[Music] welcome to this presentation on ACE inhibitors arbs and ares after completing this session you should be able to describe the usage and effects of ACE inhibitors arbs and ares and outline how ACE inhibitors arbs and arnes may affect your practice and the patient's cardiac status and Care in this slide you will see ACE inhibitors and arbs listed as vasodilator drugs specifically these agents are mixed phaso dilators which mean they work on both the arterial and Venus systems first we'll be discussing ACE inhibitors in order to understand how these agents work we need to review the RAS system or rein Angiotensin aldosterone system this is a feedback system in the body that that is activated via the kidneys when there is a lower glomular filtration pressure which indicates a lower kidney profusion pressure the purpose of this feedback system is to increase profusion pressure to the kidneys to maintain their function the result of this system is an increase in water retention and vasil constriction which increases the profusion pressure to the kidneys once this system is activated the enzyme renin is released and converts angiotensinogen to Angiotensin 1 next the ace or Angiotensin converting enzyme converts Angiotensin 1 to Angiotensin 2 it is Angiotensin 2 that stimulates at1 receptors causing vasal constriction an increase in aldosterone an increase in sodium retention and an increase in sympathetic activity the result is an increase in fluid volume retention and vasil constriction and an increase in profusion pressure ACE also promotes the breakdown of the natural vasod dilator Brady kinan resulting in further Vaso constriction in this next slide you'll see an image of how the RAS system works also notice the arrows pointing to the exact location to which ACE inhibitors work ACE inhibitors work by blocking the ace enzyme from converting Angiotensin one to Angiotensin 2 which prevents the stimulation of The at1 receptors and also the breakdown of bradykinin the effect of the RAS system is then blocked thus failing to increase aldosterone secretion failing to retain sodium and water failing to cause phasal constriction and failing to cause an increase in sympathetic activity to summarize the major factors stimulating renin release from the kidneys are an increase in sympathetic activity a low arterial blood pressure and low sodium reabsorption in the kidneys when dietary sodium is low or during diuretic therapy and a low circulating blood volume renin converts angiotensinogen to Angiotensin one ace converts Angiotensin 1 to Angiotensin 2 Angiotensin 2 stimulates at1 receptors causing Vaso constriction increased aldosterone increased sodium and water retention and increase sympathetic activity ACE inhibitors block the conversion of angiotensin 1 to Angiotensin to let's look at this with a bit more detail Angiotensin converting enzyme or Ace converts Angiotensin 1 to Angiotensin 2 and facilitates the breakdown of Brady kinan ACE inhibitors provide a dual vasodilatory effect first and foremost they act on the renin Angiotensin system by blocking the formation of angiotensin 2 which results in the inhibition of vasoconstrictory systems secondly ACE inhibitors block degradation or breakdown of Brady kinan which is responsible for the formation of phaso dilatory nitric oxide and prostacyclin it is important at this point to note that not all Angiotensin 2 is generated from the activity of Ace alone and the exact role of non-ace Pathways is still controversial take a moment to review this slide again and note the exact location on the RAS system that ACE inhibitors work for unknown reasons during prolonged ACE inhibitor therapy I'll sterone formation does not stay fully blocked but the anti-hypertensive effects of ACE inhibitors are not compromised by aldosterone formation however in severe heart failure the prolonged benefit of ACE inhibitors is compromised by aldosterone formation therefore there is a need to add an aldosterone antagonist like spironolactone or a plone to further block aldosterone activity in class 3 to four heart failure with reduced ejection fraction when left ventricular ejection fraction is less than 35% ACE inhibitors can be characterized into three groups the first is class one and includes captopril and captopril like agents the second or class two includes water soluble agents such as linil and class three includes Pro drugs or all other agents such as enalopril which become active only after hepatic metabolism indications for Ace inhibitor therapy includes heart failure of all stages hypertension especially in high-risk patients or those with Target organ damage or coexisting diseases diabetes and protein Ura early phase acute MI poinar left ventricular dysfunction nephropathy both in non-diabetic patients and those with type 1 or type 2 diabetes and for cardiovascular protection in heart failure ACE inhibitor therapy is especially important when the heart fails cardiac output drops resulting in less profusing blood pressure this drop in pressure is sensed by Barrel receptors and a lower kidney profusion pressure triggering vasil constriction via the RAS system this causes an increase in afterload increased workload for the failing heart pump and further systolic or left ventricular heart failure in addition when the heart fails decreased cardiac output results in worsening kidney perfusion which then triggers increased sodium and water retention via the RAS system resulting in increased circulating blood volume this increases the preload and causes worsening left ventricular failure causing further decreases in cardiac output and so the cycle repeats this is the Vicious Cycle of heart failure that ultimately leads to increased morbidity and mortality ACE inhibitor therapy stops this cycle early on ACE inhibitor therapy for early phase acute MI and postm Le ventricular dysfunction is also important during an acute MI there is an increased wall stress that can cause increased left ventricular dilation and remodeling result in an increase in LV failure morbidity and mortality ACE inhibitors in combination with beta blockers decrease wall stress prevent inappropriate left ventricular remodeling decrease LV failure morbidity and mortality the first dose of ace inhibitor therapy is to be given within 24 hours of hospital admission and the dose is increased as tolerated to achieve Target trial doses since a goal in pharmacological therapy is to balance oxygen supply and demand let's take a look at Ace inhibitor therapy and oxygen supply and demand ACE inhibitor therapy causes a decrease in oxygen Demand by causing Venus vasod dilation arterial vasod dilation and a decrease in sympathetic stimulation resulting in a decrease in pre-load a decrease in afterload and an increased cardiac output a inhibitor therapy also causes a decrease in aldosterone resulting in sodium excretion and potassium retention as well as decreased inappropriate heart remodeling Ace inhibitor therapy causes an increase in oxygen supply by creating an increase in cardiac output overall the effect that ACE inhibitor therapy has is a decrease in O2 demand an increase in O2 Supply and thus less oxygen deficit adverse effects of ace inhibitor therapy include hypotension renal failure although rare hyperkalemia especially in renal failure and in some cases a cough often described as dry ticklish irritating and nonproductive a inhibitor induced cough is seen in up to 20% of patients within days to months of first starting an Ace inhibitor it is not dose related and it often requires switching to an Angiotensin 2 receptor blocker or ARB other side effects include angioedema and rash angioedema is a sudden appearance of large edematous areas of skin or mucous membranes that are intensely itchy while it is rare it is potentially fatal when it occurs in the airway the rash can be severely itchy and occurs in up to 10% of patients it is typic LLY on the trunk and arms and is mostly seen with captopril please take a moment to study this slide which lists the generic names of ACE inhibitors please note that the generic names of these agents all end in the suffix pill Let's test your knowledge how do ACE inhibitors decrease oxygen Demand on the heart pause the video and think on this question before proceeding ACE inhibitors decrease oxygen Demand by causing increased phaso dilation decreased phaso constriction which decreases afterload and heart work load and by reducing preload through Veno dilation next we will be studying arbs ARB is an abbreviation for Angiotensin 2 receptor blocker recall that Angiotensin 2 stimulates the at1 receptor causing Vaso constriction increase in aldosterone and sodium and water retention and an increase in sympathetic activity arbs work by binding to the at-1 receptor effectively blocking Angiotensin 2 from binding and exerting its effects in this way arbs block the effects of the renin Angiotensin aldosterone system as we shall see in the following slide please take a moment to study the image on this slide and note the position in the RAS system where arbs block since the only location in this system where these agents block is at the at1 receptor Brady kinan is still broken down by the Angiotensin converting enzyme as a result you don't see the ace inhibitor induced cough with arbs indications for ARB therapy is when ACE inhibitors are not tolerated in patients often due to Ace inh hibitor induced cough contraindications to both ace inhibitor and ARB therapy include pregnancy severe renal failure bilateral renal artery stenosis pre-existing hypotension and severe aortic stenosis or obstructive cardiomyopathy ACE inhibitor and ARB therapy is often less effective in Black populations adverse effects of arbs include hypotension renal failure hyperkalemia as well as cough and angioedema although rare please take a moment to study this slide which lists the generic names of arbs please note that the generic names of these agents all end in the suffix sartan the last group of drugs we will be looking at in this session is the Angiotensin 2 receptor neilos Inhibitors or Ares this class of medication consists of both an Angiotensin 2 receptor blocker or ARB and a neilos inhibitor we already discussed that arbs work by blocking the at1 receptor so let's look at how the neilis inhibitor portion of the drug works first the body naturally produces natriuretic peptides which work to promote vasod dilation and nitri uresis left on their own nitri uretic pepti will eventually be broken down by the neilos enzyme in the body here's where the nilin inhibitor comes into play it works by blocking the breakdown of natural urtic peptides by inhibiting the neilos enzyme this results in prolonging the vasodilatory and natural uretic actions of the natural uretic peptides RNE therapy is indicated for the treatment of heart failure with uced ejection fraction where nyh Class 2 or 3 symptoms persist despite a 4-we trial of ace inhibitor or ARB therapy in combination with beta blocker therapy currently in tresto is the only Ary approved for use in Canada it is a combination of the neilis inhibitor sucuba tril and the ARB Val sartin the typical doses of each ingredient in the tablets are provided for your information Let's test our knowledge of the difference between ACE inhibitors and arbs how do arbs avoid ACE inhibitor induced cough recall that it is the buildup of Brady kinan that contributes to ACE inhibitor induced cough unlike ACE inhibitors arbs do not inhibit the breakdown of braady kinan that takes us to the end of this presentation on ACE inhibitors and arbs [Music] now