Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From a hemodynamic point of view, the calcium antagonists represent an interesting way of treating hypertension, because they reduce total peripheral resistance without compromising cardiac output. Blood flow is also maintained during muscular exercise. Verapamil and diltiazem induce slight reduction in heart rate, but this is compensated by increase in stroke volume. Verapamil and diltiazem also prolong atrioventricular conduction time, in contrast to the dihydropyridines. Most clinical data are available for verapamil, diltiazem, and nifedipine. In patients with mild-to-moderate hypertension, these compounds seem as effective as diuretics and beta-blockers. They do not induce disturbances in glucose metabolism, serum uric acid, or serum potassium, and unwanted disturbances in blood lipids have not been described. The dihydropyridines may safely be combined with beta-blockers, but the combination of either verapamil or diltiazem with a beta-blocker should be avoided (because of the high risk of bradycardia). The calcium antagonists seem particularly useful in patients with the combination of hypertension and angina pectoris or peripheral vascular diseases or chronic obstructive lung diseases or diabetes. They are also effective in hypertensive crises. They may also be tried as a first line drug in patients with mild and moderate essential hypertension, particularly when diuretics or beta-blockers are contraindicated. Temporary side effects due to vasodilatation (headache, flushing, and palpitations) are seen frequently, particularly on the dihydropyridines. Edema is the most frequent serious side effect of the dihydropyridines, and constipation is most common with verapamil. At this point, few long-term data are available and it is not known whether the calcium antagonists will give better or worse results, with respect to morbidity and mortality, than the beta-blockers, diuretics, or other more recent antihypertensive agents.
 ...
PMID:Clinical use of calcium antagonists in hypertension: update 1986. 245 35

To clarify the hemodynamic effects of verapamil, we investigated in normal volunteers the effects of 4-day treatment with verapamil (240 mg/day) on left ventricular function and on systemic and brachial artery haemodynamics, in comparison with the effects of placebo and atenolol (100 mg/day). Left ventricular structure and function was evaluated by echocardiography, systemic hemodynamics were assessed by pulsed Doppler velocimetry of the ascending aorta, and brachial artery hemodynamics were assessed pulsed Doppler velocimetry of the brachial artery. Verapamil decreased systemic and brachial artery vascular resistance (p less than 0.05), increased cardiac output (CO, p less than 0.01) and brachial flow (p = 0.054), and did not affect blood pressure (BP) and heart rate (HR). In contrast, atenolol decreased BP, HR, and CO (p less than 0.001) but did not significantly affect brachial flow and systemic and brachial artery vascular resistance. We conclude that short-term administration of verapamil in normal humans produces systemic and brachial artery vasodilatation, with a reflex increase of stroke volume but not of HR.
 ...
PMID:Effect of verapamil on systemic and brachial artery hemodynamics in normal humans: comparison with effect of atenolol. 247 79

The hemodynamic effects of intravenous class I and class IV antiarrhythmic drugs were investigated at different doses in comparison. In open-chest rats hemodynamic measurements in the intact circulation and isovolumic registrations 5 min after infusion of flecainide (2, 4, 8 mg/kg), disopyramide (1, 2, 4, 8 mg/kg), quinidine (5 and 10 mg/kg) and verapamil (0.35, 0.7, 1.5 mg/kg) were compared to saline controls. After clinically usual doses all investigated drugs had no effects on stroke volume, cardiac output, dp/dtmax and systemic resistance. The isovolumic pressure generating capacity of the left ventricle was not decreased at these doses. High intravenous doses of the drugs, however, caused a significant depression of myocardial performance (pressure generating capacity). Furthermore, flecainide decreased mean aortic pressure and heart rate, while disopyramide had no significant effect on the peripheral circulation. Blocking of the autonomic system (1 mg/kg propranolol and 0.1 mg/kg atropine) did not change significantly the action of disopyramide. Quinidine lowered heart rate and pressures. Verapamil reduced the heart rate and tended to decrease the mean aortic pressure. Besides the negative inotropic action of high doses the different hemodynamic profiles of class I and class IV antiarrhythmic drugs might be of importance for intravenous application in patients with left ventricular dysfunction.
 ...
PMID:Circulatory and myocardial effects of different sodium antagonistic drugs in comparison to the calcium antagonist verapamil. 251 61

Comparative haemodynamic investigations with carvedilol and verapamil were carried out on conscious, instrumented dogs. Arterial blood pressure, right atrial pressure (RAP), cardiac output (CO), heart rate, stroke volume and total peripheral resistance (TPR) were determined after intravenous (i.v.) injection of incremental doses (0.01-3 mg/kg) of the drugs. Carvedilol reduced the blood pressure in a dose-dependent manner, concomitant with a reduction in TPR. The RAP and the CO were not affected, indicating that arterial vasodilatation was induced by carvedilol. Verapamil showed a decrease in the blood pressure with a reduction of CO and SV. Moreover, at high doses the RAP was increased, indicating a reduction of the cardiac performance. Thus, in our experimental model remarkable differences between the haemodynamic effects of i.v. injections of carvedilol and verapamil have been observed, whereas after oral administration blood pressure also decreases after verapamil due to a reduction of TPR.
 ...
PMID:Comparison of the haemodynamic profiles of the hypotensive action of verapamil and carvedilol. 285 3

The treatment of verapamil toxicity was examined in lightly sedated dogs. Verapamil, administered as a bolus (0.72 mg/kg) followed by a continuous infusion (0.11 mg/kg per min), decreased cardiac output (CO) from 3.1 +/- 0.1 to 1.7 +/- 0.1 liter/min (P less than 0.001), heart rate (HR) from 85 +/- 4 to 57 +/- 3 beats/min (P less than 0.001), left ventricular derivative of pressure with respect to time (LV dP/dt) from 2,085 +/- 828 to 783 +/- 78 mm Hg/s (P less than 0.001), mean aortic pressure (AO) from 77 +/- 4 to 38 +/- 2 mm Hg (P less than 0.001) and stroke volume from 39 +/- 3 to 28 +/- 2 ml/beat (P less than 0.01). In verapamil-toxic animals isoproterenol increased HR, CO, LV dP/dt, and AO; calcium chloride increased LV dP/dt and AO; norepinephrine, epinephrine, and dopamine increased CO, AO, and LV dP/dt, atropine increased HR, CO, and AO. Phenylephrine (13-55 micrograms/kg per min) produced no changes except a small increase in AO while very high dose phenylephrine (300 micrograms/kg per min) increased AO, CO, and LV dP/dt. 4-Aminopyridine (4-AP) increased HR, CO, LV dP/dt, and AO. When administered prior to verapamil, 4-AP prevented the development of verapamil toxicity as shown by the significantly higher AO (P less than 0.001), CO (P less than 0.01), and LV dP/dt (P less than 0.01) when 4-AP followed by verapamil was compared to verapamil alone. In conclusion, there does not appear to be a single specific therapy for verapamil toxicity, however it can be partially corrected by presently available pharmacologic therapy and 4-AP.
 ...
PMID:Treatment of verapamil toxicity in intact dogs. 301 61

Ouabain and vanadate are known as potent inhibitors of Na, K-ATPase in various tissues including smooth muscles. Both agents showed contractile action on various smooth muscles in a similar fashion: stronger contractile action on the aortae of rats (WKY and stroke prone spontaneously hypertensive rats, SHRSP) and guinea-pigs, and weaker contractile actions on basilar and mesenteric arteries of the same animals. Time to peak tension, however, was far longer in ouabain-induced contraction. Phentolamine depressed ouabain-induced contractions, while vanadate-induced contractions were not affected. Elevation of K+ concentration to 20 or 30 mM potentiated vanadate-induced contraction markely, while it potentiated ouabain-induced contraction only slightly. DIDS blocked vanadate-induced contraction but showed no effect on ouabain-induced contraction. Removal of Ca abolished ouabain-induced contractions, while vanadate-induced contractions of reduced height could be observed in the absence of Ca. Verapamil depressed both ouabain- and vanadate-induced contractions of WKY and SHRSP aorte aut exhibited no effect on the guinea-pig aorta. Thus, although similarities of the action of ouabain and sodium vanadate were observed, the modes of the actions were revealed to be different in the two agents. Inhibition of Na, K-ATPase might be involved in the case of ouabain-induced contractions, and inhibition of Ca-ATPase of membranous systems might be involved in vanadate-induced contraction.
 ...
PMID:Comparison of contractile effects of sodium vanadate and ouabain in vascular smooth muscles of guinea-pigs and rats. 303 52

The effects of extracellular Ca and Ca antagonists on vanadate-induced contractions of vascular smooth muscles of aortae and mesenteric arteries from rabbits, guinea pigs, and Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) were studied. Vanadate-induced contractions of aortae were greatly diminished by extracellular Ca removal; the size of the remaining contraction was variable. Vanadate-induced contractions of mesenteric arteries, which were only observed in the presence of elevated K, were suppressed by the removal of Ca. Verapamil and nifedipine depressed vanadate-induced contractions of aortae from WKY and SHRSP, whereas they produced no or only slight inhibition of responses in guinea pig and rabbit aortae. Ca uptake into smooth muscle cell increased in the presence of vanadate, but the increase was much less than that induced by high K. In saponin-skinned smooth muscle, vanadate depressed the Ca-induced contraction. It is concluded that the vanadate-induced contraction utilizes both extracellular and intracellularly bound Ca, the relative contribution of which varies from preparation to preparation.
 ...
PMID:Extra- and intracellular calcium in vanadate-induced contraction of vascular smooth muscle. 318 65

Verapamil (1 mg/kg, i.v.) and nifedipine (0.3 mg/kg, i.v.) were tested at equi-antihypertensive doses for systemic hemodynamic responses in conscious spontaneously hypertensive rats (SHR) using the Fick method. Systemic hemodynamic effects of these agents were also evaluated in areflexic, spinal cord-transected and vagotomized SHR using the electromagnetic flowmetry technique. Both verapamil and nifedipine lowered mean arterial pressure (MAP:verapamil = -24%; nifedipine = -28%) in conscious SHR by decreasing total peripheral resistance (TPR:verapamil = -48%; nifedipine = -59%) with a concomitant rise in cardiac output (CO: verapamil = 48%; nifedipine = 86%) and stroke volume (SV:verapamil = 54%; nifedipine = 65%), but verapamil prevented tachycardia, whereas nifedipine increased heart rate (HR:13%). Verapamil and nifedipine also altered systemic hemodynamics in the areflexic SHR; verapamil reduced MAP (-31%) by reducing CO (-18%) with associated bradycardia (-25% HR), whereas nifedipine also lowered MAP (-21%) by decreasing TPR (-18%) without changes in CO and HR. It is concluded that, firstly, the antihypertensive action of verapamil and nifedipine in conscious SHR is due to systemic vasodilation that is associated with reflexly increased CO; secondly, that verapamil has a direct negative chronotropic effect, but nifedipine appears to be devoid of such an effect, and finally that the ability of verapamil to decrease TPR may depend upon resting sympathetic tone.
 ...
PMID:Effects of verapamil and nifedipine on systemic hemodynamics in spontaneously hypertensive rats. 322 Oct 97

Left ventricular (LV) intramyocardial markers (MM) were used to study the effects of intravenous verapamil on LV pump function and diastolic filling dynamics. Verapamil (0.1 mg/kg bolus followed by 0.005 mg/kg/min) was administered to 10 patients with severe coronary artery disease 4 years after coronary bypass grafting and implantation of 7 tantalum markers into the LV. MM were filmed at 100 frames/sec (biplane 30 degrees RAO/60 degrees LAO). The digitized biplane MM coordinates were transformed into 3-dimensional coordinates and maximal projection area was defined. LV volumes were calculated frame-by-frame and ejection fraction and peak filling rate derived. Pressure-volume relations were calculated in early-, mid-, and end-diastole. Verapamil caused a slight rise in end-diastolic pressure (12 to 14 mmHg, p less than 0.001) and end-diastolic volume (142 to 152 ml; p less than 0.005) and a fall in max dP/dt (1732 to 1570 mmHg/s; p less than 0.01) reflecting the drug's negative inotropic action. Verapamil reduced LV systolic pressure (136 to 126 mmHg; p less than 0.01), diastolic aortic pressure (74 to 68 mmHg; p less than 0.001) and peripheral resistance (1496 to 1348 dynes.s.cm-5; p less than 0.025); cardiac index was increased (2.7 to 2.9 l/min/m2; p less than 0.05), as were ejection fraction (47 to 49%; p less than 0.02) and stroke volume (67 to 75 ml; p less than 0.001). Great cardiac vein flow increased as well (88 to 102 ml/min; p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of intravenous verapamil on left ventricular systolic function and diastolic filling dynamics in patients with coronary artery disease: analysis of intramyocardial markers. 326 99

This overview presents the pharmacodynamic properties of felodipine as studied in animal experiments with emphasis on results from our laboratory. Felodipine is 100-fold more potent in causing inhibition of spontaneously active vascular smooth muscle than myocardium in vitro. This vascular selectivity is significantly greater than that of nifedipine (potency ratio 15). Verapamil, D-600, La3+ and reduction of [Ca2+]o lack selectivity. The cellular mechanisms underlying this variable selectivity are not clear at present. In conscious spontaneously hypertensive rats (SHR), the plasma concentration required for 20% reduction of mean arterial pressure is approximately 10 nmol. Mean arterial pressure is lowered dose-dependently as a result of reduced peripheral vascular resistance accompanied by increased cardiac output due to transient tachycardia and increased stroke volume. There was rapid resetting of the baroreflex set point but unaltered sensitivity after felodipine and hydralazine in SHR. Therefore, the reflexogenic increase in heart rate and plasma renin activity subsided within 3 to 5 hours of continuous felodipine administration in SHR. In addition, there was a uniform dilatation of the peripheral vascular beds after felodipine administration. During long term treatment of SHR with felodipine, progression of left ventricular and vascular wall hypertrophy was prevented. Within the 'therapeutic dose range', the only primary effect observed in addition to arterial vasodilation is diuresis/natriuresis caused by a renal tubular action.
 ...
PMID:Pharmacodynamic properties of felodipine. 332 82


<< Previous 1 2 3 4 5 6 7 Next >>