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Related post: sensitization on the recipient (Otto); immediately, with proper dosage (Doerr and Russ). There is the Differin Adapalene same, specificity as with other antigens. Specific sensitization may thus be secured simultaneously to several proteins. Wells and Osborne, 1911 and 1913, have studied particularly the specificity for pure proteins. They believe that the specificity is due to certain constituent groups within the protein molecule; but that the whole molecule is involved in the Purchase Adapalene reaction. The provocative injection must be considerably larger than the sensitizing in- jection. It is much more effective by vein. The response is immediate. If an animal recovers from the toxic effects, it becomes immediately refractory or immune to further injection, because the anaphylactic antibodies are saturated or exhausted (Weil and Coca, 1913). This antianaphylaxis (anergy) persists for a time, but is eventually lost. General Phenomena. However induced, anaphylaxis presents fun- damentally the same phenomena, differing merely in intensity, according to conditions. The relative predominance of the individual effects in different species may complicate the picture. The actions are essen- tially peripheral. They consist in: fall of blood pressure (shock); tonic contractions of smooth muscle, especially the bronchioles, resulting in severe respiratory disturbance; and local urticarial reactions. 370 MANUAL OF PHARMACOLOGY Symptoms of Anaphylactic Reaction. These are mainly as follows: Great restlessness; severe fall of blood pressure, generally attributed to paralysis of the splanchnic vessels and Adapalene Clindamycin consequent shock; fall of temperature (Pfeiffer and Mita, 1910), etc.; rigidity of the lungs by violent contraction of the bronchial muscles, resulting in respiratory distress and asphyxial convulsions; stimulation of other smooth muscle (uterus, stomach and intestines); diminished coagulability Purchase Adapalene Online of the blood; leucopenia; eosinophilia; loss of complement; increased lymph flow (Calvary, 1911); local inflamma- tory reaction. Repeated anaphylactic shock results in cell destruction in several organs, with subsequent chronic inflammatory changes. In the liver, the results resemble portal cirrhosis (Longcope, 1913). Analogous but less severe parenchymatous degenerations of the myocardium, liver and kidneys may occur Adapalene Differin in rabbits after a single injection of a large dose of horse-serum or egg-albumen. They develop Adapalene Cream in ten to twenty-one days, about the time when the antidodies are produced (Longcope, 1915). Susceptibility. Guinea pigs are especially susceptible, and in them the lung rigidity is most prominent, arresting respiration and producing asphyxial death in a few minutes (Auer and Lewis, 1909). In dogs and rabbits this phenomena is much less marked, the severe and prolonged fall of blood Adapalene 0.1 Gel pressure being the most prominent feature. Cats are inter- mediate (Edmunds, 1914). Man seems to be relatively insusceptible. The rare acute accidents in the injection of antitoxic sera, serum-disease, and some varieties of Adapalene Gel 0.1 asthma and hay fever (Meltzer, 1910) are probably anaphylactic manifestations. Lung Rigidity. Auer and Lewis, 1909, showed that in guinea pigs dying acutely of anaphylaxis the lungs are rigidly distended and incollapsible even after death, by tetanic contraction of the bronchial muscles. The effect occurs after destruction of the central nervous system and even after degeneration of the vagi, so that it must be exerted directly on the muscle fiber or myoneural junction (Auer, 1910). It is abolished by atropin (Auer). Chloral is uncertain (Rosenau and Anderson, 1909). Schultz and Jordan, 1911, showed that the severity of the bronchial phenomena in guinea pigs is explained by their Order Adapalene Online relatively thick mucosa; so that the contraction occludes absolutely even the larger bronchi. Blood Pressure. In guinea pigs, the circulatory changes^are mainly asphyxial (Auer and Lewis, 1910). In other animals, there is a characteristic fall of blood pres- sure, often to 20 to 30 mm. Hg. The mechanism of this "anaphylactic shock" appears to be complex. It was commonly attributed to vasodilation (Biedl and Kraus, 1909); but the later evidence Buy Adapalene indicates that it is caused by contraction of the smaller hepatic vessels, preventing the adequate return of blood to the right heart (Mautner and Pick, 1915). The blood accumulates mainly in the large veins, especially of the liver and portal system; so that the smaller vessels of the kidneys, intestines, and other parts cf the body are mechanically drained (Pearce and Eisenbray, 1910 and 1912; Edmunds, 1913); indeed, the fall does not occur if the liver has been excluded from the circula- tion. The liver therefore has a predominant share, directly or indirectly, in the fall, the blood pressure being lowered because a greater part of the blood stagnates in the portal system. Zucker and R. G. Pearce found evidence that the essential process of the anaphy- laxis, peptone or histamin "shock" does not consist in vasodilation, but in constriction of the liver vessels, resulting in deficient blood supply of the right heart, and therefore in venous stasis and fall of arterial pressure. This has been confirmed by Mautner and Pick, 1915. In carnivorous animals, in which the circulatory changes are prominent, they find swelling of the liver volume, from spasm of the smaller hepatic vessels. Adapalene Online Immunity to repeated injection is explained by paralysis of these vessels. These effects do not occur in herbivorae, frogs and turtles, whose liver vessels also fail to respond to epinephrin and barium, and which therefore probably lack constrictor inneryation. Adapalene Benzoyl Peroxide The intestinal arteries are actively constricted, during life, Adapalene Gel in all animals; the veins be- come congested later. The arteries of the lung are also constricted, constituting a further factor in the venous congestion. The vasomotor center is not directly involved in the fall; nor is there any good evidence of a peripheral action on the blood vessels. These continue Order Adapalene to contract to epinephrin or barium; they do not contract to splanchnic stimulation, but this could be explained simply by the altered distribution of the blood. It is conceivable that the ANAPHYLAXIS 371 anaphylaxis directly lowers the tone of the hepatic vessels; but this has not been proven. Airila, 1914, attributes the fall in rabbits to increased resistance of the pulmonary vessels; but Edmunds, 1914, found no evidence of deficient blood supply of the left heart in cats; to the contrary, the pressure in the pulmonary veins often rose. v. Behring, 1914, attributes the shock to clumping of the platelets and thrombosis of the cerebral vessels. The heart suffers by the low blood pressure, and is also affected directly, although this usually plays a minor part in the "shock." The changes are peripheral. As shown by electrocardiograms, on rabbits and dogs, they consist in disturbances of conduction and abnormalities of ventricular contraction, affecting especially the right heart. These may progress to final rigor (Robinson and Auer, 1913; Auer and Robinson, 1913). The heart-muscle and diaphragm show histologic changes; Generic Adapalene also with other anaphylactoid agents (Kundratitz, 1913). The isolated heart of sensitized animals is directly poisoned by the antigen (Cesaris-Demel, 1910-1912), Acute heart failure Buy Adapalene Online is also sometimes seen in intact cats (Edmunds, 1914). Treatment of Anaphylactic Shock. The continued low blood pressure furnishes nn opportunity for investigating ^ the treatment; this is of practical importance because the phenomena are very similar to those of surgical shock. The indications are evidently to relieve the splanchnic congestion and to increase the volume of blood to the heart and medulla. Pearce and Eisenbrey, 1910, found that venous transfusion with blood or saline only increases the splanchnic congestion without aiding the heart or medulla. Arterial transfusion is more successful; but the best results are obtained by combining transfusion into an artery with bleeding from a vein. Cardiac or
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