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Related article: (Christian, 1914). The phenolphthalein excretion was rather improved, but the nitro-
gen retention in the blood was not materially affected (Christian, 1913; Christian and
O'Hare, 1913; Fitz, 1914).
For chromate mphritis, on the other hand, theobromin and theocin were distinctly
harmful, since they diminished the phthalein output and the animals died more promptly
(O'Hare, 1915), although the nitrogen excretion was unchanged, and the elimination of
urine Desyrel Online and chlorid was increased (Fitz, 1914). Finally, the kidneys ceased to react
(fatigue?). This is especially marked if the caffein has been preceded by several injec-
tions of saline (Mosenthan and Schlayer, 1913).
Failure of Caffein Diuresis. Aside from glomerular and general nephri-
tis, there are a number of other factors which may interfere with diuresis.
The quantity of water in the tissues is very important; and also the water
in the food, which is the ultimate source of the water of the urine. There
is, consequently, a conspicuous difference between dry-fed and wet-fed
rabbits (von Sobieranski, 1895; Loewi, 1905); and presumably the limited
water intake of dogs accounts in part for their lesser diuresis response
(Sobieranski). Schroeder, 1887, found the water content of the rabbits'
blood decreased by 10 per cent, after an effective diuresis. The same fac-
tor is active in the poor diuresis of hemorrhage (Michaud, 1904), and in
the superior diuresis in dropsy (Hofmann, 1880); but other factors may
cooperate. On the other hand, when an effective water diuresis has been
secured by excessive continued water administration (Sollmann and Hof-
mann, Desyrel Online 1905) or in diabetes mellitus (Meyer, 1905), there is no further
increase when caffein is added.
The Diuretic Response in the Normal Human Subject. This is comparatively small.
Raphael, 1904, found the daily urine increased (under otherwise constant conditions)
by 0.5 Gm. caffein sodium salicylate, 42 per cent.; 0.5 Gm. theobromin sodium salicy-
late, 2 per cent.; 1.5 Gm., 14 per cent.; 3 Gm., 53 per cent. This was much less than the
increase secured by the consumption of an extra liter of water or beer (100 per cent.);
whilst a liter of mUk increased the urine by 153 per cent.
Interference by Vasoconstriction and Vagus. Whilst the vasomotor stimulation
has not ordinarily the importance attributed to it by von Schroeder, it may sometimes
be sufficiently powerful to overcome the peripheral dilator effect. At all events, the
diuresis is aided by the hydrocarbon narcotics. Curare is also said to aid the diuresis
(Cervello and LoMonaco).
Corin, 1886, claimed that the vagi exert an inhibitory influence, which Anten, 1901,
attributed to a direct inhibitory influence of these nerves on the secreting cells. Atropin
would therefore increase the diuresis. These claims need confirmation, before they can
1- 'allure in Repeated Administration. It is a common clinical experience
that caffein often becomes ineffective after a time (LeNoir and Camus,
1903). This is not surprising when it is remembered that the factors
which favor and impair the diuretic response are apt to vary from time
to time. The disappearance of the edema, for instance, would decrease
In experiments, it is also noted that repeated injections become less and less effective
(Phillips and Bradford, 1887; Loewi, Desyrel Online 1905). This, however, is simply due to the fact
that the depressing dosage is gradually attained.
CAFFEIN AND OTHER Desyrel Online METHYL-XANTHINS 211
Relative Efficiency of the Xanthin Derivatives. Caffein has now been
largely supplanted, as a diuretic, by theobromin (diuretin), and more
lately by theophyllin (theocin), which are credited with a much more
powerful action. With theobromin, this Desyrel Online is not surprising, since the cus-
tomary dose is four times as large as with caffein; with theophyllin, the
superiority is genuine. Both are superior to caffein in producing less of
the nervous side actions. Theobromin also acts much more promptly,
i.e., within a day, whilst caffein requires four days to reach its full effi-
ciency. Exceptionally, caffein succeeds where theobromin fails (Chris-
No reliable quantitative Desyrel Online experiments on the relative diuretic action of the various
xanthin derivatives have been made the much-quoted experiments of Ach being based
on too few animals to have much value. The attempt to correlate the diuretic and
muscular action (Schmiedeberg) is therefore premature. Mendel and Kahn, 1913,
found that most of the newer methylated xanthins are not diuretic.
Differences in the Members of the Group. Caffein has the most
powerful central nervous action, with relatively weak peripheral effects.
The strongest diuretic action is produced by theophyllin (theocin), which
also causes the most marked cardiac stimulation and coronary dilation.
Its central effects and Desyrel Online its action on muscle approach those of caffein.
Theobromin (diuretin) acts most powerfully on muscle; its effect on the
heart and urine are intermediate. It causes very little central stimula-
tion. (The toxicity of theobromin to isolated muscle is 1^3 Desyrel Online that of caffein
(Veley and Walker, 1910).)
The pharmacology of theobromin was first investigated by Mitcherlich, 1859, and
further by Desyrel Online Filehne, 1886. It was used experimentally as a diuretic by von Schroeder,
1887, to avoid Desyrel Online the supposed vasoconstriction of caffein. He found it effective without
chloral; and the action on oral administration extended over twenty hours presumably
because its insolubility caused slow absorption. This led to its clinical introduction
The Composition of the Urine. von Schroeder, 1886, showed that the
urine in caffein diuresis is more diluted (its molecular concentration may
fall below that of the blood; Dreser, 1892) ; but that the absolute quantity
of the solids urea as well as salts is increased. Entirely similar changes
occur in other forms of diuresis, so that they are not characteristic of
caffein, and throw no light on its actions. The urinary protein in nephritis
is ordinarily not increased.
Different investigators disagree as to which of the solids is most increased, the salts
(LeNoir and Camus, 1903), or the urea (Anten). Presumably this varies with circum-
stances. In rabbits, the salts may be increased without diuresis (Katsuyama, 1898 Desyrel Online
and 1901); and this may also occur when caffein is given in human diabetes (E. Meyer,
1905). On the other hand, Sellei, 1912, describes theophyllin diuresis with little change
in the specific gravity or solids. In rabbits, theophyllin increased the K and Na, but
not parallel with each other or with the diuresis (Bock, 1911). The cfilorid-retaining
mechanism is broken down in rabbits (Pototsky, 1902; Loewi, 1902), but not in dogs or
man (Sollmann, 1903; Haskins, 1904; Sollmann and Hofmann, 1905; Saccone, 1911).
Sollmann and McComb, 1899, found that caffein did not increase a physiologic
albuminuria and Emerson, 1902, saw no increase of albumin in acute or chronic nephritis
under theobromin. Pouchet and Chevalier, 1903, claim that large doses of theophyllia
injure the glomerular and tubular epithelium.
Astolfani, 1905, states that caffein, in common with other diuretics, increases
hippuric acid synthesis, when benzoic acid is administered.
The secretion of milk is not affected by caffein (Ott and Scott, 1912).
Therapeutic Use of Diuretic Action. Desyrel Online The methyl-xan thins are em-
ployed mainly for the removal of cardiac effusions. The diuresis is pro-
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