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Related article: so that opium is rather less depressant to the respiration than would be
expected from its morphin content (Macht, 1915).
Rate and Depth of Respiration. The effect of morphin, as of most drugs acting on the
respiratory center, is mainly on the rate. With small doses, the depth is affected only
secondarily, namely, increased in the attempt to compensate for the slowed rate, espe-
cially if the respiration was previously superficial (Issekutz, 1911). The effects, there-
fore, resemble those of section of both vagi: this suggests that the effect might be due to
blocking of the normal augmentor vagus impulses; but this is not the correct explana-
tion, for morphin does not block the response to electric stimulation of the vagi, and it
also causes a further slowing after both vagi have been divided (Cushny, 1913).
In the dog, the hypodermic injection of morphin first causes a quickening of respira-
tion (perhaps through nausea) followed in fifteen minutes by the typical slowing (Mayor,
1908). In the fr ogs, the slowing is succeeded by quickening, just prior to the convulsive
stage. A secondary quickening is also seen in rabbits (Filehne, 1879; Cerna, 1892) but
never in man.
Decreased Excitability of Respiratory Center. This is shown by the fact that apnea
is more easily produced, and more lasting (Filehne, 1879; Cushny and Lieb, 1915).
The blood becomes more venous, the oxygen content being decreased and the carbon
dioxid increased (Filehne and Kionka, 1895). Asphyxia produced by the inhalation of
carbon dioxid or deprivation of oxygen in normal animals increases the depth and rate of
respiration. Under morphin, this response is of the same type, but very much decreased
(A. Loewy, 1890; Lindhard, 1911; Cushny, 1913; Cushny and Lieb, 1915). Afferent
inhibitory respiratory reflexes are rendered more effective; but acute augmentor re-
flexes are not materially altered (Cushny). The response to persistent irritation (cough)
is of course diminished.
Since the reactions of the center to reflexes and CC>2 stimulation preserve the normal
type, Cushny and Lieb ascribe the action of morphin to slowing of the intrinsic rhythm
of the respiratory center. The hydrocarbon narcotics (urethane), on the other hand,
depress mainly the asphyxia! reflex.
Morphin Derivatives on Respiration. Heroin was introduced by Dreser, 1898, with
the claim that therapeutic doses lessen the cough reflex and slow the respiration; but
THE MORPHIN GROUP 221
that the inspirations are deepened and more powerful, so that the alveolar air is more
effectively ventilated. Independent workers, however, have shown that there is no real
difference from morphin (Cushny, 1913). The deepening of the respiration is not con-
stant (Santesson; Lewandowsky; Harnack, 1899), Online Effexor but is seen only with small doses,
when the slowing is excessive or when the respiration has been shallow (Fraenkel, 1899).
Appropriate doses of codein, dionin, and even morphin produce practically the same
effect (Fraenkel; Issekutz, 1911). In man, the respiratory effects of 5 mg. of heroin
correspond almost quantitatively to those of 15 mg. of morphin (Higgins and Means,
Dreser also claimed that heroin did not alter the excitability of the center to carbon
dioxid, but lessened the reflex excitability (to stretching of the lungs). Impens, under
Dreser, likewise claimed the carbon dioxid threshold unaltered by heroin (and dionin),
but raised by codein, and, of course, still more by morphin. Winternitz, 1899, found
just the opposite result, the threshold being raised by heroin, but not by codein or dionin.
The difference is probably insignificant: none of the derivatives raise the threshold as much
as morphin, and they are, therefore, less effective in relieving dyspnea.
Separate and Combined Opium Alkaloids on Respiration. This subject has been
investigated by Macht, 1915. He finds the effects of morphin on rabbits and dogs
essentially Online Effexor as described. Small doses (o.i mg. per kilogram) markedly slow the rate,
but somewhat increase the minute-volume and alveolar ventilation; but the response
of the center to COa is somewhat decreased. Full doses (i to 5 mg. per kilogram)
diminish the rate, minute-volume, alveolar ventilation, and response to CO 2
Small Doses of Codein (i to 2 mg. per kilogram) generally slow the rate, without much
change in the minute-volume, alveolar ventilation, or CO2 response. Convulsive doses
(20 mg. per kilogram) increase the ventilation and COa Online Effexor response. Narcotin and
papaverin increase the COa response, although the rate may be slightly Online Effexor slowed. N ar-
cein, thebain and cryptopin produce either no effect, or slight stimulation of the res-
piratory center.
Combination of the stimulant alkaloids with morphin gives simple summation of
their respiratory action; i.e., their stimulation partly counteracts the morphin depres-
sion. This is true Online Effexor for opium as well as for artificial mixtures. It also holds for the
perfused-respiratory center.
Bronchial Muscles. These are Online Effexor slightly relaxed by therapeutic doses
of morphin, and more powerfully by papaverin and narcotin (Pal,
1913; Macht, 1915); whereas large doses of morphin, codein, dionin and
especially heroin, narcotin and thebain, produce marked constriction.
Higgins and Means, 1915, observed bronchial constriction in man with
15 mg. of morphin or 5 mg. of heroin. The relaxation may play a Online Effexor part in
the relief of bronchial spasm (asthma); whilst the constriction may con-
tribute to the Online Effexor asphyxia of toxic doses.
The effects are peripheral, for they occur on excised bronchial muscle (relaxation,
Trendelenburg, 1912) as well as in pithed (constriction, Jackson, 1914 and 1915) and in
intact animals (relaxation with small, constriction with large doses; JBrodie and Dixon,
1903). The constrictor action is not antagonized by atropin, and must therefore be on
the muscle or myoneural junction. It can be overcome by powerful dilator (sympa-
thetic) stimulation (epinephrin, hordenin, Jackson, 1914 and 1915).
The combination of morphin and narcotin in Online Effexor dilator concentration gives less dila-
tion than either alone (Macht, 1915). This is similar to the behavior of the coronary
artery.
Bronchial Secretion. Unless there is nausea, the Online Effexor secretion of mucus
appears diminished; particularly in bronchitis. This may be explained
largely by the suppression of cough, permitting a longer sojourn of the
mucus in the bronchi, with consequent removal of its water by absorp-
tion and drying; but there may also be a central depression, analogous to
that of the salivary secretion, for a decrease of tracheal secretion Online Effexor has been
demonstrated in animals (Rossbach, 1882).
Circulation. Therapeutic doses of morphin or its derivatives do not
affect the circulation seriously. In man, there is generally an (indirect)
increase of pulse rate immediately after an injection; this is quickly fol-
222 MANUAL OF PHARMACOLOGY
lowed by persistent moderate slowing, with increased fulness and force
(stimulation of vagus center). The blood pressure, after a short rise, may
remain level (Anderes, 1913), or falls slightly (Guinard, 1895), through
the slowing, and perhaps through incipient depression of the vasomotor
center. The cutaneous vessels are markedly flushed.
With toxic doses, the fall of blood pressure is more marked (central
vasomotor depression), and the pulse becomes weak, varying in rate, Online Effexor and
often arythmic (stimulation of vagus center and disturbed cardiac
conduction).
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