indication

Used to treat knee pain in patients with joint inflammation (osteoarthritis). It is usually used in patients who have not responded to other treatments such as acetaminophen, exercise, or physical therapy. Sodium hyaluronate may also be used in plastic surgery to reduce wrinkles on the face or as a filler in other parts of the body. May be used in ophthalmology to assist in the extraction of cataracts, the implantation of intraocular lenses, corneal transplants, glaucoma filtration, retinal attachment and in the treatment of dry eyes. Finally, Sodium hyaluronate is also used to coat the bladder lining in treating interstitial cystitis.

pharmacology

Hyaluronan is similar to a substance that occurs naturally in the joints. It may work by acting as a lubricant and shock absorber in the joint, helping the knee to move smoothly, thereby lessening pain.

mechanism of action

Hyaluronan functions as a tissue lubricant and is thought to play an important role in modulating the interactions between adjacent tissues. Sodium hyaluronate is a polysaccharide which is distributed widely in the extracellular matrix of connective tissue in man. It forms a viscoelastic solution in water which makes it suitable for aqueous and vitreous humor in ophthalmic surgery. Mechanical protection for tissues (iris, retina) and cell layers (corneal, endothelium, and epithelium) are provided by the high viscosity of the solution. Elasticity of the solution assists in absorbing mechanical stress and providing a protective buffer for tissues. This viscoelasticity enables maintenance of a deep chamber during surgical manipulation since the solution does not flow out of the open anterior chamber. In facilitating wound healing, it is thought that it acts as a protective transport vehicle, taking peptide growth factors and other structural proteins to a site of action. It is then enzymatically degraded and active proteins are released to promote tissue repair. Sodium hyaluronate is being used intra-articularly to treat osteoarthritis. Cell receptors that have been identified for sodium hyaluronate fall into three main groups: CD44, Receptor for Hyaluronan-mediated motility (RHAMM) and intracellular adhesion molecule-1 (ICAM-1). CD44 mediates cell interaction with Hyaluronan and the binding of the two functions as an important part in various physiologic events, such as cell aggregation, migration, proliferation and activation; cell-cell and cell-substrate adhesion; endocytosis of Hyaluronan, which leads to Hyaluronan catabolism in macrophages; and assembly of petircellular matrices from HA and proteoglycan. CD44 has two important roles in skin, regulation of keratinocyte proliferation in response to extracellular stimuli and the maintenance of local Hyaluronan homeostasis. ICAM-1 is known mainly as a metabolic cell surface receptor for Hyaluronan, and this protein may be responsible mainly for the clearance of Hyaluronan from lymph and blood plasma, which accounts for perhaps most of its whole-body turnover. Ligand binding of this receptor, thus, triggers a highly coordinated cascade of events that includes the formation of an endocytotic vesicle, its fusion with primary lysosomes, enzymatic digestion to monosaccharides, active transmembrane transport of these sugars to cell sap, phosphorylation of GlcNAc and enzymatic deacetylation. ICAM-1 may also serve as a cell adhesion molecule, and the binding of Hyaluronan to ICAM-1 may contribute to the control of ICAM-1-mediated inflammatory activation.

toxicity

>2400 mg/kg (mouse, oral, sodium salt) >4000 mg/kg (mouse, subcutaneous, sodium salt) 1500 mg/kg (mouse, intraperitoneal, sodium salt)

biotransformation

Hyaluronan is degraded by a family of enzymes called hyaluronidases.

absorption

Hyaluronan is absorbed and diffuses slowly out of the injection site.

route of elimination

Hyaluronan is eliminated via the canal of Schlemm.