Gastrointestinal tract steroids

In severe cases, or those refractory to treatment, truncal and limb weakness may be accompanied by involvement of masticatory, bulbar, and respiratory muscles. However the most life-threatening clinical manifestations are those affecting the gastrointestinal tract, since stomach ulceration can occur and death from perforation and peritonitis are not unknown. Medication with steroidal antiinflammatory agents is necessary but weakens the childrens resistance to infection, so that systemic spread of usually self-limiting disorders, such as candidiasis, may occasionally occur. 

The pentose phosphate pathway is an alternative route for the metabolism of glucose. It does not generate ATP but has two major functions (1) The formation of NADPH for synthesis of fatty acids and steroids and (2) the synthesis of ribose for nucleotide and nucleic acid formation. Glucose, fructose, and galactose are the main hexoses absorbed from the gastrointestinal tract, derived principally from dietary starch, sucrose, and lactose, respectively. Fructose and galactose are converted to glucose, mainly in the liver. 

Steroid hormones are produced by the adrenal cortex, testes, ovaries, and placenta. Synthesized from cholesterol, these hormones are lipid soluble therefore, they cross cell membranes readily and bind to receptors found intracellularly. However, because their lipid solubility renders them insoluble in blood, these hormones are transported in the blood bound to proteins. Furthermore, steroid hormones are not typically preformed and stored for future use within the endocrine gland. Because they are lipid soluble, they could diffuse out of the cells and physiological regulation of their release would not be possible. Finally, steroid hormones are absorbed easily by the gastrointestinal tract and therefore may be administered orally. 

Indometacin, which is a non-steroidal anti-inflammatory drug, inhibits the enzyme cyclo-oxygenase implicated in inflammatory reactions. Indometacin is more effective as an anti-inflammatory agent than ibuprofen and tends to have a higher side-effect profile, including headache, diarrhoea and gastrointestinal disturbances. Rectal administration reduces but does not prevent gastrointestinal tract disturbances. 

Lanas A. Economic analysis of strategies in the prevention of non-steroidal anti-inflammatory drug-induced complications in the gastrointestinal tract. Aliment Pharmacol Ther. 2004 20 321-331. 

Many corticosteroids undergo metabolism via CYP3A4 and are substrates of P-gp. They are used to suppress inflammation in the respiratory tract, reducing mucosal oedema and decreasing bronchial secretions. They are employed both to prevent acute exacerbations of chronic airways disease and to treat acute flare-ups. They may be subject to interactions when administered orally, but interactions with high-dose inhaled formulations are thought to occur due to steroid that is deposited in the oropharynx, swallowed and absorbed via the gastrointestinal tract. 

Bj arnason I, Thjodleifsson B. Gastromtestmal toxicity of non-steroidal anti-inflammatory drugs the effect of nimesulide compared with naproxen on the human gastrointestinal tract. Rheumatology (Oxford) 1999 38(Suppl l) 24-32. 

Many metabolites produced by hepatic metabolism are eliminated into the intestinal tract via the bile. These metabolites may be excreted in feces but are often reabsorbed. Organic anions (i.e. glucuronides) and cations are actively transported into bile by carrier systems that are similar to those in the renal tubules. Similarly, charged ions can compete for transport by these systems because both are non-selective. Steroidal and related substances are transported by a third carrier mechanism. Glucuronide-conjugated metabolites undergo extensive enterohepatic recirculation— a cycle of absorption from the gastrointestinal tract, metabolism in the liver and excretion in bile—and this cycle delays elimination when the final step in elimination from the body is via the kidneys. 

Sitosterol is a steroid sapogenin that has been isolated from ginseng. Approximately 50-60% of a dose of (3 -sitosterol is absorbed from the gastrointestinal tract in rats (79). After oral administration of radiolabeled ginsenoside Rgl, blood radioactivity peaked at 2.1 hours. Bioavailability was 49% (80). 

The liver is the major site of steroid metabolism. The kidney and the gastrointestinal tract, however, also both carry out important metabolic transformation of steroids. 

With ageing, there is also reduced gastrointestinal blood flow, which can further delay absorption of drugs from the gastrointestinal tract. Alteration in absorption can also make older people more vulnerable to the ulcerogenic effects of some drugs, for example non-steroidal anti-inflammatory dmgs. 

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