 946.


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