Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the potential risk of regional anaesthesia in a verapamil-treated patient, the cardiovascular effects of a combined intravenous infusion of bupivacaine and verapamil were studied in seven conscious and chronically instrumented dogs and were compared to those obtained when each drug was infused separately in the same animals. During verapamil infusion, the decrease in arterial pressure and myocardial contractile force, and the increase in heart rate were constant during the infusion. The lengthening of PR interval correlated with the plasma level of verapamil. During infusion of bupivacaine alone, there was an increase in heart rate and arterial pressure at the end of infusion, whereas the initial depression of myocardial contractile force was compensated. PR interval remained unchanged throughout the infusion of bupivacaine. During combined infusion of bupivacaine and verapamil, there was a time-dependent decrease in heart rate, arterial pressure and myocardial contractile force. A further increase in PR interval correlated with verapamil plasma concentrations which were higher than when verapamil was infused alone; bupivacaine plasma levels were in the same range as during bupivacaine infusion alone. Short periods of second-degree atrioventricular block developed in three out of the seven dogs but no relation was found between QT interval and heart rate in the whole group. Calcium chloride during bupivacaine-verapamil returned heart rate, arterial pressure and myocardial contractile force to their control values within 5 min. Atrioventricular block disappeared and PR interval was shortened following administration of calcium. Bupivacaine and verapamil have additive cardiovascular effects which lead to atrioventricular conduction dysfunction. The effects, at these doses, are reversed by calcium chloride.
 ...
PMID:Bupivacaine accentuates the cardiovascular depressant effects of verapamil in conscious dogs. 365 84

High blood concentrations of local anesthetics are cardiotoxic. The aim of this study was to compare the effects of lidocaine and bupivacaine on the intrinsic pacemaker activity of in vitro sinoatrial nodal cells of the adult and neonatal guinea pig in the presence and absence of hypoxia and acidosis. Fifteen pairs of adult (greater than 80 days old) and neonatal (0-3 days old) hearts were isolated. Nodal tissues were suffused with Krebs-Ringer solution at 37 degrees C and exposed to increasing concentrations of either lidocaine (0.05-0.8 mM) or bupivacaine (0.01-0.4 mM). The suffusate was equilibrated either with 5% CO2, 95% O2 (pH 7.40, PO2 482 torr) or with 12% CO2, 88% N2 (pH 7.01, PO2 58 torr). Transmembrane action potentials were recorded from sinoatrial nodal cells and impulse intervals were converted to rates. We found that hypoxia and acidosis alone reduced rates in both adults and neonates, and that the reduction was additive to the effects of local anesthetics. Bupivacaine was 4-5 times more potent in decreasing rates than was lidocaine in both age groups. Lidocaine was about twice as effective in depressing neonatal rates as adult rates, and bupivacaine caused cessation of pacemaker activity in a greater percentage of nodes than did lidocaine. Our results demonstrate, in vitro, that the neonatal sinoatrial node is more sensitive to lidocaine and bupivacaine than is the adult node, that bupivacaine is more potent in depressing and stopping nodal activity, and that hypoxia and acidosis enhance pacemaker depression caused by these agents.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Comparison of lidocaine and bupivacaine depression of sinoatrial nodal activity during hypoxia and acidosis in adult and neonatal guinea pigs. 374 Apr 90

Bupivacaine without adrenaline was used for paracervical block (PCB) anesthesia in 60 low-risk parturients in whom there were no signs of fetal asphyxia. In order to evaluate its effects on fetus and uterine activity, 30 patients were given a "high dose" of 50 mg Bupivacaine, an amide-type local anesthetic agent, while 30 patients were given a "low dose" of 25 mg. Continuous fetal heart rate (FHR) monitoring in both study groups revealed nine patients with typically post PCB bradycardia and five patients with moderate PHR depression. All of them were born with excellent Apgar score. Although a decrease in fetal heart rate following PCB was noted in both groups more significant reduction was associated with the high dose block (P less than 0.05). In 11 cases, FHR depression was clearly associated with increased uterine activity, while in another three cases it was not (P less than 0.005). Oxytocin administration during the block did not affect fetal heart rate or uterine activity. The results indicate that FHR depression following PCB using Bupivacaine is dose dependent, transient and not dangerous to a normal fetus. No adverse maternal effects were noted. It is suggested that fetal heart rate depression following PCB using Bupivacaine is related to increased uterine activity.
 ...
PMID:Fetal heart rate and uterine activity following paracervical block. 381 37

The authors present a study of 20 cases of epidural obstetrical analgesia. A Bupivacaine-Fentanyl mixture was given by continuous flow to bring about this analgesia. After an initial injection of 10 ml (9 ml of 0.25% Bupivacaine and 0.05 mg Fentanyl), a mixture of 45 ml of 0.25% Bupivacaine and 0.25 mg Fentanyl was perfused into the epidural space using an electronic pump syringe, delivering at a rate of 5 ml/hr. The mean time of analgesia until the delivery is 4 h 40 mn and the women in labour received a mean of 31.14 ml of 0.25% Bupivacaine (77.85 mg) and 0.173 mg Fentanyl. It took only 5 1/2 minutes to set up this form of analgesia. Not a single patient had any pain the first stage of labour nor in the second stage, and 95% of them were able to push efficiently. There are no detectable changes in the haemodynamic parameters in either the mothers or the fetuses and no depression of maternal respiration was found. In each case the Apgar score was 10 after 5 minutes. In summary, the use of an electronic pump syringe to deliver a Bupivacaine-Fentanyl mixture in obstetrical labour is a great improvement in analgesia without any secondary effects in the mother and child.
 ...
PMID:[Peridural obstetrical analgesia using an electronic syringe]. 402 54

The actions of the tertiary local anesthetic bupivacaine were studied on the nicotinic receptor-ionic channel complex (AChR) using electrophysiological and biochemical methods. Voltage clamp studies of the frog sartorius and cutaneous pectoris neuromuscular junction revealed a concentration-dependent depression of the decay time constant of the end-plate (tau EPC) and spontaneous miniature end-plate (tau MEPC) currents. The relationship of the reciprocal of either tau EPC or tau MEPC and bupivacaine concentration up to 100 microM was linear. Voltage dependence of EPC over the range +60 to -150 mV was reduced, whereas both EPC and MEPC decays were adequately described by a single exponential function at all concentrations tested. Peak MEPC and EPC amplitudes were also depressed in a concentration-dependent manner such that 100 microM bupivacaine reduced peak amplitude by about 50%. The current-voltage relationship remained linear under all conditions tested. Nerve-evoked responses were difficult to study at concentrations greater than 100 microM because of apparent blockade of nerve conduction. Extracellular recording of the MEPC afforded results similar to those obtained with EPCs. The tau MEPC could be reduced to less than 300 mu sec at a bupivacaine concentration of 400 microM. Fluctuation analysis showed that bupivacaine at concentrations of 10 and 25 microM did not change channel conductance but decreased single-channel lifetime to 76% and 39% of control values, respectively. Biochemical studies were performed on Torpedo californica membrane fragments using [3H]phencyclidine ([3H]PCP) and [3H]perhydrohistrionicotoxin ([3H]H12-HTX) as channel probes. Bupivacaine inhibited the binding of [3H]PCP and [3H]H12-HTX with inhibition constants (Ki) of 32 and 25 microM, respectively. The corresponding inhibition constants for bupivacaine methiodide were 1.8 and 3.2 microM. The preincubation of the membranes with carbamylcholine increased the affinity of bupivacaine for the ionic channel sites 5- to 8-fold and the affinity of bupivacaine methiodide 3- to 4-fold. Bupivacaine, however, had no affinity for the agonist recognition site as determined by [3H]ACh and [125I]alpha-bungarotoxin bindings. The electrophysiological and biochemical studies indicate that bupivacaine reacts primarily with the ionic channel of the nicotinic AChR. The results are consistent with a sequential model in which the drug interacts with the sites at the ionic channel of AChR in its open conformation, producing species with little or no conductance. From the present studies there is no evidence for an interaction of bupivacaine with the agonist binding site or closed states of AChR.
 ...
PMID:Interactions of bupivacaine with ionic channels of the nicotinic receptor. Electrophysiological and biochemical studies. 609 Aug 84

In an isolated guinea pig atrial preparation, the bathing solution pH, PO2, and PCO2 were manipulated to mimic normal, acidotic, and hypoxic conditions. The effect of lidocaine and bupivacaine on spontaneous heart rate (HR) and contractile force (CF) was determined for 60 min under conditions of normal pH, PO2, and PCO2. Lidocaine (50 micrograms/ml) reduced HR by a maximum of 34.2 +/- 1.5% and CF by 38.9 +/- 8.1% (mean +/- SEM). Bupivacaine (5 micrograms/ml) reduced HR by a maximum of 30.1 +/- 1.9% and CF by 48.0 +/- 6.5%. Bupivacaine (10 micrograms/ml) caused a maximum HR reduction of 61.7 +/- 9.5% and CF reduction of 66.0 +/- 8.6%. Hypoxia or metabolic or respiratory acidosis did not further enhance the local anesthetic induced atrial depression. However, conditions of combined acidosis/hypoxia, while not significantly altering the HR and CF depression caused by lidocaine, did enhance bupivacaine-induced depression of HR and CF (93.6 +/- 6.3% and 95.2 +/- 4.8%, respectively). The effect of a protein-free bathing solution on the relative toxicities of lidocaine and bupivacaine is discussed.
 ...
PMID:Influence of lidocaine and bupivacaine on isolated guinea pig atria in the presence of acidosis and hypoxia. 669 58

To determine the efficacy of epidural morphine during labor and delivery, 40 healthy parturients who requested epidural analgesia were randomly given either a single injection of morphine sulfate (2 mg, n = 9; 5 mg, n = 10; or 7.5 mg, n = 11) or 0.5% bupivacaine (n = 10). Bupivacaine provided excellent analgesia in all patients. Morphine (2 or 5 mg) did not produce adequate analgesia and needed to be supplemented by local anesthesia. Morphine (7.5 mg) gave satisfactory analgesia in 7 of 11 patients until the end of the first stage of labor, and, in an additional patient, for almost 13 hr, at which time cephalopelvic disproportion was diagnosed. In all patients given epidural morphine, local anesthesia was needed for the second stage of labor if instrumentation or episiotomy was required. The only side effect was pruritus, which occurred in three patients. Epidural morphine did not produce neonatal depression, as evidenced by Apgar scores and neurologic and adaptive capacity scores. We conclude that 7.5 mg of epidural morphine can give satisfactory pain relief during labor but not delivery, and that 2 or 5 mg of morphine is ineffective. Although 0.5% bupivacaine provided better anesthesia, epidural morphine might prove useful for selected patients.
 ...
PMID:Maternal and neonatal effects of epidural morphine for labor and delivery. 670 48

The L5 and S1-segments of the spinal cord and relatively resistant to blockade. The extent and depth of the block are usually tested by pinprick. H-reflex depression (Hoffmann 1922, Magladery and McDougal 1950) was used to quantify differences between the 0.5%-solution and the 0.75%-solution of bupivacaine used for epidural anaesthesia. The H-reflex is a monosynaptic reflex representing the excitability of the motorneuron pool of the L5-S1 region of the spinal cord. Our results show a difference between the two concentrations favouring the 0.75% solution. The H-reflex is also a component in the complexity of control and servocircuits that play a role in the well-functioning of the spinal cord. Consequently we used its full recovery to rule out lasting toxic or irritating effects on the spinal cord. Bupivacaine 0.75% is not available in Europe whereas in the USA there is already wide experience in using this concentration. A comparison between 0.75% and 0.5% solutions reveals two important advantages in favour of the 0.75% solution: A higher intensity of motorblock [4, 15]. A lower incidence of incomplete blockade of the most resistant segments (L5-S1) [7, 8].
 ...
PMID:Effect of epidural administration of bupivacaine (Marcaine) on monosynaptic reflex-depression. 730 10

The effects of bupivacaine on Na+ and Ca2+ currents in single canine isolated left ventricular cells were examined using whole-cell voltage clamp technique to reveal the mechanism of its negative inotropism. The cells were isolated by enzymatic dispersion and superfused in an oxygenated Tyrode's solution. Bupivacaine 10(-6) M decreased the amplitude of INa and delayed the peak time. These effects were dose and frequency dependent. At a concentration of 10(-3) M, bupivacaine abolished INa. Meanwhile, bupivacaine did not modify ICa at a concentration of 10(-6) M. At 10(-5) M bupivacaine, the amplitude of ICa was depressed by 22% and the depression was dose dependent. These results suggest that low concentration (10(-6) M) of bupivacaine depresses contraction, by reducing intracellular Ca2+ secondary to reduction in intracellular Na+ activity and the Na+-Ca2+ exchange mechanism. At higher concentrations, the reduction in contraction caused by bupivacaine may result partly from a reduced influx of Ca2+.
 ...
PMID:[Effects of bupivacaine on Na+ and Ca2+ currents in single canine ventricular cells]. 773 90

Bupivacaine is clinically associated with cardiovascular toxicity. To examine the possible role of drug actions at arterial baroreceptors, we studied discharge properties of baroreceptors in an in vitro aortic nerve-aortic arch preparation from rats. We measured single fiber discharge, pressure, and aortic diameter simultaneously during perfusion of the aortic arch with bupivacaine. Perfusion mean arterial pressure was held at 80 mm Hg. Only regularly discharging, presumably myelinated, baroreceptors were studied. To assess pressure threshold, threshold frequency, and maximum discharge rate, nerve activity was evoked by slow ramps of increasing pressure (< 2 mm Hg/s) beginning at 20 mm Hg and ranging up to 150-170 mm Hg. Following replicate control measurements, test ramps were repeated in the presence of sodium nitroprusside (1 microM) and phentolamine (1 microM) to eliminate potential smooth muscle and alpha 1-adrenoceptor effects, respectively. Bupivacaine was then added to the perfusate in increasing concentrations from 0.1 to 50 microM for 15 min to construct a full concentration-response curve at each level. Individual baroreceptors showed substantial depression of maximum discharge frequency and/or increases in pressure threshold at 1-5 microM bupivacaine. In overall population averages (n = 7), 5-10 microM bupivacaine clearly reduced maximum discharge and shifted the pressure threshold to higher values (P < 0.01). The net result was a general depression of discharge. Concentrations as low as 10 microM bupivacaine completely blocked discharge in some baroreceptors. Inasmuch as the pressure-diameter relations were not changed, discharge relations plotted against diameter showed equivalent changes. Bupivacaine-free solution reversed the block in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Clinically relevant concentrations of bupivacaine inhibit rat aortic baroreceptors. 810 68


<< Previous 1 2 3 4 5 Next >>