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PubMed1989

Anti-ischemic and vasorelaxant effects of the new benzazepine calcium channel blocker SQ 31,765.

The anti-ischemic effects of SQ 31,765 or its relatively inactive enantiomer SQ 32,189 (to test for effects not related to calcium channel blockade) were determined in a model of stable angina. Anesthetized dogs were given saline (n = 6), SQ 31,765 (n = 6; 0.2 mg/kg) or SQ 32,189 (n = 6; 0.2 mg/kg) i.v. 10 min before ischemia. The effect on pacing-induced ST-segment elevation (pacing + left anterior descending coronary artery stenosis) and myocardial blood flow were determined. SQ 31,765 reduced ST-elevation (P less than .05) compared to saline at 10, 40 and 70 min after infusion (5.9 +/- 1.4 and 12.0 +/- 1.4 mV, respectively, at 70 min). SQ 32,189, which is a 10-fold less potent calcium channel blocker in coronary arteries, did not affect ST-elevation (11.8 +/- 2.1 mV). Left anterior descending coronary artery stenosis during atrial pacing resulted in a significant reduction in subendocardial flow in all groups before drug infusion (41 +/- 7, 44 +/- 7 and 35 +/- 9 ml/min/100 g for saline, SQ 31,765 and SQ 32,189, respectively) and treatment with SQ 31,765 did not affect this flow. SQ 32,189 further reduced subendocardial blood flow such that it was significantly lower compared to saline. To test for any partial agonist activity, Bay k 8644 and SQ 32,189 were tested as constrictors of porcine coronary strips in vitro. Bay k 8644 induced appreciable force whereas SQ 32,189 did not. However, the vasorelaxant potency of SQ 32,189 was decreased under hypoxic conditions. Thus, SQ 31,765 can reduce the severity of ischemia in a manner which is independent of changes in myocardial blood flow or hemodynamic alterations.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Effect of calcium-channel blockers on alcohol consumption in alcohol-drinking monkeys.

Experiments were performed to determine the effect of the calcium-channel blockers verapamil and diltiazem on ethanol preference in monkeys. Two days of administration of 10 mg/kg verapamil but not diltiazem or saline significantly decreased ethanol intake in all monkeys tested. Chronic treatment with verapamil, but not saline, dose-dependently attenuated alcohol intake, without significantly influencing water intake. These findings suggest that verapamil exerts an inhibitory action on ethanol preference in chronically alcohol-drinking monkeys, possibly by interfering with Ca(2+)-channels and/or by interacting with the activity of certain central neurotransmitters.

Alcohol Drinking↗
PubMed2001

Radiographic contrast media induced nephropathy: experimental observations and the protective effect of calcium channel blockers.

Combined acute inhibition of the synthesis of nitric oxide with L-nitroarginine methyl ester (L-NAME) and of prostacycline synthesis with indomethacin predisposes rats to severe renal injury from radiographic contrast media. The reliability of this pharmacological manipulation in the study of radiographic contrast medium induced nephropathy (RCMN) was investigated. Adult male Sprague-Dawley rats were injected with iv L-NAME (10 mg kg(-1)) and iv indomethacin (10 mg kg(-1)) 15 min apart and prior to injection of RCM or normal saline (control group). A dose-dependent reduction in renal function was observed after intravascular injection of the high osmolar RCM diatrizoate (Angiografin, 306 mgI ml(-1)). A significant (p<0.01) increase in serum creatinine (Cr) (from 54.66+/-8.39 micromol l(-1) to 171.96+/-24.49 micromol l(-1) and from 80.95+/-6.73 micromol l(-1) to 204.76+/-16.73 micromol (-1), n=5 per group) was observed 24 h after injection of 6 ml and 8 ml of diatrizoate, respectively. The increase in serum Cr after injection of 8 ml of diatrizoate recovered spontaneously to 80.87+/-8.70 micromol l(-1) 7 days after injection. No significant change in renal function was observed in the control group (n=5) receiving 8 ml kg(-1) of normal saline or after injection of 4 ml of diatrizoate (serum Cr 69.84+/-5.5 micromol l(-1) pre contrast injection and 66.67+/-13.47 micromol l(-1) 24 h post contrast injection, n=5). The increase in serum Cr observed with 6 ml of diatrizoate was significantly higher (p<0.01) than the rise induced by equivolume of the low osmolar non-ionic monomer iopromide (Ultravist, 300 mgI ml(-1)) (serum CR 68.47+/-8.39 micromol l(-1) pre contrast injection and 143.59+/-32.03 micromol l(-1) 24 h post contrast injection, n=5). The calcium channel blocker diltiazem (10 mg kg(-1) injected intraperitoneally 30 min prior to RCM injection) prevented the rise in serum Cr observed with 6 ml of diatrizoate (serum Cr pre contrast injection 70.31+/-7.28 micromol(-1) and 78.21+/-17.81 micromol(-1) 24 h post contrast injection in animals pre-treated with diltiazem, n=5). The protective effect against RCM-induced reduction in renal function was less with lower doses of diltiazem. In conclusion, the animal model used is reliable and reproduced previously established observations in the field of RCMN. The protective effect of a calcium channel blocker at the appropriate dose against RCMN has also been shown. The clinical effectiveness of this class of drugs in preventing RCMN requires further evaluation.

Animals↗
PubMed1996

Differential effects of chronic calcium channel blocker treatment on the inotropic response of diabetic rat myocardium to acute ethanol exposure.

Cardiomyopathy is a consistent feature of diabetic myocardium as well as in prolonged alcohol consumption. Diabetes-induced myocardial dysfunction has been attributed, in part, to calcium overload within individual myocytes. The present study compares the effectiveness of the calcium channel blocker nifedipine (dihydropyridine-type) with verapamil (phenylalkylamine-type) in reversing myocardial dysfunction and diminishing the negative inotropic effect of ethanol on diabetic rat myocardium. Wistar rats were made diabetic with streptozotocin (55 mg/kg, i.v.) and isolated electrically stimulated papillary muscles were studied under isometric conditions in the absence and presence of clinically relevant concentrations of ethanol (80-240 mg/dl, i e., 17.4-52.1 mM). Subgroups of diabetic and normal animals received daily injections of verapamil or nifedipine 2 weeks after induction of diabetes for 8 weeks. Untreated diabetic animals exhibited hyperglycemia, hyperlipidemia, reduced growth, cardiomegaly, and hepatomegaly. Compared to verapamil chronic nifedipine treatment normalized or reversed the effects of diabetes on myocardial mechanical function. The negative inotropic effect of ethanol was attenuated only in muscles from verapamil-treated diabetic animals. Thus, chronic nifedipine treatment may be more effective than verapamil in reducing hyperglycemia, attenuating both cardiac and liver enlargement, and restoring myocardial mechanical function, in experimental diabetes. However, chronic verapamil therapy is more effective in diminishing the negative inotropic effect of ethanol on diabetic myocardium. These findings may have clinical significance among diabetic patients who consume alcoholic beverages while receiving long-term calcium blocker therapy.

Animals↗
PubMed2002

Endothelin receptor antagonist combined with a calcium channel blocker attenuates renal injury in spontaneous hypertensive rats with diabetes.

OBJECTIVE: To investigate the effects of the mixed endothelin receptor antagonist, bosentan, combined with the long-acting calcium channel blocker, amlodipine, compared to the angiotensin-converting enzyme inhibitor, cilazapril, on the progressive renal injury in spontaneous hypertensive rats (SHR) with diabetes. METHODS: Diabetic hypertensive rats (SHR-DM) were induced by streptozotozin injected in male SHR (7-week-old),and divided into an untreated and three treated groups: 1) cilazapril treated group; 2) bosentan+amlodipine treated group; and 3) amlodipine treated group. Wistar Kyoto rats (WKY) and SHR rats served as normotensive and hypertensive control, respectively. The mean arterial blood pressure, renal function, endothelin and angiotensin II levels as well as the protein expression of renal extracellular matrix components and transforming growth factor (TGF)-beta1 were determined at the end of the 4th week. RESULTS: Mean arterial blood pressure significantly increased in SHR and SHR-DM rats compared to WKY rats. All the therapies reduced the blood pressure to normal levels. However, the enhanced urinary protein excretion, the decreased creatinine clearance as well as the increased plasma and intrarenal endothelin and angiotens in II levels were found in the untreated SHR-DM and prevented by treatment with bosentan+amlodipine and cilazapril. Similarly, these two kinds of therapies in SHR-DM abolished the overexpression of renal TGF-beta1 by Western blot analysis and reduced the accumulation of collagen type IV, laminin and fibronectin proteins by an immunochemical approach. Amlodipine monotherapy had no detectable effects on the above parameters. CONCLUSION: Bosentan combined with amlodipine can offer similar renoprotective effects on that of cilazapril and may be a potent therapy to attenuate renal injury by reducing renal protein levels of TGF-beta1 in diabetes with a hypertensive state.

Amlodipine↗
PubMed2003

Hyperkalemia induced by the calcium channel blocker, benidipine.

A 73-year-old hypertensive, non-diabetic woman without obvious renal dysfunction had frequently been hyperkalemic over four years after receiving antihypertensive drugs including the calcium channel blocker (CCB) benidipine. One week after all medications were accidentally discontinued, the serum potassium level returned to normal. After we obtained the informed consent of the patient, benidipine alone was administered again for over two weeks and hyperkalemia developed once more. This previously uncommon side effect of hyperkalemia induced by benidipine is not very serious but it is apt to be overlooked. Since CCBs are now widely prescribed, the development of hyperkalemia should be considered.

Aged↗
PubMed1995

The dihydropyridine calcium channel blocker BAY t 7207 attenuates the exercise induced increase in plasma ANF and cyclic GMP in patients with mildly impaired left ventricular function.

In man, chronic antihypertensive calcium antagonist treatment improves cardiac function and reduces plasma ANF concentrations. Physical exercise increases cardiac workload and plasma ANF levels. In the present study, we investigated the effects of acute administration of the dihydropyridine calcium antagonist BAY t 7207 (BAY) during bicycle exercise on plasma ANF and plasma cyclic GMP levels, on mean arterial pressure (MAP), heart rate (HR), and on natriuresis and urinary urodilatin excretion. In a randomized, double-blind placebo controlled cross-over trial, 8 patients (age 56.8 +/- 2.5 y) with documented coronary artery disease and mildly impaired left ventricular function (EF 50.0 +/- 1.3%), received oral BAY (20 mg) or placebo. Forty-five minutes after medication, patients underwent a standardised exercise bicycle test in the supine position (6 min 25 W, 6 min 50 W). Before exercise, MAP was lower after BAY (88.8 +/- 4.1 mmHg) than after placebo (95.7 +/- 3.5 mmHg; p = 0.024), and HR was higher after BAY (76.8 +/- 3.5 bpm) than after placebo (69.5 +/- 3.6 bpm; p = 0.049). Plasma ANF tended to be higher after BAY (31.2 +/- 5.6 pg/ml) than after placebo (26.7 +/- 5.0 pg/ml), and plasma cGMP was not different (BAY 3.4 +/- 0.3, placebo 3.8 +/- 0.3 pmol/ml). During exercise, the relative increases in HR (+43%) and MAP (+17%) were identical after BAY and placebo. In contrast, ANF levels during exercise increased by 130 +/- 28% after placebo but only by 36 +/- 11% after BAY (p = 0.011). In parallel, plasma cyclic GMP increased by 61 +/- 13% after placebo and by 20 +/- 8% after BAY (p = 0.013). At the end of exercise, the BAY-induced reduction in plasma cyclic GMP reflected the reduction in diastolic arterial pressure (r = 0.717; p = 0.045). Compared to placebo, BAY treatment increased the fractional excretion rate of sodium from 0.46 +/- 0.11 to 0.90 +/- 0.22% (p = 0.016), without relation to urinary urodilatin excretion. Thus, the calcium antagonist BAY t 7207 attenuated the exercise-induced increase in plasma ANF and cyclic GMP probably due to its vasodilator effect. The relationship between blood pressure and the ANF system during exercise, which parallels findings during chronic antihypertensive treatment, may open a perspective for early evaluation of long-term therapy with calcium channel blockers.

Atrial Natriuretic Factor↗
PubMed1995

Isradipine, a calcium channel blocker, attenuates the ischemia-induced release of dopamine but not glutamate in rats.

This study was designed to investigate the role of the L-type voltage sensitive calcium channel blocker, isradipine, in the ischemia-induced release of neurotransmitters. Male spontaneously hypertensive rats were subjected to cerebral ischemia for 60 min by bilateral carotid artery occlusion, and recirculated for 120 min. Isradipine (0.25 mg/kg n = 6) or vehicle (n = 6) was administered subcutaneously at 20 min before ischemia. In the striatum, cerebral blood flow was determined by the hydrogen clearance method and concentrations of extracellular dopamine and glutamate were measured by in vivo brain dialysis technique. Extracellular dopamine in the vehicle-treated group increased by 180-fold from the basal level, and glutamate by 24-fold during cerebral ischemia. Isradipine significantly attenuated the ischemic release of dopamine to 33-34% (P < 0.05) of the vehicle group, while it did not affect glutamate release. It is suggested that the release mechanism of dopamine and glutamate during cerebral ischemia may be different, especially in the dependence on the L-type calcium channels.

Animals↗
PubMed2005

Calcium channel blocker versus angiotensin II receptor blocker in autosomal dominant polycystic kidney disease.

BACKGROUND: Although hypertension is commonly found in patients with autosomal dominant polycystic kidney disease (ADPKD), there is no consensus about which antihypertensive agents are most appropriate. The effects of calcium channel blockers (CCB) and angiotensin II receptor blockers (ARB) on blood pressure and renoprotection were compared in hypertensive patients with ADPKD. METHODS: We randomly assigned 49 participants to CCB amlodipine-based (2.5-10 mg/day) or ARB candesartan-based (2-8 mg/day) regimens. Twenty-five patients (13 males and 12 females) received amlodipine, and 24 patients (13 males and 11 females) received candesartan. This was followed up for 36 months. RESULTS: Baseline characteristics were similar, and blood pressure was well controlled in both groups throughout the study period. Six out of 25 (24.0%) amlodipine and 1 out of 24 (4.2%) candesartan patients were terminated from the protocol due to a twofold increase in serum creatinine and/or decrease in creatinine clearance (Ccr) to half of the baseline. The renal event-free survival rate was significant (p < 0.05, Breslow-Gehan-Wilcoxon test). Serum creatinine was higher in the amlodipine group than in the candesartan group at 24 and 36 months (p < 0.05). The decrease in Ccr at 36 months was larger in the amlodipine group than in the candesartan group (DeltaCcr: -20.9 +/- 13.1 vs. -4.8 +/- 13.8 ml/min, p < 0.01). Urinary protein excretion was significantly lower in the candesartan group than in the amlodipine group at 36 months. Urinary albumin excretion was significantly lower in the candesartan group than in the amlodipine group at 12, 24 and 36 months. CONCLUSIONS: The renoprotective effect of candesartan is considered more favorable than amlodipine in the treatment of ADPKD. This is independent of the antihypertensive effect per se.

Adult↗
PubMedDate not supplied

Effect of the calcium channel blocker nilvadipine on urinary albumin excretion in hypertensive microalbuminuric patients with non-insulin-dependent diabetes mellitus.

A 24-week study was conducted to evaluate the effects of the dihydropyridine calcium channel blocker nilvadipine on urinary albumin excretion in eight microalbuminuric hypertensive patients with non-insulin-dependent (type II) diabetes mellitus. Blood pressure and urinary albumin excretion measurements before the administration of nilvadipine (8 mg) were compared with those after 4, 8, 12 and 24 weeks of treatment. No significant changes were observed in the mean values of haemoglobin A1C. Systolic blood pressure was significantly reduced from 174 +/- 23 mmHg before treatment to 144 +/- 13 mmHg after 24 weeks of treatment (P < 0.02). Diastolic blood pressure was significantly reduced from 93 +/- 11 mmHg at baseline to 79 +/- 8 mmHg after 24 weeks of treatment (P < 0.05). Urinary albumin excretion was significantly reduced from 65.4 +/- 37.4 mg/g creatinine at baseline to 51.6 +/- 41.1 mg/g creatinine (P < 0.05) after 4 weeks, and to 39.1 +/- 26.9 mg/g creatinine (P < 0.02) after 24 weeks of treatment. These data suggest that in hypertensive microalbuminuric patients with non-insulin-dependent diabetes mellitus, treatment of hypertension with the calcium blocker nilvadipine may slow the progression of diabetic nephropathy.

Aged↗
PubMed1989

Prevention of radiocontrast-media-induced nephrotoxicity by the calcium channel blocker nitrendipine: a prospective randomised clinical trial.

Despite the development of new non-ionic low-osmolality contrast media, nephrotoxicity of intravascular radio-opaque contrast media remains a severe clinical problem, particularly in patients with risk factors. Widely accepted mechanisms of contrast-media-induced nephrotoxicity are disturbances of renal microcirculation due to prolonged intrarenal vasoconstriction, and direct damaging effects on glomerular and tubular cells. Calcium channel blocking agents have been shown experimentally and clinically to ameliorate ischaemic and toxic renal injury. In the present prospectively randomised, double-blind clinical trial, we investigated a total of 35 patients after intravascular administration of contrast media to determine the effects on renal function of a 3-day treatment with the calcium channel blocker nitrendipine (20 mg/day orally, starting 1 day before X-ray examination, n = 16), compared to findings in a placebo-treated control group (n = 19). Despite the fact that baseline renal function was significantly more compromised in the investigational group, the prophylactic application of nitrendipine preserved the glomerular filtration rate, whereas control patients showed a significant (27%) reduction in GFR on day 2 after contrast-media injection (P less than or equal to 0.01). Moreover, the increase in enzymuria of three different renal enzymes (gamma-GT, AAP, and beta-NAG), as well as urinary protein excretion, was significantly ameliorated by nitrendipine. These data confirm previous findings of our group in patients after kidney transplantation, indicating that prophylactic and/or therapeutic application of calcium channel blockers is of substantial value in preventing ischaemic or toxic renal injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Contrast Media↗
PubMed1998

Renal effects of the calcium channel blocker aranidipine and its active metabolite in anesthetized dogs and conscious spontaneously hypertensive rats.

The purpose of this study was to investigate the renal effects of aranidipine, a novel calcium channel blocker of the dihydropyridine type, and its active metabolite in anesthetized dogs and conscious spontaneously hypertensive rats (SHRs). When infused into the renal artery in anesthetized dogs, aranidipine (0.03 microg/kg/min) induced sustained increases in urine volume and urinary excretion of sodium and of potassium. This effect was greater than that elicited by nifedipine (0.1 microg/kg/min). The aranidipine metabolite, M-1 (0.1 microg/kg/min), also caused diuresis and natriuresis almost equal to those of nifedipine. The stop-flow experiment using the anesthetized dog showed that intrarenal infusion of aranidipine (0.03 microg/kg/min), as well as nifedipine (0.1 microg/kg/min), produced natriuresis at the distal tubular site rather than at the proximal site. Aranidipine (0.3, 1, and 3 mg/kg), when administered orally, dose-dependently increased urine volume and urinary excretion of electrolytes in conscious saline-loaded SHRs. M-1 (10 mg/kg, p.o.) also showed diuretic and natriuretic effects comparable to those of nifedipine (10 mg/kg) in SHRs. In addition, after repeated oral administration of aranidipine for 7 days, short-term tolerance was not found for its diuretic and natriuretic effects in SHRs. These results suggest that, apart from antihypertensive efficiency, aranidipine may offer a therapeutic advantage by producing diuresis and natriuresis in hypertensive patients. The metabolite of aranidipine may contribute, in part, to the diuretic, natriuretic, and antihypertensive effects of aranidipine.

Administration, Oral↗
PubMed2000

Improving effects of topical administration of iganidipine, a new calcium channel blocker, on the impaired visual evoked potential after endothelin-1 injection into the vitreous body of rabbits.

PURPOSE: To investigate the effect of topical iganidipine, a new dihydropyridine derivative calcium channel blocker, on impairment of the ocular circulation caused by endothelin-1 (ET-1), we examined modification of the effect of ET-1 on visual-evoked potential (VEP) in albino rabbits. METHODS: To clarify whether VEP could be used to indicate the extent of ocular circulatory impairment, we evaluated the dose dependency of changes in VEP over 2 hours after intravitreal injection of 3 ET-1 doses (1.0, 3.3, or 10 pmol) and the vehicle. Then modification of the effect of ET-1 on the VEP by iganidipine was examined. One hour after the topical instillation of 0.1% iganidipine (20 microl) or its vehicle, 10 pmol of ET-1 was injected into the vitreous in rabbits. The VEP was measured for 2 hours after ET-1 application, and the response was compared between the eyes with iganidipine and vehicle pretreatment. RESULTS: Intravitreal injection of ET-1 dose-dependently reduced the VEP amplitude. Topical administration of 0.1% iganidipine significantly suppressed the reduction of VEP amplitude for the entire 2-hour monitoring period after intravitreal injection of 10 pmol ET-1. There was no significant change of the systemic blood pressure as well as intraocular pressure after topical administration of iganidipine. CONCLUSIONS: Iganidipine eyedrops may be useful for the treatment of ischemic retinal and optic nerve disorders related to abnormal ET-1 production for the maintenance of visual function.

Administration, Topical↗
PubMed2000

Angiotensin-converting enzyme inhibitors, calcium channel blockers, and breast cancer.

BACKGROUND: The use of angiotensin-converting enzyme (ACE) inhibitors has been linked to a decreased risk of developing cancer, and longer-term use of calcium channel blockers (CCBs) has been associated with an increased risk of developing cancer in general and breast cancer in particular. METHODS: Using data from the General Practice Research Database, we conducted a large case-control analysis. Previous exposure to ACE inhibitors, CCBs, and beta-blockers was compared between 3706 postmenopausal women who were diagnosed with incident breast cancer between 1992 and 1997 and 14155 matched-control women. RESULTS: Compared with nonusers of antihypertensive drugs, women who used ACE inhibitors (odds ratio [OR], 1.0; 95% confidence interval [CI], 0.7-1.5), CCBs (OR, 0.9; 95% CI, 0.7-1.2), or beta-blockers (OR, 1.0; 95% CI, 0.8-1.2) for 5 or more years were not at an increased or decreased risk of developing breast cancer (adjusted for smoking and body mass index [calculated as weight in kilograms divided by the square of height in meters]). The risk of breast cancer did not differ between users of different ACE inhibitors or different CCBs (dihydropyridines, diltiazem hydrochloride, and verapamil hydrochloride) or between users of short-acting (OR, 1.0; 95% CI, 0.7-1.4) or sustained-release (OR, 1.0; 95% CI, 0.8-1.3) nifedipine preparations. CONCLUSION: The findings of this large case-control analysis do not support the hypothesis that longer-term use of ACE inhibitors or CCBs affects the risk of developing breast cancer.

Adrenergic beta-Antagonists↗
PubMed2003

Clinical trial experience around the globe: focus on calcium-channel blockers.

Although certain classes of drugs appear to possess benefits apart from their blood-pressure lowering capability, reduction of blood pressure remains the single most important action of antihypertensive therapy. Calcium-channel blockers (CCBs) have long been recognized as potent agents for hypertension therapy. This is especially true for the prevention of stroke in hypertensive patients as evidenced from the Systolic Hypertension in Europe (Syst-Eur) and Systolic Hypertension in China (Syst-China) trials with a long acting dihydropyridine CCB. The same can be said for beta blockers in patients post myocardial infarction. However, most recent clinical trials have underscored the necessity of multiple drug therapy to achieve the goals of blood pressure reduction coupled with outcomes reduction. For example, the many recent large-scale clinical trials have required an average of three or more agents to achieve goal. Thus, the paradigm for hypertension management has been altered to determine the best treatment regimen rather than the best initial agent. While response rates to individual agents across a wide spectrum of patients vary little, not all drugs are equally suited as companion products. In this article, we discuss the most recent outcome trials with the long acting CCBs alone or in combination with other drugs. The evidence shows that calcium antagonists remain an important part of hypertension management, including in those individuals at risk of cardiac and cerebrovascular events.

Amiloride↗
PubMed2000

Effect of calcium channel blockers on baroreceptor reflex in anaesthetized cats.

The baroreflex-induced changes in heart rate in chloralose anaesthetized and artificially ventilated cats (2.5-4.0 kg) before and after pretreatment with calcium channel blockers (CCBs) were compared. Baroreflex mediated changes in heart rate (HR) were elicited by raising and lowering the systemic blood pressure with intravenous injections of phenylephrine and sodium nitroprusside, respectively. The effects of three CCBs, verapamil, diltiazem and nifedipine administered either intravenously (i.v.) or intracisternally (i.c.) were studied. Verapamil administration markedly inhibited the reflex bradycardia as well as the tachycardia following either i.v. or i.c. administration. Intracisternally, a relatively smaller dose of verapamil produced an effect comparable in magnitude and duration, to a higher i.v. dose. The reflex bradycardia was inhibited following i.v., but not i.c. administration of nifedipine while the reflex tachycardia was not affected significantly by either i.v. or i.c. nifedipine. Intravenous diltiazem did not appear to affect the reflex bradycardia or tachycardia significantly. It is suggested that verapamil administration interacts with central cardiovascular integrating mechanisms to reduce the gain of the baroreflex function. Nifedipine and diltiazem are relatively free from this effect.

Animals↗
PubMed1998

Calcium channel blockers attenuate cardiovascular responses to tracheal extubation in hypertensive patients.

PURPOSE: Hypertensive patients exhibit exaggerated cardiovascular responses to tracheal extubation. This study was undertaken to examine the inhibitory effects of calcium channel blockers, nicardipine and diltiazem, on haemodynamic changes after tracheal extubation. METHODS: Sixty hypertensive patients (ASA physical status II) undergoing elective orthopaedic (upper and lower extremity) surgery received, in a randomized, double-blind manner, 30 micrograms.kg-1 nicardipine, 0.2 mg.kg-1 diltiazem or saline (as a control) (n = 20 of each) i.v. before tracheal extubation. Changes in heart rate (HR), mean arterial pressure (MAP) and rate-pressure product (RPP) were measured before and after tracheal extubation. RESULTS: The HR, MAP and RPP increased after tracheal extubation in the control group (P < 0.05). The increases in these haemodynamic variables were attenuated with nicardipine or diltiazem. The inhibitory effects of diltiazem on these cardiovascular responses to tracheal extubation were greater than those of nicardipine (HR; 86 +/- 7 vs 101 +/- 10, RPP; 11,437 +/- 1,575 vs 14,675 +/- 2,874, mean +/- SD, P < 0.05). CONCLUSION: Compared with nicardipine, administration of diltiazem produced greater attenuating the circulatory responses to tracheal extubation in hypertensive patients.

Adult↗
PubMed2002

A spectroscopic investigation of hydrogen bond patterns in crystalline and amorphous phases in dihydropyridine calcium channel blockers.

PURPOSE: To gain insight into the molecular structure of amorphous compounds by investigating hydrogen bonding patterns and strength in a series of structurally related compounds. Seven 1,4-dihydropyridine calcium channel blockers were evaluated. METHODS: FT-Raman and FT-infrared spectra of the compounds in the crystalline and amorphous states were obtained. RESULTS: For crystalline compounds, the position of the NH vibration varied considerably. indicating that the strength of hydrogen bonding differs between the different compounds in agreement with published single crystal X-ray data. For the amorphous phases, the NH vibration occurred at approximately the same position for all compounds, suggesting a uniform average hydrogen bonding strength. Somewhat surprisingly, for some compounds, the average hydrogen bond strength in the amorphous state was found to be greater than in the crystalline compound, although for others, it was weaker as anticipated. Hydrogen bonding patterns (acceptor group) varied between the crystalline compounds, but were remarkably consistent in the amorphous compounds; thus the acceptor group in the amorphous phase is not necessarily the same as in the crystalline counterpart. CONCLUSIONS: Hydrogen bond patterns and strength within a group of chemically related amorphous compounds were found to be very similar, but were different from those in the equivalent group of crystalline substances.

Calcium Channel Blockers↗