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Biomedical subjects

S Agoston

Publications and source records attributed to S Agoston.

At least 73 records · Page 4Linked to original sources
PubMed1984

Comparison of the pharmacological actions of some new 4-aminopyridine derivatives.

The pharmacological actions of 2,4-diaminopyridine (2,4-DAP) and 3-[(dimethylamino)-carbonyl] amino 4-aminopyridine (LF-14) were examined and compared with those of 4-aminopyridine (4-AP) in anaesthetized rats and on isolated rat and guinea-pig tissues. Both compounds were more potent than 4-AP in reversing the neuromuscular block caused by pancuronium bromide. The ED50S of LF-14, 2,4-DAP and 4-AP were 100 micrograms/kg, 140 micrograms/kg and 450 micrograms/kg, respectively. LF-14 and 2,4-DAP were also more potent in their in vitro actions on the neuroeffector junctions in the ileum and the isolated heart. 2,4-DAP and LF-14 either did not facilitate or only slightly facilitated the recovery time from xylazine/ketamine anaesthesia which was used as a test for their central action; 4-AP significantly reduced the recovery time. We therefore conclude that both 2,4-DAP and LF-14 are stronger peripherally acting compounds with less central action, and that they may be possible replacements for 4-AP as antagonists of non-depolarizing muscle relaxants.

Aminopyridines↗
PubMed1984

Effective treatment of verapamil intoxication with 4-aminopyridine in the cat.

To study the value of 4-aminopyridine as an antidote to verapamil intoxication, we subjected 12 adult cats to verapamil poisoning by administering doses of 4.0-25.0 mg/kg verapamil by intravenous infusion. Six animals were given 4-aminopyridine 2 X 0.5 mg/kg i.v. after the verapamil infusion was stopped and the other six animals (the control group) were not. Verapamil caused profound cardiovascular depression and also partial neuromuscular block, both of which were completely reversed by 4-aminopyridine within 50 min, in spite of extremely high serum verapamil concentrations (ranging between 3,700 and 13,500 ng/ml). The six animals that received 4-aminopyridine survived the verapamil intoxication, whereas four of the six animals in the control group died. The results suggest that 4-aminopyridine may be useful in the treatment of verapamil intoxication.

4-Aminopyridine↗
PubMed1984

Ataranalgesia. A review.

A review is given of the pharmacodynamic effects of Ketamine and the commonly used Benzodiazepines especially regarding the clinical application of the substances in combination as socalled ataranalgesia. The literature as well as own experimental results show the advantages of ataranalgetic combinations for induction and maintenance of general anesthesia. Special comment is given for new results about the reversal of hypnotic action by means of 4-aminopyridine.

4-Aminopyridine↗
PubMed1983

The effect of some new aminopyridines on mammalian non-myelinated nerve fibres.

We evaluated the action of 2,4-, 3,4-diaminopyridine and 3-[(dimethylamino)carbonyl]amino,4-aminopyridine (LF-14) on non-myelinated fibres of the guinea-pig vagus nerve. The amplitude and duration of the compound action potential were enhanced similarly by all of the aminopyridines. The propagation velocity of the compound action potential and electrogenic sodium pumping were not changed by the aminopyridines. The results show that 2,4-diAP and LF-14 affect non-myelinated nerve fibres of the guinea-pig in the same way as does 3,4-diAP; sodium pumping was not modified by the aminopyridines.

4-Aminopyridine↗
PubMed1983

Clinical and pharmacological actions of a bolus injection of suxamethonium: two phenomena of distinct duration.

Twenty-five healthy adult patients undergoing general anaesthesia for elective surgery were randomly allocated to five groups (n = 5) and their mechanical isometric adductor pollicis activity (twitch height (TH)), was monitored. The patients in groups I, II and III received suxamethonium 1 mg kg-1 followed by Org NC 45 40 micrograms kg-1 5 min (group I), 15 min (group II) or 30 min (group III) after complete recovery from muscle paralysis. The patients in groups IV and V received only Org NC 45 and 80 micrograms kg-1, respectively. Mean maximum TH depression (about 42% of initial value in group IV and 5% in group V) decreased to less than 4% in groups I, II and III regardless of the time interval between the injections of suxamethonium and Org NC 45. Mean duration to 90% recovery of Org NC 45-induced blockade was prolonged in patients in groups I, II and III when compared with the patients in group IV (28 min v. 12 min).

Adult↗
PubMed1983

Succinylcholine-vecuronium (Org NC 45) sequence for cesarean section.

Vecuronium (Org NC 45) was used in 27 parturients undergoing elective cesarean section under general anesthesia. One of the parturients had a twin pregnancy. Neuromuscular transmission was assessed clinically by stimulating the ulnar nerve and observing the contraction of the fingers. An initial bolus of 0.05 mg . kg-1 of vecuronium was injected after recovery from succinylcholine block. Complete neuromuscular block resulted in all cases and lasted for a mean duration of 19.3 +/- 6.02 min. Muscular relaxation was maintained by incremental doses of 0.01 mg . kg-1 of vecuronium. Administration of vecuronium did not cause significant changes in blood pressure, pulse rate, or plasma cholinesterase activity. Also, there was no correlation between the plasma cholinesterase activity and the duration of neuromuscular block of vecuronium. The residual neuromuscular block could be antagonized at the end of the procedure by a mixture of 0.005 mg . kg-1 of glycopyrrolate and 0.025 mg . kg-1 of neostigmine. In all parturients, antagonism was adequate as evidenced by maintained tetanic response (50 Hz for 5 sec) and sustained head lift. Nine infants were delivered before the injection of vecuronium; 19 infants were delivered after its injection. There was no significant difference between the Apgar scores in the two groups, suggesting that vecuronium does not cross the placenta in concentrations that affect the newborn. Vecuronium may be advantageous in parturients undergoing cesarean section under general anesthesia because it maintains cardiovascular stability, is noncumulative, is readily antagonized by neostigmine, has no effect on the plasma cholinesterase activity, and has no deleterious effect on the newborn.

Anesthesia, General↗
PubMed1983

Muscular relaxation with atracurium, vecuronium and duador under balanced anaesthesia.

The neuromuscular effects of three new nondepolarizing neuromuscular blocking drugs, atracurium, vecuronium and Duador, were investigated in surgical patients under balanced anaesthesia. (The numbers of patients in each study are given in the tables.) There were no significant differences in the neuromuscular effects of the three agents. None showed any cumulation after repeated administration of maintenance doses. Muscular relaxation for upper abdominal surgery was adequate as long as the isometric twitch tension (P) was no more than 25% of control. Conditions for tracheal intubation were satisfactory within less than 3 min after the start of injection. Spontaneous recovery of P to 90-95% of control, after the last dose of neuromuscular blocker was the fastest with vecuronium (35.8 +/- 2.4 min) and about the same with atracurium (54.3 +/- 2.4 min) and Duador (54.2 +/- 4.7 min). The T4/T1 ratio at the time of greater than 90% recovery of P was 0.44, 0.52 and 0.56 with vecuronium, Duador and atracurium, respectively, indicating the need for the reversal of the residual neuromuscular block. This could be accomplished within 2 min by the i.v. injection of edrophonium 0.5 mg kg-1, preceded by atropine 0.01 mg kg-1. No side-effects were observed with vecuronium. Atracurium caused mild to moderate histamine release in four of 50 patients included in this study, all of whom received an initial dose of 0.5 mg kg-1. The initial dose of Duador caused a 16.7% increase in heart rate. The findings indicate that the three new muscle relaxants merit further clinical trial. In our opinion, until the results of such studies become available, atracurium should not be used in patients with a history of allergic diathesis and Duador in those in whom increased heart rate may be harmful.

Androstanes↗
PubMed1982

Epidemiology of adverse reactions in anaesthesia in Germany and the Netherlands.

We consider 292 anaphylactoid reactions from the own material (1964-1980) out of two different Departments of anesthesiology to attempt to review the continental epidemiology of this life-threatening adverse drug reaction. We conclude the following: The specialty of this type of adverse reaction is likely to prove a special separating name i.e. "anaphylactoid reaction". The overall frequency can be estimated for 1 : 400-600 in anesthesiology, a preponderance of females may be possible. There is no predictability of the reaction, not even by sophisticated history. But it is possible to avoid the development of severe shock by early diagnosis and immediate full causative therapy. With growing experience in diagnosis and therapy the mortality of anaphylactoid reaction should be irrelevant in the near future.

Adjuvants, Anesthesia↗
PubMed1982

4-Aminopyridine kinetics.

Nine healthy subjects (7 men; 2 women) received single 20-mg IV injections of 4-aminopyridine (4-AP). Six of the subjects received the same dose in the form of enteric-coated tablets and four the same dose in uncoated tablets; treatments were at least 2 wk apart. Blood, saliva, and urine were assayed for 4-AP using a high-performance liquid chromatography. Kinetic analysis of serum concentrations after intravenous dosing resulted in the best fitting of a triexponential model in five and a biexponential model in four subjects. The apparent volume of distribution (V) was 2.6 +/- 0.9 (mean +/- SD) 1 kg-1, the terminal half-life (t 1/2) 3.6 +/- 0.9 hr, and the total serum clearance 0.61 +/- 0.14 1 hr-1 kg-1. Saliva concentrations were higher than those in serum after 5 min, with a mean correlation coefficient of 0.989 (n = 5). The t 1/2 and V calculated from serum and saliva concentrations were of the same order. The total urinary excretion of unchanged 4-AP was 90.6 +/- 7.8% after intravenous doses and 88.5 +/- 4.8% after oral doses of enteric-coated tablets. The bioavailability of the enteric-coated tablets calculated from the area under the serum concentration curve (95 +/- 29%) did not differ from that calculated from urinary excretion (98 +/- 8%). Protein binding of 4-AP was found to be negligible. Biotransformation is unlikely.

4-Aminopyridine↗
PubMed1982

Age-dependent dose-response relationship of ORG NC 45 in anaesthetized patients.

The effects of age on the dose of Org NC 45 were studied in 24 healthy, anaesthetized patients using an on-demand infusion of the drug which produced a stable twitch height of 10% of its initial value. The patients were allocated as follows: group I = age less than 40 yr; group II = 40-60 yr and group III = age greater than 60 yr. A steady-state dose measured every 10 min, was achieved in all the patients 30 min after the start of the administration of Org NC 45. Significant decreases of steady-state dosage requirement (P = 0.01) and rate of recovery from blockade (P less than 0.01) were observed between group III and the other two groups.

Adult↗
PubMed1981

Pharmacodynamics and reversal of benzodiazepine-ketamine ataranalgesia.

We describe the combined use of ketamine with benzodiazepines, which produces a state of ataranalgesia. From our investigation of the combination of ketamine with three such drugs--diazepam, flunitrazepam and midazolam--we conclude that the ketamine-midazolam sequence is the best combination in terms of preservation of physiological homeostasis and recovery time. In addition, we describe the reversal of ketamine-diazepam ataranalgesia by the new cholinergic agonist, 4-aminopyridine.

Aminopyridines↗
PubMed1981

Pharmacokinetics of 4-aminopyridine in human volunteers. A preliminary study using a new GLC method for its estimation.

The concentrations of 4-aminopyridine hydrochloride in the blood and urine from volunteers were measured following a bolus injection i.v. of 0.3 mg kg-1. The drug was assayed by means of a new GLC method which is described. The pharmacokinetics of 4-aminopyridine are complicated by an additional increase in plasma concentration during the elimination phase of the drug.

4-Aminopyridine↗
PubMed1981

The effect of dantrolene sodium in relation to blood levels in spastic patients after prolonged administration.

In 25 patients with spasticity, pharmacokinetics and effects of dantrolene sodium were investigated after prolonged administration. A beneficial effect occurred in seven patients. The results were better on 100 mg daily than on a higher daily dose. An increase of the daily dose from 200 to 400 mg was not associated with higher blood levels. Many side effects were noted such as: anorexia, nausea, drowsiness, depression and muscle weakness. From this study we conclude that dantrolene sodium is a muscle relaxant with a weak to moderate effect in patients with spasticity; the effect at doses higher than 200 mg daily is probably poor.

Adult↗
PubMed1980

Failure of neostigmine to prevent tubocurarine neuromuscular block in the isolated arm.

Neostigmine failed to modify the development of neuromuscular block in the presence of a high local concentration of tubocurarine. Only when the concentration of tubocurarine was reduced, and a suitable concentration gradient established between the receptor area and the plasma, did neostigmine increase the rate of recovery from the action of non-depolarizing neuromuscular blocking agents.

Arm↗