Immunopharmacology 1
CYCLOSPORINE AND TACROLIMUS
•Mechanism of action:
- Bind to cyclophilin (cyclosporine) or FK-binding protein (tacrolimus)
J, calcineurin (cytoplasmic phosphatase) j, activation of T-cell transcription factors j, IL-2, IL-3, and interferon-y
•Uses:
-Cyclosporine is DOC for organ or tissue transplantation (+/- mycophe nolate, +/- steroids, +/- cytotoxic drugs)
-Tacrolimus used alternatively to cyclosporine in renal and liver transplants
-Mycophenolate, an inhibitor of de novo synthesis of purines, has adjunc- tive immunosuppressant actions, permitting dose reductions of cyclospo rine to limit toxicity.
•Side effects: nephrotoxicity (both), gingival overgrowth (cyclosporine)
AZATHIOPRINE
Immunosuppressant converted to 6-mercaptopurine-same properties as 6-MP.
ANTl-D IMMUNOGLOBULIN
•Human IgG antibodies to red cell D antigen (rhesus antigen)
•Uses: Administer to Rh-negative mother within 72 hours of Rh-positive deliv ery to prevent hemolytic disease of newborn in subsequent pregnancy
lmmunopharmacology 2 Practice Questions
1 . A patient is treated with an immunosuppressant drug following a liver transplant. The drug is known to bind to cyclophilin and inhibit the actions of calcineurin. For what drug toxicity should this patient be monitored?
A.Pulmonary fibrosis
B.Hypotension c. Hypoglycemia
D.Nephrotoxicity
E.CHF
2. Which one of the following agents has utility in the management of acute coronary syndromes such as unstable angina?
A.Abciximab
B.Interferon-a c. Aldesleukin
D.Filgrastim
E.Trastuzumab
Answers
1. Answer: D. This patient is being treated with cyclosporin, a drug that binds to cyclophilin and inhibits calcineurin. As a result, the transcription of various T-cells factors such as IL-2, IL-3, and Interferon-')' are inhibited. Cyclosporin is associated with nephrotoxicity, gingival hyperplasia, hypergly cemia, hypertension, and hirsutism.
2. Answer: A. Abciximab is an antibody-based drug that targets glycoprotein IIb/IIIa receptors. Binding of the drug to these receptors results in decreased platelet aggregation by preventing the cross-linking reaction. It is useful in acute coronary syndromes such as unstable angina and post-angioplasty.
