2. Supervisor : Prof. Dr.Hekma Coordinator : Ph.Fatmah Bakhder Umm Al-Qura University Faculty of pharmacology department

5. OBJECTIVES Trade and generic names Mechanism of action Clinical use Side effects Drug interactions Life style

6. Therapeutic class : Lipid-Lowering Agents Pharmacological class : HMG-CoA Reductase Inhibitors

7. Trade name : Inegy generic name: Simvastatin & Ezetimibe

8. Uses of Inegy: The main effects that produce from this drug are: lower levels of total cholesterol, (LDL cholesterol) and triglycerides in the blood. Raises levels of (HDL cholesterol). Hypercholesterolaemia

9. So. It can use if patient has: Homozygous Familial Hypercholesterolaemia (HoFH) patients not appropriately controlled with a statin alone patients treated with a statin and ezetimibe

14. Side effect Headache. Fatigue Constipation Abdominal pain Indigestion Diarrhea Nausea,vomiting. Hot flushes. Myopathy and Rhabdomyolysis. Myoglobinuria and acute renal failure. Photosensitivity, purpura, and alopecia.

15. Drug - drug interaction Mainly for Simvastatin Warfarin Aspirin Niacin Fibrate Erythromycin Verapamil

16. Drug interaction classification Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.

17. Simvastatin ↔ Warfarin It acts by affecting hepatic/intestinal enzyme CYP3A4 metabolism that lead to: Reversible Rhabdomyolysis. Acute renal failure

18. Simvastatin&ezetimibe ↔ cholestyramine cholestyramine decreases levels of ezetimibe and simvastatin by inhibition of GI absorption.

19. Simvastatin ↔ Niacin Either increases toxcity of the other by pharmacodynamic synergism that increase risk of : (Rhabdomyolysis ) for Both

20. simvastatin ↔ fibrate E.g. Gemfibrozil. Either increases effects of the other by pharmacodynamic synergism lead to : Liver damaged. Severe myopathy and Rhabdomyolysis – renal failure secondary to Myoglobinuria and may result in death. increased risk of musculoskeletal toxicity.

21. simvastatin ↔ verapamil Simvastatin ↔ erythromycin Verapamil hypertension angina pectoris cardiac arrhythmia hypertension angina pectoris cardiac arrhythmia erythromycin Anti-biotic – infections Anti-biotic – infections

22. simvastatin ↔ verapamil Simvastatin ↔ erythromycin They will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism that lead to : myopathy and Rhabdomyolysis – renal failure secondary to Myoglobinuria and may result in death. increased risk of musculoskeletal toxicity.

23. simvastatin level Bosentan – (pulmonary artery hypertension) Carbamazepine – (seizure disorders and neuropathic pain.) Efavirenz – ( human immunodeficiency virus (HIV) infection. ) Rifampicin – (tuberculosis )

32. DONE BY Afraa 3esa Anan fatani Anmah Kinsarah Ghofran Rawas Lamiaa alsalmy Lujain Andargiri Maram Kafyah Nazmeyah alkyyal Razan basalman Waad alhajjaje

33. REFERENCE Textbooks: Anand Ramachandran, Pharmacology recall, 2 nd edition, 2007. Medical Website : SharePractice. Featured Dx: Hyperlipidemia. 04/02/2014. http://sharepractice.com/blog/featured-dx- hyperlipidemia/ (Accessed 30 Mar 2014). http://sharepractice.com/blog/featured-dx- hyperlipidemia/ University of Maryland medical center. 06/04/2012. Familial combined Hyperlipidemia. May 31, 2013. http://umm.edu/Health/Medical/Ency/Articles/Familial- combined-hyperlipidemia (Accessed 30 Mar 2014). http://umm.edu/Health/Medical/Ency/Articles/Familial- combined-hyperlipidemia

34. SIU School of Medicine. Hyperlipidemia. http://www.siumed.edu/surgery/vascular/hyperli pidemia.html (Accessed 30 Mar 2014). http://www.siumed.edu/surgery/vascular/hyperli pidemia.html Medscape. When Do Triglycerides Matter? 2014. http://www.medscape.org/viewarticle/457696_7 (Accessed 30 Mar 2014). http://www.medscape.org/viewarticle/457696_7 Anupama Kizhakkeveettil, Parla S. Jayagopal and Kevin Rose. June 30, 2011. Hypercholesterolemia and Ayurvedic Medicine: A Case Report. http://www.tihcij.com/Articles/Hypercholesterole mia-and-Ayurvedic-Medicine-A-Case- Report.aspx?id=0000282 (Accessed 30 Mar 2014). http://www.tihcij.com/Articles/Hypercholesterole mia-and-Ayurvedic-Medicine-A-Case- Report.aspx?id=0000282