Percutaneous factors

Alcohol and alcohol ether sulfates have also been studied to determine their toxicity by percutaneous absorption in rats and guinea pigs [354-356]. Alcohol ether sulfates penetrate in the order of 1 ng/cm2/day and alcohol sulfates are less penetrant by a factor of 10. The surfactant absorbed was metabolized. Since it is known that human skin is less permeable than animal skin, only very small amounts of alcohol or alcohol ether sulfates can be absorbed even in the case of complete body exposure. 

Delayed. Usual onset of symptoms occurs approximately 2 h after aerosol exposure. Depending on inhaled or ingested dosage, symptoms may appear at times ranging from 30 min to 20 h after exposure. Effects from skin contact may appear 36 h later. Dimethylsulfoxide as a "carrier" increases the percutaneous effect by a factor of at least 25. 

DE Wurster, SF Kramer. Investigation of some factors influencing percutaneous absorption. J Pharm Sci 50 288-293, 1961. 

Typically, there is a latent period with no visible effects between the time of exposure and the sudden onset of symptoms. This latency can range from 1 minutes to 18 hours and is affected by such factors as the amount of agent involved, the amount of skin surface in contact with the agent, and the area of the body exposed (see Liquids). Moist, sweaty areas of the body are more susceptible to percutaneous penetration by solid nerve agents. 

Another key factor is the part of the body that is exposed to the agent. It takes more time for the agent to penetrate areas of the body that are covered by thicker and tougher skin. The regions of the body that allow the fastest percutaneous penetration are the groin, head, and neck. The least susceptible body regions are the hands, feet, front of the knee, and outside of the elbow. 

Percutaneous absorption is another route of interest for the administration of peptides [158], with metabolism being a complicating factor [159]. Thus, [Leu5]enkephalin and Tyr-Pro-Leu-Gly-NH2 were rapidly degraded on the dermal side after penetration through rat skin preparations [160]. The use of inhibitors confirmed the involvement of serine proteases and metalloenzymes. 

Monraats PS, Pires NM, Agema WR, et al. Genetic inflammatory factors predict restenosis after percutaneous coronary interventions. Circulation. Oct 18 2005 112(16) 2417-2425. 

Imiquimod (Aldara) is an immunomodulator approved for the treatment of external genital and perianal warts in adults. The precise mechanism of its action is not fully understood but is thought to be related to imiquimod s ability to stimulate peripheral mononuclear cells to release interferon- and to stimulate macrophages to produce interleukins-1, -6, -8, and tumor necrosis factor-. Imiquimod should be applied to the wart tissue 3 times per week and left on the skin for 6-10 hours prior to washing off with mild soap and water. Treatment should be continued until eradication of the warts is accomplished, but not for more than a total of 16 weeks. Percutaneous absorption is minimal, with less than 0.9% absorbed following a single-dose application. Adverse side effects consist of local inflammatory reactions, including pruritus, erythema, and superficial erosion. 

The permeability of the skin to a toxic substance is a function of both the substance and the skin. The permeability of the skin varies with both the location and the species that penetrates it. In order to penetrate the skin significantly, a substance must be a liquid or gas or significantly soluble in water or organic solvents. In general, nonpolar, lipid-soluble substances traverse skin more readily than do ionic species. Substances that penetrate skin easily include lipid-soluble endogenous substances (hormones, vitamins D and K) and a number of xenobiotic compounds. Common examples of these are phenol, nicotine, and strychnine. Some military poisons, such as the nerve gas sarin (see Section 18.8), permeate the skin very readily, which greatly adds to then-hazards. In addition to the rate of transport through the skin, an additional factor that influences toxicity via the percutaneous route is the blood flow at the site of exposure. 

Abbreviations aPTT, activated partial thromboplastin time AT, antithrombin HC, heparin cofactor HIT, heparin-induced thrombocytopenia PCI, percutaneous coronary intervention PF, platelet factor UFH, unfractionated heparin. 

Alexander JH, Dyke CK, Yang H, et al. Initial experience with factor-Xa inhibition in percutaneous coronary intervention the XaNADU-PCI Pilot. J Thromb Haemost 2004 2(2) 234-24l. 

Hey has been shown to reduce binding of tPA to its endothelial cell receptor, annexin II, in cell cultures (50). Animal studies have indicated that elevated plasma tHcy could cause acquired dysfibrinogenemia, leading to the formation of clots that are abnormally resistant to fibrinolysis (51), Elevated plasminogen activator inhibitor and tHcy in patients with acute coronary syndrome have been shown to be associated with increased risk for major adverse cardiac events (MACE) after successful percutaneous coronary intervention (PCI) and stenting (52), whereas factor V Leiden mutation and lipoprotein (a) were not. 

Okamoto S, Inden M, Setsuda M, Konishi T, Nakano T Effects oftrapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, in preventing restenosis after percutaneous transluminal coronary angioplasty. Am Heart J 1992 123(6) 1439-1444. 

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