Cutaneous pharmacology

Baynes, Ronald E., Cutaneous Pharmacology and Toxicology Center, College of Veterinary Medicine, North Carolina State University, Raleigh, NC... 

In general, the basic architecture of the integument is similar in most mammals. However, differences in the thickness of the epidermis and dermis in various regions of the body exist between species and within the same species (Table 1.1). In addition, the number of cell layers and the blood flow patterns between species and within species (body site differences) can differ. It is important to understand these variations in the skin for studies involving biopharmaceutics, dermatological formulations, cutaneous pharmacology, and dermatotoxicology (Monteiro-Riviere etal., 1990 Monteiro-Riviere, 1991). 

Hegemann, L., Forstinger, C., Partsch, B., Lagler, I., Krotz, S., and Wolff, K. (1995). Microdialysis in cutaneous pharmacology kinetic analysis of transdermally delivered nicotine, J. Invest. Dermatol, 104 839-843. 

Wester RC, Maibach HI (1983) Cutaneous pharmacology 10 steps to percutaneous absorption. Drug Metab Rev 14 169-205... 

They differ to some extent from signs and symptoms that occur during anaphylaxis not associated with anesthesia. Early subjective symptoms such as malaise, pruritus, sensation of heat, and dizziness are absent in the anesthetized patient. Cutaneous signs in a completely wrapped patient may escape the attention of the anesthetist. The increase in heart rate, a decrease in blood pressure and an increase in airway resistance may be initially misinterpreted as a result of a pharmacological dose-related effect of the drugs, or of excessively light anesthesia. Many differential diagnoses have to be considered (table 1). 

Like bacterial infections of skin, cutaneous fungal infections are treated with either topical or systemic agents. The pharmacology and toxicities of these agents are discussed in Chapter 52. 

Groth L, Jorgensen A, Serup J. Cutaneous microdialysis in the rat insertion trauma and effect of anaesthesia studied by laser Doppler perfusion imaging and histamine release. Skin Pharmacology and Applied Skin Physiology 1998, 11, 125-132. 

Post-phlebrtic syndrome, a complication of acute DVT is estimated to occur in approximately 4% of the population (213). This syndrome is characterized by persistent pain, edema, hyperpigmentation, induration of the skin, and stasis ulceration (214). The post-phlebrtic syndrome may be due to venous hypertension as a result of outflow obstruction or damage to the valves and in the cutaneous microcirculation may manifest as tissue hypoxia and lymphatic obstruction. Chronic venous insufficiency may lead to post-phlebetic syndrome. The syndrome may be the result of abnormalities in the superficial, the perforator, or the deep venous system. The diagnosis is purely clinical. The pharmacologic treament of post-phlebetic syndrome is rather limited, with pentoxifylline reported to improve the healing rate of skin ulcers. 

The mechanism of the psychotogenic effect remains unclear. LSD and some natural hallucinogens such as psilocin, psilocybin (from fungi), bufotenin (the cutaneous gland Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms... 

A comprehensive study comparing the epidermal histologic thickness and the cutaneous blood flow as assessed by LDV was conducted in nine species (mouse, rat, rabbit, cat, dog, pig, cow, horse, and monkey) at five cutaneous sites (buttocks, abdomen, skin over the humeroscapular joint, skin over the thoracolumbar junction and ear). Blood flow did not correlate to skin thickness across species and body sites but rather were independent variables, suggesting that they must be evaluated separately in pharmacology, dermatology, and toxicology studies. 

Albrecht G. Cutaneous side effects in patients on longterm lithium therapy. In Birch NJ, editor. Lithium Inorganic Pharmacology and Psychiatric Use. Oxford IRL Press, 1988 144. 

Roberts DT The risk/benefit ratio of modem antiftmgal pharmacological agents in Aly R, Beutner KR, Maibach H (eds) Cutaneous infection and therapy. New York, Dekker, 1997, pp 183-190. 

Inagaki, N., Miura, T., Daikoku, M., Nagai, H. and Koda, A. (1989). Inhibitory effects of jS-adrenergic stimulants on increased vascular permeability caused by passive cutaneous anaphylaxis, allergic mediators, and mediator releasers in rats. Pharmacology 39, 19-27. 

When a topically applied compound induces a biological response following skin absorption, the quantitation of that response may provide a basis for assessing skin absorption. Indeed, such physiological or pharmacological responses have been employed as endpoints in assessing skin absorption in vivo, and perhaps the most successful example is the vasoconstrictor response to topical corticosteroids. However, while these pharmacodynamic endpoints may be very sensitive and selective for defined classes of compounds, it should be noted that the parameter measured is the product of both the quantity and the potency of the compound under investigation and may not necessarily reflect the extent of skin absorption, cutaneous metabolism, or disposition. 

Stuetz A, Grassberger M, Meingassner JG. Pimecrolimus (Elidel, SDZ ASM 981) preclinical pharmacological profile and skin selectivity. Semin Cutan Med Surg 2001 20 233-241. 

A variety of macrocyclic natural products, either peptides or peptide-mimetic structures with HD AC inhibitory activity and promising pharmacological effects, have been reported. Some of them are shown in Fig. 5 for illustration for instance, romidepsin 9 (FK228) exhibits excellent class I inhibitory activity and has recently been approved by the FDA for the treatment of cutaneous T-cell lymphoma patients [58, 59]. Similarly, the marine natural product largazole 10 that demonstrates potent antiproliferative activity [60] and HC-toxin 11, a fungal metabolite with immunosuppressant activity, have been investigated as cytostatic agents [61, 62]. 

KIMBER, I. CUMBERBATCH, M. (1992) Dendritic cells and cutaneous immune responses to chemical allergens. Toxicology and Applied Pharmacology, 117, 137-146. 

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