Blood vessel reactions

C. It is secreted along with noradrenaline by the adrenal medulla, from which it may be obtained. It may be synthesized from catechol. It is used as the acid tartrate in the treatment of allergic reactions and circulatory collapse. It is included in some local anaesthetic injections in order to constrict blood vessels locally and slow the disappearance of anaesthetic from the site of injection. Ultimately it induces cellular activation of phosphorylase which promotes catabolism of glycogen to glucose. 

A base, formed by the bacterial degradation of histidine, and present in ergot and in many animal tissues, where it is liberated in response to injury and to antigen-antibody reactions. If injected it causes a condition of shock with dilatation of many blood vessels, loss of plasma from the capillaries to the tissues and a rapid fall in blood pressure. It is normally prepared from protein degradation products. 

Another important reaction of diketene derivatives is the Hant2sch pyridine synthesis (101). This synthesis is the preparation of 1,4-dihydropyridines (14) starting either from two acetoacetic esters, which react with an aldehyde and ammonia or a primary amine or from 3-aminocrotonates and 2-alkyhdene acetoacetic esters, both diketene derivatives. Several such dihydropyridines such as nifedipine [21829-25-4] (102), nimodipine [66085-59-4] and nicardipine [55985-32-5] exhibit interesting pharmaceutical activity as vasodilators (blood vessel dilation) and antihypertensives (see Cardiovascularagents). 

Eye. Adverse effects may be produced by splashes of Hquids or soflds, and by materials dispersed in the atmosphere. The eye is particularly sensitive to peripheral sensory irritants in the atmosphere. Toxic effects that may be induced include transient acute inflammation, persistent damage, and, occasionally, sensitivity reactions. ToxicologicaHy significant amounts of material may be absorbed by the periocular blood vessels in cases of splash contamination of the eye with materials of high acute toxicity (58). 

Dismption of the endothehal surface of blood vessels expose coUagen fibers and connective tissue. These provide surfaces that promote platelet adherence, platelet release reaction, and subsequent platelet aggregation. Substances Hberated from the platelets stimulate further platelet aggregation, eg, adenosine diphosphate maintain vasoconstriction, eg, serotonin and participate in blood coagulation, eg, platelet Factors III and IV. In addition, the release reaction modifies platelet membranes in a manner that renders phosphoHpid available for coagulation. The thrombin [9002-04-4] elaborated by the coagulation mechanism is a potent agent in the induction of the platelet release reaction. 

Hemostasis is the process that stops bleeding in a blood vessel. Normal hemostasis involves a complex process of extrinsic and intrinsic factors. Figure 44-1 shows the coagulation pathway and factors involved. The copulation cascade is so named because as each factor is activated it acts as a catalyst that enhances the next reaction, with the net result being a large collection of fibrin that forms a plug in the vessel. Fibrin is the insoluble protein that is essential to clot formation. 

Q Ineffective Tissue Perfusion related to adverse drug reactions Q Risk for Injury related to adverse drug reactions Q Pain related to obstruction of blood vessel... 

Primary irritants cause inflammation. Inflammation is one of the body s defence mechanisms. It is the reaction of a tissue to harm which is insufficient to kill the tissue and is typified by constriction of the small vessels in the affected area, dilation of the blood vessels, increased permeability of the vessel walls, and migration of the white blood and other defensive cells to the invading harmful chemical. The aim is to concentrate water and protein in the affected area to dilute the effect and wash away the chemical. Production of new cells is speeded up and contaminated surface cells are shed. 

Low levels of exposure often cause weakness, headache, disorientation, nausea, and vomiting. Higher levels may result in loss of consciousness or may terminate respiration, leading to death within 15 minutes. An immediate lethal dosage often causes violent contractions of blood vessels accompanied by severe shock. This reaction may cause death prior to asphyxiation.1... 

Vitamin C is essential for the formation of collagen, the principal structural protein in skin, bone, tendons, and ligaments, being a cofactor in the hydroxylation of the amino acids proline to 4-hydroxyproline, and of lysine to 5-hydroxylysine. These hydroxyamino acids account for up to 25% of the collagen structure. Vitamin C is also associated with some other hydroxylation reactions, e.g. the hydroxylation of tyrosine to dopa (dihydroxyphenylalanine) in the pathway to catecholamines (see Box 15.3). Deficiency leads to scurvy, a condition characterized by muscular pain, skin lesions, fragile blood vessels, bleeding gums, and tooth loss. Vitamin C also has valuable antioxidant properties (see Box 9.2), and these are exploited commercially in the food industries. 

Histamine (B). Histamine is stored in basophils and tissue mast cells. It plays a role in inflammatory and allergic reactions (p. 72, 326) and produces bronchoconstriction, increased intestinal peristalsis, and dilation and increased permeability of small blood vessels. In the gastric mucosa, it is released from enterochromaffin-like cells and stimulates acid secretion by the parietal cells. In the CNS, it acts as a neuromodulator. Two receptor subtypes (G-pro-tein-coupled), H and H2. are of therapeutic importance both mediate vascular responses. Prejunctional H3 receptors exist in brain and the periphery. 

In a complex reaction, NO arises from arginine in the endothelial cells of the blood vessels [1 ]. The trigger for this is Ca -calmodulin (see p. 386), which forms when there is an increase in the cytoplasmic Ca " level. 

Norepinephrine is the primary neurotransmitter produced and released by adrenergic neurons, and in literature it is also described as and called (-) noradrenaline or levarterenol. This vasopressor catecholamine reduces both the resistance and capacity of blood vessels by stimulating a-adrenoreceptors and having a direct cardiostimulatory effect, which is accomplished by activation of )3i-adrenoreceptors. Norepinephrine exhibits significantly less activity than epinephrine as a drug for widening blood vessels through the activation of jSj-adrenoreceptors. Elevation of both stylistic and diastolic blood pressure is a typical reaction to intravenous introduction of norepinephrine. 

Although Celsinger had the mild form of OTC deficiency, he volunteered for a University of Pennsylvania trial to test the safety and efficacy of increasing doses of an OTC vector because he wanted to help severely affected newborns. He died four days after the vector was injected into a blood vessel in his liver. An autopsy showed that he died of a severe inflammatory response to the adenoviral vector, which led to a blood reaction that caused most of his organs to shut down. 

The clinical uses of catecholamines are based on their actions on bronchial smooth muscle, blood vessels, and the heart. Epinephrine is also useful for the treatment of allergic reactions that are due to liberation of histamine in the body, because it produces certain physiological effects opposite to those produced by histamine. It is the primary treatment for anaphylactic shock and is... 

Prompt intensive treatment with corticosteroids may be lifesaving when an excessive inflammatory reaction has resulted in septic shock. A massive infusion of corticosteroids can restore cardiac output and reverse hypotension by sensitizing the response of adrenoceptors in the heart and blood vessels to the stimulating action of catecholamines. This protective role of steroids may be due to a direct effect on vascular smooth muscle. The combination of glucocorticoids and dopamine therapy preserves renal blood flow during shock. 

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