Continued research on coronary artery disease and beta-blockers,calcium-channel blockers, and statins

            My new blog title is Mammary Artery Conduits versus Venous and Radial Conduits in CABG Surgery. This week I focused my research on drugs. I conducted extensive research on various blood pressure, heart rate-lowering and cholesterol-lowering medications. Specifically I researched calcium-channel blockers, beta-blockers and statins. The main reason why I researched these three drugs is because high cholesterol levels and high blood pressure are risk factors for atherosclerosis in the coronary arteries. 

            Statins are the main drugs used to lower low density lipoprotein (LDL) cholesterol levels. This is a very important function because LDL cholesterol is the bad type of cholesterol. By lowering the lipid level of LDL cholesterol, statins prevent VLDL (very low density lipoproteins) from sticking to the arterial wall and clumping together. This prevents VLDL from releasing their fatty acid cores inside the artery, which prevents cholesterol build-up from forming in the artery. The significance of preventing cholesterol synthesis is that this leads to the stabilization of plaque build-up inside the arteries, because cholesterol is a main component of plaque. This in turn diminishes atherosclerosis (plaque build-up) inside the arteries. When I conducted a biochemical analysis of the function of statins, what I observed was as follows. Statins block LDL cholesterol synthesis by occupying a portion of the HMG CoA substrate. This blocks the HMG CoA substrate from binding to the active site of the HMG CoA reductase enzyme, thus limiting the main step in the synthesis of cholesterol. The most intriguing part of my research on statins was how different dosages of statins are sometimes required for different races. Specifically in an uptodate study it was found that approximately 7% of African Americans and Caucasians lacked the drug-oxidizing CYP2D6 gene. It was found, however, that almost all Asians have the CYP2D6 gene. This CYP2D6 gene is important for patients treated with the simvastatin drug, as this drug-oxidizing enzyme affects the amount of lipids lowered and the patient's tolerability to the drug. Therefore physicians can deduce that because almost all Asians have the CYP2D6 gene, they can lower their simvastatin dosage. However, physicians need to perform a gene test for Caucasians and African Americans and prescribe the dosage amount of simvastsatin accordingly. 

          The second drug I studied were beta-blockers, also known as beta-adrenergic inhibitors. Beta-blocker's main function is to lower heart rate by blocking Beta1 receptors. Heart rate increases because nerves from both the adrenergic nervous system and the adrenal gland enter the heart and stimulate it (via neurotransmitters) to beat more rapidly and work harder (contract more). The heart muscle contracts more for patients during exercise, which is a normal response. However if the heart muscle contracts rapidly and the patient is not undergoing high levels of exercise, this can indicate an occluded blood vessel or a weak heart muscle in the patient, which can ultimately lead to heart failure (HF) in the patient. Beta-blockers depress cardiac activity in the following ways. Beta-blockers block the Beta1-adrenergic receptors on the adrenergic nerves in the heart. This causes the heart to contract less, effectively lowering the heart rate. Beta-blockers like carvedilol can also reduce blood pressure by blocking Beta 2-adrenergic receptors from binding to the adrenergic nerves in the arteries. This causes the arteries to relax and dilate, which lowers blood pressure.

          The final drug I studied was calcium-channel blockers. The main function of calcium-channel blockers is to inhibit calcium (+2) ions from entering the muscle cells of the arteries. This inhibits muscle contractions from occurring in the arteries, which lowers the patient's blood pressure. When conducting a biochemical analysis of the function of calcium-channel blockers, the process I observed was as follows. A muscle contraction first begins when a neuromuscular junction is formed and an action potential occurs down the junction. This action potential causes the nerve cell to release calcium (+2) ions, which then signals the release of acetylcholine. Acetylcholine then signals the muscle to contract. Calcium-channel blockers are very effective at lowering blood pressure because they are strong vasodilators (dilate the arterial blood vessels). There are two main types of calcium-channel blockers, those being dihydropyridines and non-dihydropyridines. For my research, I will focus solely on non-dihydropyridines because they are vasodilators as well as cardiac depressants. Due to the fact that I am studying CABG surgery on the coronary arteries in the heart, I want to focus on the development of a coated drug form of verapamil (a non-dihydropyridine) to be placed onto the left internal mammary artery graft. I want to only use a coated form of verapamil on patients who are experiencing muscle spasms in their left internal mammary artery graft or who have irregular cardiac arrhythmias.