Dr: Wael H.Mansy, MD Assistant Professor College of Pharmacy King Saud University

3. Pathophysiology of Varicose Veins: Veins are thin-walled vessels that are easily distended by the chronic pooling of blood in the lower extremities. Chronic distention of veins can reduce effectiveness of one-way venous valves that are present in the lumen to prevent the back flow of blood and lead to a condition termed valvular incompetence. These venous valves work in conjunction with skeletal muscle pumps in the legs to move blood back to the heart from the extremities. Varicose Veins

7. The most common manifestations are : Aching and edema Their appearance through the skin is unsightly. May be associated with varicocele or inguinal hernia. Treatment often involves: The use of support stockings to prevent venous pooling. Surgical interventions may also be used to improve appearance and reduce discomfort. Varicose Veins

8. Chronic venous insufficiency The presence of varicose veins and valvular incompetence can lead to a condition called chronic venous insufficiency. As a result of chronically impaired blood flow, congestion, edema and poor tissue nutrition, pathologic changes may eventually occur in the lower extremities.

9. Manifestations may include: skin atrophy, dermatitis, ulceration and tissue necrosis. Infection or trauma of the lower extremities that occurs in a patient with chronic venous insufficiency may have serious consequences because poor blood flow reduces delivery of immune cells and impairs wound healing. Treatment involves: interventions similar to those for varicose veins. Chronic venous insufficiency

10. Venous Thrombosis A thrombus is A blood clot that forms in the lumen of a blood vessel. A thrombus may form in an artery, but it is more common in veins due to the lower pressure and reduced blood flow found in the venous circulation. Factors that may contribute to the formation of a thrombus include the following: 1. Stasis of blood due to poor blood flow, immobility, heart failure, myocardial infarction and hypotension 2. Damage to blood vessels from trauma, surgery, IV drugs, catheters or immune response 3. Hypercoagulability of blood resulting from pregnancy, malignancies, coagulation disorders, dehydration or use of oral contraceptives

11. Thrombi may form in superficial vessels of the skin and extremities or in deep veins of circulation or tissues. Most superficial thrombi are benign and self-limiting, but deep vein thrombus (DVT) can be much more dangerous. Although a thrombus may present with pain, tenderness and swelling, it is estimated that nearly half of all deep vein thrombi are asymptomatic. As most deep vein thrombi occur in the lower extremities, painful compression or tenderness and swelling of the calf or thigh region might be used to diagnose a DVT in these areas. DVT are associated with significant mortality and morbidity and require intensive treatment. Venous Thrombosis

12. Treatment and prevention of venous thrombus Prevent blood stasis in susceptible patients through ambulation, use of elastic stockings, exercise or elevation of legs Anticoagulation therapy (warfarin, heparin) Thrombolytic therapy to dissolve clots (streptokinase, TPA). Surgical removal of clots.

13. Embolism Unfortunately, for many patients with DVT the first manifestation of the thrombus is a pulmonary embolism. An embolism is a thrombus that breaks loose and travels through circulation. Common sites for lodging of emboliare the small pulmonary blood vessels of the lungs. Emboli that lodge in cerebral or coronary blood vessels may be rapidly fatal. A bolus of fat released by the breakage of long bones or an injection of air o foreign matter into the bloodstream through intravenous or intra-arterial lines can also act as an embolism. Ischemia and possible death of tissues may occur when blood flow is blocked by an embolus.

14. Anticoagulant and thrombolytic drug therapy Anticoagulant drugs prevent the formation of blood clots by interfering with distinct steps in the blood-clotting cascade (see Chapter 3). Two of the most commonly used anticoagulants are warfarin (administered orally) and heparin (administered intravenously). Warfarin prevents the reduction of vitamin K, which is a cofactor necessary for activity of a key carboxylase in the clotting cascade. Heparin acts via an effect on antithrombin III. As a result of its mechanism of action, warfarin does not exert an anticoagulant effect in vitro (i.e., blood in test tube) whereas Anticoagulant drugs prevent the formation of blood clots by interfering with distinct steps in the blood-clotting cascade . Two of the most commonly used anticoagulants heparin does. Neither warfarin nor heparin has any action against clots that have already formed. Both drugs are bound to a significant extent to circulating plasma proteins that can alter their bioavailability. A main potential adverse effect of both warfarin and heparin is unwanted bleeding and hemorrhage. Drugs that inhibit microsomal metabolism, inhibit platelet aggregation or displace oral anticoagulants from plasma proteins can enhance the action of anticoagulants and increase the risk of unwanted bleeding.

15. Aspirin is a potent inhibitor of platelet aggregation through its inhibition of the enzyme cyclo-oxygenase. Inhibition of the cyclo-oxygenase enzyme reduces the formation of thromboxane A2 , a substance that stimulates platelet aggregation . Since platelet aggregation and activation appear to play a major role in thrombus formation, drugs like aspirin may be of significant therapeutic value in preventing their occurrence. A number of clinical trials have demonstrated the effectiveness of aspirin in preventing the tissue damage that accompanies blood vessel occlusion in arteriosclerosis and myocardial infarction. Anticoagulant and thrombolytic drug therapy

16. Anticoagulant and thrombolytic drug therapy Thrombolytic drugs are also known as fibrinolytic or clot-dissolving drugs. Unlike anticoagulants that prevent the formation of blood clots, thrombolytic drugs cannot prevent their formation. A number of thrombolytic drugs are now available for clinical use, including streptokinase, anistreplase, alteplase (tissue plasminogen activator) and urokinase. These agents promote the formation of plasmin (from plasminogen), an enzyme that degrades the fibrin proteins that make up the framework of a thrombus. The most common unwanted effects of these thrombolytic agents are unwanted bleeding and hemorrhage. Thrombolytic drugs have proved to be of clinical benefit in reducing mortality in patients experiencing myocardial infarction.