Pharmacodynamic properties
Heparin
Heparin inhibits blood coagulation. Owing to its strong anionic charge, it forms a complex with cationic protein bodies. This applies particularly to antithrombin III (AT III), a α2-globulin and endogenous inhibitor of the coagulation system, leading to a significant increase in its inhibitor reaction speed.
The essential action mechanism is the activation of AT III, which for its part inhibits thrombin and other serine proteases. Thus, not only thrombin (IIa), but also the activated factors XIIa, IXa, Xa and kallikrein are inactivated. This inactivation is dose-dependent.
Heparin also possesses a lipolysis-promoting action by activating the clearing factor and catalysing the release of lipoprotein lipase from endothelial cells, whereby large-molecular chylomicrons are solubilised in the plasma.
Heparin is involved in allergic and anaphylactic reactions. Heparin and histamine are released in the degranulation of mast cells. In haemostasis caused by shock, the presence of heparin reduces the coagulability of the blood. In addition, heparin acts as a mediator in the release of the histamine-degrading enzyme diamine oxidase.
Hydroxyethyl salicylate
Hydroxyethyl salicylate, an ester of salicylic acid, is very readily absorbed.
The salicylic acid released after absorption has an analgesic and anti-inflammatory effect. The action mechanism lies in the inhibition of prostaglandin synthesis and reduced formation of the pain-producing bradykinin from its precursors.
The released salicylic acid supports the antithrombotic effect of heparin by means of inhibition of platelet aggregation.
The keratolytic properties of salicylic acid further loosen the epidermis and facilitate absorption of the other active substances.
Levomenthol
Levomenthol dissolved in alcohol has an antipruritic effect when applied to the skin and a mild local anaesthetic effect on the sensitive nerve endings of the skin.
At the same time it stimulates the cold receptors in the epidermis, whereby a cooling effect is felt, which is increased by the evaporation of the alcohol on the skin surface.
Heparin: Antithrombotic
Hydroxyethyl salicylate:Anti-inflammatory, analgesic; keratolytic
Levomenthol:Local anaesthetic, antipruritic
Pharmacokinetic particulars
Heparin
After absorption through the skin, heparin develops its complex effects in the superficial subcutaneous tissue. Penetration through healthy skin is dose-dependent and is proven for concentrations of 300 IU/g and above. After application to the skin, no systemically therapeutic concentrations are reached.
Hydroxyethyl salicylate
The salicylate is readily released from the hydrophilic gel base of Compagel and rapidly absorbed through the skin. In the tissue it is metabolised into salicylic acid and ethylene glycol. Part of the salicylate is degraded by oxidation and the rest is bound to glucuronic acid and excreted renally. Ethylene glycol is oxidised and excreted as oxalate.
Levomenthol
Levomenthol is absorbed through the skin. It is metabolised in the liver by hydroxylation and subsequent glucuronidation.