Pleiotropy (drugs) Pleiotropy (drugs) In pharmacology, pleiotropy includes all of a drug's actions other than those for which the agent was specifically developed. It may include adverse effects which are detrimental ones, but is often used to denote additional beneficial effects. For example, statins are HMG-CoA reductase inhibitors that primarily act by decreasing cholesterol synthesis, but which are believed to have other beneficial effects, including acting as antioxidants and stabilizing atherosclerotic plaques. Steroid drugs, such as prednisone and prednisolone, have pleiotropic effects, including systemic ones, for the same reason that endogenous steroid hormones do too: cells throughout the body have receptors that
Discovery and development of statins must be metabolized to their active hydroxy-acid forms in order to inhibit HMGR. Type 2 statins all exist in their active hydroxy-acid forms. Fluvastatin has indole ring structure, while atorvastatin and rosuvastatin have pyrrole and pyrimidine based ring structure respectively. The lipophilic cerivastatin has a pyridine-based ring structure. Studies have shown that statins bind reversibly to the HGMR enzyme. The affinity of statins for HGMR enzyme is in the nanomolar range, while the natural substrate's affinity is in the micromolar range. Studies have shown that statins use the conformational flexibility of the HMGR enzyme that causes a shallow hydrophobic groove