Topically applied

Because of the outbreak of antimony-resistant leishmania sis and the need to develop an oraky-adrninistered therapy, the use of many other compounds has been considered. Those that appear to have clinical utility ate aHoputinol (62), ketoconazole (63), and both systemicaHy and topically applied paromomycin (8) (see Antiparasitic agents, antimycotics). 

Blum and Kearns (1) showed in the American cockroach that topically applied pyrethrum shows a negative temperature coefficient of action between 15° and 35°C. The 24-hour LDso for pyrethrum is about 1 g. at 15°C. and about 6 Mg- at 35°C. 

Effects of topically applied liposomes on disposition of epinephrine and inulin in the albino rabbit eye, Int. J. Pharm., n, 263-272. 

M. S. Determination of the effect of lipophilidty on the in vitro permeability and tissue reservoir charaderistics of topically applied solutes in human skin layers. J. Invest. Dermatol. 2003, 120, 759-764. 

Erythema, inflammation, pain, and itching caused by contact dermatitis can be effectively treated with topically applied corticosteroids. With such a wide range of products and potencies available, an appropriate steroid selection is based on severity and location of the lesions. Table 62-6 shows a list of topical steroids and their potencies. Higher-potency preparations are used in areas where penetration is poor, such as on the elbows and knees. Lower-potency products should be reserved for areas of higher penetration, such as on the face, axillae, and groin. Low-potency steroids are also recommended for the treatment of infants and children.32,33... 

Several topically applied local anesthetics are routinely used by the eye care specialist in certain routine diagnostic procedures and for various relatively simple surgical procedures such as insertion of punctal plugs and surgical vision correction. The first of these to be used was cocaine, in concentrations ranging from 1 to 4% [30]. More modern local anesthetics, however, such as tetracaine hydrochloride and proparacaine hydrochloride, have replaced cocaine as drugs of choice in these procedures. For surgical procedures of a more complex nature, lidocaine hydrochloride and similar local anesthetics as retrobulbar injections have been used [31]. 

The eye is unique in its therapeutic challenges. An efficient mechanism, that of tears and tear drainage, which quickly eliminates drug solution, makes topical delivery to the eye somewhat different from most other areas of the body [137]. Usually less than 10% of a topically applied dose is absorbed into the eye, leaving the rest of the dose to potentially absorb into the bloodstream [138], resulting in unwanted side effects. The goal of most controlled-delivery systems is to... 

Transdermal Administration. The development of the stratum corneum is complete at birth and is considered to have permeability similar to that of adults, except in preterm infants [81], Preterm neonates and infants have an underdeveloped epidermal barrier and are subject to excessive absorption of potentially toxic ingredients from topically applied products. 

Scheme 1 Ocular penetration routes for topically applied drugs. l,Transcornealpathway 2, noncorneal pathway 3, systemic return pathway 4, lateral diffusion. (From Ref. 1.)... 

Figure 6 Epithelial penetration routes for topically applied drugs. The transcellular route (1) is preferred by lipophilic drugs, while the paracellular route (2) is preferred by hydrophilic drugs.

Nevertheless, there are reports on enhancement of ocular drug absorption by bile salts [33], surfactants [200], and chelators [149], Newton et al. [35] demonstrated that Azone, an enhancer widely tested in transdermal drug delivery [201], increased the ocular absorption of cyclosporine, an immunosuppressant, by a factor of 3, thereby prolonging the survival of a corneal allograft. In 1986, Lee et al. [34] reported that 10 pg/mL cytochalasin B, an agent capable of condensing the actin microfilaments, increased the aqueous humor and iris-ciliary body concentrations of topically applied inulin (5 kDa) by about 70% and 700%, respectively, in the albino rabbit. 

MG Doane, AD Jenson, CH Dohlman. (1978). Penetration routes of topically applied eye medications. Am J Ophthalmol 85 383-386. 

TF Patton, JR Robinson. (1976). Quantitative precorneal disposition of topically applied pilocarpine nitrate in rabbit eyes. J Pharm Sci 65 1295-1301. 

SC Chang, DS Chien, H Bundgaard, VHL Lee. (1988). Relative effectiveness of prodrug and viscous solution approaches in maximizing the ratio of ocular to systemic absorption of topically applied timolol. Exp Eye Res 46 59-69. 

C Newton, BM Gebhardt, HE Kaufman. (1988). Topically applied cyclosporine in azone prolongs corneal allograft survival. Invest Ophthalmol Vis Sci 29 208-215. 

VHL Lee, LW Carson, S Dodda Kashi, RE Stratford Jr. (1986). Metabolic and permeation barriers to the ocular absorption of topically applied enkephalins in albino rabbits. J Ocular Pharmacol 2 345-352. 

A Kupferman, MV Pratt, K Suckewer, HM Leibowitz. (1974). Topically applied steroids in corneal disease. III. The role of drug derivative in stromal absorption of dexamethasone. Arch Ophthalmol 91 373-376. 

SS Chrai, MC Makoid, SP Eriksen, JR Robinson. (1974). Drop size and initial dosing frequency problems of topically applied ophthalmic drugs. J Pharm Sci 63 333-338. 

AM Luo, H Sasaki, VHL Lee. (1991). Ocular drug interactions involving topically applied timolol in the pigmented rabbit. Curr Eye Res 10 231-240. 

It is important to realize that there is a great deal of overlap in the topics covered in this chapter. For example, the chemistry of metal carbonyls is intimately related to metal alkene complexes, because both types of ligands are soft bases and many complexes contain both carbonyl and alkene ligands. Also, both areas are closely associated with catalysis by complexes discussed in Chapter 22, because some of the best-known catalysts are metal carbonyls and they involve reactions of alkenes. Therefore, the separation of topics applied is certainly not a clear one. Catalysis by metal complexes embodies much of the chemistry of both metal carbonyls and metal alkene complexes. 

LESSER MEALWORM, Alphitobius diaperinus, topically applied ... 

Henny, C.J., L.J. Blus, E.J. Kolbe, and R.E. Fitzner. 1985. Organophosphate insecticide (famphur) topically applied to cattle kills magpies and hawks. Jour. Wildl. Manage. 49 648-658. 

The antiinflammatory properties of such topical agents as halcinonide are usually determined by a vasoconstrictor assay. Topically applied corticosteroids cause a blanching at the site of application, which can be the forearm or the upper back of healthy adults where stratum corneum is removed with cellophane tape. ° The test areas, containing various concentrations of halcinonide, are occluded with plastic wrap and are evaluated on an all-or-none basis. Percutaneous absorption studies with 0.1%... 

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