Mechanism of Action of Venopharmaceuticals and Their Use in the Treatment of Chronic Venous Insufficiency
Venopharmaceuticals are the cornerstone of conservative treatment for chronic venous insufficiency (CVD). Their mechanism of action is complex and not yet fully understood. They act on both micro- and macrocirculation, influence the tone of the venous wall, and their anti-inflammatory action is also significant.
Effect of Venopharmaceuticals on Venous Wall Tone and Their Anti-inflammatory Action
Most venopharmaceuticals increase the tone of the venous wall through modulation of adrenergic signaling. This includes drugs such as flavonoids (rutin and diosmin), as well as aescin, butcher's broom extract (Ruscus), and calcium dobesilate. While flavonoids inhibit the metabolism of norepinephrine indirectly, butcher's broom extract acts directly as an agonist on α1 receptors. Diosmin also reduces venous reflux, preventing further progression of chronic venous insufficiency.
Research in vivo indicates that inflammation is central to all pathologies associated with CVD and is present at all stages of CVD, even before clinical symptoms appear. Therefore, the anti-inflammatory effects of venopharmaceuticals and their ability to suppress the production and effects of free radicals are crucial. Flavonoids, proanthocyanidins, aescin, and calcium dobesilate act as scavengers (radical catchers). The anti-inflammatory effects also include reducing the production of adhesion molecules involved in the development and regulation of the inflammatory response. Proanthocyanidins reduce the expression of adhesion molecules by endothelial cells, while flavonoids similarly affect their expression in neutrophils and monocytes.
Reducing Capillary Permeability
Capillary hyperpermeability and subsequent edema are not only caused by venous hypertension. Studies have shown the influence of oxidative stress and neutrophil interactions with the endothelium on increased capillary wall permeability. Venopharmaceuticals (flavonoids, aescin, butcher's broom extract, and calcium dobesilate) reduce permeability through their antioxidant and anti-inflammatory effects.
The vascular endothelial growth factor (VEGF) plays an important role in regulating capillary permeability. Elevated levels of VEGF in plasma have been observed in CVD patients, particularly in the stage of skin changes.
Preventing the Development of Skin Changes
Chronic inflammation and persistent venous hypertension in CVD lead to the development of skin changes. Increased expression of adhesion molecules promotes leukocyte infiltration into the perivascular space, affecting fibroblast function. The result is undesirable remodeling and damage to skin structures and small vessels. Inflammation also plays a key role in pain perception. C-fibers in the venous wall act as nociceptors and are activated by inflammatory mediators. Therefore, using venopharmaceuticals with anti-inflammatory and antioxidant effects appears justified for preventing and alleviating symptoms.
Lymphatic Drainage and Hemorheological Effects
Advanced stages of CVD are known to be associated with impaired lymphatic drainage. Dysfunction can result from a combination of venous hypertension, reflux, chronic inflammation, and lipid accumulation usually removed by lymph. Coumarins, whether in monotherapy or in combination with rutin, flavonoids, butcher's broom extract, or calcium dobesilate, have been shown to improve lymphatic drainage. These venopharmaceuticals also reduce blood viscosity and/or erythrocyte aggregation.
(mafi)
Sources:
1. Nicolaides A, Kakkos S, Baekgaard N et al. Chapter 8: Venoactive drugs. In: Management of chronic venous disorders of the lower limbs. Guidelines According to Scientific Evidence. Part I. Int Angiol 2018; 37 (3): 232–249, doi: 10.23736/S0392-9590.18.03999-8.
2. Marketed products listed in ATC group C05C (capillary stabilizing agents). Databáze SÚKL. Available at: www.sukl.cz/modules/medication/search.php
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.
