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FIG. 9. Diagram of the Actions of Cocain on Respiration and Circulation. (A^rise of the curve
signifies an increase or stimulation ; a fall, the reverse.)
lation of the vasomotor center; this is followed by a temporary fall due to
Moderate doses quicken the pulse, mainly by central and peripheral
depression of the vagus (v. Anrep, 1880) with some stimulation of the
accelerator center (Mosso, 1887). The pressure rises (v. Anrep) from stimu-
lation of the vasomotor center (Berthold, 1885), aided by the faster heart
rate. The vasomotor factor is predominant, for the rise is practically
absent if the cord is cut.
Large doses cause a great fall of pressure and slow and weak pulse (v.
Anrep), from the depression of the medullary centers (collapse) and of the
Actions on Heart Rate. This demands some further discussion: Lasix Online Lasix Online The slowing from
small doses does not Lasix Online occur if the vagi have been cut, so that it is of central Lasix Online origin. The
quickening from moderate doses is also less marked if the vagi have been divided, so
that it is probably due in part to a depression of the vagus center. The vagus ganglia
are also depressed, for electrical stimulation of the vagus trunk is only partly successful
(v. Anrep, 1880). In the frog these ganglia can be paralyzed completely by the local
application of cocain, but in the intact mammal the paralysis is not complete. Some
quickening occurs, however, even when the vagi have been divided, but none is seen
if the accelerators have also been cut. The final slowing is due to a direct paralysis of
the muscle, for it is accompanied by weakening of the contraction, and it occurs after
atropin, and in the excised heart.
256 MANUAL OF PHARMACOLOGY
The Excised (Langendorff) Mammalian Heart. This has been investigated by
Hedbom, 1899; Kochmann and Daels, 1908; and Prus, 1913. Low concentrations slow
and strengthen the contractions; higher concentrations cause slowing and weakening;
fatal concentrations give diastolic arrest. Kuroda, 1915, observed no stimulation in
excised hearts of mammals or frogs.
The excised frog's heart is stimulated by small concentrations (Mosso, 1890), and
depressed by high concentrations. The terrapin's heart is similarly affected (H. G.
The effects on blood pressure have been described mainly by Ott, 1874; v. Anrep,
1880; Vulpian; Mosso, 1800, and Reichert, 1891. The comparative effects of cocain i
and novocain have been investigated on dogs by Kamenzove, 1911.
Splanchnic Circulation; Influence on "Shock." The intravenous injection of cocain
has a very pronounced effect on the splanchnic circulation. The intestines appear
unusually pale. Handling of the viscera and other measures of "shock" which cause a
splanchnic dilation and consequent fall of blood pressure in normal animals, have less
or no Lasix Online effect after cocain. Burning and stimulation of the sciatic, which cause a rise of
pressure normally, are also ineffective (Crile, 1901). Fere, 1906, on the other hand,
claims that local anesthesia (by cocain, its substitutes, or freezing) does not abolish the
depressant reflexes (decrease of muscular work, of sharpness of vision, etc.); these occur
from procedures which would ordinarily be painful, even when Lasix Online the sensation of pain is
Cerebral Circulation. This is increased by cocain, and still more by novocain
(Frankfurther and Hirschfeld, 1910). The vessels of the retina and pia mater Lasix Online are
constricted (Hirschfelder, 1915).
The urine flow is generally diminished, but sometimes increased, depending mainly
on the vasomotor effect.
Temperature. Cocain causes a rise of temperature, due essentially
to increased heat production, and this largely from muscular excitement
(see Lasix Online chapter on "Heat Regulation"). ,
Effect on Metabolism. In rabbits, large doses of cocain cause rapid loss of weight.
The quantity of urine, its specific gravity, and particularly the urea, are diminished,
whilst the incompletely oxidized (extractive) nitrogen is increased. During recovery,
the quantity of urine returns promptly to normal or above; the disturbances of the
nitrogen metabolism persist for some time (Maestro, 1904).
The effects of repeated injection on dogs have been investigated by Underhill and Black,
1912: Doses of 10 mg. (per kilogram) produce no change in fat or nitrogen metabolism;
15 mg. gave a slight impairment of fat Lasix Online utilization, and considerable decrease of body
weight; 20 mg. markedly decreased the nitrogen and fat utilization. The nitrogen
balance may become negative. Lactic acid excretion was markedly increased in well-
fed dogs, but not in starvation the increase being probably due to the muscular activ-
ity. The ammonia output bore little relation to the lactic acid.
Blood-sugar. This is not changed (cats, 15 to 35 mg. per kilogram), except as a
result of excitement (Schaer, 1915).
Fate of Cocain. This is partly destroyed in the organism, but mainly
excreted unchanged in the urine (contrary to the results of Wiechowski,
Rifatwachdini, 1913, recovered 42 to 85 per cent, from the urine of rabbits after
acute poisoning, and all in chronic poisoning. None was present as ecgonin; but if
ecgonin itself was injected, 25 per cent, was recovered from the urine. Cocain left
for several hours in a ligatured limb was not destroyed.
Destruction of Cocain in Vitro ; Sterilization. Long-continued boiling
decomposes cocain into benzoyl-ecgonin and methyl alcohol. It was
therefore believed that solutions could not be sterilized by boiling. In
fact, however, the decomposition on boiling half an hour, is insignificant
(Merck, 1907; Holbrook, 1912); and even longer boiling only decreases the
activity, for the decomposition products are merely inactive and not toxic.
Benzoyl Ecgonin. This was found by Stockman, 1886, to resemble caffein in its
central and muscular action. It had no effect on sensory nerves or the Lasix Online pupil.
COCAIN GROUP; LOCAL ANESTHETICS 257
ACUTE COCAIN POISONING; ETIOLOGY
This is of special importance, since cocain poisoning is not a very
uncommon occurrence in the therapeutic employment of the drug. Very
large amounts are sometimes used in a most careless manner for local
anesthesia, and since the absorption is fairly rapid, serious and even fatal
results may follow. The susceptibility varies enormously, due partly to
the uncertainty of the absorption; partly to the rapidity of destruction;
and partly to the varying intensity of the effects. In some cases 2 drops
of a 4 per cent, solution (= 0.005 g m -) m the conjunctival sac caused
serious collapse, whilst very much larger doses produced no effect in other
cases. The ordinary fatal dose is considered by Kunkel to be about 1.2
gm. (18 gr.); but death has been reported from as little as 0.08 gm. (i^
gr.). The toxicity is greatly lessened by the addition of epinephrin. Lasix Online
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