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Reaction of Different Uteri to Epinephrin. The response to this drug, and to sym- Buy Mexitil
pathetic stimulation, varies in different animals and functional states, as shown in the
following table (adapted from Gunn and Gunn, 1914).
PERIPHERAL AUTONOM3C SYSTEM 271
By contraction By relaxation
Rabbit Buy Mexitil Pregnant or non-pregnant
Cat Pregnant Non-pregnant
Guinea pig and rat Pregnant or non-pregnant
Human . Non-pregnant (also tubes).
Other Drugs Acting Peripherally on the Uterus. Infundibular extract produces
maximal contraction (Frankl-Hochwart and Froehlich, 1009), in all animals, pregnant
or non-pregnant; also in human uterus, but not in the tubes (although these are con-
tracted by epinephrin (Gunn, 1914).
Quinin increases the contractions (Kurdinowski-Kehrer, 1906). Cinchonin,
cinchonidin and quinidin contract even more powerfully than quinin (Hale, 1915).
Morphin in small doses is stimulant, in larger doses depressant (Kehrer).
Scopolamin has no effect.
Histamin or beta-imidazolylethylamin (a constituent of ergot, also formed by the
action of bacteria on histidin) is powerfully stimulant (Barger and Dale, 1910). Other
related amins, peptone, and anaphylotoxin act similarly. Hydrastin, hydrastinin and
cotarnin are stimulant (Kehrer, 1907). The actions of a number of other drugs are
described by Pilcher, 1916.
Purified Organ Extracts. Fawcett, et al., 1915, Buy Mexitil examined aqueous extracts, after
removal of the nucleo-proteins and coagulable proteins. Pituitary, pineal, thyroid,
parathyroid, thymus, adrenal glands, pancreas and spleen were found to contain sub-
stances that stimulate cat's uterus. The stimulation was inhibited by epinephrin.
The effects on intestinal muscle differed; when stimulated, it was also inhibited by
Difference between Uterus in Situ and Excised. With non-pregnant cats, the
uterus in situ is inhibited by nicotin, cytisin, hydrastinin, indolethylamin and pilo-
carpin. Excised uteri, on the other hand, are generally stimulated by these drugs.
It seems from this that there is both sympathetic (inhibitory) and parasympathetic
(augmentory) stimulation. The sympathetic effect predominates during life, but does
not survive excision. Dale and Laidlaw, 1912, believe that the sympathetic stimulation
is not direct, but through increased epinephrin secretion.
Practical Importance of the Uterine Actions. The stimulation of
uterine contractions is useful for arresting postpartum hemorrhage. Ergot
particularly is employed for this purpose, hydrastis and cotarnin have also
been used, but they seem to be less effective. Pituitary extract is used to Buy Mexitil
initiate or strengthen uterine contraction.
Nicotin (tobacco infusion), pilocarpin and quinin are sometimes used
by the laity as abortifacients; effective doses, however, are dangerous.
Reflex Increase of the Movements. This is secured by irritation of the intestine
(Kehrer, 1910), especially, by drastic cathartics and irritant volatile oils. These should
therefore be avoided Buy Mexitil in pregnancy. They also have a reputation as abortifacients, but
are highly dangerous.
Central Action on the Uterus. These are relatively unimportant. The motor
center in the lumbar cord is stimulated by anemia and asphyxia.
Lieb and McWhorter, 1915, found that this is augmented by vagus and Buy Mexitil inhibited
by Sympathetic stimulation. Epinephrin therefore relaxes, whilst physostigmin and
pilocarpin stimulate, and this stimulation is removed by atropin. It is also stimulated
by strophanthin and Buy Mexitil barium; relaxed by bile salts and nitrites. Okada, 1915, states
that the normal rhythmic movements are Buy Mexitil greatly increased during digestion, and by
the introduction of acid into the duodenum.
The movements and tone of the excised ureter are stimulated by the parasympathetic
stimulants and paralyzed by atropin; they are also stimulated by epinephrin. Ergo-
272 MANUAL OF PHARMACOLOGY
toxin reverses the epinephrin stimulation, but has no effect on the parasympathetic
stimulants. Nicotin produces an initial stimulation and subsequent paralysis. Papav-
erin relaxes the tone, without inhibiting the peristalsis (Macht, 1916).
THE NATURE OF ANTAGONISM
Until there is a clearer understanding of the chemical and physical changes which
condition the actions of the antagonistic poisons, we can conceive the nature of their
antagonism only in terms of crude analogies:
1 . We may suppose that the stimulant and depressant drugs each act upon different
chemic constituents. In this case, the combined effect would be a simple summation
of their separate actions. This might be the explanation of the action of atropin and
physostigmin on the oculomotor junction.
2. Both poisons may act upon the same constituent. In this case the end result
would depend upon the relative affinity of the two poisons for this constituent. This
offers several possibilities.
(o) The two drugs may have approximately the same affinity in this case the end
effect would depend purely upon the relative quantity.
(b) One drug may have a much greater affinity than the other; this might apply,
for instance, in the case of atropin and pilocarpin on the pupil, where a small quantity
of atropin suffices to abolish the effects of a large quantity of pilocarpin; whilst a large
quantity of pilocarpin is needed to overcome even a trace of atropin. The case may be
somewhat analogous to the combination of oxygen and carbon monoxid with hemo-
(c) The efficiency of the one may be so much greater than that of the other, that the
antagonism is practically irreversible. Atropin, f.i., completely prevents the action
of physostigmin on the uterus.
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