Question 3 of 5
(demo test)
Product Demo for BASIC Exam
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Which of the following is the correct mechanism of action of cyclosporine?
Cyclosporine is an immunosuppressant that inhibits calcineurin by binding to cyclophilin.
Cyclosproine, tacrolimus, and pimecrolimus are all calcineurin inhibitors. Calcineurin is a phosphatase that is activated when in the presence of calmodulin and calcium that is necessary for cytokine synthesis within T cells. It does so by dephosphorylating nuclear factor of activated T-cells, cytoplasmic 1 (NFAT-1). Ultimately, inhibiting calcineurin prevents interleukin-2 (IL-2) production, which decreases the release of histamine and inflammatory cytokines and prevents T cell proliferation.
As noted above, cyclosproine, tacrolimus, and pimecrolimus are all calcineurin inhibitors, however, their associated mechanisms of action differ:
- Cyclosproine inhibits calcineurin by binding to cyclophilin
- Tacrolimus and pimecrolimus inhibit calcineurin by binding to FKBP12 (also called FK506 binding protein)
In addition to its use as an anti-rejection agent in organ transplantation, cyclosporine is also not infrequently utilized in dermatology. Its uses include but are not limited to the following dermatologic disorders:
- Erythrodermic psoriasis
- Autoimmune bullous disorders
- Lichen planus
- Severe atopic dermatitis
- Behçet's disease
- Pyoderma gangrenosum
- Nephrotoxicity: Generally an acute increase in plasma creatinine (typically reversible with dose reduction) or chronic, progressive renal disease (generally irreversible)
- Hypertension, which is reversible with discontinuation
- Electrolyte abnormalities (hyperkalemia, hyperuricemia, and hypomagnesemia)
- Hyperlipidemia
- Gingival hyperplasia
- Neurotoxicity (Tremor, headaches, paresthesias and dysesthesias)
Mycopehnolate mofetil is an inhibitor of inosine monophosphate dehydrogenase (IMPDH) which blocks guanosine nucleotide synthesis. Its immunosuppressive effect is secondary to the fact that both T and B lymphocytes are dependent on the above pathway for proliferation.
