Since the discovery of their anti-inflammatory potential, glucocorticoids have become invaluable to the medical profession. In veterinary medicine, glucocorticoids now are one of the most commonly prescribed classes of drugs. Advances have been made to improve the efficacy and decrease the adverse effects of newer synthetic glucocorticoids compared with the endogenously produced glucocorticoid, cortisol. A common example is the additional unsaturation present in ring A of the common steroid nucleus of prednisolone. This modification leads to increased anti-inflammatory effects and reduced mineralocorticoid effects.
Nonetheless, important risks still accompany glucocorticoid use. Few studies have been performed on the effects of glucocorticoids in cats, despite the drugs' widespread use in feline medicine and cats' physiologic differences from other species. Understanding these feline-specific differences is important when prescribing these commonly used drugs. This review covers basic glucocorticoid pharmacology and attempts to summarize the evidence-based information on glucocorticoid use in cats.
MECHANISMS OF ACTION
Glucocorticoids have effects on nearly every organ system in the body. They are most commonly used, however, for their beneficial effect on the activity of the immune system. Glucocorticoids mediate their effects through various mechanisms, the most important of which seems to be through modulation of gene transcription. Glucocorticoids, like thyroid hormones, can enter the nucleus and access the DNA. Certain genes in the DNA carry regions known as glucocorticoid response elements (GREs). Binding of GREs by a glucocorticoid can result in either an increase or decrease in gene transcription and subsequent protein production.1,2 Glucocorticoids also can interfere with the ability of other factors that regulate gene transcription (Figure 1).2 Because glucocorticoids can induce the production of new proteins, the effects of these drugs, or biologic half-life, can persist beyond their pharmacokinetic half-life.1,2
Figure 1. Mechanism of action of glucocorticoids: 1) Glucocorticoids (GCs) enter the cell and bind to glucocorticoid receptors (GRs) in the cytoplasm. 2) GR-associated chaperone proteins are released, and the GC-GR complex moves through the nuclear membrane into the nucleus. 3) The GC-GR complex binds to positive or negative glucocorticoid response elements (pGREs and nGREs) on genes in the DNA, leading to increased or decreased mRNA production, respectively. 4) A GC-GR complex also may interfere with the action of other transcription factors bound to DNA. (Adapted from reference 2.)