Glucocorticoid absorption

THERAPEUTIC USES Many inflammatory skin diseases respond to topical or intralesional administration of glucocorticoids. Absorption varies among body areas the steroid is selected on the basis of its potency, the site of involvement, and the severity of the skin disease. Often, a more potent steroid is used initially, followed by a less potent agent. Twice-daily apphcation is sufficient, and more frequent apphcation does not improve response. In general, only nonfluorinated glucocorticoids should be used on the face or in occluded areas such as the axiUae or groin. 

Due to the side-effect problems seen with high doses of inhaled glucocorticoids resulting from systemic absorption and the use of oral glucocorticoids in severely affected patients, there has been a search for safer glucocorticoids for inhalation and even for oral administration. As discussed above, a major mechanism... 

If possible, give glucocorticoid via administration routes that minimize systemic absorption (such as inhalation or dermal). 

Glucocorticoids decrease bone formation through decreased proliferation and differentiation, and enhanced apoptosis of osteoblasts. They also increase bone resorption, decrease calcium absorption, increase renal calcium excretion, and result in secondary hyperparathyroidism. 

A second example is the colon-specific delivery of glucocorticoids linked to dextran via a succinic acid or glutaric acid spacer [256a]. Such conjugates resist hydrolysis in the upper gastrointestinal tract, but are rapidly degraded by bacteria in the colon and caecum where little drug absorption occurs. 

The rate equation describes the variation in response variable R (with initial value of Rq) the measure response appears at a constant rate (zero order) of and is eliminafed by the first-order constant. The indirect response models will generally fall info fwo caf-egories inhibition or stimulation function. The inhibition response is classically described in ferms of IC q, fhe drug concenfration fhaf produce 50% of maximal inhibition (e.g., action of S5mfhefic glucocorticoid on adrenal glands or effecf of furosemide on sodium absorption in fhe loop of Henley) and is a number from 0 fo 1 where 1 represents total inhibition ... 

Large doses of glucocorticoids have been associated with the development of peptic ulcer, possibly by suppressing the local immune response against Helicobacter pylori. They also promote fat redistribution in the body, with increase of visceral, facial, nuchal, and supraclavicular fat, and they appear to antagonize the effect of vitamin D on calcium absorption. The glucocorticoids also have important effects on the hematopoietic system. In addition to their effects on leukocytes, they increase the number of platelets and red blood cells. 

For the treatment of inflammatory bowel disease involving the rectum or sigmoid colon, rectally administered glucocorticoids are preferred because of their lower systemic absorption. 

For a list of the local effects of topical glucocorticoids see separate monograph. The percutaneous absorption of high-potency topical glucocorticoids has been documented, but hypothalamic-pituitary-adrenal axis suppression, leading... 

The ocular hypertensive response in this case could have been due to systemic absorption of glucocorticoid through the skin of the eyelid, especially when there was a surgical wound. Alternatively, a sufficient amount of ointment could have seeped over the eyelid margins, causing the rise in intraocular... 

Systemic absorption of glucocorticoids can occur after rectal administration. 

Systemic availability of inhaled glucocorticoids can be reduced in two ways. First, by using esters that reduced local absorption in the case of beclomethasone the dipropionate is used. Secondly, by using glucocorticoids that are extensively metabolized in the liver after absorption from the gut, such as fluticasone and budesonide. These strategies can be combined fluticasone is given as the ester fluticasone propionate. 

The systemic availability of an inhaled glucocorticoid represents the additive and complex combination of pulmonary and gastrointestinal drug absorption. Absorption is influenced by many factors, including delivery device, the use of a spacer, the particle size of the inhaled drug, and the absorption and metabolism of the swallowed drug (1). 

In healthy volunteers, high doses of both budesonide and fluticasone were readily absorbed after inhalation from a mete red-dose aerosol (2). Fluticasone is extensively metabolized by the liver, so measurable concentrations of parent drug in the systemic circulation reflect efficient absorption across the lung. Lower doses of these inhaled glucocorticoids also result in some systemic absorption, reflected in effects on the hypothalamic-pituitary-adrenal axis (3). 

Other factors that determine the absorbed fraction of inhaled glucocorticoids include the age of the child, as lung deposition of inhaled drugs increases with age (80). Therefore, the minimum effective dose may fall as the child becomes older. Moreover, it is reasonable to hypothesize that systemic absorption will increase once asthma control is established (81). Furthermore, patient adherence and inhaler technique are two factors that can have a large influence on the amount of glucocorticoid inhaled and absorbed. 

Vitamin D is a precursor for a number of compounds that increase intestinal absorption and decrease renal excretion of calcium and phosphate. Metabolites of vitamin D and their pharmacologic analogs are typically used to increase blood calcium and phosphate levels and to enhance bone mineralization in conditions such as osteodystrophy, rickets, or other situations where people lack adequate amounts of vitamin D. Vitamin D analogs such as calcitriol have also been combined with calcium supplements to help treat postmenopausal osteoporosis,4,9 and to treat bone loss caused by antiinflammatory steroids (glucocorticoids see Chapter 29 28.76 Specific vitamin D-related compounds and their clinical applications are listed in Table 31-5. 

---