McKenna's Pharmacology for Nursing, 2e

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P A R T 8  Drugs acting on the cardiovascular system

the area of the injury. These actions maintain the closed nature of the cardiovascular system (see Figure 48.3). Clot resolution and anticlotting process Blood plasma also contains anticlotting substances that inhibit clotting reactions that might otherwise lead to an obstruction of blood vessels by blood clots. For example, antithrombin III prevents the formation of thrombin, thus stopping the breakdown of the fibrin threads. Another substance in the plasma, called plasmin or fibrinolysin, dissolves clots to ensure free movement of blood through the system. Plasmin is a protein-dissolving substance that breaks down the fibrin framework of blood clots and opens up vessels. Its precursor, called plas- minogen , is made in the liver and is found in the plasma. The conversion of plasminogen to plasmin begins with the activation of Hageman factor and is facilitated by a number of other factors, including antidiuretic hormone (ADH), adrenaline, pyrogens, emotional stress, physical activity and the chemicals urokinase and streptokinase. Plasmin helps to keep blood vessels open and functional. Very high levels of plasmin are found in the lungs (which contain millions of tiny, easily injured capillaries) and in the uterus (which in pregnancy must maintain a constant blood flow for the developing fetus). The action of plasmin is evident in the female menstrual flow, in that clots do not form rapidly when the lining of the uterus is shed; the blood oozes slowly over a period of days (Figure 48.4). ■■ The transformation of fluid blood into a solid state to seal breaks in the vascular system is known as coagulation. ■■ The coagulation process involves vasoconstriction, platelet aggregation to form a plug and intrinsic and extrinsic clot formation initiated by Hageman factor to plug any breaks in the system. ■■ The conversion of prothrombin to thrombin, which results in insoluble fibrin threads, is the final step of clot formation. ■■ To prevent the occlusion of blood vessels and the denying of blood to the tissues, a formed clot must be dissolved. ■■ The base of the clot-dissolving system is the conversion of plasminogen to plasmin (fibrinolysin) by several factors, including Hageman factor. Plasmin dissolves fibrin threads and resolves the clot. KEY POINTS

Low-molecular-weight heparin Bivalirudin

A

Factor X a

Prothrombin

Thrombin

Antithrombin III Heparin

Fibrinogen

Fibrin

Clot

Antithrombin III Heparin

Antithrombin III Heparin

B

Plasminogen (=profibrinolysin; a plasma protein)

Plasmin (=fibrinolysin)

Facilitated by: Factor XI Hageman factor (=XII ) ADH Adrenaline Pyrogens Emotional stress Physical activity Streptokinase Reteplase a a

Fibrin clot

Dissolution of clot

Anistreplase Alteplase Tenecteplase

fall into two main categories: (1) conditions that involve overproduction of clots, or thromboembolic disorders; and (2) conditions in which the clotting process is not working effectively, resulting in risk for excess bleeding. Thromboembolic disorders Medical conditions that involve the formation of thrombi result in decreased blood flow through or total occlusion of a blood vessel. These conditions are marked by the signs and symptoms of hypoxia, anoxia or even necrosis in areas affected by the decreased blood flow. In some of these disorders, pieces of the thrombus, called emboli, can break off and travel through the cardio­ vascular system until they become lodged in a tiny vessel, plugging it up. Conditions that predispose a person to the forma­ tion of clots and emboli are called thromboembolic disorders . Coronary artery disease (CAD) involves a narrowing of the coronary arteries caused by damage to the endothelial lining of these vessels. Thrombi tend to form along the damaged endothelial lining. As the damage builds up, the lumens of the vessels become narrower and narrower. Over time, the coronary arteries are unable to deliver enough blood to meet FIGURE 48.4  A. Anticlotting process. Antithrombin III (in plasma) inhibits the activity of Stuart factor (factor Xa) and thrombin; the drug heparin enhances the activity of antithrombin III. Steps in clot formation that are inhibited by heparin are shown in red. B. Fibrinolytic process: Clots are dissolved. The step that is facilitated by the clot-dissolving drugs and by other agents is shown in blue.

DISORDERS AFFECTING BLOOD COAGULATION

Disorders that directly affect the coagulation process are referred to as haemorrhagic disorders. These disorders