HEALTH AND MEDICAL PRODUCTS:TOPICAL ANTI-INFLAMMA TORY TREATMENTS.

TOPICAL ANTI-INFLAMMA TORY TREATMENTS

Inflammation is generally considered a localized physiological response to injury or pathogen infection of the body tissues. Inflammation is categorized as a type of nonspecific response to tissue injury from physical trauma (e.g., impact, abrasion, distortion), intense heat, or irritating chemicals. The common factor among these triggers of inflammation is a cascade involving cell death, connective tissue fiber damage, and/or gen- eral tissue injury. In addition, tissue injury may allow for the introduc- tion of foreign proteins or pathogens (disease-causing agents) such as viruses, fungi, and bacteria. Overall, the changes within the interstitial biological environment lead to a complex process called the inflamma- tory response. The purpose of this response includes temporary repair of the damaged tissue at the injury site and prevention of additional pathogen entry, prevention (or slowing) of the spread of pathogenic agents to other body areas, disposal of cell debris and pathogens, and mobilization of systemic immune defenses to allow for regeneration and wound healing. Such a process causes an increase in vasodilation (dilation of blood vessels) and interstitial fluid accumulation at the injury site, an alteration in the chemical composition of interstitial tissue fluid, and the release of chemical signals (e.g., prostaglandins and histamine), protein factors (e.g., heparin, kinins, complement, and lymphokines), and potassium ions. For example, histamine (released from cells called mast cells and basophils) promotes the vasodilation of local arterioles, increases the permeability of local capillaries, and promotes exudate formation, whereas prostaglan- dins (fatty acid molecules produced from arachidonic acid and located in all cell membranes) sensitize blood vessels to the effects of other inflammatory mediators, induce pain, and allow for the generation of pain- and inflammation-causing free radicals.

Four key medical signs of acute (short-term) inflammation at an ana- tomical body site are redness and heat (attributable to the increased blood flow and blood volume), swelling, and the sensation of pain (attributable to the increased presence of interstitial fluid exudates and edema-causing adjacent nerve ending stimulation). Many over-the-counter products used as topical anti-inflammatory treatments typically provide temporary relief from minor skin inflammation, itching, and superficial rash caused by medical conditions such as eczema, psoriasis, hives (urticaria), seborrheic dermatitis, and diaper rash and from skin contact with potential allergic reaction-causing environmental factors such as soaps, detergents, poison ivy, poison oak, poison sumac, insect bites, jewelry, and cosmetics. These topical treatments typically contain the compound hydrocortisone (i.e., cortisol; C21H30O5), which is a steroid hormone produced by the cortex of the adrenal (suprarenal) gland that is naturally secreted in a characteristic diurnal rhythm and is manufactured synthetically for medical use. Topical corticosteroids (including hydrocortisone) share potent combined anti-inflammatory, antipruritic (relieving and/or preventing itching), and vasoconstrictive (constriction of blood vessels) actions. Hydrocorti- sone inhibits inflammation and pain by stabilizing lysosomal membranes and preventing vasodilation, potentially acts as an antioxidant to counteract the production of free radicals, relieves the sensation of itching by inhibiting the release of histamine, and diminishes redness and swelling by enhancing the vasoconstrictive effects of the hormone epinephrine. These combined effects cause an overall depression of the local inflam- matory response cascade to provide temporary comfort while also causing a delay in wound healing.

The extent of topical corticosteroid absorption through the skin and the subsequent therapeutic effect is determined by many factors, including the chemical vehicle (i.e., the chemical consistency of the ointment or cream product containing the hydrocortisone), the integrity of the epidermal barrier (i.e., applying the treatment on normal healthy skin versus diseased or inflamed skin), and the use of protective and occlusive barrier dressings on the skin. Once absorbed through the skin, hydrocor- tisone typically binds to plasma proteins within the bloodstream, is me- tabolized primarily by the liver, and is excreted from the body by the kidneys.

Some topical over-the-counter creams and ointments contain combi- nations of corticosteroids and antibiotics (e.g., bacitracin zinc, polymyxin B sulfate, neomycin sulfate) and are used to treat ear, eye, and skin infec- tions caused by the presence of bacteria. In addition, these products may also contain lubricants (e.g., glycerin, white petroleum, beeswax, light min- eral oil), emulsifiers (e.g., glyceryl stearate, PEG-40 stearate, polysorbate 60, ceteareth-20), emollients (e.g., isostearyl neopentanoate, cetyl pal- mitate), humectants (e.g., stearyl alcohol, purified water), pH-regulating agents (e.g., calcium acetate, sodium citrate), preservatives (e.g., citric acid, sorbic acid, methylparaben, propylparaben), surfactants (e.g., stearyl alcohol, sodium lauryl sulfate), vitamins (e.g., tocopheryl acetate [vita- min E], vitamin A palmitate, vitamin D), solution binders (e.g., malto- dextrin), skin-soothing natural anti-itch products (e.g., Aloe barbadensis leaf juice or gel, Avena sativa [oat] kernel flour), and agents that en- hance hydrocortisone drug permeation through the skin (e.g., isopropyl myristate).