Use and need of new synthetic analgesics in obstetrics; Demerol: an example
Author: Bert B. Hershenson, M.D., Duncan E. Reid, M.D.
Pages: 36 to 37
Creation Date: 1956/01/01
Duncan E. Reid, M.D. Obstetrician-in-Chief, Boston Lying-in Hospital, Professor of Obstetrics and Head of the Department of Harvard Medical School
In the field of obstetrics the recent availability of such powerful synthetic analgesic agents as mepiridine, methadone and numerous others makes possible a broader perspective of the pharmacologic factor in labour. The growth of such knowledge depends to a considerable extent upon the number and variety of synthetic agents that attain a status to command clinical investigation. From this standpoint, it is evident that analysis of the labour mechanism can progress at a rate which is related closely to that of the output of new and interesting obstetric synthetic agents. For a more rational control of the outcome of labour the evidence obtained by the comparison of the effects of an ever-increasing variety of drugs is imperative.
A dose of a drug that is insufficient to be toxic to the mother may have serious effects upon the labour mechanism and the foetus. The difficulties of achieving uniformly satisfactory obstetrical analgesia are well recognized. Morphine in doses capable of relieving pain in active labour can influence the progress of the labour mechanism. The intervals between uterine contractions tends to be increased under the influence of morphine. Morphine is known to influence the progress of labour in other ways, by depressing maternal and foetal respiration and reflex irritability. We must preclude the acceptance of obstetric analgesic agents which involve dangers of toxic, irritating, or undesirable side-effects disproportionate to their therapeutic value.
Demerol (meperidine) has enjoyed considerable use as an obstetric analgesic agent. Demerol has been used for the past fifteen years at the Boston Lying-in Hospital, an institution which has approximately 6,000 deliveries annually. The drug was selected because the action of this agent is better known than that of other synthetic analgesics. Recently a series of 3,000 cases was carefully studied, in which Demerol was used in labour. It became clear that Demerol, like other agents, is not able to meet all the requirements necessary for safe, controllable and effective obstetrical amnesia and analgesia; yet this drug possesses certain advantages over morphine and other analgesic agents in obstetrics. This emphasizes the fact that there is definite need for the synthesis and development of new superior agents for the field of obstetrical analgesia.
Demerol was administered parenterally in dosages of 10 to 100 mgms. at intervals of two to four hours; the larger doses at less frequent intervals. Demerol employed alone was found to be lacking in amnesic effect. When combined with scopolamine, it can produce satisfactory amnesia-analgesia in over 90% of the mothers during labour. Demerol must be combined with scopolamine if amnesia as well as analgesia is desired. It is thought that Demerol has a more discrete locus of action as compared to morphine, Demerol acting on the higher cortical centres, whereas morphine is presumed to act on all levels of the cerebrospinal axis.
The course of labour is favourably influenced, and uterine contractions are not adversely altered under Demerol administration in the regimen employed. The average length of labour under Demerol-scopolamine was shorter than the average unpremedicated patient. Demerol does not appear to influence the normal postpartum involution of the uterus, while blood loss during delivery was normal except in those instances of known trauma.
Demerol was originally thought to be a spasmolytic substitute for atropine, but it was soon realized hat the drug possessed analgesic potency. Demerol possesses greater activity when compared to morphine in suppression of secretory activity. Demerol has definite antihistaminic action when compared to morphine. Demerol is known to relax bronchial spasm induced by histamine and other bronchospastic agents.
Demerol is believed to have an antispasmodic action when compared to morphine. The smooth muscle of the colon is uniformly rendered spastic with morphine, whereas it is either unaffected or relaxed by Demerol. Demerol, unlike morphine, does not alter bowel habits nor cause constipation. Unlike morphine, Demerol does not cause urinary retention. Demerol does not alter rhythmic uterine contractions when administered in the dosage plan referred to and when labour is established.
Maternal respiration is rarely depressed by Demerol, but is quite uniformly depressed by morphine. This is a distinct advantage of Demerol over morphine in obstetrics. Respiratory embarrassment of the new-born is quite evident under the influence of morphine as compared to Demerol. Unlike morphine, Demerol does not depress the cough reflex. Demerol possesses the potentiality of respiratory depression when administered in toxic doses or by the intravenous route. We have employed Demerol intravenously but do not recommend this route of administration for ordinary use because of the increased incidence and severity of undesirable effects.
We gained the impression that Demerol has the capacity of an antipsychomotor agent during labour; it possesses distinct analgesic potency; it provides psychic sedation with little euphoria as compared to morphine; it will not depress respiration to the same degree as compared to morphine; it is more effective as a secretory depressant as compared to morphine; it possesses more relative freedom from toxic reactions and unfavourable side effects than morphine; and it is relatively less depressant than morphine. The combination of Demerol and scopolamine possesses distinct merit over the combination of morphine and scopolamine as an obstetric analgesic therapeutic procedure.
Demerol points up the importance of the further development of better analgesic agents for obstetrical usefulness. Fresh impetus to the synthesis of new drugs for obstetric use is the introduction of highly effective narcotic antagonists. That an opiate antagonist such as Nalorphine should prove to be equally effective against Demerol illustrates strikingly the unexpected turns in the path towards new knowledge in this field.
The demonstration that the modern chemist and the pharmacologist could produce compounds equal or superior in therapeutic value to the natural opiates has stimulated vigorous research. These efforts should be encouraged and stimulated, for there are examples in which drugs of totally different chemical structure possess similar actions. A comparison of the structures of nitrous oxide and Demerol would hardly lead one to believe that they may have certain pharmacological actions-the production of analgesia-in common. Several of the newer synthetic analgesics are even more potent than morphine.
All of this should encourage the efforts of synthetic chemistry to evolve new drugs with distinct improvements over the existing analgesic agents. It is imperative to keep all channels open to the finding of safer synthetic analgesic agents with clinical advantages over morphine in obstetrics.