Pituitrin

Pituitrin (Pituitrinum; Pituitrinum sic-cum Ph. VII) - an extract from the pituitary gland. Despite the fact that the anterior lobe of the pituitary gland has, according to all data, very great significance for the development and vital activity of the organism, only in the most recent time have successful experiments been described with extracts obtained from it. On the contrary, extracts from the posterior lobe were obtained as early as 1894, which had a characteristic effect on the organism (Oliver, Schafer). It is therefore understandable that most pituitary gland preparations are extracts from its posterior lobe, and according to Ph. VII, pituitrin is called an extract precisely from the posterior lobe of the pituitary gland. These same extracts also bear other names: pituitrin, Hypophysin, Pituglandol, Hypophen, Pituigar and others. The posterior lobe of the pituitary gland contains two layers, so-called posterior and intermediate parts (pars posterior et pars intermedia), closely connected anatomically and apparently functionally. When preparing preparations from the posterior lobe, it is usually not dissected, and the extract is made from both the posterior and intermediate parts. The active principles of the posterior lobe of the pituitary gland have not yet been obtained in pure form, and their chemical structure remains unknown. All available pituitary preparations are extracts, purified to varying degrees from ballast substances. Apparently the most purified substance was obtained by Abel in the form of tartrate salts. This preparation had an effect on the uterus in a dilution of 1:20 billion, and yet it cannot be considered a chemically pure substance. It must be assumed that the hormones themselves in pure form possess even more powerful physiological action, however¹ their content in the pituitary gland is very insignificant. In general, it can be considered that the substance contained in the posterior lobe that acts on the uterus constitutes less than one ten-thousandth of the weight of this lobe. The small absolute amount of active principles contained in the pituitary gland creates difficulty in attempts to isolate them. Another difficulty in working with the isolation of active principles of the pituitary gland, as well as in obtaining active extracts, is caused by the low stability of the hormones of this gland. It is known that the active principles of the posterior lobe of the pituitary gland are easily destroyed by proteolytic enzymes. This explains the rapid loss of activity of the gland after the death of the animal. When preparing extracts from pituitary glands that have lain and not been subjected to rapid processing, the preparations obtained contain only traces of specifically active substances, but in them there may be histamine-like protein breakdown products formed during postmortem autolysis of the organ. Such preparations, having relatively weak pituitrin action, may possess toxicity and undesirable side effects. At the present time it has been established that the posterior lobe of the pituitary gland contains not one, but at least two, and possibly more hormones. In 1928 Kamm with colleagues divided pituitrin into two preparations, separately isolating a preparation possessing predominantly uterine action - Oxytocin and predominantly vascular action - Vasopressin. The latter also possesses the inherent anti-diuretic action of pituitrin and an effect on the melanophores of amphibian skin, however these properties apparently depend on the presence of special hormones. Action on the uterus. The most characteristic property of P. and at the same time the most important therapeutically is its ability to enhance uterine contractions. The action of P. on the uterus was first discovered by Dale in experiments on the isolated horn of the guinea pig's uterus (1905). Experiments on the isolated uterus prove that P. acts directly on the uterus itself. The nature of P.'s action on the uterus depends on the dose used. In small concentrations P. enhances normal uterine contractions, while in large doses it causes prolonged spastic contraction of the entire uterine musculature. The sensitivity of the excised uterus to P. is extremely great, and it reacts to dilutions of 1:1,000,000 and more based on the weight of the fresh gland. The uterus of different individuals shows different sensitivity, which to some extent also depends on the condition of the organ. It is known, for example, that the pregnant uterus, especially at the end of pregnancy and immediately after childbirth, is more sensitive to the action of uterine-stimulating substances than the non-pregnant uterus. In view of the theoretical as well as practical interest that P.'s action on the uterus presents, it has been the subject of numerous studies both by experiments on the excised uterus and on the uterus in situ. Action on other smooth muscle organs. P. excites contraction of other smooth muscle organs, although the sensitivity of the latter to P. is much less than the sensitivity of the uterus. Under the influence of sufficient doses of P., the urinary bladder, ureter, gallbladder and bile duct contract. P. acts directly on all these organs, as this action can be observed on isolated organs; its action, in contrast to adrenaline, P. manifests on all smooth muscles regardless of which of the two systems - sympathetic or parasympathetic - the exciting nerve fibers of a given smooth muscle belong to. The described action of P. on smooth muscle organs is being attempted by the clinic for therapeutic and diagnostic purposes, but relatively large doses of the preparation are required to manifest this action. Action on blood vessels. The ability of pituitary extract to cause an increase in blood pressure when administered intravenously was discovered in 1895 by Oliver and Schafer. In 1898 Howell proved that the action of the pituitary extract described by these authors, depending on its vascular effect, belongs to the active principle of the posterior lobe. In height this increase in blood pressure is inferior to the effect caused by adrenaline, but is more prolonged. P. has the peculiarity of giving with repeated injections already a much smaller pressor effect or not having any blood pressure raising effect at all. The term tachyphylaxis has been applied to this phenomenon. Before the rise in blood pressure P. often causes some decrease in it; with repeated injections, when due to tachyphylaxis the pressor effect disappears, this decrease is more pronounced. Some authors attribute the decrease in blood pressure to a special pituitary hormone, but it is undoubtedly that in experiments with commercial pituitary preparation this decrease must be partly attributed to the presence of histamine or histamine-like substances in these preparations. Histamine in small quantities may be present in commercial preparations of P. even of better quality, but some preparations depending on the method of their preparation and quality of the raw material contain histamine in excess, which increases the toxicity of P. and in particular gives it the property of causing a sharp drop in blood pressure. Since P. constricts blood vessels of various areas regardless of the nature of their innervation, its action should apparently be attributed directly to the muscular wall of the vessels. Special relation to P. is shown by the vessels of the kidneys, which are little subject to its constricting influence or according to some authors even somewhat expand from the direct action of P. The dilation of renal vessels clearly manifests itself in experiments on the whole animal with intravenous administration of P., since the rise in blood pressure caused by P. leads to passive dilation of the renal vessels. Krogh sees in P. a hormone that tones the capillary network. It is not known however, to what extent the results of his researches, made on frogs, can be transferred to warm-blooded animals. Action on the heart. Extracts obtained from the posterior lobe of the pituitary gland have been repeatedly studied in terms of their effect on the heart. Some contradictions in the results obtained by different authors have to be explained by the fact that not only the specifically active principles of the pituitary gland but also ballast substances participated in the observed effect. According to most authors P. has a depressing effect on the heart, with the rhythm slowing down and the force of contractions decreasing (the latter is especially noticeable in rabbits and dogs). In experiments on the whole animal the slowing of the heart rhythm is expressed more significantly due to increased tone of the vagus in response to the rise in blood pressure. Action on the kidneys. The action of P. on diuresis varies depending on the conditions in which pituitrin is applied, namely - from anesthesia, water load, state of salt exchange and other conditions. At first a diuretic action of P. was discovered (Magnus, Schafer; 1901), confirmed by many researchers. It clearly manifests itself with intravenous administration of P. to an anesthetized animal. This increase is preceded by a brief (about 1-2 min.) delay in urination, apparently occurring from spasm of the ureter. However van den Velden (1913) discovered the opposite, anti-diuretic action of P., which*found important clinical application in diabetes insipidus.

The antidiuretic action of Pituitrin is observed not only in diabetes insipidus, but also in healthy people in whom diuresis is increased by abundant drinking. Such an effect is also produced by Pituitrin in experimental conditions on non-anesthetized animals: subcutaneous administration of Pituitrin delays the excretion of water given per os. Experimental testing of Pituitrin for its antidiuretic action makes it possible to judge the suitability of this preparation for use in diabetes insipidus. The most vivid experiments have been conducted on dogs with exteriorized ureters (chronic fistulas), on which the course of urination can be constantly monitored. On such dogs, the diuresis curve is established when a certain amount of water is given per os, and then on another experimental day the effect of subcutaneous administration of Pituitrin on this diuresis is tested. The mechanism of the antidiuretic action of Pituitrin is not finally established. Judging from experiments on an isolated kidney included in a heart-lung preparation, this action is due to the direct influence of Pituitrin on the kidney and is apparently explained by increased reabsorption of water by the epithelium of the renal tubules. However, many authors also admit an indirect action of Pituitrin on urination by changing tissue metabolism. In the decrease in urination caused by Pituitrin, the specific gravity of urine significantly increases, and the concentration of chlorides in it sharply increases. This increase is so great that the total amount of chlorides excreted, despite the decrease in diuresis, may even increase, which is especially noticeable with a chloride-poor diet. The increase in the concentrating ability of the kidneys under the influence of Pituitrin also concerns certain nitrogenous products, in particular creatinine. Action on glands. Data regarding the effect of Pituitrin on the secretion of the digestive tract glands are very contradictory. Only the enhancement of bile excretion after injection of Pituitrin is fully established. This phenomenon is explained by the squeezing out of bile from the gallbladder and ducts contracting under the influence of Pituitrin. A pronounced exciting effect of Pituitrin on milk secretion in lactating women has also been described. But in this case too, the action of Pituitrin apparently amounts only to the mechanical squeezing out of existing milk reserves by the smooth muscle elements of the mammary glands, since despite the significant increase in milk secretion after administration of Pituitrin, according to the data of most authors, the total daily milk secretion does not increase. Hogben showed another side of Pituitrin's action, admittedly without clinical significance; preparations of the posterior lobe of the pituitary injected under the skin of a frog cause a noticeable darkening of its coloration, which occurs due to the expansion of the skin's melanophores. This effect depends on the influence of the hormone produced mainly by the intermediate layer of the pituitary gland, and such a reaction indicates the presence in the preparation of the active principle of this part of the pituitary gland. The diverse action of Pituitrin described above is observed with its subcutaneous, intramuscular, and intravenous administration. When taken per os, Pituitrin either does not produce any significant action or its effect is limited only to the intestines. This is explained by the very poor absorbability of the active principles of the posterior lobe of the pituitary gland by the mucous membrane of the digestive tract and their destruction under the influence of trypsin. Therefore, subcutaneous or intramuscular administration is usually used. The latter method ensures a faster effect. Intravenous administration is resorted to only in exceptional cases due to the depressing effect of Pituitrin on the heart, as well as because it is not a chemically pure substance and inevitably contains some proteinogenic impurities. Intravenous administration is used only when it is necessary to obtain an immediate and powerful effect; in this case, it is necessary to administer Pituitrin slowly, mixed with a physiological solution. For the practical use of Pituitrin, a comparative evaluation of the strength of action of its various preparations is of essential importance. Some preparations, despite the large, according to the label, content of pituitary active principles, upon testing proved almost ineffective; others contained harmful impurities. Such inconsistency of preparations with the same name sometimes led to the absence of the expected effect or to an unexpectedly sharp effect with dangerous consequences. The 2nd Conference of the International Commission of the Hygiene Section of the League of Nations (1925) adopted as the basic method for standardizing Pituitrin its testing on the excised uterus of a guinea pig and comparison with the dry powder of the posterior lobe of the pituitary gland prepared according to the method of Vogtlin (see Pituitary gland, chemistry of the pituitary gland). As additional methods, the conference recommended testing the antidiuretic action of Pituitrin and its effect on blood pressure. It was decided to express the strength of preparations in units, taking as such the strength of action of 0.5 mg of Vogtlin's powder, which corresponds to 3.5 mg of fresh gland. The Soviet pharmacopoeia, as a standard, did not adopt the international powder, but histamine, with which Pituitrin must be compared on the uteri of guinea pigs. This method (histamine), which was formerly in the pharmacopoeia of the USA, is now recognized as unsuitable by all authorities and therefore has been discarded. There is no constant ratio between international units (I.U.) and the histamine units (H.U.) adopted by the USSR, but one I.U. corresponds approximately to 30 H.U. The USSR Pharmacopoeia requires that 1 cm³ of commercial Pituitrin contain not less than 100 H.U. At present, the strength of action of preparations of the posterior lobe of the pituitary gland produced by large firms has become more definite. According to 'Grundlagen der Arzneimittelverordnung' by P. Trendelenburg (Leipzig, 1926), 1 cm³ of the most reliable German preparations - Hypophysin Hochst, Pituglandol (Schenz), Hypophen Gen - corresponds to 6-10 mg of fresh gland, i.e., when converted to international units - 1.7-2.8 units. Some factories indicate on the labels the strength of their preparations in international units, in particular the factory 'Hochst' for the preparation Hypophysin reports a strength of 3 international units in 1 cm³. A stronger Pituitrin is produced by the American firm Parke and Davis. In 1 cm³ of this preparation there are 10 international units. At present, some German factories, among them the firm Hochst, in addition to preparations of ordinary strength, produce strengthened preparations, to the name of which they add: 'strong' ('stark'). Hypophysin Hochst stark according to the label has 10 international units in 1 cm³, i.e., in strength it is equal to Pituitrin of Parke and Davis. It should be noted that both the firm Hochst and Parke and Davis supply these strong preparations in ampoules of 0.5 cm³, i.e., 5 international units per ampoule. The firm Henning produces preparations - Pituigan with a content of 3 I.U. and Pituigan forte with 6 I.U. in 1 cm³. The strengthened preparations of German firms, produced alongside ordinary ones, are designed for cases when relatively large doses of Pituitrin need to be administered simultaneously. The most purified preparation containing the uterine-active principle of the pituitary gland is Pytoxyn by Parke and Davis (Oxytocin). The corresponding German preparation (firm J. G. R.) is called Orasthin. It is supplied in ampoules containing 3 and 10 I.U. in 1 cm³, and is especially recommended in cases where it is necessary to stimulate the labor activity of the uterus of a parturient woman in whom an increase in blood pressure is contraindicated (nephropathia gravidarum, eclampsia). Of the preparations of Pituitrin produced in the USSR, the most widespread are pituitrin-farmakon (of the 'Farmakon' factory in Leningrad) and pituitrin of the State Endocrinological Institute in Moscow. The first is obtained from the posterior lobe of the pituitary gland and contains 6-7 international units in 1 cm³. The second is produced in three forms: pituitrin A - from the anterior lobe, pituitrin P - from the posterior lobe, and pituitrin T - from the entire gland. Thus, only pituitrin P is Pituitrin in the generally accepted sense. Pituitrin is established in histamine units and according to the label contains 300 H.U. in 1 cm³. When prescribing Pituitrin, especially in obstetric practice, one must necessarily take into account the strength of the preparation used and dose it according to the content of action units in it. According to a special joint investigation by pharmacologist Burn and clinician-obstetrician Bourne, to enhance the labor activity of the uterus, an injection of 2 I.U. is sufficient, which dose, in the absence of direct contraindications, does not give complications. The pressor action of Pituitrin finds its application in cases of falling blood pressure, for which reason this preparation can be prescribed in collapses during infectious diseases and in poisoning. Although with intravenous administration of Pituitrin its action on blood pressure is much stronger than with subcutaneous or intramuscular injection, in the mentioned cases the latter methods are resorted to from fear of the depressing action of Pituitrin on the heart, which may manifest itself with rapid administration into the blood. In the mentioned cases, the combined use of Pituitrin with adrenaline is indicated.

The latter acts more powerfully and quickly, and when prescribing it together with Pituitrin, one can expect a longer-lasting effect. Keeping in mind the possibility of tachyphylaxis (see above), repeated injections of Pituitrin for its vasoconstrictive effect should be administered only 1-1½ hours after the first injection. The most purified pressor preparation of the hypophysis is Pitressin (Vasopressin). Pituitrin, due to its stimulating effect on smooth muscle organs, is used with the aim of causing contractions of the latter when indicated. For example, Pituitrin is resorted to in cases of postoperative atonic condition of the urinary bladder. Due to the lesser sensitivity to Pituitrin compared to the smooth muscle of the uterus of other smooth muscle organs, in order to cause contractions of the latter, relatively higher doses are used, injecting 2-3 cm³ of Pituitrin of medium strength subcutaneously or intramuscularly. A favorable effect of Pituitrin has also been described in postoperative atony of the intestine. In these cases, large doses of Pituitrin with physiological saline are also required. For example, Bumm recommends for intestinal atony to administer intravenously 3-5 cm³ of Pituitrin in 300-500 cm³ of physiological saline. The German firm J. G. E. produces a preparation corresponding to vasopressin under the name 'Tonephin', especially recommending its use in intestinal atony. In order to cause contraction of the gallbladder and expulsion of gallbladder bile, injections of Pituitrin are used as a diagnostic means in diseases of the bile ducts. Finally, there are indications of a favorable effect of Pituitrin in nephrolithiasis. The pronounced specific effect of Pituitrin is manifested when used in patients with diabetes insipidus (see Diabetes insipidus). The prescription of pituitrin in such cases can be considered as replacement therapy (see Organotherapy). This is consistent with the fact that Pituitrin, despite the strength of its antidiuretic effect, does not affect the underlying process, and its beneficial effect ceases when the injections are stopped. In diabetes insipidus, Pituitrin is administered subcutaneously in doses of 1-2 cm³; in severe cases, several times a day. Besides the cases described, Pituitrin is also used in bronchial asthma, although this application is not justified either theoretically or experimentally. In this case, Pituitrin is injected subcutaneously in combination with adrenaline. For this purpose, a special preparation called Asthmolysin is available for sale, containing equal parts of Pituitrin and adrenaline. Toxicity of Pituitrin. The general toxicity of Pituitrin is comparatively low. Fechtlin considers the lethal dose for mice to be 10 mg of his powder (20 M.E.) per 1 kg with subcutaneous administration. In rats, according to his experiments, even larger doses are required, namely: 80 mg (160 M.E.) per 1 kg. In rabbits, symptoms of poisoning (convulsions) occur with subcutaneous administration of extract from 200 mg of fresh gland (corresponding to 57 M.E.) per 1 kg of body weight, but without a fatal outcome. In humans, with subcutaneous and intramuscular use of ordinary doses of Pituitrin, no general symptoms of poisoning are observed. Only with a very large increase in therapeutic doses or with careless intravenous administration of Pituitrin, symptoms of toxic action have been described - pallor, a feeling of constriction in the chest, nausea, which is explained mainly by disturbance of blood circulation.

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S. Anichkov. Application of pituitrin in obstetrics and in diseases of women. Extracts of the pituitary gland are used in obstetrics for individual complications of pregnancy, complications of the labor and postpartum periods, and especially for insufficient, weak labor activity. In recent years, the opinion is increasingly prevailing that with pituitary extracts during labor, maximum caution must be observed due to the unequal individual susceptibility (Bokharev), since otherwise one risks the occurrence of a series of harmful side effects, up to the point of uterine rupture. All available data at present show that the broad, routine application of P. should not have a place in the modern clinic, and that the obstetrician, in order to avoid complications, especially when introducing P. during labor, must form for himself a precise, clear picture of the case and introduce P. only in the presence of certain indications, while at the same time taking into account all contraindications. The indications for the introduction of P. during labor are not encountered so often - only in cases of actual weakness of labor activity during the expulsion period. The application of P. during pregnancy is extremely limited. Individual authors have successfully used it for dermatoses of pregnancy (Hofbauer) and osteomalacia (Bab, Neu). Wagner's proposal to use P. for differential diagnosis in ectopic pregnancy has not become widespread and can hardly be considered advisable. Attempts to induce abortion or artificial premature labor by injections of P. have not been successful. When P. is used in combination with other means, however, an effect can be achieved in inducing late miscarriage or premature labor [P. + fractional doses of quinine (0.1-0.2) every 1-2 hours after preliminary dilation of the cervix, puncture of the membranes, or concurrently with a metrotomenter]. Some have noted a favorable effect of P. in 'abortion in progress,' in febrile miscarriage (Hamm, Hofbauer) (both with the independent introduction of P. and in combination with quinine). For these indications, it is better not to resort ( as recommended by individual authors) to strongly acting preparations (for example Pituigan forte). In recent years, P. has been tried for inducing labor in prolonged pregnancy. Thus, Adler (Adler, 1927) carried out in 100 cases a modified method of Stein (P. + 0.1 Ricini) and noted positive results in 60%. (Adler gave in the morning 1-2 tablespoons of 0.1 Ricini and with the beginning of intestinal peristalsis, which usually occurred after 2 hours, introduced 0.5 Physor-mon intramuscularly, repeating this same dose every 3/4 hour another 3 times; labor activity usually began after the 3rd or 4th injection, on average 2 hours after the first; the average duration of labor was 13 hours; asphyxia of the fetus did not occur once, postpartum hemorrhage was noted in 6 1/2%). Although Adler points to the complete safety of the method, it has not received particular spread. Also unsuccessful was the proposal (Hofbauer, Oliver and others) to induce labor by introducing P. per os (3 hours after an enema, the administration of 0.1 Ricini and quinine per os 4 times with 1/2-hour intervals, 0.6 cm3 of P. with 0.32 g of sugar with 4 cm3 Aq. dest. was given; of 20 cases, an effect was obtained in 9) or through the nose (after cleansing the nose, a small cotton tampon with 1.2 cm3 of pituitrin is inserted; with this method it was possible to induce labor in 56 women at the end of pregnancy or with its prolongation). Little in practice has been implemented and the proposal of Ben-thin to introduce P. for the purpose of differentiating false labor pains from true labor pains, since although extracts can serve as an indicator of whether the nerve centers are excited for labor activity or not, the possibility of complications can never be excluded, especially with repeated injections (tetanic contractions, asphyxia of the fetus). Most often, pituitrin finds its application during labor, in the second and postpartum periods. It is also used for prophylactic purposes in operations of artificial abortion, cesarean section, pelvotomy. In view of the rather frequent complications (in mother and fetus), P. should be used only in the presence of actual weakness of labor contractions, not used in normally proceeding labor, to sharply distinguish weakness of labor activity from incorrect contractions, and when introducing P. to take into account all contraindications (see table). In the presence of one or another contraindications, the use of pituitrin should not take place; it should not be introduced by a beginning obstetrician, while the midwife in her independent work under no circumstances has the right to use it. The best results and the smallest percentage of complications are obtained in the second stage of labor or at the end of the first. Swiss obstetricians even consider that complete dilatation is one of the basic conditions for the introduction of P. This condition is shared by many obstetricians of other countries and is based on the fact that in view of the impossibility of excluding complications from the fetus in any case, the appropriate conditions for ending labor must always be present (many recommend when using P. to always have forceps ready). The therapeutic effect (acceleration of the labor act, resumption of labor contractions) usually occurs after one injection in 2-5-10 minutes. Stein even points out that contractions as a rule begin after 2-3 min. In order to avoid complications, the most careful observation after injection is necessary, since the possibility of the appearance of spasmodic contractions, tetanization of the uterus, caused by increased irritability of the muscular tone of the uterus, a kind of idiosyncrasy, can never be excluded. For a clearer representation of the effect of the pituitrin being introduced, it is desirable to keep records of the appearance of the first contraction, subsequent ones and the intervals between them; these records, giving a vivid picture of the nature of the action of pituitrin, besides the Main contraindications to the use of pituitary extracts (during labor). Of a general nature depending on pregnancy not depending on pregnancy Of a local nature High blood pressure. Albuminuria. Kidney (nephropathy) of pregnancy. Dropsy of pregnancy. Eclampsia. Eclampsia Severe heart diseases (insufficiency, uncompensated defects, myocarditis). Arteriosclerosis. Diseases of the lungs. Diseases of the kidneys. Goiter (Shlaperovsky) Narrow pelvis. Incompatibility of the fetal head with the pelvis. Incorrect insertions. Incorrect positions of the fetus. Certain types of fetal malformation (e.g. hydrocephalus). Hypertonia of the uterus. Inertia of the uterus of a tetanic nature. Tetanus of the uterus. Overdistension of the uterus (lower segment). Threatened rupture of the uterus. Rigidity of the cervix. Stenoses, scarred strictures and generally pathological conditions of the soft birth canals. Inflammatory diseases in the past and operations undergone (in the abdominal cavity and on the sexual organs). Fibroma of the uterus (Essen-Moller) Do not use with irregular fetal heartbeat (threatening or beginning asphyxia) Do not use with normal labor activity. Do not use with the aim of facilitating the engagement of the head in the pelvis or its passage through it Observe special caution in nervous, easily excitable, weakened and anemic (Lozinsky) Observe special caution and even better refrain from use in twins and hydramnios Observe special caution in the first stage of labor with insufficient dilatation of the uterus. General nature depending on pregnancy not depending on pregnancy Local nature High blood pressure. Albuminuria. Kidney (nephropathy) of pregnancy. Dropsy of pregnancy. Eclampsia. Eclampsia Severe heart diseases (insufficiency, uncompensated defects, myocarditis). Arteriosclerosis. Diseases of the lungs. Diseases of the kidneys. Goiter (Shlaperovsky) Narrow pelvis. Incompatibility of the fetal head with the pelvis. Incorrect insertions. Incorrect positions of the fetus. Certain types of fetal malformation (e.g. hydrocephalus). Hypertonia of the uterus. Inertia of the uterus of a tetanic nature. Tetanus of the uterus. Overdistension of the uterus (lower segment). Threatened rupture of the uterus. Rigidity of the cervix. Stenoses, scarred strictures and generally pathological conditions of the soft birth canals. Inflammatory diseases in the past and operations undergone (in the abdominal cavity and on the sexual organs). Fibroma of the uterus (Essen-Moller) Do not use with irregular fetal heartbeat (threatening or beginning asphyxia) Do not use with normal labor activity. Do not use with the aim of facilitating the engagement of the head in the pelvis or its passage through it Observe special caution in nervous, easily excitable, weakened and anemic (Lozinsky) Observe special caution and even better refrain from use in twins and hydramnios Observe special caution in the first stage of labor with insufficient dilatation of the uterus. For a clearer representation of the effect of the pituitrin being introduced, it is desirable to keep records of the appearance of the first contraction, subsequent ones and the intervals between them; these records, giving a vivid picture of the nature of the action of pituitrin, besides can serve as an indication of permissibility (for more correct labor activity and to avoid spasmodic contractions along with P., it is appropriate to introduce narcotics, of which pantopon is most often used subcutaneously). The dose of the substance introduced, the method of administration (subcutaneously, intramuscularly, intravenously or directly into the uterine muscle) and some technical details connected with it also have significance. All agree that before the birth of the fetus moderate doses must be used, the extracts should be introduced only subcutaneously or intramuscularly (the syringe should not be washed with alcohol before introducing P.; for a more rapid effect it is advisable to lightly massage the injection site). In most cases one injection is quite sufficient; many advise first to introduce 1/2 cm3 and only if necessary repeat the same dose, while some, for example Essen-Moller, generally recommend introducing no more than 1/2 cm3 and not resorting to a repeated injection. Recently, to strengthen contractions during labor, it has been proposed to combine pituitary extracts with extracts of other endocrine glands (for example with extracts of the thyroid gland). In the second and postpartum periods, P. is used for hemorrhages both before the expulsion of the placenta and for atonia and hypotonia of the uterus after its expulsion.

The proposal by some authors (Jess) to use pituitrin intravenously prophylactically at every delivery for a better course of the postpartum period is not shared by the majority, despite the fact that Jess, in parallel observations (with prophylactic administration of pituitrin and without it), noted in both normal and pathological deliveries a more rapid separation of the placenta, less blood loss, and less frequent use of the Crede method. Similarly, most obstetricians do not resort to prophylactic injection of pituitrin for the expulsion of the placenta, believing that after P. a more frequent retention of membranes and tetanic contractions of the uterus (Muller) is observed, and it becomes necessary to give anesthesia to expel the placenta or to manually remove it, that such administration is not safe, and that it should only be used if there is a tendency to atony or if there is reason to suspect the possibility of hemorrhage (Es-seri-Moller and others). Very favorable results have been noted in postpartum atonic hemorrhages, and according to a number of authors, the effect of P. in them cannot be equated to any other remedy, but due to the fact that it is short-acting, it is necessary to add injections of ergotin, hynergen or any other similar means. Although intravenous administration of P. is not contraindicated in atony, just like stronger preparations [for example Pituitrin forte, to which Jogansen always advises resorting in atony and deliveries where there were previously hemorrhages], it is still better to avoid large doses in these cases, and to administer strong solutions only intramuscularly. As for gynecological diseases, P. is recommended for uterine hemorrhages, chronic metritis, dysmenorrhea and for amenorrhea. Bienenfeld and Eckstein (V. Bienenfeld, I. Eckstein) administered P. (Pituitrin-Heiming) in 62 cases of uterine hemorrhages (intramuscularly at intervals of 1-2 days) and speak of it as a good remedy (especially in the absence of an inflammatory process in the tubes and ovaries) for pubertal, climacteric hemorrhages and hemorrhages post abortum. Poujot (Poujot) points out that in hemorrhages, P. gives especially good effect in cases where they are caused by ovarian hyperfunction. Cases of the use of P. in amenorrhea (Mishin, Solovyev F.) show that it is most indicated where amenorrhea is combined with significant obesity, and is ineffective in Basedow's disease and in cases of 'war amenorrhea', seepitsky.