Case 4 Chang Chia-Chieh(Tony)

Mr. Reyes was prescribed Lovastatin 20mg. b.i.d. and told to return in 6 weeks.

Is there any value to having Mr. Reyes adjust his diet while on Lovastatin, or is it necessary?  Patients taking Lovastatin should avoid alcohol and no more then one quart grapefruit juice per day. While Lovastatin does decrease the level of LDL, but it does not increase the level of HDL. Patients on Lavastatin are still advise to change their daily diet to low cholesterol, low-fat diet such as cottage cheese, fat-free milk, fish (not canned in oil), vegetables, poultry, egg whites, and polyunsaturated oils and margarines (corn, safflower, canola, and soybean oils) to improve the level of HDL.

What is the mechanism of action of Lovastatin?  Lovastatin is in a class of medications called HMG-CoA reductase inhibitors, the major regulatory enzyme of the mevalonate pathway, and induces a significant apoptotic response in human acute myeloid leukemia (AML) cells. It works by slowing the production of cholesterol in the body. Buildup of cholesterol and fats along the walls of the blood vessels (atherosclerosis) decreases blood flow and, therefore, the oxygen supply to the heart, brain, and other parts of the body. Lowering blood levels of cholesterol and fats may help to prevent heart disease, angina (chest pain), strokes, and heart attacks.

Laboratory tests at 6 weeks showed an AST of 62 U/L and ALT of 31 U/L and Mr. Reyes’ physician informed him he was to be switched to another drug, and prescribed Cholestyramine.

Was the switch necessary? Why or why not?  Yes, the switch was necessary. The elevated AST/ALT level indicate that Lovastatin was causing problems to Mr. Reyes’ liver. This is a known side effect of Lovastatin, to cause acute renel failure.

What might Mr. Reyes have complained of that would lead to discontinue the Lovastatin?  Mr. Reyes might have complained about constipation, muscle pain, tenderness or weakness, especially on the back, lack of energy or fever, yellowing of the skin or eyes.

Many drugs have wide inter-patient variation in their pharmacokinetics. Do you think this is likely for cholestyramine?  It is less likely that cholestyramine would have wide inter-patient variation in their pharmacokinetics, because cholestyramine does not need to be absorb by the body to insert its actions.

What is the action of Cholestyramine?  Binds to bile acids in the intestine. This inhibits their reabsorption and increases their excretion by up to tenfold. Since cholestyramine is not absorbed into the body, these substances also pass out of the body without being absorbed.  Increases apoB,E receptor activity.  Increases LDL clearance from the plasma.  Reduces plasma level of LDL.  Weakly stimulate VLDL synthesis resulting in small increases in VLDL, HDL, and triglyceride.

In a patient who tolerates Lovastatin but who is achieving insufficient lowering of LDL, can cholestyramine be added to the regimen, or must the Lovastatin be stopped?  Cholestyramine can be used together with Lovastatin.

If a patient’s hyperlipedemia is not predominantly due to increase LDL cholesterol but instead but instead to elevated triglyceride levels, what pharmacological treatments might be effective?  Prescription drug therapy includes niacin and gemfibrozil.  People with high triglycerides are typically advised to reduce their weight and limit the consumption of processed foods, simple sugar, alcohol, and saturated fats.