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Biomedical subjects

S Agoston

Publications and source records attributed to S Agoston.

At least 91 records · Page 5Linked to original sources
PubMed1980

Antagonism of ketamine-diazepam anaesthesia by 4-aminopyridine in human volunteers.

Five healthy human volunteers were anaesthetized on two separate occasions, 1 week apart, using a standard diazepam-ketamine induction followed by an infusion of ketamine for 1 h. Ten minutes after stopping the infusion, either 4-aminopyridine 0.3 mg kg--1 in saline or the same volume of saline alone was administered i.v. It was concluded that 4-aminopyridine enhanced dramatically the rate of recovery of the subjects to full consciousness and normal motor co-ordination when compared with the saline controls.

Aminopyridines↗
PubMed1980

Effect of experimental cholestasis on neuromuscular blocking drugs in cats.

Pancuronium, Org 6368 and gallamine were compared in control cats and in cats with experimental cholestasis. A decrease in the plasma clearance and a prolongation of neuromuscular blockade with Org 6368 and pancuronium were found in the latter; no significant difference was detected in the biotransformation pattern of Org 6368 and pancuronium compared with controls. Inhibition of hepatic uptake of Org 6368 and pancuronium in extrahepatic cholestasis might explain the significant alterations in the pharmacokinetics of the two steroid neuromuscular blocking drugs. The pharmacokinetics of gallamine were normal during cholestasis. The results suggest that, under pathological conditions involving increased plasma concentrations of bile salts, neuromuscular blocking agents that are cleared from the plasma by the liver may have an impaired hepatic uptake and consequently a prolonged duration of action.

Animals↗
PubMed1980

Pharmacology of ORG NC 45 compared with other non-depolarizing neuromuscular blocking drugs.

From results of pharmacological tests on the neuromuscular and autonomic blocking actions of a series of pancuronium analogues, Org NC 45, the C16 monoquaternary analogue of pancuronium, was selected for detailed study. Org NC 45 has a non-depolarizing mechanism of action, is more rapid in onset and shorter in duration of action than pancuronium. It shows less cumulation than pancuronium or tubocurarine, and is easily antagonized by anticholinesterases and aminopyridines. Org NC 45 exhibits a low propensity to release histamine. Its ability to inhibit cholinesterases is not likely to be important at neuromuscular blocking doses. Org NC 45 possesses negligible ganglion-blocking activity and there is a wide margin between neuromuscular and vagal blocking doses. Thus cardiovascular side-effects are unlikely to occur with the use of Org NC 45. It will hydrolyse mainly to its 3-hydroxy analogue which, like Org NC 45, possesses a wide margin between neuromuscular and vagal blocking doses. Org NC 45 has a high selectivity for the neuromuscular junction and represents a potentially useful addition to the armamentarium of clinically useful muscle relaxants.

Aminopyridines↗
PubMed1980

The neuromuscular blocking action of ORG NC 45, a new pancuronium derivative, in anaesthetized patients. A pilot study.

The neuromuscular blocking effects of the new monoquaternary analogue of pancuronium, Org NC 45, have been investigated in anaesthetized patients. In different doses administered as a single i.v. bolus or as an initial bolus followed by several small maintenance doses or by a continuous infusion. Org NC 45 appears to be approximately as potent as pancuronium, but has a more rapid onset of action, considerably shorter duration of action and faster recovery rate than pancuronium. It showed no cumulative effects even after 10 maintenance doses were injected in succession. Doses of 0.08 mg kg-1 provided ideal intubating conditions in 90--95 s. Infusions of Org NC 45 provided much smoother control of neuromuscular blockade than did pancuronium. No cardiovascular side-effects were noted even at the greatest dose (0.12 mg kg-1) used. Org NC 45 has clear advantages over pancuronium and represents a potentially valuable addition to the armamentarium of clinically useful muscle relaxants.

Anesthesia, General↗
PubMed1980

A new method for studying the relationship between hepatic uptake of drugs and their pharmacodynamic effects in anaesthetized cats.

1 A new in vivo experimental method is described whereby the liver can be temporarily excluded from the general circulation by means of a portocaval shunt operation. The influence of this manoeuvre upon the effects of pancuronium and Org 6368 was investigated using the tibialis muscle preparation of anaesthetized cats. 2 The procedure also allowed intraportal injections of the drugs to be made so that the effect of first-passage uptake by the liver could be compared with hapatic exclusion in the same animal. 3 Hepatic exclusion greatly increased the duration of action of both drugs. Whereas intraportal injection did not significantly alter the effect of pancuronium on the tibialis muscle, the effect of Org 6368 was greatly diminished when given by this route. 4 The liver appears to tolerate short periods of hepatic exclusion and it is concluded that this technique may become a useful tool for studying the handling of drugs by this organ.

Anesthesia↗
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↗