Hyaluronic acid (HA) is a high molecular weight biopolysacharide, discovered in 1934, by Karl Meyer and his assistant, John Palmer in the vitreous of bovine eyes. Hyaluronic acid is a naturally occurring biopolymer, which has important biological functions in bacteria and higher animals including humans. It is found in most connective tissues and is particularly concentrated in synovial fluid, the vitreous fluid of the eye, umbilical cords and chicken combs. It is naturally synthesized by a class of integral membrane proteins called hyaluronan synthases, and degraded by a family of enzymes called hyaluronidases. Hyaluronan synthase enzymes synthesize large, linear polymers of the repeating disaccharide structure of hyaluronan by alternating addition of glucuronic acid and N-acetylglucosamine to the growing chain using their activated nucle¬otide sugars (UDP – glucuronic acid and UDP-N-acetlyglucosamine) as substrates. The number of repeat disaccharides in a completed hyaluronan molecule can reach 10 000 or more, a molecular mass of ~4 million daltons (each disaccharide is ~400 daltons). The average length of a disaccharide is ~1 nm. Thus, a hyaluronan molecule of 10 000 repeats could ex¬tend 10 μm if stretched from end to end, a length approximately equal to the diameter of a human erythrocyte. Although the predominant mechanism of HA is unknown, in vivo, in vitro, and clinical studies demonstrate various physiological effects of exogenous HA. Hyaluronic acid possesses a number of protective physiochemical functions that may provide some additional chondroprotective effects in vivo and may explain its longer term effects on articular cartilage. Hyaluronic acid can reduce nerve impulses and nerve sensitivity associated with pain. In experimental osteoarthritis, this glycosaminoglycan has protective effects on cartilage. Exogenous HA enhances chondrocyte HA and proteoglycan synthesis, reduces the production and activity of proinflammatory mediators and matrix metalloproteinases, and alters the behavior of immune cells. In addition to its function as a passive structural molecule, hyaluronan also acts as a signaling molecule by interacting with cell surface receptors and regulating cell proliferation, migration, and differentiation. Hyaluronan is essential for embryogenesis and is likely also important in tumorigenesis. HA plays several important organizational roles in the extracellular matrix (ECM) by binding with cells and other components through specific and nonspecific interactions. Hyaluronan-binding pro¬teins are constituents of the extracellular matrix, and stabilize its integrity. Hyaluronan receptors are involved in cellular signal transduction; one receptor family includes the binding proteins aggrecan, link protein, versican and neurocan and the receptors CD44, TSG6, GHAP and LYVE-1. The chondroprotective effects of hyaluronic acid, e.g., that it stimulates the production of tissue in¬hibitors of matrix metalloproteineses (TIMP-1) by chondrocytes, inhibits neutrophil-mediated cartilage degradation and attenuates IL-1 induced matrix de¬generation and chondrocyte cytotoxicity have been observed in vitro. Articular chondrocytes cultured in the presence of HA have a significantly greater rate of DNA proliferation and ex¬tracellular matrix production, compared with chon¬drocytes cultured without HA.

Lofexidine is newly FDA approved in the United States under the brand name LUCEMYRA for the treatment of opioid withdrawal symptoms in adults. Lofexidine acts as an agonist to α2 adrenergic receptors. These receptors inhibit adenylyl cyclase activity, leading to the inhibition of the second messenger, cyclic adenosine monophosphate (cAMP). The inhibition of cAMP leads to potassium efflux through calcium-activated channels, blocking calcium ions from entering the nerve terminal, resulting in suppression of neural firing, inhibition of norepinephrine release. Lofexidine replaces the opioid-driven inhibition of cAMP production and moderating the symptoms of opioid withdrawal.

Alfuzosin is a quinazoline-derivative alpha-adrenergic blocking agent used to treat hypertension and benign prostatic hyperplasia. Alfuzosin is marketed in the United States by Sanofi Aventis under the brand name Uroxatral. UROXATRAL (alfuzosin HCl extended-release tablets) is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia. UROXATRAL is not indicated for the treatment of hypertension. Alfuzosin is a non-subtype specific alpha(1)-adrenergic blocking agent that exhibits selectivity for alpha(1)-adrenergic receptors in the lower urinary tract. Inhibition of these adrenoreceptors leads to the relaxation of smooth muscle in the bladder neck and prostate, resulting in the improvement in urine flow and a reduction in symptoms in benign prostate hyperplasia. Alfuzosin also inhibits the vasoconstrictor effect of circulating and locally released catecholamines (epinephrine and norepinephrine), resulting in peripheral vasodilation.

Pioglitazone (brand name Actos) is a prescription drug of the thiazolidinedione class with hypoglycemic action used in the treatment of type 2 diabetes. Pioglitazone selectively stimulates the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) and to a lesser extent PPAR-α. It modulates the transcription of the genes involved in the control of glucose and lipid metabolism in the muscle, adipose tissue, and the liver. As a result, pioglitazone reduces insulin resistance in the liver and peripheral tissues, decreases gluconeogenesis in the liver, and reduces the quantity of glucose and glycated hemoglobin in the bloodstream. Pioglitazone is used to lower blood glucose levels in the treatment of diabetes mellitus type 2 (T2DM) either alone or in combination with a sulfonylurea, metformin, or insulin. Pioglitazone cannot be used in patients with a known hypersensitivity to pioglitazone, other thiazolidinediones or any of components of its pharmaceutical forms. It is ineffective and possibly harmful to diabetes mellitus type 1 and diabetic ketoacidosis. Pioglitazone can cause fluid retention and peripheral edema. As a result, it may precipitate congestive heart failure (which worsens with fluid overload in those at risk). It may cause anemia. Mild weight gain is common due to increase in subcutaneous adipose tissue. In studies, patients on pioglitazone had an increased proportion of upper respiratory tract infection, sinusitis, headache, myalgia and tooth problems.

Dexmedetomide (biologically active dextroisomer of medetomidine) is an alpha2-adrenergic agonist which was approved by FDA for the sedation purposes. Upon administration the drug activates the alpha2 receptors thus inhibiting the release of norepinephrine and terminating the propagation of pain signals. Also it inhibits sympathetic activity and thus can decrease blood pressure and heart rate.

Tamsulosin, a sulfamoylphenethylamine-derivative alpha-adrenoceptor blocker with enhanced specificity for the alpha-adrenoceptors of the prostate, is commonly used to treat benign prostatic hyperplasia (BPH). The drug is commercially available in a racemic mixture of 2 isomers, and is pharmacologically related to doxazocin, prazosin, and terazosin. However, unlike these drugs, tamsulosin has a higher affinity for the alpha-1A- adrenergic receptors, which are located in vascular smooth muscle. Studies show that tamsulosin has about 12 times greater affinity for alpha-1 adrenergic receptors in the prostate than those in the aorta, which may result in a reduced incidence of adverse cardiovascular effects. Tamsulosin is sold under the trade name Flomax.