HEALTH AND MEDICAL PRODUCTS:PRURITUS (ITCH) TREA TMENTS.

PRURITUS (ITCH) TREA TMENTS

Pruritus, synonymous with itch, is often defined as an unpleasant sensation on the skin that provokes the desire to rub or scratch the affected area to obtain relief. Itch of cutaneous origin (also referred to as “pruritoceptive” or “peripheral” itch) is a very common medical symptom, consciously perceived as being a mere prickling or tingling or may be so intense as to be nearly intolerable. There are regional differences in the severity of the body’s reaction to the itch, and chronic itching may lead to constant discomfort and frustration, with extreme cases causing disturbed sleep, anxiety, and depression.

Localized pruritus may result from the fact that certain parts of the body have a predilection for certain disease processes (e.g., scalp: eczema, psoriasis; eyelid: airborne irritants or allergens; nose: hay fever; fingers: eczema, scabies; legs: gravitational eczema; groin: vaginitis). General pruritus that occurs over large body areas may be the result of external causes such as exposure to severe changes in environmental climate (e.g., temperature, humidity), exposure to irritating particulate matter, allergens, or chemicals (e.g., detergents), or excessive bathing (e.g., aquagenic pruritus). General pruritus may also be the result of various skin problems (e.g., overly dry skin, dermatitis, prickly heat, acne, eczema, psoriasis, sunburn, urticaria), pregnancy, and various general systemic diseases, in- cluding microorganismal infestation (e.g., viruses, parasites, bacteria, fungi), endocrine disorders (e.g., diabetes, hypothyroidism or hyperthyroidism, hypoparathyroidism), nerve disorders (e.g., multiple sclerosis), liver mal- function (e.g., cholestasis, obstructive jaundice, cirrhosis), kidney failure, blood imbalances (e.g., iron deficiency anemia, polycythemia), autoimmune syndromes, and various types of malignant cancers. In some cases, itching can be the first sign of a serious internal illness. Itch can also be a side effect of a wide variety of drugs, including aspirin, birth control pills, testosterone, morphine, penicillin, and the antimalaria drug chloroquine. While pruritus also may be solely psychogenic or psychiatric in origin, emotional stress and psychological trauma intensify all forms of pruritus.

Sensory receptors are specialized cells or cell processes that provide the CNS (brain and spinal cord) with information concerning the inside or outside of the body. A sensory receptor detects an arriving stimulus and translates the stimulus into an electrochemical signal that can be con- ducted to the CNS for processing. Cutaneous itch receptors are unspe- cialized free nerve endings located near the dermal-epidermal junction of the skin. These nerve endings lack an electrochemical signal conduction velocity-enhancing covering called a myelin sheath and are very small in diameter, characterized as type C fibers that conduct impulses very slowly at one meter per second or less. These itch-transmitting unmyelinated C fibers enter the dorsal horn area of the spinal cord gray matter, synapse there with other secondary neurons (nerve cells), which in turn cross over to the contralateral spinothalamic tract (a collection of nerve fibers in the CNS) and ascend to the thalamus of the brain. Within the thala- mus, tertiary (third-order) neurons then relay the sensation of itch to the cerebral sensory cortex. The cerebral cortex is the part of the brain in- volved with processing conscious awareness and allows the sensation of a low-intensity stimulus affecting the skin to be perceived as an “itch” that needs to be scratched.

Biochemicals that have been shown to be direct mediators of the phys- iological itch response include histamine and substance P. Histamine, produced by mast cells within the dermis, is released and causes itching by promoting the dilation of local blood vessels, increasing the permeability of local capillaries, and promotes exudate formation as a result of dermal mast cell injury. Of the two different subclasses of histamine receptors (H1 and H2) identified in human skin, only the H1 receptor has been shown to be involved in histamine-induced itching. Substance P, a neurotransmitter peptide released by the unmyelinated type C fibers, dilates blood vessels and indirectly activates mast cells to release histamine, thereby causing additional redness, swelling, and itching of the skin.

As already described, pruritus is an obvious sensory feature of many different external and internal sources. The motor response that the sen- sation of itching evokes (i.e., scratching with the nails of the hands or feet), if not controlled, often perpetuates and intensifies the symptom and may lead to serious skin damage (e.g., abrasion, laceration, lichenification [skin thickening]), thereby reducing the ability of the skin to function as a protective barrier against infectious disease. It has been suggested that the act of scratching excites the local nerve plexus (through which the itch sensation is transmitted), which then disrupts the rhythmic system- atic flow of afferent impulses traveling toward the spinal cord required for the itch sensation, alleviating the itch. However, skin damage caused by scratching itself leads to the release of itch-mediating chemicals (e.g., histamine), which once again elicits a scratch response. Thus, controlling the itch-scratch-itch cycle with home remedies, including cold com- presses and soaking in tepid baths containing colloidal oatmeal, or with topical over-the-counter anti-itch products, is of paramount concern.

Topical treatments that provide symptomatic relief of pruritus can in- clude active ingredients such as diphenhydramine HCl, pramoxine hydrochloride, camphor, menthol, phenol, dimethicone, zinc acetate, and calamine. Diphenhydramine hydrochloride [2-(diphenylmethoxy)-N,N- dimethylethylamine hydrochloride; C17H21NO·HCl], an H1 antagonist of the ethanolamine class, acts as an antihistamine by competing with

free histamine for binding at H1 receptor sites. Blockage of such sites also suppresses the formation of edema, flare, and pruritus that normally result from histaminic activity. Topical diphenhydramine provides temporary relief from pruritic skin irritation, possibly attributable to an anesthetic (numbing) effect resulting from the decreased permeability of nerve cell membranes to sodium ions, thereby preventing the transmission of nerve impulses. Pramoxine hydrochloride (morpholine 4-[3-(4- butoxyphenoxy)propyl]-, hydrochloride) is also a local anesthetic that in- terferes with the function of nerves that sense pain and thus temporarily relieves minor pain, itching, and discomfort. In addition, both camphor (C10H16O), a ketone synthesized from oil of turpentine ingredients or obtained naturally by steam distillation of the wood of the camphor tree (Cinnamomum camphora), and menthol (C10H19OH), a stearopten ob- tained from oil of peppermint (Mentha piperita), also exhibit anesthetic properties by producing sensations of warmth, followed by a chilling sensation. Phenol (C6H5OH), an aromatic alcohol obtained from coal tar, acts as an antiseptic and disinfectant to decrease the chance of wound in- fection. Dimethicone ([-Si(CH3)2O-]n) imparts lubricity and softness to the antipruritic cream product and serves as a skin protectant, while both zinc acetate [(CH3COO)2Zn2H2O] and calamine [(ZnOH)2SiO3] act as skin protectants and drying agents.