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Related article: Emesis. Morphin is employed as an ant-emetic, but the doses which can be safely
prescribed are often ineffective.
Dosage of Opiates for Children. This is best adjusted to the weight:
with children above ten months, the weight (in pounds) is divided by 150;
below ten months, by 300. The adult dose is multiplied Purchase Glucophage by the factors
thus obtained (Doebeli, 1912).
Recapitulation of the Chief Differences of the Morphin Derivatives.
The action of all morphin derivatives are quantitatively identical, so
long as they involve only changes in the outlying side-chains (R. Stockman,
1891). Even the quantitative differences are not of very great practical
importance.
Morphin. Produces the strongest narcotic, analgesic, hypnotic and
intestinal effects, and the weakest stimulation. It causes the greatest
derangement of digestion; and, with heroin, is most apt to induce a
habit.
Codein (Methyl-morphin) is less narcotic, less constipating, and less
apt to induce a habit or tolerance. It has some advantage in the treat-
ment of cough. Bastedo uses 15 to 30 mg., but Fraenkel, 1899, claims that
at least 40 to 60 mg. are required to affect cough. This dosage is Purchase Glucophage some-
240 MANUAL OF PHARMACOLOGY
what quieting, but not narcotic, and scarcely analgetic. Larger dosage
produces restlessness instead of quieting. The susceptibility is the same
for all ages (Doebeli, 1911).
It increases the spinal reflexes more than morphin (v. Schroeder, 1883). Frank-
further and Hirschfeld, 1910, claim a greater dilation of the cerebral vessels (without rise
of blood pressure).
Dionin (Ethyl Morphin) seems to stand intermediate between morphin
and codein, in all respects. Mering advises it in cough. Lindenmayr,
1912, uses it in colds, 0.05 Gm. before retiring. It sometimes causes
itching of the skin (Seifert, Nebenwirk., 1915, p. 61). It has a special
action on the conjunctiva (edema).
Heroin (Diacetylmorphin) approaches still more to morphin, of which
it shares all the disadvantages, and over which it has no serious advantage.
Bastedo finds it inferior to codein (Side actions, Seifert, Nebenwirk.,
1915, p. 69>.
Thebain is so markedly convulsant that it may be placed in the strychnin group
(Cl. Bernard; Stockman and Dott). '
Structure of Opium Alkaloids. These belong to two groups, those con-
taining a phenanthren nucleus (morphin and its esters) ; and those derived
from isoquinolin (papaverin, narcotin, narcein). The difference in the
nuclei is shown in the diagram.
x\
Phenanthren nucleus Isoquinolin nucleus
Structure of Morphin and its Derivatives. -Morphin is a complex deriva-
tive of phenanthren. It contains two OH groups (one phenolic, the other
alcoholic) in which substitutions can be made, either by alkyl or acid
radicals.
The more important alkyl esters are the monomethyl (Codein), di-
methyl (Thebain) and ethyl (Dionin). Heroin is the di-acetyl derivative.
The nature of Purchase Glucophage the radicals whether acid or alcoholic, aromatic or aliphatic is not Purchase Glucophage
of great importance. Replacement of a single H (codein, dionin) diminishes the nar-
cotic actions and increases the respiratory and tetanic action, and the toxicity for ani-
mals. When both OH groups are replaced by acids (heroin) the narcotic action is
stronger than for codein, the tetanic action is weaker than with morphin.
Comparative Activity of the Two Groups. The alkaloids of both the
phenanthren and isoquinolin are more or less narcotic and convulsant.
The essential differences are in the peripheral actions: whilst the phen-
anthren alkaloids produce but few peripheral actions, the isoquinolin
group causes extensive depression, as described under "Papaverin."
Convulsant-narcotic Series. In general, the narcotic actions on the brain, on the
one hand, and the stimulant action on the cord and Purchase Glucophage medulla on the other, are in inverse
ratio; morphin being the most Purchase Glucophage narcotic and least convulsant, and thebain the most
THE MORPHIN GROUP 241
convulsant and least narcotic; the other morphin esters and the isoquinolin alkaloids
being intermediate. Claude Bernard arranged Purchase Glucophage them in the order of: Morphin, codein,
narcotin, papaverin, laudanosin, thebain. Buergi, 1914, places them as: Morphin,
papaverin, codein, narcotin, narcein, thebain.
Mcconic Acid. This has no effect in the doses which would be administered in
opium. Larger doses produce narcosis, muscular fibrillation; medullary convulsions;
diarrhea; curare action (Barth, 1912).
Papaverin. This was recommended as an analgesic by Baxt, 1869, and Macht,
1915; but its central effects are insignificant (Pal). Its toxicity is low. Bouchet
claims that i Gm. produced no effects on man. Its important peripheral actions have Purchase Glucophage
been investigated mainly by Pal, 1913, 1914. He finds that it relaxes the tonus of all
smooth muscle, especially when this has been spasmodically contracted, and this without
paralyzing the contractility of the muscle; f.i., he claims that it Purchase Glucophage inhibits intestinal
tonus Purchase Glucophage without interfering with normal peristalsis or producing constipation; that small
doses lower abnormally high blood pressure, whilst it requires much larger doses to
lower the normal pressure. Macht, 1916, claims that it lowers blood pressure, mainly
by peripheral vasodilator action, especially in the splanchinic area. The coronary
circulation is increased. Small doses slow the heart, with tendency to stronger con-
tractions. Popper claims that the isoquinolin alkaloids relax the longitudinal coat
of the intestines; the phenanthrens the circular coat. Macht, Herman and Levy,
1916, find that 40 mg. hypodermically in man, produces marked analgesia with some
vasodilation, fall of blood pressure and slight constipation.
Papaverin and narcotin are toxic to protozoa; Pick and Wasicky, 1915, have there-
fore suggested the trial of papaverin against amebic dysentery.
Therapeutic Use of Papaverin. Pal advises its use in gastric and intestinal spasms
and colics, and in spastic constipation (30 to 80 mg. by mouth or hypodermic; 5 to 30
mg. by vein several times). Stoerk, 1915, employs it against the tenesmus of bacterial
dysentery (0.06 Gm., three times daily, continued as long as required). It has also
been tried with less reason, in hypertension, angina pectoris; vomiting, gastric crises;
asthma and pertussis (Pal; Popper, 1914; L. Levy, 1914). It is a local anesthetic, and
has been used on the cornea as solution of 4 to 10 per cent. Macht, 1916, finds that
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