Calcium Channel Blockers ; pharmacology ; therapeutic use ; Cerebral Infarction ; drug therapy ; Coronary Disease ; drug therapy ; Humans ; Pyrazines ; pharmacology ; therapeutic use ; Vasodilator Agents ; pharmacology ; therapeutic use

The purpose of the present study was to discuss the effects of risedronate on osteoarthritis (OA) of the knee by reviewing the existing literature. The literature was searched with PubMed, with respect to prospective, double-blind, randomized placebo-controlled trials (RCTs), using the following search terms: risedronate, knee, and osteoarthritis. Two RCTs met the criteria. A RCT (n = 231) showed that risedronate treatment (15 mg/day) for 1 year improved symptoms. A larger RCT (n = 1,896) showed that risedronate treatment (5 mg/day, 15 mg/day, 35 mg/week, and 50 mg/week) for 2 years did not improve signs or symptoms, nor did it alter radiological progression. However, a subanalysis study (n = 477) revealed that patients with marked cartilage loss preserved the structural integrity of subchondral bone by risedronate treatment (15 mg/day and 50 mg/week). Another subanalysis study (n = 1,885) revealed that C-terminal crosslinking telopeptide of type II collagen (CTX-II) decreased with risedronate treatment in a dose-dependent manner, and levels reached after 6 months were associated with radiological progression at 2 years. The results of these RCTs show that risedronate reduces the marker of cartilage degradation (CTX-II), which could contribute to attenuation of radiological progression of OA by preserving the structural integrity of subchondral bone. The review of the literature suggests that higher doses of risedronate (15 mg/day) strongly reduces the marker of cartilage degradation (CTX-II), which could contribute to attenuation of radiological progression of OA by preserving the structural integrity of subchondral bone.
Animals ; Calcium Channel Blockers/pharmacology/*therapeutic use ; Cartilage/drug effects ; Diphosphonates/therapeutic use ; Etidronic Acid/*analogs & derivatives/pharmacology/therapeutic use ; Humans ; Osteoarthritis, Knee/*drug therapy

OBJECTIVETo compare the effects of amlodipine, benidipine and nifedipine on myocardial hypertrophy and evaluate the underlying mechanism.

METHODSMyocardial hypertrophy model was created by transverse aortic constriction (TAC) in C57 BL/6 mice, and plasma catecholamine concentrations were measured 7 days after surgery to confirm the sympathetic activation. The 3 drugs were administered in TAC mice for 7 days and cardiac hypertrophy was evaluated according to the heart-to-body weight ratio (HW/BW). Effects of those drugs on the protein synthesis stimulated by phenylephrine in cultured neonatal cardiac myocytes were also examined.

RESULTSHW/BW and plasma concentrations of catecholamine were significantly increased in TAC mice one week after surgery in comparison with to sham-operated mice. One week after TAC, the HW/BW ratio was significantly lower in the amolodipine but not nifedipine-treated group than in the TAC group. Administration of nifedipine via minipump infusion for one week did not decrease HW/BW ratio. Treatment with amlodpine or benidipine, but not nifedipine, decreased the neonatal rat myocyte protein synthesis induced by phenylephrine stimulation.

CONCLUSIONAntihypertrophic effect of DHEs on myocardium is dependent on their potential of blocking N-type calcium channel, and the underlying mechanism involves the sympathetic inhibition.

Amlodipine ; pharmacology ; therapeutic use ; Animals ; Calcium Channel Blockers ; pharmacology ; therapeutic use ; Calcium Channels, N-Type ; drug effects ; Cardiomegaly ; drug therapy ; etiology ; Dihydropyridines ; pharmacology ; therapeutic use ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Nifedipine ; pharmacology ; therapeutic use

BACKGROUNDTamsulosin, an alpha-1 receptor antagonist, has been demonstrated effective in promoting distal ureteral stone passage and in reducing pain associated with stone expulsion. This study aimed to evaluate the effect of tamsulosin in comparison with nifedipine and extracorporeal shock wave lithotripsy (ESWL) on the expulsion rate of distal ureteral stones at different sizes.

METHODSWe assigned 314 patients to three categories: I, the stone with maximal diameter of 4.0 - 5.9 mm; II, 6.0 - 7.9 mm, and III, 8.0 - 9.9 mm. Patients in each category were randomly subdivided into three treatment subgroups: group A (nifedipine group), group B (tamsulosin group), and group C (ESWL group). Stone-free rate and the dose of analgesics were recorded weekly during the 4-week follow-up period.

RESULTSThree hundred and three patients completed the study. The results showed that nifedipine and tamsulosin treatments promoted a small (4 - 8 mm, categories I and II) stone expulsive rate that was comparable with ESWL treatment. Nonetheless, when the stone diameter was 8.0 - 9.9 mm, ESWL showed a greater stone free rate than nifedipine and tamsulosin treatments; no significant difference existed between the latter two therapies. Although the ESWL treatment group required the least analgesics, tamsulosin treatments required less pain medication than nifedipine (P < 0.05).

CONCLUSIONSTamsulosin treatment is recommended for patients with the stone diameter smaller than 8 mm because of its feasibility, effectiveness and safety. ESWL is more appropriate than tamsulosin therapy for the patients whose stones are larger than 8 mm.

Adrenergic alpha-Antagonists ; pharmacology ; Adult ; Calcium Channel Blockers ; pharmacology ; Female ; Humans ; Lithotripsy ; Male ; Middle Aged ; Nifedipine ; therapeutic use ; Sulfonamides ; therapeutic use ; Treatment Outcome ; Ureteral Calculi ; drug therapy ; therapy

BACKGROUNDRenin-angiotensin system inhibitor and calcium channel blocker (CCB) are widely used in controlling blood pressure (BP) in patients with chronic kidney disease (CKD). We carried out a meta-analysis to compare the renoprotective effect of the combination of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and CCB (i.e., ACEI/ARB + CCB) with ACEI/ARB monotherapy in patients with hypertension and CKD.

METHODSPublications were identified from PubMed, Embase, Medline, and Cochrane databases. Only randomized controlled trials (RCTs) of BP lowering treatment for patients with hypertension and CKD were considered. The outcomes of end-stage renal disease (ESRD), cardiovascular events, BP, urinary protein measures, estimated glomerular filtration rate (GFR), and adverse events were extracted.

RESULTSBased on seven RCTs with 628 patients, ACEI/ARB + CCB did not show additional benefit for the incidence of ESRD (risk ratio [RR] = 0.84; 95% confidence interval [CI]: 0.52-1.33) and cardiovascular events (RR = 0.58; 95% CI: 0.21-1.63) significantly, compared with ACEI/ARB monotherapy. There were no significant differences in change from baseline to the end points in diastolic BP (weighted mean difference [WMD] = -1.28 mmHg; 95% CI: -3.18 to -0.62), proteinuria (standard mean difference = -0.55; 95% CI: -1.41 to -0.30), GFR (WMD = -0.32 ml/min; 95% CI: -1.53 to -0.89), and occurrence of adverse events (RR = 1.05; 95% CI: 0.72-1.53). However, ACEI/ARB + CCB showed a greater reduction in systolic BP (WMD = -4.46 mmHg; 95% CI: -6.95 to -1.97), compared with ACEI/ARB monotherapy.

CONCLUSIONACEI/ARB + CCB had no additional renoprotective benefit beyond than what could be achieved with ACEI/ARB monotherapy.

Angiotensin Receptor Antagonists ; pharmacology ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; therapeutic use ; Calcium Channel Blockers ; pharmacology ; therapeutic use ; Drug Therapy, Combination ; Glomerular Filtration Rate ; Humans ; Hypertension ; drug therapy ; Kidney ; drug effects ; Renal Insufficiency, Chronic ; drug therapy

Calcium channels exist extensively in the membrane of cardiac, skeletal, smooth muscle cell and neuron. Calcium channel blockers (CCB) were widely used for the treatment of cardiovascular diseases because they could relax vascular smooth muscle. Experimental researches on calcium channel blockers relaxing corpus cavernosum smooth muscle have been reported recently. Whether the blockers can be used for the clinical diagnosis and treatment of erectile dysfunction still need to be further investigated.
Animals ; Calcium Channel Blockers ; pharmacology ; therapeutic use ; Calcium Channels ; metabolism ; Cardiovascular Diseases ; drug therapy ; Humans ; Male ; Muscle Relaxation ; drug effects ; Muscle, Smooth, Vascular ; drug effects ; Myocytes, Smooth Muscle ; drug effects ; Penile Erection ; drug effects

OBJECTIVEWe used the individual patient data from clinical trials, pooled in the INDANA data set, to explore whether blood pressure reduction was related to the baseline individual characteristics, and quantify the potential associations.

METHODSWe used the data from 31 140 patients with essential hypertension recruited in four randomized placebo-controlled clinical trials, MRC35-64, MRC65-74, STEP and SYST-EU. Thiazide diuretics, β-blocker, and calcium channel blocker, three of six major BP lowering drugs were analyzed. Patients were all with the same first dosage of the drug in each trial. Age, body weight, height, level of total cholesterin (TC), systolic blood pressure (SBP) and diastolic blood pressure (DBP) when initialed and at first visit of follow-up, pharmacological treatment, gender, status of smoking, history of myocardium infarction were factors taken into model. Data were managed by software SAS(®). Statistical analyses were performed with SAS(®) and R. Model was developed to evaluate the relationship between decrease of SBP and characteristics of patients.

RESULTSInitial SBP is the only modifier of treatment effect on SBP response in the 3 BP lowering drug classes (β = 0.09, 0.37 and 0.18, respectively). Age and initial DBP were factors significantly correlated with SBP fall for diuretic (β = 0.17 and 0.14), and age was one of factors significantly correlated with SBP fall for β-blocker (β = -0.17). Smokers would receive less SBP fall compare to non-smokers in β-blocker active treated group (β = -2.07). There is converse effect of age between the diuretic and β-blocker; older people seem sensitive to diuretic, while young people are sensitive to β-blocker. As to calcium channel antagonist class, body weight is another modifier (β = 0.06) (All P value are 0.000 except 0.050 for body weight in calcium channel antagonist class).

CONCLUSIONWe identified 5 significant modifiers (baseline SBP and DBP, age, smoking status and body weight) for SBP response to treatment effect, while gender, TC and history of myocardial infarction are not modifiers for SBP response to treatment effect.

Adrenergic beta-Antagonists ; pharmacology ; therapeutic use ; Adult ; Age Factors ; Aged ; Antihypertensive Agents ; pharmacology ; therapeutic use ; Blood Pressure ; Body Weight ; Calcium Channel Blockers ; pharmacology ; therapeutic use ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Male ; Middle Aged ; Models, Theoretical ; Randomized Controlled Trials as Topic ; Smoking ; Sodium Chloride Symporter Inhibitors ; pharmacology ; therapeutic use ; Systole

BACKGROUND: The effects of antihypertensive agents on endothelial function have not been fully evaluated in human hypertension and data on the forearm circulation of humans are controversial. The aim of this study was (1) to evaluate the endothelial function in hypertensive patients (2) to investigate whether vitamin C administration has any benefit on the endothelial function and (3) to determine whether treatment with calcium antagonist improves endothelial dysfunction in hypertensive patients. METHODS: The endothelial function was estimated using venous occlusion plethysmography (VOP) in 8 hypertensive patients and 8 healthy volunteers. The patients in the hypertension group were treated with amlodipine, then examined again. The change of forearm blood flow (FBF) was measured with acetylcholine infusion through brachial artery and also with intra-arterial vitamin C. RESULTS: Forearm blood flow response to acetylcholine was significantly enhanced with intra-arterial infusion of vitamin C in hypertensive group before antihypertensive treatment. Co-infusion of L-NMMA, an inhibitor of nitric oxide synthase, blunted forearm blood flow response to acetylcholine. After treatment with amlodipine for 2 months in hypertensive group, endothelium-dependent vasorelaxation to acetylcholine was significantly improved compared to pretreatment, and vitamin C did not affect the improved endothelial function by amlodipine treatment. CONCLUSION: Vitamin C (acutely) and amlodipine (chronically) improved endothelial function in hypertensive patients. These results suggest that increased oxidative stress, at least in part, may be involved in the decreased endothelial function in hypertension.
Adult ; Aged ; Amlodipine/*therapeutic use ; Antihypertensive Agents/therapeutic use ; Ascorbic Acid/*therapeutic use ; Calcium Channel Blockers/therapeutic use ; Endothelium, Vascular/*drug effects/*physiopathology ; Enzyme Inhibitors/pharmacology ; Female ; Human ; Hypertension/*drug therapy/*physiopathology ; Male ; Middle Age ; Nitric-Oxide Synthase/antagonists & inhibitors ; Vasodilation/drug effects ; omega-N-Methylarginine/pharmacology