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Related article: nervous system from above downward; leading to stimulation of the psy-
chic areas (insomnia, etc.); of the medullary centers (respiratory, vaso-
motor and vagus) ; and with large doses to heightened reflexes and tetanic
convulsions. With toxic doses, the stimulation * is accompanied by
paralysis.
2. Cheap Cleocin Increased ease of muscular Cheap Cleocin contraction, progressing to loss of elas-
ticity and to rigor; this affects all forms of muscle to a varying degree.
The heart rate is thereby quickened.
3. Vasodilation by a direct action on the vessels with moderate doses;
this combines with the cardiac stimulation to quicken the circulation.
4. Diuresis results through the interaction of several factors.
Caffein is used as a psychic, muscular and respiratory stimulant; and
as a cardiac tonic and diuretic. Theobromin and theophyllin are probably
more effective when the peripheral actions are desired.
Psychic Functions. In man, moderate doses of caffein (to 0.3 Gm.)
produce a quicker and clearer flow of thought; disappearance of drowsiness
and fatigue; more sustained intellectual effort; more efficient appreciation
of sensory impressions, and more perfect association of ideas (Kraepelin,
1872; Diet! and Vintschgau, 1878; Ach, 1900; Hollingsworth, 1912).
The central actions of theobromin are relatively much weaker than those
of caffein (Filehne, 1886). Theophyllin is intermediate (Dreser, Pouchet,
Thomas).
With larger doses, these effects pass into wakefulness, excitement, and the other
unpleasant reactions described under the toxicology.
The lower mammals react by restlessness and excitement. The cat is said often
to become frantic. Frogs do not exhibit any symptoms referable to the brain.
Use as Antidote in Narcotic Poisoning. Caffein is often used as an
antidote against acute poisoning by morphin (Bennett, 1874); alcohol
202 MANUAL OF PHARMACOLOGY
(Binz, 1878); Cheap Cleocin paraldehyd (Schroeder, 1887); chloral (Airila, 1913, Soll-
mann). The psychical actions are directly antagonistic, the mental
and muscular coordination being immediately improved, although the
effect is not lasting. The respiration and circulation may also be some-
what stimulated, but the effects easily become additive, so that with fatal
alcohol poisoning, caffein is actually deleterious. With morphin, the con-
ditions are probably more favorable.
As a stimulant antidote, the caffein is usually administered as a very strong, hot,
black coffee, to secure the synergistic stimulant action of the heat and oils. Strongly
boiled tea, through its tannin, would be a chemical antidote in poisoning by corrosive
metals. Coffee has not this precipitant effect.
Mutual Antagonism of Alcohol and Caffein. This has been studied especially by
Pilcher, 1912. He found that with the smaller doses, each drug tends to act qualitatively
as if present alone. In alcohol sleep, small doses of caffein cause awakening, restore
the reflexes, and diminish the fall of temperature. With larger doses, there is a qualita-
tive change in the direction of greater depression. Light alcohol coma is intensified
by moderate or large doses of caffein; the reflexes are further depressed. With toxic
doses, the fatality is greatly increased if both drugs are present, mainly by their deleteri-
ous action on the heart.
Medullary Centers. These are moderately stimulated by caffein,
similarly to strychnin. There are, however, some important differences:
With caffein the stimulation is on Cheap Cleocin the whole weaker for toxic doses, but
rather stronger and much more prolonged with therapeutic doses; and
there is little or no subsequent depression, even with toxic doses. The
most conspicuous effect is on the respiration. The stimulation of the
vasomotor and vagus centers is interfered with by other factors, as de-
scribed under "Circulation."
Respiration. In man, the respiration is only moderately increased
(Edsall and Means, 1914), or scarcely affected by oral therapeutic doses
(Newburgh, 1914; Taylor, 1914); unless cardiac dyspnea is improved by
the circulatory effect. With hypodermic injection of 0.15 to 0.25 Gm.,
there is definite evidence of respiratory stimulation. The CO 2 tension is
markedly lowered, inducing a lowered threshold of the respiratory center.
The rate and depth of the respiration, and the minute- volume are increased.
There is also increased gas metabolism, and sometimes bronchial dilation
(Higgins and Means, 1915).
Anesthetized animals respond by increased rate (Binz, 1878; and gen-
erally also increased depth of the respiration (Heinz, 1890; Impens, 1899).
The latter is probably due to partial awakening from the anesthesia; for
with decerebrated animals, Cheap Cleocin the increase is confined to the rate, the depth
being unchanged or more shallow (Cushny, 1913). Inhibitory reflexes are
less effective.
Use in Asthma. Coffee somtimes gives relief Cheap Cleocin in asthmatic attacks. The action is
probably partly psychic, partly bronchial; for in guinea pigs, it relaxes the bronchial
spasm produced by peptone or muscarin (Pal, 1912). Bronchial dilation is also some-
times observed in man (Higgins and Means, 1915). F. Meyer, 1915, concludes that
caffein acts mainly by stimulating the respiratory center to greater effort. He con-
siders it less efficient than atropin, epinephrin or nicotin.
Spinal Cord. Ordinary doses of caffein heighten the reflexes (Wood, 1912; Leeu-
wen, 1913). Toxic doses produce convulsions of spinal origin (Bing, 1901), which agree
in all essential respects with those of strychnin; except that the tetanus is neither as
violent nor as prolonged. The exhaustion in the intervals is also less pronounced. The
tetanus may produce death by fixation of the respiratory muscles. Cheap Cleocin The convulsant
dose is relatively large, and it is therefore doubtful whether it has ever been observed
in man. Ordinary toxic doses produce only tremor. In frogs, the tetanus is not in-
CAFFEIN AND OTHER METHYL-XANTHINS 203
creased or hastened by removal of the cerebrum (difference from morphin; Githens,
1914).
The paralytic action of large doses can Cheap Cleocin be shown in frogs by protecting the muscles
from rigor; i.e., by ligating a leg exclusive of the nerve. Caffein will then destroy its
reflexes.
Skeletal Muscle. Ordinary doses of caffein increase the functional
activity Cheap Cleocin of skeletal muscle so that it contracts more readily and more
completely and powerfully, and is less easily fatigued (Wood, 1912).
This improvement can be demonstrated by the ergograph, as well as in the
excised or curarized frogs' muscle (Fig. 7). It is, therefore, at least hi
large part, peripheral. Larger doses depress the musgle, and eventually
cause it to go into rigor, even in the living animal.
The Stimulant Phase. A Cheap Cleocin smaller stimulus suffices to produce contraction (Paschkis
and Pal, 1886). The latent period is shortened. The height and rapidity of the con-
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