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S Agoston

Publications and source records attributed to S Agoston.

At least 19 recordsLinked to original sources
PubMed1992

Suramin reverses non-depolarizing neuromuscular blockade in rat diaphragm.

Unexpectedly, it was observed that the P2-purinoceptor antagonist, suramin (10 microM to 1 mM), reversed the muscle paralysis caused by structurally unrelated non-depolarizing relaxants. Suramin competitively reversed the blocking action of pancuronium. Both the pre- and postsynaptic blockade of nicotinic receptors by pancuronium was counteracted, as shown by the action of suramin, using train-of-four stimulation. Suramin did not affect the paralysis caused by the depolarizing relaxant, succinylcholine. The reversal action of suramin was not due to an increase in the acetylcholine concentration in the synaptic cleft, since neither the contraction of preparations partially paralysed by diminished acetylcholine release in the presence of low Ca2+ or high Mg2+ nor acetylcholinesterase activity were affected. Suramin did not affect the reduction in twitch tension caused by adenosine and potentiated the ATP-induced reduction in twitch, indicating that ATP-sensitive receptors are not involved in the reversal action of suramin. Consequently, these results suggest that the action of suramin is due to binding with a site on the acetylcholine receptor also occupied by non-depolarizing relaxants, but different from the site occupied by succinylcholine.

Acetylcholine↗
PubMed1992

Porcine model for studying the passage of non-depolarizing neuromuscular blockers through the blood-brain barrier.

A method has been developed for blood-brain barrier disruption to provide reproducible access to the cerebrospinal fluid of the cerebello-medullary cistern. The technique was used successfully to investigate transfer of pancuronium to the cerebral CSF compartment in pigs. After osmotic disruption of the blood-brain barrier, pancuronium concentrations increased significantly in the cerebrospinal fluid.

Animals↗
PubMed1992

Atracurium-induced neuromuscular block in the isolated arm.

A modification of the isolated arm technique was applied in 10 females under opioid-based i.v. anaesthesia for comparison of the offset of an atracurium-induced neuromuscular block in an isolated arm to an arm with maintained circulation. The neuromuscular blocking effect of a bolus dose of atracurium 0.5 mg.kg-1 was measured bilaterally using the integrated adductor pollicis EMG response (integrated T1 EMG response in % of baseline value and T4/T1 ratio) after bilateral ulnar nerve train-of-four (TOF) stimulation. At 10% T1 recovery, one arm was isolated from the general circulation for 20 min by means of a tourniquet cuff (isolated arm), while normal circulation was maintained in the other arm (control arm). In both arms, the TOF response, peripheral skin temperature, mixed peripheral venous pH and plasma concentrations of atracurium and laudanosine were then measured and compared. Core and peripheral skin temperatures in both arms remained stable and normal throughout the study, and mixed peripheral venous pH stayed within physiological limits in both arms in all subjects. In the isolated arm, recovery of the neuromuscular block was markedly delayed compared to the control arm, the integrated EMG T1 response and TOF ratio being significantly reduced in the isolated arm after 20 min of isolation. The decline in plasma concentration of atracurium was less in the isolated arm than in the control arm, whereas laudanosine levels increased in the isolated and decreased in the control arm. Normal peripheral circulation is of major importance for termination of an atracurium-induced neuromuscular block.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia Recovery Period↗
PubMed1979

Stimulation of phrenic nerve activity by an acetylcholine releasing drug: 4-aminopyridine.

The effect of the acetylcholine releaser 4-aminopyridine on ventilation was studied by recording and quantifying the efferent phrenic nerve activity in 40 paralysed and vagotomized cats; with arterial Po2, PCO2 and pH kept constant. 4-Aminopyridine, given intravenously or in the vertebral artery, stimulates the phrenic nerve activity in a dose dependent manner. The stimulatory effects of 4-aminopyridine on the phrenic nerve activity could be abolished completely by administration of high doses of atropine. We conclude that 4-aminopyridine, which is used clinically for the reversal of a neuromuscular block, stimulates the phrenic nerve activity. Since the role of cholinergic mechanisms in the central chemoreception has been well established, the effect on the phrenic nerve activity is most probably by an increased release of acetylcholine at the site of the central chemoreceptors.

Aminopyrine↗
PubMed1979

Prolongation by bile salts of the duration of action of a steroidal neuromuscular blocking agent.

The influence of bile salts on the duration of action of the steroidal non-depolarizing neuromuscular blocking agent ORG 6368 was investigated in cats. The intravenous administration of ORG 6368 (100 microgram/kg body wt) caused a maximum neuromuscular blockade of 71 +/- 6% with a duration of action of 3.4 +/- 0.1 min. However, intraportal administration of the same dose caused no significant neuromuscular blockade. Following an infusion of dehydrocholate 320 mumol, lasting for 8 min, the magnitude and the duration of action of the neuromuscular blockade produced by ORG 6368 were increased markedly. This effect of the bile salt is possibly a result of inhibition of the hepatic uptake of ORG 6368, thereby retarding its disappearance from the plasma and consequently prolonging the neuromuscular blockade. The neuromuscular blocking effect of intraportally administered gallamine (1 mg/kg body wt) was not influenced significantly by the infusion of dehydrocholate.

Animals↗
PubMed1979

4-Aminopyridine potentiates neostigmine and pyridostigmine in man.

To elucidate the interaction of 4-aminopyridine with neostigmine and pyridostigmine, the authors studied 57 anesthetized surgical patients using a technique of constant infusion of pancuronium to quantitate antagonist activity. 4-Aminopyridine, 0.15 or 0.35 mg/kg, produced no antagonism, while 0.5 mg/kg produced a mean 24 +/- 6 per cent (peak) antagonism. The dose that produced 50 per cent antagonism (ED50) of neostigmine alone was 22 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 7 micrograms/kg. The ED50 of pyridostigmine alone was 110 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 27 micrograms/kg. 4-Aminopyridine prolonged the onset times of both neostigmine and pyridostigmine, but prolonged the duration of action of neostigmine only. At a given level of antagonism of pancuronium, adding 4-aminopyridine 0.35 mg/kg, to neostigmine and to pyridostigmine decreased the amounts of atropine needed to prevent a change in heart rate by 68 and 70 per cent, respectively. The authors conclude that 4-aminopyridine potentiates antagonism of a pancuronium-induced neuromuscular blockade by neostigmine or pyridostigmine. Also, less atropine is needed to prevent cardiac muscarinic stimulation when 4-aminopyridine is used with either neostigmine or pyridostigmine.

Adult↗
PubMed1979

Plasma concentrations of pancuronium and neuromuscular blockade after injection into the isolated arm, bolus injection, and continuous infusion.

To establish whether the plasma concentration of pancuronium reflects magnitude of neuromuscular blockade, the authors determined times of recovery from neuromuscular blockade and associated plasma concentrations following equipotent doses of pancuronium using three methods of pancuronium administration: the isolated-arm technique in conscious volunteers (n = 4), and the bolus intravenous injection (n = 7) and continuous-infusion methods (n = 3) in anesthetized patients. Although maximum depressions of twitch tension were similar (85 +/- 11,91 +/- 6, and 92 +/- 4 per cent, respectively) with the three techniques, times to recovery from neuromuscular blockade differed significantly, being 10 +/- 2 min with the isolated-arm technique, 23 +/- 7 min with the bolus-injection technique, and 46 +/- 5 min with the continuous-infusion method. The plasma concentration of pancuronium necessary for neuromuscular blockade was least with the isolated-arm technique and greatest with continuous infusion. At 25 and 75 per cent recovery, mean plasma concentrations were 0.07 +/- 0.01 and 0.04 +/- 0.01 microgram/ml in the isolated arm; 0.13 +/- 0.04 and 0.09 +/- 0.02 microgram/ml after bolus injection, and 0.20 +/- 0.04 and 0.11 microgram/ml during continuous infusion, respectively. It is concluded that the relationship between plasma concentration of pancuronium and magnitude of neuromuscular blockade depends on the method of pancuronium administration.

Humans↗
PubMed1979

Effect of different anesthetics on the pharmacokinetics and pharmacodynamics of pancuronium in the cat.

To investigate the effect of different anesthetics on the pharmacokinetics and pharmacodynamics of pancuronium, 120 microgram/kg i.v., cats were anesthetized with either pentobarbital (N = 4), ketamine (N = 4), enflurane (N = 5), or halothane (N = 5). A longer onset time and duration of neuromuscular blockade occurred during enflurane and halothane anesthesia. The apparent elimination half-life was longer and the total voluem of distribution at steady state larger during halothane anesthesia. The plasma concentration of pancuronium required for neuromuscular blockades was less during enflurane than during the other three anesthetics. We conclude that inhalation anesthetics may prolong a neuromuscular blockade by altering both the pharmacokinetics and pharmacodynamics of pancuronium.

Adjuvants, Anesthesia↗
PubMed1979

Effects of the analeptic drug, 4-aminopyridine, upon post-operative respiratory depression in patients. A preliminary study.

The analeptic agent, 4-aminopyridine, was given to patients who had undergone elective ear, nose and throat surgery and showed severe central respiratory depression due to intra-operative fentanyl administration. The respiratory depression due to fentanyl was found to be partially antagonised by 4-aminopyridine. In view of these preliminary findings it is suggested that the drug might find a use in combatting postoperative fentanyl-induced respiratory depression.

Aminopyridines↗
PubMed1979

Antagonism of the cardiovascular effects of ketamine by diazepam in volunteers.

In healthy volunteers pretreated with atropine (0.5 mg), ketamine given as a bolus i.v. injection (2 mg/kg) followed by an infusion of ketamine (1 mg/kg/hr) for one hour, caused a significant rise in blood pressure and heart rate. This cardiovascular stimulation was rapidly counteracted by diazepam (0.2 mg/kg i.v.) given when the response to ketamine was already maximal.

Adult↗
PubMed1978

Pancuronium pharmacokinetics in patients with liver cirrhosis.

The serum and urinary concentrations of pancuronium were measured in 14 surgical patients with cirrhosis and 12 patients free from liver disease undergoing abdominal surgery. A two-compartment open model was used in the pharmacokinetic analysis of the data. A two-fold increase in both the distribution half-life (T 1/2 alpha) from 11 min to 24 min and in the elimination half-life (T 1/2 beta) from 114 min to 208 min was observed in patients with cirrhosis. In these individuals, the total apparent volume of distribution of pancuronium was increased by 50%. Plasma clearance of pancuronium was decreased by 22%. No significant difference was found in the urinary excretion and biotransformation pattern of pancuronium. These results suggest that there is a risk of prolonged duration of action of pancuronium in patients with cirrhosis. In these patients, the initial dose to achieve adequate muscle relaxation is high and simultaneously there is slow disappearance of pancuronium from plasma. These alterations are mainly a consequence of the increase in the distribution volume of pancuronium in patients with cirrhosis.

Abdomen↗
PubMed1978

A preliminary investigation of the renal and hepatic excretion of gallamine triethiodide in man.

The fate of gallamine triethiodide has been investigated in patients undergoing cholecystectomy with choledochostomy (group I), pelvic operations (group II) and orthopaedic operations (group III). Following a single i.v. injection of gallamine 2.5 mg kg(-1) the disappearance of the drug from the serum occurred in three phases with half-lives of less than 5, 30, 138 min, less than 5, 39, 141 and less than 5, 48, 144 min in the respective groups. Twenty-four hours after injection the renal excretion of the unchanged drug was 53% (15-100%) of the administered dose in group I, 67% (40-90%) in group II and 95% (89-100%) in group III. The biliary excretion of gallamine appeared to be negligible in man. The relationship between renal excretion and duration of action of gallamine, and the influence of some intraoperative factors on drug disposition, are discussed.

Adult↗
PubMed1978

Effects of 4-aminopyridine in Eaton Lambert Syndrome.

The effects of 4-aminopyridine (a non-anticholinesterase antagonist of curare-like agents) on the evoked muscle action potentials (EMAP) in a patient with Eaton Lambert Syndrome are reported. On two separate occasions the i.v. administration of 0.31 mg kg(-1) and 0.62 mg kg(-1) was followed by a 300% increase of EMAP for about 2 h without serious side-effects.

Action Potentials↗
PubMed1978

Potentiation of neostigmine and pyridostigmine by 4-aminopyridine in the rat.

The interaction between 4-aminopyridine and neostigmine or pyridostigmine was studied in vivo in the rat sciatic nerve-anterior tibialis preparation using the constant infusion of pancuronium technique. The ED50 (dose of drug which produced a 50% antagonism) of neostigmine, pyridostigmine and 4-aminopyridine were 18, 49 and 440 microgram kg(-1) respectively. The addition of 100 microgram kg(-1) of 4-aminopyridine, which produced no antagonism by itself, decreased the neostigmine ED50 to 7.4 microgram kg(-1). The addition of 200 microgram kg(-1) of 4-aminopyridine, which produced a 30% antagonism by itself, decreased the ED50 of pyridostigmine to 11 microgram kg(-1). We conclude that both neostigmine and pyridostigmine interact with 4-aminopyrine synergistically.

Aminopyridines↗
PubMed1978

Comparative clinical pharmacokinetics of tubocurarine, gallamine, alcuronium and pancuronium.

Data about plasma concentration, renal and biliary elimination of tubocurarine, gallamine, alcuronium and pancuronium are taken from the literature for synoptical pharmacokinetic analysis. All plasma concentration curves can be described by triexponential functions according to an open three-compartment pharmacokinetic model in line, the elements of which are an application and measuring compartment, a pharmacologically specific compartment and a non-specific one. The corresponding results for all drugs represent the same range and there is no substantial basis for a further differentiation of clinically significant drug specific characteristics, neither regarding the time course of neuromuscular blockade nor the excretory or metabolic disposition. Thus no particular advantage or disadvantage of any drug can be stated from the kinetic or metabolic point of view and especially none seems to have a striking advantage in patients with impaired renal function. Drug specific peculiarities are more likely to be found in the field of side effects.

Alcuronium↗
PubMed1978

Kinetics of intercompartmental disposition and excretion of tubocurarine, gallamine, alcuronium and pancuronium in patients with normal and impaired renal function.

Pharmacokinetic data of tubocurarine, gallamine, alcuronium and pancuronium in patients with normal and without renal function are taken from the literature. They are adapted to an open three compartment pharmacokinetic model, and the proportional intercompartmental distribution is calculated as a function of time from 1 min to 8 h. All drugs show similar kinetic properties: During the first 10 min rapid disappearance from compartment 1 results in saturation of compartment 2. Maximum saturation of compartment 3 is achieved after 1 to 2 h followed by a gradual disappearance of the relaxants from the whole system. 20-25% of the dose undergo sequestration apart from intercompartment equilibrium. In normal individuals sequestration is observed after 2 to 3 h whereas in anuric patients it is already demonstrated during the first hour. Intercompartmental redistribution is the basic principle governing the pharmacodynamic profile of all of the four drugs if given in clinical dosage.

Alcuronium↗
PubMed1978

Pharmacokinetics of pancuronium in patients with normal and impaired renal function.

Plasma concentration curves of patients with normal and impaired renal function are fitted to a tri-exponential function according to an open three compartment pharmacokinetic model. A detailed discussion of the relationship between theoretical distribution volumes, clinical pharmacodynamics and morphological or biochemical structures provides the basis for the concept of a central application and measuring compartment, a pharmacologically specific compartment and a non specific one. The distirbution of pancuronium from the application compartment to the specific compartment results in the onset of muscular paralysis. The recovery is governed by renal elimination of the unchanged drug as well as by its redistribution into the non specific compartment. In anuric patients the spontaneous recovery after 3--4 h is the effect of redistribution only. Neither metabolic degradation nor increased biliary elimination can sufficiently compensate for the lack of the renal pathway. The clinician should always keep in mind that after the recovery from pancuronium-induced muscular paralysis, both in patients with or without renal pathology, considerable residues of the active drug are stored at nonspecific and even specific receptor sites for many hours.

Anuria↗