Mark Swerdlow

Anticonvulsant drugs used in the treatment of lancinating pain. A comparison

The value of anticonvulsant drugs in the treatment of some cases of lancinating pain is now established. The results in 170 consecutive cases in an ongoing series are reported with special reference to the efficacy of four anticonvulsants–carbamazepine, clonazepam, phenytoin and valproate. The findings are discussed.

A STUDY OF POSTOPERATIVE PAIN

This investigation was carried out on 223 patients after abdominal surgery. Three new analgesics—oxymorphone, phenazocine and dextromoramide—were compared with morphine in the relief of postoperative pain. The drugs were administered intramuscularly under ‘double‐blind’ conditions in the following dosages per kg body weight: morphine, 0.15 mg; oxymorphone, 0.02 mg; phenazocine, 0.03 mg; dextromoramide, 0.08 mg.

The respiratory effects of pethidine and levallorphan.

Pethidine was introduced in 1939 by Eisleb and Schaumann. It rapidly became a popular alternative to morphine and even replaced it for many purposes. Pethidine has the advantages that it is less liable than morphine to cause nausea, vomiting and constipation, that it is effective by mouth and that it is shorter acting than morphine. It was also claimed that it is less depressant to the respiration, but Prescott and Loeschckes have shown that in equipotent dosage the two drugs cause similar respiratory depression. This respiratory depressant effect is one of the drugs chief disadvantages and limits the freedom with which it can be used. The effccts of pethidine on the respiration have already been studied by several workers under various experimental conditions but always in conscious subjects. Thus Loeschckes administered 15Omg of the drug intramuscularly to six resting men and found that fifteen minutes later the mean respiration rate had increased by 8.4 per cent, the mean minute volume had fallen 10.3 per cent and the tidal volume 17.6 per cent. Orkinlo injected lOOmg pethidine intravenously in four minutes to ten conscious, unpremedicated subjects and measured the changes in minute volume with a Benedict Roth spirometer. He found an immediate increase in respiratory rate to 1 10-1 15 per cent and this increase persisted throughout one hours observation. The tidal volume fell to 45 per cent of normal within three minutes but had returned to 80 per cent within fifteen minutes. The minute volume fell to 50 per cent within three minutes but fifteen minutes later was 85-90 per cent of normal. Other workers have studied respiratory response to carbon dioxide stimulation. Prescott 1 1 gave lOOmg pethidine intramuscularly to eight volunteers. He then measured minute volume response to stimulation with 5 per cent carbon dioxide at half hourly intervals for three and a half hours. He found that half an hour after injection the mean depression of response was 35.8 per cent; at the end of the experiment the depression was 9.2 per cent. Eckenhoff3 administered

FURTHER CSF PRESSURE STUDIES

In a recent paper Swerdlow, Foldes and Sikerl reported the effects of Nisentil and the narcotic antagonist levallorphan tartrate on C S F pressure. It was found that levallorphan given before, together with or after nisentil significantly prevented or reversed the rise in C S F pressure which followed administration of the analgesic alone. The present work investigates the antidotal effects of levallorphan and N-allylnormorphine on pethidine-induced rise in C S F pressure.

Respiratory effects of anæsthetics

We have already reported the effects of nisentil and levallorphan tartrate on the respiration in conscious patientsl. It was shown that this narcotic antagonist, in a ratio of 1 :50 with nisentil, will markedly reduce the respiratory depressant effect of the analgesic. The application of this finding to clinical anesthesia permits the use of larger doses of analgesic with apparently adequate ventilation throughout: considerably less thiopentone than normal is necessary and earlier emergence from anesthesia results2 3. In the present study the respiratory ventilation was followed during thiopentone, nitrous oxide-oxygen anesthesia supplemented with nisentil and levallorphan and comparison was made with the ventilation when thiopentone or nisentil was used as the sole supplementing agent under similar conditions.

Anileridine in anaesthesia. A clinical trial.

Since Neff et all first used pethidine to supplement thiopentonenitrous oxide-oxygen anaesthesia a large number of analgesic drugs have been tried for this purpose. With the possible exception of alphaprodine2 none of the drugs employed to date has any appreciable advantages over pethidine which remains the most widely used narcotic analgesic for supplementation of anaesthesia. FIG. 1 Formulae of pethidine and anileridine

THE USE OF NARCOTIC ANTAGONISTS IN ANAESTHESIA

The effects of the opiate antagonists are briefly described. A detailed account is then given of the use of these antagonists in pre‐ and postoperative medication and in anaesthesia. Finally, the value of the antagonists in the treatment of opiate overdosage is discussed.

Behandlung der akuten Narkotica-Vergiftung

Vor Einfuhrung der spezifischen Narkotica-Antagonisten in die klinische Praxis durch Eckenhoff und seine Mitarbeiter [436, 437, 443] war die Behandlung von Patienten mit akuter Narkotica-Intoxikation ahnlich derjenigen einer akuten Vergiftung, welche durch andere auf das Zentralnervensystem depressorisch wirkende Substanzen hervorgerufen wird (z. B. Barbiturate). Obgleich die spezifischen Antagonisten wichtige Hilfsmittel in der Therapie einer Narkotica-Vergiftung geworden sind, darf nicht angenommen werden, das diese Mittel eine universelle Losung des Problems darstellen. Befolgung der Grundprinzipien der Wiederbelebung und richtige Behandlung des wiederbelebten Patienten sind noch - und werden es auch weiterhin bleiben - von vordringlicher Bedeutung.

Pharmakologie der morphinartigen Analgetika und ihrer Antagonisten

Selbst wenn Zeit und Platz unbegrenzt zur Verfugung stunden, so ware eine ausfuhrliche Besprechung der Pharmakologie der Morphinderivate eine auserst schwierige Aufgabe. Das Problem wird noch weiterhin erschwert, wenn man versucht in den verhaltnismasig engen Grenzen einer hauptsachlich klinischen Monographie die zahlreichen pharmakologischen Wirkungen dieser Verbindungen darzustellen. Tatsachlich waren die Schwierigkeiten unuberwindlich gewesen, hatte man nicht auf die ausgezeichneten Monographien und Ubersichten von Krueger, Eddy und Sumwald [852], Isbell und Frazer [765], Eddy, Halbach und Braenden [452, 453], Braenden, Eddy und Halbach [168], Reynolds und Randall [1172] und anderen zuruckgreifen konnen. Die entsprechenden Kapitel des Buches von Goodman und Gilman [615] leisteten als Fuhrer durch die grose Zahl der Literaturangaben unschatzbare Dienste, und haufig wurde auch von den Buchern von Drill [385] und Sollman [1355] Gebrauch gemacht.

Die Geschichte der Narkotica in der Anaesthesie

Opium wurde schon im Altertum als Narkoticum und Hypnotikum verwandt. Bereits Theophrastus [1424] (300 v. Chr.) kannte Opium, und Dioscorides unterschied zwischen einer hoheren Qualitat — dem aus Mohnkopfen ausgeschwitzten Saft — und einer niederen, Meconion genannten Qualitat, die aus ausgepresten Kapseln und Blattern des Mohns gewonnen wurde [1550]. Es ist jedoch schwierig genau festzustellen, wann Opium erstmalig in Verbindung mit der Chirurgie angewandt wurde. Tatsache ist, das man vom 12. Jahrhundert an haufig Hinweise uber den Gebrauch von Schlafschwammen (Schwamme, getrankt mit dem Saft von Opium, Hyoscyamin, Maulbeersaft, Alraunensaft und anderen Drogen) antrifft. Das erste bekannte Rezept fur einen Schlafschwamm datiert zuruck bis ins 9.