Drug treatment of venous disease is highly restricted in the United States. It is limited to the use of anticoagulation and anti-inflammatory treatment for complications of thrombosis or the use of antibiotics when infection is present. In Europe, however, a large number of drugs are used to improve venous function and promote reflux in the treatment of lipid scleroderma and venous ulcers. The drugs used include: 1. Particulate-purified flavonoids Typically represented by Evelam, the active ingredients are diosmin and hesperidin, which improve venous and lymphatic reflux and, according to a large double-blind, randomized, placebo-controlled trial in Europe, reduce edema and nocturnal cramps in patients with venous disease, improve transcutaneous oxygen partial pressure and stasis dermatitis, and may help ulcer healing. 2. Zinc preparations The use of this class of drugs is mainly due to the fact that some investigators have formally shown lower than normal serum zinc levels in patients with chronic venous insufficiency and venous ulcers. One study compared different serum zinc levels in patients with venous ulcers treated with compression therapy alone or compression therapy combined with zinc and found that only patients with lower than normal serum zinc levels were given additional zinc therapy to facilitate ulcer healing, while other patients had no significant effect with zinc supplementation. 3. Fibrinolytic drugs In general fibrinolytic drugs are not effective in the treatment of chronic venous insufficiency. Representatives of this class include stanozolol, an androgen with significant fibrinolytic activity, and hexaconitine, a non-selective phosphodiesterase inhibitor with partial fibrinolytic activity. The former has been used to treat patients with chronic venous insufficiency presenting with lipodystrophy and was found to be effective, but a placebo-controlled crossover trial confirmed no significant effect. The latter, despite a small study confirming beneficial ulcer healing, had more side effects than it was worth. In addition to the above-mentioned effects, hexoketococine reduces leukocyte adhesion, inhibits cytokine-mediated neutrophil activation, and reduces the release of superoxide radicals produced in neutrophil degranulation. A multicenter study involving 80 patients with venous ulcers demonstrated a significant reduction in ulcer size with the combination of hexoketococine and compression therapy for 6 months compared to patients treated with compression alone. A higher percentage of ulcers healed in patients treated with hexaconitine compared to controls (60% vs. 29%). Furthermore, one study confirmed that there was no significant difference in side effects between treatment with hexaconitine and treatment with placebo. 4. Calcium hydroxybenzenesulfonate increases lymphatic return to the lower extremities and enhances macrophage-mediated proteolysis, with a net effect of reducing edema. Calcium hydroxybenzenesulfonate was used in 352 patients to reduce the symptoms of chronic venous insufficiency and to reduce the circumference of swollen limbs, but there was no control group in the study. 5. Triclutidine has an anti-erythrocyte aggregation effect and improves the symptoms of patients with mild chronic venous insufficiency. The effect on venous ulcers is not known. 6, aspirin and non-carrier anti-inflammatory drugs There are reports of higher ulcer healing rate with 300mg/d of aspirin treatment, the mechanism of which is unknown. It is speculated that it may be because aspirin can reduce the associated inflammatory response or inhibit the function of platelets. Patients with chronic venous ulcers have higher levels of cyclooxygenase-1 and 2 in the skin than in normal skin. Cyclooxygenase-1 produces prostacyclin, which contributes to angiogenesis. Cyclooxygenase-2 causes a persistent inflammatory response in chronic venous ulcers. There is speculation that chronic venous ulcers can be effectively treated with cyclooxygenase-2 inhibitors; however, this speculation has not been tested in clinical practice.