The methonium compounds / by W.D.M. Paton and Eleanor J. Zaimis.

  • William Paton
Date:
[1952?]
Catalogue details

Licence: In copyright

Credit: The methonium compounds / by W.D.M. Paton and Eleanor J. Zaimis. Source: Wellcome Collection.

    5/36 page 223
    Absorption and Distribution Decamethonium is poorly absorbed by mouth in animals, and roughly 50- 100 times as much must be given to produce an effect comparable, at its peak, with that of a given intravenous dose (137). By the subcutaneous and intra¬ muscular routes, about two to three times the intravenous dose is required to produce an equal degree of paralysis, although the duration of paralysis is lengthened when the former routes are used. No studies of this sort have been made in man. Hexamethonium likewise is poorly absorbed by mouth (81, 120a). When the urinary excretion is used as an index of the amount absorbed, absorption may range from 0.2% to 34% of the dose given, usually about 5-10%. This corre¬ sponds with the clinical observation that roughly 10 times more must be given by mouth to obtain the same effects as with parenteral dosage. The part not ab¬ sorbed is discharged with the faeces, and the total methonium recovered from faeces and urine after an oral dose accounts for at least 60-70% of the drug given (81, 120a). This reinforces the evidence that the drug is little or not at all metabolised in the body. The factors controlling absorption are still obscure; but there is evidence (81) that some salts of hexamethonium are more readily absorbed from the alimentary tract than others. There is also corresponding clinical evidence that the halides differ in their relative activity by oral administration in depressing spontaneous gastric secretion (98). This is a puzzling observation since the salts when dissolved in the intestinal fluids must be completely ionized, so that the fates of hexamethonium ion and the anion accompanying it should be indepen¬ dent. Absorption is more complete when the drug is given on an empty stomach (81). Again this is confirmed by clinical evidence that fasting patients are more sensitive to the hypotensive action of hexamethonium (98). After parenteral administration, the concentration of hexamethonium in the blood corresponds to a solution in a volume about 10-30% of the total body volume (121), and is probably to be regarded as passing only into the extra¬ cellular space. The view that hexamethonium cannot readily penetrate the cell membrane is concordant with its very slow entry into the cerebro-spinal fluid and into the red blood cell (129), with the manner of its renal excretion by glomerular filtration without secretion or reabsorption, and with its poor ab¬ sorption from the alimentary tract. Decamethonium, like d-tubocurarine, fails to pass the placental barrier. Hexomethonium, however, passes fairly rapidly and, after prolonged administration, the concentration in the amniotic fluid may rise considerably above that in the maternal blood; it seems probable that the foetus secretes hexamethonium in its urine, and that there is a complete cellular barrier separating the maternal circulation from the amniotic fluid into which the urine passes (180-182). The extracellular existence of hexamethonium follows from its quaternary nature. It is generally accepted that, compared with free bases, ions penetrate cell walls very slowly. Salts of quaternary nitrogen in aqueous solution can only exist in the ionized form, so that such slowness of permeation into cellular ele-
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