Drug Class Information

Glucocorticoids are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebrate animal cell.

Mechanism of Action

Glucocorticoids work well in treating autoimmune and autoinflammatory diseases due to their inhibitory effect on B cells, T cells, and phagocytes. The cytosolic glucocorticoid receptor is activated which results in transrepression and transactivation. Transrepression is the repression of proinflammatory molecules, and transactivation is the upregulation of anti-inflammatory molecules. While transrepression results in many of the desired effects, transactivation results in many of the undesired side effects (Gensler, 2013). 

 

Pharmacokinetics

 

Absorption

Glucocorticoids can either be absorbed through inhalation, injection, or orally. When inhaled, the glucocorticoids target more specific sites of inflammation whether through the nose (allergic rhinitis) or the windpipe (asthma). When absorbed through injection or by swallowing,  glucocorticoids have a systemic effect on the body. Inhaled glucocorticoids have less common and less severe adverse effects than those administered orally or by injection (Nicolaides, 2018).

Distribution

Glucocorticoids, once in the bloodstream, bind to proteins such as globulin (67%-87%) and albumin (7%-19%). This means that about 95% of the glucocorticoids are bound to a protein within the plasma. The greater the dose, the more rapid of a clearance rate occurs. 

 

Metabolism

The major site of metabolism is in the liver. Once in the liver, glucocorticoids are reduced, oxidized, or hydroxylated, thus making them susceptible for excretion. Glucocorticoids are reduced by inactivating the keto group, the 3-keto, delta-4 double bond structure (Kovac, 2017). 

 

Excretion

Glucocorticoids are excreted by the kidneys. More than 90% of secreted glucocorticoids are ultimately excreted in the urine. Unlike other steroids that bind to CBG, synthetic glucocorticoids fail to bind to CBG preventing reabsorption and leading to greater excretion. Though the majority of glucocorticoids are excreted through the kidneys, some topical glucocorticoids are excreted into bile.