Veterinary Medicine - May 2008 - (Page 266) CE PEER-REVIEWED A busy clinician’s review of CYCLOSPORINE This oral immunosuppressive drug used to treat canine atopy is probably already in your armamentarium. But do you know which formulation to avoid, how obesity affects the dose, or when to decrease the dosage? Alison Diesel, DVM, and Karen A. Moriello, DVM, DACVD M ost familiar as a drug used to prevent organ transplant rejection, cyclosporine has gained popularity over the last two decades in treating in ammatory skin diseases in both people and animals. It can be dif cult to keep the vast available information straight. With this article, we want to give you the need-to-know information about cyclosporine’s mechanism of action, pharmacokinetics, and adverse effects and how cyclosporine can be used in companion animals with atopic dermatitis, sebaceous adenitis, and perianal stula. MECHANISM OF ACTION Cyclosporine is a potent immunosuppressive agent that modulates the adaptive immune system. At doses indicated for dermatologic conditions, cyclosporine has anti-in ammatory effects on various leukocytes.1,2 By binding to cyclophilin (an intracel- lular receptor), cyclosporine inhibits the activity of calcineurin, a key enzyme in T cell activation. Calcineurin inhibition results in impaired cytokine transcription, namely of interleukin-2, interleukin-4, and alpha-interferon, thereby inhibiting activation of helper and cytotoxic T lymphocytes, macrophages, and monocytes.1-3 Decreased cytokine production subsequently inhibits activation of various in ammatory cells. Cyclosporine impairs mast cell and eosinophil production and survivability, and it impairs mast cell degranulation. Activation and proliferation of most T lymphocytes are decreased, thereby modulating the humoral and cellmediated immune system. The number of Langerhans cells may be decreased in patients receiving cyclosporine, leading to decreased antigen presentation by these epidermal dendritic cells.1,2 In addition, cyclosporine alters keratinocyte function, leading to diminished cytokine production. A decrease in keratinocyte proliferation has also been noted in vitro; however, the clinical relevance of this nding is unknown.2 PHARMACOKINETICS The pharmacokinetics of cyclosporine depends on the formulation (modi ed vs. unmodi ed) and on the patient’s species. Concurrent medications and a patient’s weight also in uence cyclosporine’s effects. Formulation For dermatologic conditions, oral formulations are preferred, specifically 266 May 2008 VETERINARY MEDICINE Illustration by KO Studios
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