Adverse effects of the amlodipine on bone healing of the mandibular fracture: an experimental study in rats.

BACKGROUND: Calcium channel blockers are effective antihypertensive agents, but they may affect many metabolic processes, including bone metabolism. PURPOSE: The aim of this study was to evaluate by radiographic, histologic, and biochemical analyses the effects of amlodipine on bone healing of a defect simulating a fracture in mandibular ramus of rats. METHODS: Fifty male Wistar rats were submitted to the same unilateral surgical procedure simulating a mandibular fracture. Experimental group received oral doses of amlodipine 0.04 mg/rat/day starting 12 days before procedure, while control group received water. Animals were sacrificed at 1, 7, 14, 30, and 90 days postoperatively. Numerical values were submitted to statistical analyses. RESULTS: Radiographic analysis showed larger radiolucent area into bone defect to the experimental group at the periods of 14 (p = 0.016), 30 (p = 0.009), and 90 (p = 0.028) days. In the histological analysis, the experimental group had a slight delay in the chronology of the repair process. In the histomorphometric analysis, the experimental group presented significant lowering of newly formed bone volume at 7 and 14 days periods (p = 0.049). There was a significant decrease of alkaline phosphatase levels in experimental group in the initial periods (p = 0.049). CONCLUSIONS: It was concluded that chronic use of amlodipine compromised bone neoformation in the repairing process of surgical defect in the mandibular ramus of rats, but no precluded occurrence of fracture consolidation.

Amlodipine 2.5 mg once daily in older hypertensives: a Brazilian multi-centre study.

OBJECTIVES: The use of low-dose amlodipine has not yet been well established in the elderly. This study therefore aimed to evaluate the efficacy and tolerability of low-dose amlodipine in elderly patients with Joint National Committee VI stage I or II hypertension. PATIENTS AND METHODS: Sixty-five hypertensive individuals (aged 66.3 +/- 5.3 years) received amlodipine 2.5 mg per day for 12 weeks before and after two periods of 4 weeks of placebo. At weeks 0, 12 and 16, patients were submitted to office, 24 h ambulatory blood pressure monitoring and home blood pressure measurement. RESULTS: Office systolic and diastolic blood pressure showed decreases at weeks 8 (153 +/- 17, 90 +/- 9 mmHg) and 12 (152 +/- 16, 90 +/- 9 mmHg) compared with weeks 0 (164 +/- 16, 99 +/- 6 mmHg) and 16 (162 +/- 19, 95 +/- 9 mmHg). During ambulatory monitoring, a decrease was observed in the average 24 h systolic and diastolic pressure at week 12 (143 +/- 13, 86 +/- 7 mmHg) compared with weeks 0 (155 +/- 15, 93 +/- 6 mmHg) and 16 (152 +/- 16, 92 +/- 8 mmHg). A daytime and night-time reduction in systolic and diastolic pressure was observed on home blood pressure monitoring at week 12 (146 +/- 16/88 +/- 8, 144 +/- 16/93 +/- 8 mmHg) compared with weeks 0 (159 +/- 17/94 +/- 8, 161 +/- 19/93 +/- 8 mmHg) and 16 (153 +/- 16/93 +/- 8, 154 +/- 17/92 +/- 8 mmHg). Adverse reactions were infrequent. CONCLUSIONS: Amlodipine at a dose of 2.5 mg per day showed efficacy and good tolerability in elderly hypertensives.

Efficacy and tolerability of the combination valsartan/hydrochlorothiazide compared with amlodipine in a mild-to-moderately hypertensive Brazilian population.

Most hypertensive patients need more than one drug to reach recommended blood-pressure targets. We investigated the effects on 24-h ambulatory blood pressure (ABP) of the angiotensin-receptor blocker, valsartan, in combination with hydrochlorothiazide (HCTZ), compared with the calcium-channel blocker amlodipine in a Brazilian population in a multicentre, double-blind, double-dummy, parallel group, controlled study in 373 patients with essential hypertension. After a 2-week washout period, patients with a mean sitting systolic blood pressure (SBP) of 160-190 mmHg were randomized to receive either valsartan 160 mg o.d., or amlodipine 5 mg o.d. for 2 weeks and subsequently force-titrated to valsartan 160 mg/HCTZ 25 mg o.d. or amlodipine 10 mg o.d. This regimen was continued until the end of the study at week 8. The primary efficacy parameter was the change from baseline to week 8 in mean 24-h SBP. Secondary endpoints were change in mean 24-h diastolic blood pressure (DBP), tolerability and safety of treatments. Valsartan/HCTZ achieved a mean reduction in systolic ABP of -19.1 +/- 11.3 mmHg compared with -20.7 +/- 12.0 mmHg with amlodipine (p = 0.324 for the comparison) and in diastolic ABP by -11.1 +/- 7.4 mmHg vs -11.6 +/- 7.2 mmHg by amlodipine (p = 0.853 for the comparison). The valsartan/HCTZ group exhibited markedly lower rates of adverse events and discontinuations than the amlodipine group. Peripheral oedemas were far more frequent with amlodipine than with valsartan/ HCTZ (1.6% with valsartan/HCTZ; 16.8% with amlodipine). Thus, the valsartan 160 mg/HCTZ 25 mg combination appears to be as efficacious as amlodipine 10 mg in this patient population but better tolerated.