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Related article: THE MORPHIN GROUP 217
caffein slightly accelerates the action. The secretion of gastric juice has been investi-
gated by Pincussohn, 1006, using dogs with the Pawlow gastric pouch. Coffee gave
a considerable but brief increase of quantity and acidity. "Malt coffee" (the type Purchase Doxycycline Online of
the coffee substitutes prepared by roasting cereals) has a similar, but weaker action.
Tea and ordinary cacao decrease the secretion; but cacao in which the fat has been re-
duced to 15 per cent, causes some increase.
Chronic Caffein Poisoning in Animals. Salant and Rieger, 1910, found that the
continued administration of doses which did not cause acute effects, eventually pro-
duced emaciation, often ending in death. The stomach and, to a less degree, the intes-
tine showed inflammatory changes.
On the other hand, they found that habituation increased the tolerance to acute
poisoning, the fatal dose being 15 to 80 per cent, larger than ordinary. Gourewitsch,
1907, also claims a "histogenetic" habituation.
Mice kept continuously under caffein were found to exhibit less than the normal
activity, but showed a normal gain in weight (Nice, 1912).
THE MORPHIN GROUP
Members. The morphin group comprises opium and most of its
alkaloids: Morphin, codein, narcotin, papaverin; also the esters formed
by replacing the H of one or both of the hydroxyls of morphin: Methyl
morphin (codein); diacetyl morphin (heroin); ethyl morphin (dionin), etc.
These resemble each other in their pharmacologic actions, but present
minor differences which are of practical significance. Since morphin is
the most important member, it will be considered first.
Central Purchase Doxycycline Online Nervous System. The most important actions of morphin
are on the central nervous system. It depresses Purchase Doxycycline Online the brain, especially its
higher functions. The medullary centers are first stimulated, then de-
pressed. The reflexes and the spinal functions are mainly stimulated.
The effects are broadly identical in all vertebrate animals, although the
dosage varies greatly, and Purchase Doxycycline Online the symptoms show considerable differences in
the relative prominence of certain phenomena and in the time required to
produce the successive actions.
Narcotic Action. The descending depressant action of morphin is well
illustrated by the frog, in which the development of the symptoms corre-
sponds very closely to those produced by progressive removal of the brain.
This is also the general course in mammals; but with these the symptoms
are more confused. The difference is explained by the more rapid action Purchase Doxycycline Online
of the drug, and by the more intimate correlation of the nervous centers.
Effects of Morphin on Frogs. After doses of 20 to 50 mg. the symptoms start with
diminution, and then absence, of voluntary movements, but the animal reacts normally
when stimulated. (This corresponds to ablation of the hemispheres.) The frog sits
quietly in the normal position; he will climb up an inclined plane and give the croaking
reflex when stroked. When placed in a tumbler filled with water and inverted in a
large vessel of water, it will leave the glass to seek the air. As the narcosis deepens,
it will remain under the glass. Placed on the table, its leaps become more and more
clumsy, and it does not avoid obstacles in jumping (corresponding to excision of the
corpora quadrigemina). Then the animal fails to leap even when stimulated (paralysis
of cerebellum) ; but when turned on its back, it will resume its normal sitting position.
This reaction also becomes more and more delayed, and can be obtained only by rein-
forcing the stimulation through pinching, etc., until finally it fails altogether (paralysis
of medulla oblongata). The reflexes are weakened, but present. The respiration is
decreased.
Morphin Tetanus Purchase Doxycycline Online in Frogs. After the frog has Purchase Doxycycline Online remained in this depressed condition
for some time (a few minutes to several hours; the shorter, the larger the dose), the
respiration becomes spasmodic, resembling superficially the Cheyne-Stokes type; then
the spinal reflexes return; and the frog passes gradually into a tetanus of the strychnin
type, located in the spinal cord. The delayed appearance of this tetanus is due to the
2l8 MANUAL OF PHARMACOLOGY
slow absorption of the effective dose, for it appears at once on intravenous injection
(Stockman, 1891). The convulsions occur more promptly if Purchase Doxycycline Online the heart is tied off (Gith-
ens and Meltzer, 1911), presumably because thus more of the morphin reaches the
nervous axis (Abel, 1912). The onset is also hastened, and the necessary dose Purchase Doxycycline Online reduced,
by cold, and by removal of the cerebrum, which inhibits convulsions. The results are
more prompt if the medulla is not destroyed (Githens, 1913).
McGuigan and Ross, 1915, find that the previous injection of morphin sensitizes
frogs to strychnin, so that strychnin tetanus develops more quickly provided that a
latent period of one-half to two hours elapses between the morphin and strychnin
injections. They believe that the tetanizing action is due to an oxidation product of
morphin, since an artificially oxidized morphin tetanizes more rapidly. Along the same
lines, they explain the usual absence of tetanus in mammals by assuming rapid destruc-
tion of the tetanizing substance. The explanation involves some unproven assumptions.
Death. The tetanus is mixed with Purchase Doxycycline Online paralytic phenomena, the animal lying lax be-
tween the spasms. Eventually the paralysis becomes permanent and ends in death.
The heart is still beating at this stage and is indeed little affected directly. Death may
also occur during a spasm. The convulsive stage may be absent with very large or
very small doses.
Recovery. If recovery occurs, the depressed functions recover in inverse order to
their appearance (Witkowski, 1877. This paper also gives the older bibliography of
the experimental work with morphin).
Invertebrates do not show typical morphin effects.
Narcotic Symptoms in Human Subjects. The first effect, produced
by doses too small to elicit any other symptoms (5 mg.), consists in dimin-
ished sensibility to lasting impressions; especially such as give rise to pain,
cough, fatigue, hunger, discomfort, and other disagreeable sensations.
Somewhat larger doses (10 mg. or more) depress the attention and thus
weaken the appreciation of other external impressions. A sudden stimulus
may evoke a normal or exaggerated reflex response ; there is even increased
acuteness of perception of external impressions (Kraepelin, 1892); but
persistent or gradual stimuli are neglected. The stimuli are evidently
transmitted to the brain, but do not fix the attention. The faculties of
concentration,. of judgment and Purchase Doxycycline Online of memorizing (Weygandt, 1903) are all
seriously disturbed, constituting a narcosis. 1 Through this exclusion of
external stimuli, the patient is quieted, and then passes through a dreamy,
apathetic, drowsy state, into natural sleep. Exceptionally, the disturbed
balance of the brain leads to excitement (especially in cats) and even to
delirium.
Larger doses cause a much more extensive depression, the sleep becom-
ing so profound that the patient can be aroused only incompletely and
with difficulty. Eventually the coma and insensibility are complete.
Relative Analgesic Action of Opium Alkaloids. Morphin is decidedly
the strongest hypnotic and analgesic member of the group.
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