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These statements, however, are not sufficiently substantiated, in view of the diffi-
culty of predicting the spontaneous cessation of such hemorrhages, and the history of
other Cheap Kamagra "internal hemostatics." The claims are flatly contradicted by at least one of the
warmest advocates of Cotarnin (Vieth).
Local Hemorrhage. The topical application of cotarnin in substance or strong solu-
tion (10 to 50 per cent.) to superficial wounds apparently produces a local vasoconstric-
tion with prompt arrest of bleeding. This has been used successfully especially in
tooth extraction (Munk, 1899; Marcus; Sigrist, 1913), epistaxis; and in nasal and genito-
urinary operations. Its effects would be more lasting than those of epinephrin, and
devoid of the coagulant action of the astringents. It is said to be effective even in
hemophilia (Hulisch, 1899). This local effect of strong solutions is quite distinct from
the systemic administration; Cheap Kamagra for Marcus states specifically that the latter was ineffec-
tive, either prophylactically or remedially, in tooth extraction.
The local styptic effect has also been confirmed experimentally (K. Abel, 1905).
Ammonium phthalate likewise acts as a local styptic, and this may contribute to the
local effects of Styptol; although it can play no part in the systemic action (Offergeld,
Experiments on Mechanism of Action. The numerous investigations so far made
have yielded little of practical value. They show that cotarnin has a low toxicity.
Very large doses produce some lassitude, ataxia, general depression, and finally death by
paralysis of respiration. The narcotic action is not pronounced. Intravenous injec-
tions produce brief, inconstant and usually slight changes in the circulation, which can
play no part in the therapeutic action. The contractions of the excised uterus are
stimulated, but the clinical data show that this does not occur with therapeutic doses.
Perfusion of excised organs have failed to show any peripheral or central effects on the
systemic vessels. The local styptic action is obtained with high concentrations, and
can not therefore apply to the systemic administration. There remains the possibility
of a specific constrictor effect confined to the uterine vessels. The only direct evidence
for this consists in the histologic observations of la Torre, which require confirmation on
General Symptoms. K. Mohr, 1905. found that o.i to 0.2 Gm. per kilogram, in
rabbits, dogs or cats produced only some lassitude and drowsiness. Larger doses had a
pronounced sedative action, especially in cats and dogs. Ataxia was also pronounced.
With fatal doses, these effects were followed by some excitement, then progressive
248 MANUAL OF PHARMACOLOGY
paralysis till death. Toward the end, the respiration became very slow and shallow,
sometimes interrupted by asphyxial convulsions.
Laidlaw, 1910, on guinea pigs, describes indefinite depression of the central nervous
system and death by paralysis of the respiratory center. Relatively small doses slowed
the respiration, without change of depth.
Fatal Dose. This ranges from about o.i Gm. per kilogram for guinea pigs (Laidlaw)
to 0.3 to 0.4 Gm. per kilogram for rabbits, and even higher for dogs and cats (Mohr).
Uterine Contractions. Kehrer, 1907, found that cotarnin stimulates the uterus,
both excised and in situ, pregnant or non-pregnant; increasing the contractions and
tonus. This has been confirmed for the excised organ by all subsequent workers
(Laidlaw, 1910; Ruebsamen and Kligermann, 1912; Lieb, 1914). The results in situ are
contradictory. Kehrer's stimulant effects were obtained with cats. With a pregnant
rabbit, Mohr, 1905, obtained no stimulation. Laidlaw, 1910, also found the results on
living rabbits negative, whilst the excised organ responded. La Torre, 1912, observed
no histologic evidence of contraction, such as is seen after ergot and hydrastinin.
Chiappe and Ravano found that the pregnancy of guinea pigs was not affected by toxic
doses; and that even fatal doses produced no abnormalities.
The clinical data are in harmony with these negative results. All reporters agree
that cotarnin never provokes uterine pains, even in late pregnancy; that it does not
hasten the involution of the uterus; and that it has no Cheap Kamagra influence on postpartum
Mohr claimed that cotarnin depresses the excitability of the uterus Cheap Kamagra to hypogastric
stimulation; but his conclusion appears to be based on a single very imperfect experiment
with enormous doses, and must therefore be rejected.
It appears, from all this, Cheap Kamagra that cotarnin stimulates the excised uterus, on local con-
tact; but that, with systemic administration, the uterus does not respond, at least in
rabbits; and certainly not with therapeutic doses in the human.
Other Smooth Muscles. Offergeld quotes contraction of the intestines and bladder;
but Laidlaw found the bladder Cheap Kamagra irresponsive.
Systemic Circtt/a/iow. Intravenous injection produces variable changes in the
blood Cheap Kamagra pressure; sometimes a fall; or a momentary fall followed by a slight rise (Kehrer,
1907; Laidlaw, 1910; Lieb, 1914). If the vagi were divided, the rise is more prominent
(Pilcher and Sollmann, 1915). The vasomotor center is not affected directly, but may
be stimulated by the slowed respiration (Pilcher and Sollmann); and Cheap Kamagra this probably
accounts for the rise. The fall of pressure appears to be cardiac; for the Langendorff
heart is slowed and weakened (Laidlaw). Kehrer and Heinz also consider the fall
This diminished output of the heart has been credited with being the cause of the
hemostatic effect; but this is most improbable. There is no evidence that it occurs
with therapeutic doses; and even with the experimental doses, it is too slight and espe-
cially too evanescent, to influence a persistent hemorrhage.
Direct Action on Systemic Arterioles. All the earlier investigators (Falk, Marfori
and Cheap Kamagra Ronsse) affirm that cotarnin has no effect on the arterioles, with systemic admin-
istration. This has been confirmed by the negative results of perfusion experiments
(Laidlaw, leg). The positive results of direct contact with strong solutions have no
bearing on this. Cotarnin does not produce the gangrene changes characteristic of
Coagulation of Cheap Kamagra Blood. This is not affected, whether the cotarnin is added directly
to the blood, or injected into the animal (Laidlaw; Marfori).
Uterine Vessels. Many of the clinical authors explain the action of cotarnin by a
special action on the uterine vessels, a stimulation of their vasomotor nerves, etc.
(K. Abel, 1905). This appears to be pure assumption. More recently, however, La
Torre, 1912, reports histologic evidence of contraction of the larger uterine vessels in
animals treated with Cheap Kamagra cotarnin. Since postmortem appearances usually give a very
imperfect picture of the changes during life, this evidence requires confirmation by
Dosage and Administration. The cotarnin salts may be used by mouth or hypo-
dermically, the latter being much more efficient. The intramuscular dose is 0.25 to
0.5 Gm., as 10 or 20 per cent, solution, repeated daily as needed. The injections are
not Cheap Kamagra irritant. By mouth, the dosage is from 0.05 to o.i Gm. four to five times daily.
Smaller doses are inefficient. In menorrhagia, it may be started several days before the
Side Actions. None have been reported from oral administration or from hypo-
dermic injections of 0.5 Gm. Offergeld found some lassitude with 0.7 Gm. and a single
case of temporary collapse with 0.65 Gm. by intramuscular injection.
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