 Let's continue on discussing our pharmacology in association with hypertension We'll now talk about nitrates. How do nitrates work? Nitrates work by vasodilating They do this in the vascular smooth muscle by increasing nitric oxide So what you see here is a increase in cyclic GMP and an increase in smooth muscle relaxation It affects the veins much greater than it does the arteries So what is that going to do to our preload? It's going to decrease our preload if we're affecting the veins prior to the heart our preload will go down We use this in angina acute coronary syndrome and pulmonary edema Some of the adverse effects associated with nitrates are a reflex tachycardia hypotension and headache So how do we reduce the risk or treat? Reflex tachycardia well as we discussed earlier we can add a beta blocker to this medications Administration so that will decrease the risk of a reflex tachycardia We will avoid using nitrates for patients that have a right ventricular infarction So we want to always make sure prior to administering nitrates that we're not dealing with a right ventricular infarction by using an EKG We also will avoid it in Cases of hypertrophic cardiomyopathy and as well as if patients are concurrently using a pd5 inhibitor What is the pd5 inhibitor? Well a good example of pd5 inhibitor is that little blue pill also known as Viagra We know this in its generic name as Sildenafil some examples of nitrates include nitroglycerin isosorbide dinitrate and Isosorbide mononitrate Let's continue on and look at some more cardiac medications Rhenolazine functions by inhibiting the late phase of the inward sodium current Which therefore reduces our diastolic wall tension and oxygen consumption. So what does that mean? Well our inward flow of sodium is actually during that plateau phase of our depolarization cycle so if we are able to Inhibit that inward flow that means we reduce this plateau phase making that plateau phase gradually shallower You can see here on the right our late sodium channels when they are open allow sodium to pass through Which then concurrently will allow calcium to pass through which will allow our sarcomeres to contract When we administer Rhenolazine That causes those late sodium channels to close up Therefore our concentration of sodium in the cell cannot participate in The sodium calcium transporter exchange Which means we don't have calcium in the cell to allow for contraction of our sarcomeres This is useful in angina. It does not affect heart rate or blood pressure Side effects include constipation dizziness headache and nausea Let's continue on with more cardiac pharmacology Sacubitril is a medication that inhibits naprilocene which prevents the degradation of natrietic peptides The natriotic peptides that inhibit specifically our angiotensin 2 and substance P So what effects would we see by inhibiting? Substance P and angiotensin 2 well We're going to see an increase in our vasodilation and we will see a decrease in our extracellular fluid volume So we can use this when patients have heart failure and that heart failure gives us a reduced ejection fraction as well As we can add it to Valsartan We don't use this with the ace inhibitors though because ace inhibitors would give us an increased risk of angioedema So we can use the ARBs like Valsartan to add in here for more effect But we don't use it with ace inhibitors Adverse effects include hypotension hyperkalemia cough and dizziness