The Effect of Some Curarizing Drugs in Unanaesthetized Man

Poulsen, H; Hougs, Willy; Orkin, Louis R.

doi:10.1097/00132586-195812000-00006

Cited by 6 publications

(9 citation statements)

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“…A similar effect has been reported in the cat tenuissimus muscle in vivo (Maclagan, 1962), but in the absence of measurements of plasma concentration of the drug it was attributed to a reduction in the infusion rate. These results in the cat are comparable to those obtained in vivo in the rat (Creese & Maclagan, 1970) and in man (Poulsen & Hougs, 1958 (Creese & Maclagan, 1970) are comparable to those obtained by many authors in isolated muscle from the frog (Gissen & Nastuk, 1966), cat (Maclagan, 1962), rat (Thesleff, 1955;Gibberd, 1966;Harris & Leach, 1970), guinea-pig (Jenden, 1955), rabbit (Jenden, Kamijo & Taylor, 1954) and man (Creese, Dillon, Marshall, Sabawalla, Schneider, Taylor & Zinn, 1957). In vitro, as in vivo, the recovery of the twitch during prolonged application of the drug is critically dependent on the dose (Jenden et al, 1954;Gissen & Nastuk, 1966).…”

Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 85%

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Labelled Decamethonium in Cat Muscle

Creese

Maclagan

1976

British J Pharmacology

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I Tritium-labelled decamethonium was infused intravenously in 12 cats at final rates of 1.3-4.2 nmol kg-' min-' to produce a steady plasma concentration which ranged between 0.21-1.3 gimol/l in different experiments. Muscle contractions were elicited by nerve stimulation and the potential at the end-plate regions of superficial fibres was recorded by extracellular electrodes. 2 Under these conditions, it was not possible to obtain a steady degree of neuromuscular block. The initial decrease in muscle contractions was followed by recovery towards the original value although the concentration of decamethonium in the plasma remained constant, or in some cases rose. The initial depolarization of the end-plate region also waned during the constant infusion of the drug. 3 Once the twitch tension had returned to control values during infusion of the drug, prolongation of the infusion for a total of four hours did not produce a secondary neuromuscular block. 4 Scintillation counting showed that during infusion oflabelled decamethonium the radioactivity ofthe muscles increased progressively with time. The uptake was less in the soleus muscle than in the fastcontracting flexor longus digitorum and extensor longus digitorum muscles. Muscles which had been denervated 12-13 days previously showed a greater uptake of labelled drug than control muscles from the contralateral limb. 5The labelled drug was localized by autoradiography of frozen sections of leg muscles following intra-arterial injection of decamethonium. Grain counts in individual fibres showed that small amounts of decamethonium had entered the muscle fibres along their entire length, and there was increased uptake of the drug into the cell in the region of the end-plate. 6 The mechanisms underlying the waning of the pharmacological response during constant application of depolarizing drugs are discussed.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 85%

Labelled Decamethonium in Cat Muscle

Creese

Maclagan

1976

British J Pharmacology

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“…Sub-maximal stimuli of 9 ms duration at a frequency of 50 Hz were applied for 1.2 s every 6 s and the resultant contractions were recorded with an ink writer through a mechanically operated system. Poulsen & Hougs (1957) also used sub-maximal tetanic stimuli of the median, tibial and peroneal nerves in their study of the effects of various curarising drugs in conscious volunteers.4…”

Section: Mechanism Of Neuromuscular Transmissionmentioning

confidence: 99%

Clinical assessment of neuromuscular transmission.

Payne

Hughes

1981

Brit J Clinical Pharma

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“…203 Its first manifestation is a gradually decreasing sensitivity (tachyphylaxis) to the effects of repeated identical doses. 2 0 1 , 285,317,318,381 This °ln terms of milligrams per kilograrn of body weight. decreased sensitivity to depolarizing relaxants is accompanied by an increased sensitivity to nondepolarizing agents.…”

Section: Neuromuscular Transmission and Neuromuscular Block In Manmentioning

confidence: 99%

“…135 Because of its fleeting action, the potency of SCh cannot be accurately assessed in the absence of an AChE. The potency of several neuromuscular blocking agents in decreasing muscle strength by 75 to 100 per cent on electrical stimulation of the nerves and causing less than 30 per cent reduction in tidal volume in unanesthetized subjects determined by Poulsen and Hougs 317 is summarized in Table III. The head-drop dose of d-Tc and dimTc, respectively, was found to be 0.16 and 0.04 mg. per kilogram in a single subject. 274 All the relaxants investigated had a greater effect on grip strength than on vital …”

Section: Foldesmentioning

confidence: 99%

The pharmacology of neuromuscular blocking agents in man

Foldes

1960

Clin Pharma and Therapeutics

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Because of great species variation in the effectsThe pharmacology of neuromuscular blocking agents has been studied extensively in laboratory animals and has been the subject of numerous publications. Because of the large quantitative and qualitative species variation in the neuromuscular and other effects of relaxants,125,303,406 the results of animal experiments are frequently not applicable to man and it has been emphasized repeatedly that their pharmacologic actions should be studied in human subjects. 124 ,304.376,382 Considerable information is available on the human pharmacology of neuromuscular blocking agents in monographs 124 ,331 and symposia,321,368 but so far no attempt has been made to review in a single publication the literature on the human pharmacology of muscle relaxants.In the foUowing pages an attempt will be made to correlate the pharmacologic effects of neuromuscular blocking agents with their safe and efficient clinical administration. This survey will deal primarily with the quaternary ammonium type myoneural blocking agents and, of these, only those compounds will be discussed which have been widely used clinically or the study of which serves to emphasize basic principles of the human pharmacology of relaxants.The list of neuromuscular blocking agents to be reviewed is presented in Table 1.Limitations inherent in the pharmacologic study of any drug in human subjects have also influenced the investigation of neuromuscular blocking agents. Thus, little or no information is available on their acute and chronic toxicity in man and, with few exceptions, all observations were made in the intact organism, instead of on isolated nerve-muscle preparations. On the other hand, in eonjunetion with their clinieal use, there has been ample opportunity to observe the influence of various pathologie conditions and of other drugs on the pharmacologic action of relaxant drugs. Further- 345

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The Effect of Some Curarizing Drugs in Unanaesthetized Man

Cited by 6 publications

References 0 publications

Labelled Decamethonium in Cat Muscle

Labelled Decamethonium in Cat Muscle

Clinical assessment of neuromuscular transmission.

The pharmacology of neuromuscular blocking agents in man

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