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All right. Um Good evening morning. Um Thank you very much for joining us this evening. Um I hope you can even and see me. Ok. So if anybody from the audience could please just confirm that in the chart, that would be very good. I'll wait until that confirmation comes through. Nothing yet, but hopefully soon. Ok, lovely. Thanks very much stuff. Um So the other one, thank you very much for doing this and this. We're gonna have a medical student um deliver a talk on cardiac pharmacology as part of our kind of lecture series for this academic year. Um I'm doing kind of back on answering any questions. Should there be any? And we'll follow up some polls throughout some questions to keep the lecture kind of engaging for all of you. If you have any questions, please go ahead and put them in the chat throughout and at the very end, we will have a feedback form. So please make sure to fill it out to get your certificate. Um So I'll hand it over to you and uh thank you very much. Thanks doctor. Hi, everyone. Um Thank you all so much for joining us. Um This is the QB cardio, so ninth lecture in our lecture series this year. Uh and I'm very excited to be giving my second lecture. Um and today's topic will be cardiac pharmacology. So I hope you all enjoy uh the lecture and if you have any questions, put it in the chat and if you can't hear me or see me at any point, um put that in the chat as well and I'll try to fix that as soon as possible. So just some learning outcomes of what I want everyone to kind of get out of the session today, I'll be going over quite a few drugs, uh about 13 different broad classes of drugs. So I want everyone to kind of recognize uh drugs commonly see in cardiac patients on the wards. Um not only in cardiac wards, you'd see these drugs everywhere in GP and um in the theaters in your general medical ward in ed. So it's very important to be familiar with these drugs. Um So for each one, I'll go over the indications, um some examples, including the generic versions of these drugs, how they work. Um And then we'll go over briefly some side effects um and some contraindications that they may have in any monitoring requirements they may have, then we'll tie all of this in together at the end um with diseases that these drugs help treat. Um this will be mainly going over nice guidelines and kind of seeing how these drugs fit into the guidelines. Then um briefly we'll touch on some trials and, and studies um for certain drugs and then we'll apply all of these to some questions at the end. So, um this is roughly um the drugs that I'm going to go over today. So, um ace inhibitors, angiotensin, um angiotensin two receptor blockers, also known as Arbs beta blockers, calcium channel blockers. Um blood thinners including antiplatelets and anticoagulants, vasodilators specifically will look at nitrates. Um some antiarrhythmics, specifically digoxin and amiodarone. And then also in the general classes of antiarrhythmics, the four classes. Um and then some antihyperlipidemic, specifically statins, some diuretics and then SGL T two inhibitors. So, without further ado, let's start with our first drug today. It's gonna be, it's gonna be a, a long one. So I hope you all don't get too bored. Um but we'll start with ace inhibitors uh which are commonly used in hypertension, heart failure and also post M I. So some examples of ace inhibitors, you'll notice all these drugs end with um the suffix Pril. So, Ramipril, Lisinopril and Ramipril. These are all examples of ace inhibitors. So how they work is they work on this um system in the kidneys called the renin angiotensin aldosterone system or the ras. So ace itself, uh angiotensin converting enzyme, it's part of the system and I'll get to the diagram um into the next slide which will make it a bit more clear. But ace is this enzyme part of the system. And what it does is it converts angiotensin one to angiotensin two. And angiotensin two is a very potent vasoconstrictor. And when you um when you inhibit angiotensin two, that helps vasodilate um your vessels peripherally and that helps to drop the BP and also um decreases endo secretion. So this is a diagram that can kind of help you understand the rash um running, running an angiotensin system. So if you see angiotensin one and angiotensin two, it's being converted by ace the enzyme. So when an ace inhibitor works um in between this and stops angiotensin two from being created, that then causes the vasoconstriction to stop. It helps it causes vasodilation instead that helps to reduce the BP. Um We'll also come back to this diagram when I talk about a RBS because it's also part of the RAAS system and it works on the system as well. So some side effects of ace inhibitor is very common exam questions and also quite common for you to see in GP um or in the wards, a dry cough is very common, especially when you're first starting an ace inhibitor. And sometimes this can be quite intolerable for patients. So um you might try them on an Ace inhibitor for a few weeks and see if that first of all, it helps to reduce the BP. But secondly, to see if they can tolerate the side effect like the dry cough. And if they can't, then you'll think of switching them to something else. Um like an A RB for example. So another common um side effect is hyperkalaemia, which you must uh look out for. And it's important to, to remember this because when you use other drugs that can also cause hyperkalaemia in combination with ace inhibitors that can cause it to precipitate quite quickly. Um As ace inhibitors cause vasodilation, they can also cause dizziness, hypertension, headaches and syncope. Um It's important to look out for that and make sure the BP isn't dropping too low. Ace inhibitors can also cause A KS uh in the short term though in long term, they are nephroprotective, um can also cause angioedema which is a rare but life threatening side effect that you must watch out for. So absolute contraindications, if the patient has any hypersensitivity reactions like anaphylaxis towards this ace inhibitors also uh con contraindicated in pregnancy as are Arbs because these are associated with teratogenicity. Um If the patient has poor poor renal function, aortic stenosis or hypovolemia, you can use these but in caution. Um and you must also monitor their renal function, their potassium and BP when you're starting ace inhibitors. So, Arbs then they work in the same system, the RS but instead of blocking angiotensin one to angiotensin two, what they do is they block the receptor on angiotensin two itself. So also used like ace inhibitors on in hypertension um used in congestive heart failure and in chronic kidney disease, including diabetic nephropathy. It's quite protective for the kidneys in diabetic patients. Um So, like I mentioned, it's a good alternative in somebody who can't tolerate the dry cough um or the angioedema caused by ace inhibitors. So A BS um all end in suffix. So Losartan, Candesartan and Valsartan are examples of ARB S. Um So they bind and inhibit the angiotensin two type one receptor. Um and it works in a similar, well, it works in the same system. Um since angiotensin two is a vasoconstrictor by inhibiting that, that causes vasodilation and decreases aldosterone secretion, lowering your BP. Uh Just a side note there, another common cardiac drug you might come across something called entresto. Um So this is a combination of an ARB, Valsartan and also another drug called Sacubitril, that's a Neprolyzin inhibitor. So, Entresto is very commonly used in heart failure with reduced ejection fraction. It helps um preserve some cardiac output. So, um side effects of ARB are not as significant as ace inhibitors. There's less incidence of angioedema and dry cough, but they can still cause some of the same side effects like low BP um and an AKI in the short term. So, contraindications, similarly, pregnancy hyperkalemia, uh bilateral renal artery stenosis because in patients with um existing uh kidney disease, that can be quite catastrophic if you start them on an ARB and in patients who with heart failure, who have quite severe hypertension as well. So, monitoring requirements are similar, you monitor their BP, check their renal function and potassium regularly. Beta blockers are also another very common drug that you'll come across everywhere throughout um your time in hospital and in GP. So they're used in many, many conditions. There's a long list there. Um Some of the common ones are tachycardia hypertension. Um M I during heart attacks and congestive heart failure. Um many types of arrhythmias and coronary artery disease and some other noncardiac um conditions as well like hyperthyroidism and essential tremor. And there's a long list of other conditions. Beta blockers are used in. So um some examples then they end in the suffix ol. So propranolol, bisoprolol, and mono metoprolol. All examples of beta blockers. So how they work. Um So we'll go over what the beta receptors are. First of all. So, there are three distinct beta receptor forms in the human body. So beta 12 and 33 is less significant. So I won't really talk about it, but beta one are receptors that you could call cardioselective. So they're mainly found in the heart and they work on the cardiac muscle. Beta two then are found throughout the body in many different organ systems. Um and they control different aspects of your metabolic activity and they cause smooth muscle relaxation. So beta two are non nonspecific nonselective, not um like beta one. So some of these drugs, um some of your beta blockers work on only beta one or some work on beta two and beta one at the same time. So how they work is um beta one receptors can induce re release and that increases your BP and your beta two receptors, as I mentioned, cause smooth muscle relaxation and also increase metabolic effects like glycogenolysis. So the beta blockers then they will bind to either your beta one or beta one and beta two receptors and then they inhibit the activity of these. Um and as they're inhibiting the increase of BP or smooth muscle relaxation causing the opposite effect. And that helps you drop your BP and helps you um uh reduce your heart rate as well. So, beta blockers have uh negative chronotropic and inotropic um effects. So, chrono and the name itself chrono for time. So it reduces your heart rate and IO being for contraction. So it reduces the um the strength of contraction of the heart. So this helps um with chest pain. So, when you have reduced contraction and reduced heart rate, that reduces the oxygen demand of the heart and that helps with the heart, heart pain, chest pain. So, um they also help as a side effect, reduce BP by decreasing renin and cardiac output as well. So, as I mentioned, beta blockers can be nonselective or cardioselective. Um if they work on only beta one they're cardioselective such as atenolol bisoprolol or metoprolol. If they're working on both beta one and beta two, they are nonselective, for example, propranolol, um which you'll see quite often used. Um not used, sorry in asthma because of it working on beta two as well and carvedilol and sotalol as well. Some beta blockers also bind to alpha receptors to some degree. So that's just another diagram of kind of where um you'd find these receptors and, and which um neurotransmitters work on these receptors. So some side effects of beta blockers, um since it, it's work is to reduce your heart rate and contraction. But if that gets quite severe, it can cause um bradycardia and that can be symptomatic. Sometimes you might see a very low BP. The patient may be quite tired, fatigued. Um They can complain of nausea or constipation. Um and it can also induce hyperglycemia. And since um your beta blockers kind of block your signs of the hyperglycemia, um uh the the normal signs that you'd see with hyperglycemia, you might miss it. So it's important to be aware of that. Um beta blockers can also increase your risk of heart block. Um It can cause bronchospasm if you're using your nonselective beta blockers are the ones that work on both beta one and beta two, which is why you don't use that in asthmatics. Um It can also so contraindications then, um of course, in asthmatics, you wouldn't use nonselective beta blockers for a time. Um They wouldn't use any beta blockers in asthmatics. But now people use with caution cardioselective beta blockers in asthmatics as well. Um It can cause both acute or chronic bradycardia and or hypertension as well. So if a patient has that you would not give them beta blockers. Um it's also important to monitor the QTC interval um because uh it can cause QT prolongation. So it's important to keep an eye on that on the ECG. And in patients with preexisting Long Qt syndrome, you would not use beta blockers because that could cause uh ventricular tachycardias to precipitate specifically to science. So it's important to monitor the heart rate and BP um which you probably try and bring down but not too low. And then also important to monitor the QTC, especially on a drug like sotalol. So calcium channel blockers then um so calcium channel blockers can be divided broadly into two types. So there are dihydropyridine calcium channel blockers and non dihydropyridine calcium channel blockers. They're both used um for different things. It's kind of a middle ground with dilTIAZem which has an effect with, with kind of both sides. Um But broadly speaking, uh it's, it's divided into these two. So, dihydropyridine calcium channel blockers are used in high BP, coronary artery disease. Uh and chronic stable angina also in migraines and non dihydropyridine calcium channel blockers also used in hypertension. Um They're but not, not as often um they're used for peral SVT conversion also for prophylaxis of the condition. They're used in atrial fibrillation and flutter also in chronic stable angina and vasoplasty angina. So some examples of dihydropyridine calcium channel blockers, they all end in the suffix dipin. So, Amlodipin, uh Nifedipine and felodipin and then non dihydro and calcium channel blockers don't have the same kind of same suffix at the end. Um But verapamil and dilTIAZem are two examples of those. So how they work is calcium channel blockers. In the name itself, it's it's blocking the movement of calcium um back into the heart in the smooth muscle and in the pancreas, uh and dihydro Peridin calcium channel blockers mainly work in the peripheries. Uh They don't have much effect on the heart, which is why they're kind of used more frequently for hypertension. Um And the nondihydropyridine calcium channel blockers work mainly on the essay and A B nodes. This helps to slow the conduction and the contractility of the heart. So it's similar to the beta blocker effect of negative chronotropic and IPIC effects. So again, another diagram of how um beta blocker, sorry, calcium channel blockers block the movement of calcium into the heart um and into the smooth muscle cells. So you can see on the left uh that is how dihydropyridine calcium channel blockers work. So, mainly in the in the periphery that's causing um well, the in the influx of calcium cause vasoconstriction. And if you block that you cause vasodilation, helping drop the BP. And on the right, you can see if it's working on the V and sa nodes. Um the nondihydropyridine calcium channel blockers will block the activity um of calcium in flux that causes reduction in the velocity of conduction, reducing the heart rate and contractility, good. So, side effects of specifically dihydropyridine calcium channel blockers like amLODIPine. Um so lightheadedness, flushing headaches, these are quite general side effects. Um some peripheral edema as well. You might see um it can cause an acute M I can cause more um angina and it can cause acute, sorry, that's hypotension, syncope. Um can also, you may also see everything m multiform or you might cause some liver inflammation as well. Contraindications to dihydropyridine calcium channel blockers, hypersensitivity, the to the drug as with any drug. Um if a patient has sick sinus syndrome or very severe low BP, if they've just had a heart heart attack, um pulmonary congestion and if they've had renal or liver injury, it can be used. But with caution. So you'd monitor their BP and heart rate here as well. Yeah. And then nondihydropyridine calcium channel blockers can cause constipation can cause orthostatic hypertension specifically where you get a drop in BP. When you stand up, um your liver enzymes may be deranged. You could be patient could feel dizzy, uh fatigued and you might see very, very slow heart rate and very severe hypertension uh with the very severe hypertension, you can instead of it, it seems a bit like an oxymoron where you have bradycardia. But with the severe hypertension, they may have reflex tachycardia instead. Um it can also cause A B blocks and arrhythmias. You may see Steven Johnson syndrome as well and Chron and congestive heart failure um and the liver may be damaged again here. So, absolute contraindications for non dihydropyridine Calton channel blockers like verapamil. Um you would not give them, uh you would not give a patient with heart failure with reduced ejection fraction risk as it can cause as it uh reduces the contra of the heart. This can be fatal for a patient with uh a reduced ejection fraction. If they've got second or third degree AV block or very low BP, you wouldn't give them uh these drugs as well. So, again, hypersensitivity, um sick sinus syndrome. If they've got bradycardia and reduced cardiac output, you wouldn't give them calcium channel blockers, nondihydropyridine calcium channel blockers. Um very severe hypertension, acute M I pulmonary congestion, similar to your dihydropyridines as well and you'd use it in caution in renal and liver injury. Um So here, because of, of how it can affect the liver, you'd monitor, um you'd get a baseline liver function test and keep an eye on that. And then you'd monitor BP and heart rate as per usual and you may do an E CG just to check for a V block, moving on then to some blood thinners. So I'm going to go over antiplatelets first. Um So antiplatelets and the name itself, it works on the platelets. Um And they're used in acs Stable Angina post um cabbage surgery, prevention of coronary artery disease. And they're also used in post PCI procedures, either with a stent or PCI S for peripheral arterial disease. They're used in mechanical valves, uh sometimes in combination with warfarin uh an anticoagulant. Um And they're used in closure of different holes in the heart as well. Um They're used after an ischemic stroke or in uh prevention of stroke in patients with af also used in Kawasaki disease. So some examples of antiplatelets, sorry, there's a spelling mistake there. Aspirin, for example, um which is a Cox inhibitor, um clopidogrel tag PSL, all of these are platelet aggregation inhibitors. And then another example of antiplatelets is something called dipyridamol. So, II speak specifically about aspirin. Um as it's probably the most common one you'll come across. So, aspirin is um a drug that's a Cox inhibitor. It's also an NSAID. So it irreversibly inhibits um Cox which is cyclooxygenase enzyme. Um It inhibits the activity of this enzyme and it prevents formation of thromboxane A two which induces platelet aggregation and vasoconstriction. Um So, aspirin at low doses um or your, your standard 75 to 1 50 mg dose, um which is your maintenance dose of aspirin at that dose, it's complete or near complete inhibition of cox one. Um while when you want to inhibit cox two, you need a larger dose of aspirin. So this is a diagram of kind of where aspirin works in this um in this form. So you can see thromboxane A two there. What it does is it induces plate platelet aggregation. It's also a very potent vasoconstrictor. Um and as aspirin works in this area um with cox one and Cox two, it can also cause um some analgesic effect as well. So some side effects of aspirin. Um Aspirin can cause aspirin induced asthma specifically. Um It can cause nasal polyps as well. You might be at risk of upper gi bleeds from chronic chronic gastritis. Um There can be some other kind of bleeding disorders. So you might see ecchymosis in wounds. Um you might get hematuria or nose bleeds. Um and then tag can cause tag related dyspnea or shortness of breath. Um And generally with antiplatelets, you might see hemorrhage or thrombocytopenia at a very low count of your platelets. So, contraindications for antiplatelets include large esophageal varices as these can can bleed quite profusely. Um If a patient's had a recent stroke in the last two years, um any history of any intracranial hemorrhage, um or significant low platelets, thrombocytopenia. Um if a patient is having major surgery within 72 hours, um acute significant clinic, sorry, acute, clinically significant bleed. Um If the patient has very severe renal or liver disease or if their BP is quite high at 200/100. So just a note there on major surgery within 72 hours, um Generally the advice when somebody's going for surgery is that the antiplatelets are held for seven days that because the life cycle of um a platelet is seven days. So if you give time for them to regenerate, um by the end of holding it for seven days, your platelet function should be back to normal. So, moderate monitoring requirements for antiplatelets, you'd want to assess patients for bleeding risk. Um and also um age uh female gender and renal function are also important factors uh when it comes to the bleeding risk. So, anticoagulants are another type of blood thinners. So, rather than working on the platelets, they work in the uh coagulation cascade at different points in the coagulation cascade. So, they're used in similar diseases. Um So acute Mr S when there's a thrombus in or aneurysm in the left ventricle in atrial fibrillation in prostatic heart valves. Um they're also used for treatment or prophylaxis of venous thromboembolisms. Um They also heparin is used um in heparin induced thrombocytopenia. So, for example, uh some examples of anticoagulants then uh in fractionated heparin um which is just heparin itself, low molecular weight heparin such as enoxaparin or delta Perin and Oxin will come across very frequently on the wards. Um It's used as VT prophylaxis quite often um if there's no contraindication and then Vitamin K agonists like Warfarin. Um there are direct thrombin inhibitors like the valerin and there are direct factor 10 A inhibitors like Apixaban, Rivaroxaban and Edoxaban. And you'll notice here um with the factor 10 A inhibitors, there's a pattern with how they're named. So the Apixaban, the Xa is for the 10 A inhibitor. That's, that's how it helps you remember that. Um So the mechanism of these drugs, they all act a bit differently. But the common thing they have is they all work at different points of the coagulation cascade um or they modify it in some ways. So some are directly inhibiting an enzyme in the cascade or others. Um work indirectly, they bind to antithrombin or they prevent the synthesis of some of these factors from the liver, for example, your Vitamin K dependent factors. So this is a refresher um that I'm sure everyone loves to memorize uh the coagulation cascade. So these drugs will work at different points of this um or help to modify different points of this. So, anticoagulants, absolute contraindications for them include active bleeding, coagulopathy, any any clotting disorders. Um recent major surgery, if the patients had an acute intracranial bleed or major trauma as well, and then you use them um with caution in patients with gi bleeds in low risk surgeries and in aortic dissections or aneurysms and also be careful of using them in older patients or in pregnant patients as well. So you'd monitor, um, you get baseline bloods when you're starting these medications. Um, and you may need to monitor the drug levels themselves. Um, if the patient is bleeding or having thrombosis, if they're undergoing a procedure, um, if they're getting thrombosed, if they've had a overdose of any of these drugs, um, or just to check therapeutic levels and make sure that they're getting the anticoagulation that they need, um or if they're having liver disease. So quite um everyone quite knows that Warfarin needs monitored quite regularly. And so it's essential to, to check the inr and make sure it's within the range specifically for whichever indication you're using Warfarin. So for example, if you're using it for um a mechanical heart valve and you need it within a certain level, say 2 to 3 and you need to keep it within that level to make sure that you're getting the anticoagulation you need, but you're not overly anticoagulated them, which can cause bleeding. Um So do a then came in um and they're not as stringent as warfarin with monitoring. So you do need baseline bloods with DOAC say every six months to a year, but they're not as frequent as Warfarin um which patients prefer. So, Doac levels don't need routinely monitored. Um But generally, if you're looking to monitor for anticoagulants, you check the full blood count, um the bleeding time clotting time, you check the PT and I Nr their A PTT and thin time and just do a general um clotting screen and clotting factors assay. So, vasodilators, then I will mainly be speaking about nitrates here. Um As that's the one you'll come across most commonly. Um So vasodilators are used in hypertension in angina in heart failure in any hypertensive emergency, like in acute mi I pe and aortic dissection and I've put angina there twice. I'm sorry about that. So, examples of vasodilators. Um So there are direct acting vasodilators like nitrates, hydrALAZINE and minox. Um And then there are also drugs that we've talked about before calcium channel blockers and your ace inhibitors and ARB S, they're all vasodilators as well, your beta two receptor agonists. Um So instead of what your beta blockers do, they do the opposite, they vasodilate like your salbutamol. Um And then your alpha one receptor antagonists like prazosin and alpha two receptor agonists like cloNIDine are also vasodilators. So, nitrates can be then further divided into the drugs themselves, nitroglycerin like what you find in your GTN sprays um and then your isosorbide mononitrate as well. So how nitrates work is they increase the amount of nitric oxide in vascular smooth muscle cells that causes vasodilation. Um and they dilate veins more than arteries and they decrease preload as well. So some um side effects of nitrates, nitrates can cause just with the drop in BP, it can cause reflex tachycardia. Um it can cause headaches and it can cause flushing as well if you think about the blood vessels, um being dilated and racing, raising to the surface of the skin. So it can cause a bit of flushing. Um It can cause orthostatic hypotension. Um and something called methyl methyl globm. I can never say that. Um but it's basically this buildup of methemoglobin in the blood. It's quite rare. Um So some contraindications with nitrates, specifically patients with an inferior M I or a right ventricular infarction. Um they're contraindicated in these patients because nitrates can decrease preload and this can cause quite a drastic drop in BP and very much reduced cardiac output. So, it's important to monitor the level of um the drug itself and also check the BP and heart rate. Um overdoses with these drugs are rare diuretics. Then um diuretics are used in a variety of different diseases as well such as heart hypertension, um heart failure, pulmonary edema and peripheral edema. So, some examples of diuretics, they can be divided into many different classes. And so loop diuretics um are the oldest class of diuretics. They'd be for example, furosemide, opumide, thiazide and thiazide like diuretics. Um you see quite often in in hypertension. So, hydrochlorothiazide and indapamide, hydrochlorothiazide is a thiazide diuretic indapamide is a thiazide like diuretic. So, potassium sparing diuretics then are for example, spironolactone and amyloride. Um and then they're carbonic anhydrase inhibitors such as acetaZOLAMIDE um which are diuretics as well. So they all work in slightly different ways. Um But what they all do in common is they, they target iron transport receptors in the kidneys. So, in the renal tubules, um and they affect the amount of electrolytes or water excreted through the urine. Um So generally what they do is they try to get liquid out. So you're trying to excrete more water, but they work in different ways in terms of the salts that they keep or don't keep in the blood, they're all albumin bound. And that's, that's how they work. It's uh a prerequisite for their action. So a side effect, then if you're taking out too much water through the urine, you can get quite low volume of blood circulating through the body. Um and that can cause low BP as well. So from this patients can be dizzy, they can feel faint, they can have headaches. Um and just as they're working on the kidneys, they might have increased urinary frequency as well, which may be a complaint. They have um patient can feel quite restless, so weak and tired, they might also complain of any gi disturbances like nausea, vomiting, constipation and diarrhea. So patients can have quite severe, sorry, there's contraindications. Um If the patient is quite severely dehydrated or if they've had established anuria where they're not producing any urine, you shouldn't give them any diuretics cause it'll only worsen the situation. Um hypersensitivity to any of the agents in um gout loop and thiazide diuretics are not, um you should not be giving them that because it can cause the gout to become worse. Um Loop diuretics can worsen hypokalemia, and potassium diuretics can worsen hypokalemia. So you can't give them that in that case. So it's essential to monitor um the extracellular fluid volume. So you look at the flu fluid balance chart. Um you check their urine output and also check the electrolyte levels. For example, if you're using loop diuretics or potassium sparing diuretics, specifically look at their potassium. Um you can check their acid base status as well, check their glucose BP and check for any end organ damage that these drugs could cause. So, lipid lowering agents, um they're used in raised lipid profiles like a raised cholesterol also used in atherosclerosis um for primary and for secondary prevention of cardiovascular events. So, some examples are statins. Um So they all end in the in the suffix statin. For example, atorvastatin, rosuvastatin, simvastatin. Um some other types of lipid lowering agents. These are classes are acetum fibrates, nicotinic acid, um bile acid sequestrants and PC SK nine inhibitors. So I'll talk mainly about uh statins. Statins are competitive inhibitors of HMG coa reductase. This is an enzyme that's involved in cholesterol biosynthesis. So, the formation of cholesterol. So, by inhibiting this, it reduces the, the formation of cholesterol and increases LDL clearance from the serum sorry by upregulation of LDL receptors on the liver it can also reduce um the LDL which is very low density lipoprotein. Um They also have a modest effect in increasing HDL, which is known as your good cholesterol. So, lipid lowering agents, um for example, statins uh specifically have uh a very kind of classical side effect of muscle injury. So, patients usually at the start can complain of muscle aches and soreness. Um but it can be, it can be something um as, as simple as myalgia, but can also be something quite, quite severe like myonecrosis or rhabdomyolysis. So important to keep an eye on that as well. Um And then contraindications if the patient has any hypersensitivity reactions and if they've had any liver disease or unexplained, raised aminotransferase levels and the, and the liver function tests as well. So, the liver profile is very important to be monitored when you're starting a patient on um any lipid lowering agent. So, within um 48 weeks, you should be monitoring, you should get a baseline and then you should monitor after you've started them on, on this agent. Um And then you'd follow up every 6 to 12 months, you check um a lipid profile just to make sure that it's adequately lowering. Um the cholesterol, if not, you might want to think about increasing the dose or changing to another agent or adding another agent. So, moving on to antiarrhythmics. Um So, digoxin doesn't really fall into any of the classes of the antiarrhythmics but its main um main work is as antiarrhythmic. Um So it's used in heart failure. Um It's used in atrial fibrillation and atrial flutter also used in SVT S. So, digoxin comes from this Foxglove plant called Digitalis lanata. Um and it has two main effects. It has a pos positive inotropic effect. Um inotropic, which we talked about earlier with your beta blockers, inotropic is contractility. So a positive inotropic effect, it increases the force of cardiac contraction and contractility. So that's how it helps in heart failure. So, heart works is inhibits um the myocardial sodium potassium apase pump. Um so it increases the amount of intracellular sodium levels and it causes an influx of calcium into the heart that increases the cardiac contractility. Kind of the opposite of how the beta blocker works. Um increasing cardiac output decreases ventricular filling pressures as well, which all reduces the strain on the heart. And the other way, digoxin works is it inhibits the A V node. So it stimulates the parasympathetic nervous system. Uh it causes a kind of effect similar to what the vagus nerve would cau would would cause. So vagal mimetic effect on the AV node, this slows the contraction through the AV node, reducing the heart rate and leads to a decreased ventricular response. So, digoxin uh toxicity is very significant and it's also a very common exam question that they like to ask about. Um So it's very um very, very important to know about it because it can cause quite fatal arrhythmias. Um toxicity is, is uh easy to spot because it has quite classical signs as well. Um And it's depending on the dose of the digoxin. So it's more frequent to get toxic levels at higher doses. That's why the digoxin um levels are monitored in your blood um to make sure you're at therapeutic levels but not at toxic levels. So, hyperkalemia um itself is a kind of trigger for digoxin toxicity. So, it's important to monitor the potassium level as well. Um Some general side effects that you might see with digoxin um or toxicity is nausea, vomiting and anorexia or reduced appetite. So, these can be quite vague. Um Some other side effects you might see is visual color changes. Um and this yellow or green tinted vision is quite typical, quite classical of digoxin toxicity. Um at toxic levels. Digoxin can also cause arrhythmias. So, instead of preventing the arrhythmias, like its job is it can, it can be proarrhythmic instead and cause ventricular tachycardias or atrial tachycardias. Um and ectopic beats as well. You might also see a rash. Um the patients might complain of headaches or gynecomastia with digoxin. So, contraindications for digoxin if patients had an acute mi if they have ventricular fibrillation or if they've had in the past hypersensitivity to digoxin. So how you can measure um digoxin is you measure plasma levels. Um and digoxin has a very narrow therapeutic index. So you'd be doing um you'd be measuring the digoxin plasma levels regardless of whether you think there's toxicity or not, just to make sure it's reaching um the therapeutic levels. So, recommended levels are between 0.8 to two nanograms per milliliter. And how you'd measure them is you give the patient a dose of digoxin and then you draw blood about 6 to 8 hours after the last dose to make sure it's gone, you know, adequately in the blood stream and gone all all over the body. Um And you're making sure you're measuring the the accurate serum digoxin levels. So other kind of antiarrhythmics, then um they can be generally classified into four categories. So there's this Vaughan Williams um classification system um where you can, you can put these antiarrhythmics into four different classes. And we've already spoken about two of these classes. So class two are your beta blockers in class four, are your calcium channel blockers. So I'll be mainly talking about class one and class three, then your sodium channel and potassium channel blockers. So all of these are used to um m manage different types of arrhythmias. And so this is a diagram of how the action potential works um along with a single beat on the E CG. So if you remember where um certain certain uh electrolytes kind of come in and out of the neuron during the action potential, that kind of helps you remember where each class um of antiarrhythmic works. So if you look at this again, class class one is a sodium channel blocker and class three is a potassium channel blocker. Class four is a calcium channel blocker. So this is where they work at different points of the action potential. You can see the potassium here, sodium there. Um and the calcium is here and the beta blockers don't work on this, but it's important to keep this in mind because different drugs working at different points of the um actin potential can cause different changes in the ECG which is why sometimes you can see something like QTC prolongation um as a side effect of some of these drugs. So a general side effect um most of these, while they are similar to digoxin antiarrhythmic um as as is their um mechanism of action if they are either too high um or if the patient isn't tolerating them, well, they can have proarrhythmic potential. So, um for example, class one antiarrhythmic sodium channel blockers, it can prolong the QTC interval that increases your risk of BT. Uh for example, toads, specifically, um general side effects, patients can feel nauseous or dizzy and have a headache. They can also cause quite low heart rate or even maybe block. So, contraindications to antiarrhythmics, hypersensitivity reactions. If the patient has a second or third degree block or sick sinus syndrome, which is that with uh reduced cardiac output. Um So, monitoring requirements, then IV administration should be done only under cardiac monitoring just to monitor for any uh arrhythmias that might arise. So, uh you should be keeping a close eye on that and then do an E CG before and after monitor the heart rate, especially the QTC interval. Um just in case the patient may go um or have the risk of going into VT. So, amiodarone is another type of um antiarrhythmic. So, amiodarone is in this class. Uh in this, in this bug William classification, it's class three antiarrhythmic. Um So it's a potassium channel blocker and it's mainly used to suppress ventricular arrhythmias, also used for advanced cardiac life support in wide complex tachycardia and also in atrial fibrillation. So, as a potential, sorry as as a potassium channel blocker, it results in increased action potential reation and prolonged effective refractory period in myocytes. So it kind of prolongs that action potential um and and reduces the chance of an arrhythmia from forming. So um the myocyte excitability is reduced that causes um a stop in the continuation of any kind of tachy arrhythmias that have already formed. Uh It prevents the reentry of these, of these um electric currents from coming back into the heart. Um And then in the E CG, you can see this by the prolonging of the QR S duration um and also by the prolonging of the Q TC interval. So, side effects of amiodarone are quite specific and also quite many Um So patients might not be able to tolerate these. Well, they're not the best um or not the nicest of drugs. Um So patients, 90% of patients who use amiodarone can get these corneal micro deposits. Um It's believed to be because this drug is screwed in the lacrimal glands. Um so your tear ducts and then it can be taken up by the corneal epithelium itself. So it's good to get um an ophthalmology assessment when taking this drug. Um and then it can also cause cardiac toxicity. So, very slow heart rate, bradycardia, um atrioventricular intraventricular conduction abnormalities as well. Uh You can get some lung injury from this of pulmonary toxicity. It kind of looks a bit like interstitial lung disease. Uh is what it's described as. Um and then amiodarone can also cause problems with your thyroid, either a very high or very low thyroid. Um and also issues with your liver or your neurological system. So, contraindications for amiodarone, if the patients had cardiogenic shock or sick sinus syndrome, if they've had a second or third degree A V block, but they don't have any pacemakers. Um You can't give them amiodarone. So you should um be quite cautious when you're using amiodarone in pulmonary liver or cardiac toxicity. And in patients with preexcitation syndromes, for example, Wolf Parkinson White Syndrome, where um concurrent atrial fibrillation is also present. Amiodarone is quite dangerous in them. So, it's important to monitor um amiodarone continuously when you're, when you're giving the drug and to, to monitor for any side effects of the drug. So it's good to get regular vital signs and get an ECG done. So, baseline liver function tests are also important as it can cause liver toxicity. Uh you might want to get a chest X ray and pulmonary function test just to see um if, if any pulmonary toxicity comes about monitor their BP electrolytes as well. ECG is good and get an ophthalmology assessment for any corneal micro deposits. So our last drug, we've come to the end of the drugs here. Um SGLT two inhibitors, these are used in, well, they were first use in type two diabetes. Um and now used in the management of heart failure including heart failure with reduced preserved or moderately reduced ejection fractions. Um They're used to reduce the risk of major adverse cardiovascular events as well or death even from a heart disease in both type two diabetes and heart failure with reduced ejection fraction. Um They're also now being used to reduce the risk of egfr decline in chronic kidney disease. And SGL T twos have become kind of a miracle drug um as they're being used in many different organ systems and different diseases. I think now they're even being used in um rheumatoid arthritis. Um and there, there, there's good evidence to support um their use in all of these conditions. So there are four agents. Um and they're all end in the sex flosin. So, canagliflozin was your first SGLT two inhibitor. There's dopergin pilosin or two gliflozin as well. So how they work is uh they work in the kidneys and the sodium glucose transport two proteins or SGLT two proteins which are found in the proximal convoluted tubules. So how they normally work these proteins is they reabsorb um filtered glu glucose. Um and then the estr T two inhibitors will inhibit the work of these proteins preventing the reabsorption of the glucose. And that helps to um excrete the glucose through, through the urine. And that's how it helps in type two diabetes. So, um it's been proven that ut two inhibitors help lower HBA1C by about 0.7%. Um and then by inhibiting both glucose and sodium reabsorption as it's uh they work together at sodium glucose um transport. So they go hand in hand as you inhibit both glucose and sodium reabsorption, there's increase um in the distal tubular sodium load. So there's more sodium at the end of the tubes. And this then inhibits the renin angiotensin aldosterone system, which we spoke about at the start um that reduces your afterload and preload both helping to protect the heart. Uh It's cardioprotective, reducing your BP and your cardiac output. So SGL T two inhibitors um then reduce the afterload by arterial vasodilation and preload by sis which is removing sodium diuresis, which is reduce, removing water and decreased uric acid levels as well. So, pilosin has been shown to decrease your mean arterial pressure. Dapagliflozin induces vasodilation that improves the endothelial function. Uh and arterial stiffness and canagliflozin has slowed down the advancement um in serum anti P which is your um monitoring um your what you look for when you're looking at heart failure and how severe the heart failure is. Um You're looking at your BN P which is your brain natural peptide. Um It also has been shown to reduce triple one levels in patients with type two diabetes. So this could explain your benefit in patients with heart failure and how SGLT two inhibitors help with heart failure. So some um uh I think SGLT two inhibitors are quite um exciting drugs to kind of watch as there are new drugs and there are still studies being done on them on the minute at the minute. Um And and it's quite interesting to kind of watch the progression. So these trials, your DPA heart failure and reduced trials or something you can look up um and see how they've changed. So, side effects of SGL T two inhibitors as they work um in the kidneys, it can cause infections in the kidneys. So uti su or ses of pyelonephritis, patients may also be um complaining of increased urinary frequency um which may be quite um inconvenient for them. It can also cause other infections like genital mycotic infections, including candidiasis. Um patients may be at risk of lower limb amputations as well, especially if they've had preexisting risk factors such as peripheral vascular disease, neuropathy or a history of diabetic foot ulcer. They can also have DKA. Um and so both these lower limb amputations and DKA are more common in the diabetic population, which is the target demographic for these drugs. Um SGLT two inhibitors can also cause AKI s uh very low glucose or hypoglycemia or even four grand clean um and contraindications for these drugs. Um You can't give them these drugs if they're on dialysis as um it's working on, on the kidneys and also hypersensitivity to any of these agents. So when you start patients on SU LT two inhibitors, you'd like to get a baseline volume status assessment uh and check their renal function. All four of the agents can cause um red reduction in the intravascular volume that can cause potentially symptomatic drop in BP um and also transient, raised uh serum creatinine. And then after that, you can do routine uh tests including a renal function, checking their BP, full blood count, you need lipids as well. Um And then for their diabetic uh control, if they are diabetic, you could check blood glucose and HBA1C and then if the patient has heart failure and that's what you're using to treat them. Um You can check their ejection fraction to see how well they're responding to the SGLT two inhibitor. So now we're going to go over some of the um nice guidelines on um these different drugs. So I don't know how clearly you can see um these pictures, but these are all available um for you to look up. And so this is a diagram that everybody should kind of know in and out. It's how to prescribe a hypertensive drug. So I'm just going to show you the examples of, of all the drugs we've talked about here. So for example, if the patient has hypertension with type two diabetes or if they're under the age of 55 and not of Black African or African Caribbean family origin, an ace inhibitor or an ARB is your first choice for hypertension. But if they are over the age of 55 or if they have Black African or African Caribbean family origin, you want to start them on a calcium channel blocker. So um moving on to step two, then you'd use a combination of either that with um A thiazide like diuretic or you'd switch to the other side, use an ace with a calcium channel blocker or calcium channel blocker with an A B, for example, and on step three, you'd combine all of those together. So an ace, a calcium channel blocker and Thiazide, you wouldn't use an ace or an A RB together um that can cause quite um catastrophic effects both for the, for the potassium. Um and otherwise, and then once you go to step four, you have your diuretic like spironolactone if the potassium level is below four, because spironolactone is a potassium sparing diuretic. So, if potassium is too high, you want to give them spironolactone. If the potassium is more than 4.5 you'd consider an alpha blocker or a beta blocker for their BP. So, a CS drugs, um if you were there for my talk on A A CS, we went through this quite thoroughly. But um some examples of the drugs that are on this guideline here, you have um aspirin, which is an antiplatelet tagal and clopidogrel are also antiplatelets, um and pressure as well. And then unfractionated, heparin Bivalirudin are anticoagulants. So, these are all um things that you should be thinking about in terms of blood thinners, when you have a CS to reduce the risk. Um well, to, to reduce the um narrowing of the artery and, and reduce the um thrombus um at, at the point of narrowing, but also to reduce risk of uh reinfarction at any point. Um So these patients will generally be on anticoagulation um or antiplatelet therapy for life. So, um that's this is the part where um you get them cardiac rehabilitation or secondary prevention. So you think of them starting, uh for example, if they've got high BP or if they've got high cholesterol, you'd start them on an ace inhibitor or a statin um or a beta blocker as well. And then the patients will be on dual antiplatelet therapy. So, aspirin and another antiplatelet, for example, clopidogrel um for up to 12 months and then you'd continue with aspirin for life. So you could give them um ace inhibitors or beta blockers as well just to reduce the strain on the heart. And also if they've had history of hypertension that would help um reduce the risk of future A CS heart failure drugs, then um heart failure with preserved ejection fraction hasn't had as many. Well, it doesn't really have any um treatment options, but there's more and more evidence now that your SGLT two inhibitors can help um even with a preserved ejection fraction or at least reduce the risk of um or reduce the um mortality and morbidity of these patients. But for heart with reduced ejection fractions, there is um quite a clear guideline here. You'd offer them an ace inhibitor or a beta blocker that helps with um reducing the contractility and the strain on the heart. Um You might give them um an MRA as well if they still, they're still symptomatic. And then you can consider um other drugs like ARB S or hydrALAZINE and nitrates as well. Um And if they have um heart failure with sinus rhythm um to improve your symptoms, you might wanna get them digoxin as well, but monitor for any side effects there. And then um these are two guidelines. The left is on your adult tachycardia from your recess Council um algorithm and then on the right, this is um for atrial fibrillation and kind of the stroke prevention, uh aspect of atrial fibrillation. So, looking at your adult tachycardia just for some of the drugs that you might want to use. Um Here, you can see amiodarone is being used in a broad QR S but with a regular rhythm, um if it's BT, you can use amiodarone there. Um and then you might um then you might also consider, if the patient has a narrow QR s complex with irregular rhythm, you might think they have um atrial fibrillation. So there you can either rate or rhythm control. So if you rate control, you give them a beta blocker, for example, or if your rhythm control, you might consider digoxin or amiodarone. Um And then speaking of uh atrial fibrillation, then for stroke prevention, um or to reduce the risk of a stroke, you'd want to give them a blood thinner. Um And now the new guidelines um say dox are your first choice of uh blood thinner. So, for Apixaban is something you'd give to prevent stroke. Um and this will all depend on your TRANS VSC score and then your orbit score. So your chance VSC to see your risk of stroke with atrial fibrillation and your orbit score to see your risk of bleeding um on any anticoagulation. So first choice would be something like Apixaban A doac. Um But if those are contraindicated or the patient can't tolerate them. Well, you might think of something like a Vitamin K agonist like Warfarin. So now we're gonna move on to some questions. Um Just to kind of put all of those together. Um I'm gonna start up the pool here the first question. Um A 53 year old man, he presents to his GP for an appointment for his high BP. He's got a past medical history of diabetes, gout and heart failure. He takes Metformin Ramipril, Bisoprolol, Allopurinol. His BP is measured and raised at 1 67 98. And another medication should be added to reduce his BP. What is your choice? So I give you guys a couple of minutes to get your answers, right? Yeah. OK. So the answer here is a amLODIPine. So this patient is already on an ace inhibitor, Ramipril for his BP. Biopol also helps with the BP, but he's probably not on it. Um As for his BP in the first place. Um So the next step according to the nice guideline is either a calcium channel blocker or a thiazide like diuretic. So you'd give um a thiazide, sorry, a calcium channel blocker, for example, amLODIPine, a dihydropyridine one and not something like verapamil, which is a nondihydropyridine calcium channel blocker. Um That's because your non dihydropyridines can have your negative chronotropic and inotropic effects. And since he's already got a history of heart failure, that can be quite catastrophic for him. Um, your thiazide like diuretics can lead to hyperuricemia and since he's got gout here, you would not think of getting something, um, like your indapamide, uh, as, as that can worsen both the blood glucose regulation as well. And, um, he's got a history of diabetes here. So your answer would be adipine. So, same question, I'll stop the poll or maybe if you want to read this first. Um, so a 62 year old female patient attends an outpatient cardiology clinic for review. She's got a past medical history of heart failure, hypertension, ischemic heart disease type two diabetes and osteoporosis. She's been taking novo lapid 10 units three times daily. Uh Lantus three units once daily and Ramipril 10 mg once daily. AmLODIPine 10 mg once daily. Bisoprolol, five mg once daily and aspirin 75 mg once daily and also add CAL D3 2 tablets once daily for three years without any side effects. Recently, she was started on spironolactone 25 mg. Blood test shows the following. Um And if you can't see the blood test, what it shows you is um a raised potassium level, her blood test uh shows you the following which of her medications is likely to have interacted with her new prescription to cause a blood abnormality that I Yeah, good. So most people got Ramipril um which is your answer here. So um what you started on was spironolactone which is a potassium sparing diuretic So it, it um in cases of low potassium, that's good. But in cases where um the patient's already on something that has um a risk of causing hyperkalemia like Ramipril an ace inhibitor. Uh putting these two together can both increase the risk of hyperkalaemia precipitating. Um And that's why she's got a raised potassium. So, third question, 72 year old man presents to the ed feeling generally unwell and lethargic for the past two weeks. Um He's got a past medical history, significant for atrial fibrillation, depression and a myocardial infarction. 23 years ago, he takes numerous tablets that come in blister pack. He doesn't know the names of them which of the following combinations is most consistent with digoxin toxicity. Yep. So most of you guys went straight for the for the obvious classic answer which is nausea and yellow or green vision. So, digoxin toxicity, it has quite a characteristic constellation of symptoms. It comes with um nausea is a bit nonspecific, but it's quite common in digoxin toxicity almost in 50% of cases. Um and then your yellow green vision is classic. Um So associated with digoxin toxicity and considered patho. Um it involves inhibition of your sodium potassium apase pumps in the retinal cells in the eyes that affects color perception. Um So going over some of the other options. Tinnitus is more common in solicitate toxicity or immunoglycoside antibiotics. Um gynecomastia can occur with long term digoxin toxicity. Um But not, it's not usually a feature of acute toxicity. Uh diarrhea can also occur but it's not specific or characteristic. And headache is not really a typical feature. So, so this is the same patient then. His only other symptom besides feeling generally unwell and lethargic is a yellow green tinge to his vision. He's got a past medical history um of atrial fibrillation, depression and a myocardial infarction. Three years ago, he takes numerous tablets that come in. The blister pack doesn't know the names of them. So they've taken a blood test and see the digoxin levels are raised 3 mcg per liter. Um which drug may have precipitated in this clinical picture. Ok. Ok. So this might be a bit of a difficult one. So it's asking for a few steps here. Um You want to first diagnose the digoxin toxicity and then kind of think of what could cause digoxin toxicity. Um And then from the list of your five drugs here, you want to think of which of these drugs can cause that. So the answer is bendroflumethiazide. So a thiazide diuretic um so digoxin toxicity, uh we've established here, it can be triggered by hypokalemia. So, of all the five drugs there, bendroflumethiazide can cause hypokalemia. Um So since potassium is a competitive inhibitor of digoxin, lower levels of potassium can mean digoxin has more effect on your sodium ATPase pump that leads to higher levels um of the digoxin concentration and then toxicity So your answer um is dependent on you kind of knowing that thiazide diuretics can cause hypokalemia. So a final question, then a 76 year old lady visits her GP with ankle swelling over the last two weeks, swelling is bilateral with pitting edema to the mid shin. She's had a recent change to her medication two weeks ago, which medication is most likely to have caused this. This sounds good. So a majority got amLODIPine, which is the answer. So um amLODIPine is a dihydropyridine calcium channel blockers and it commonly causes um ankle edema. So this tends to only be partially responsive to diuretics. So the treatment for this is usually to stop um the calcium channel blocker and try something can also cause other side effects uh associated with vasodilation like flushing and headaches. So, uh an important distinction between amLODIPine and anti ramipril is ramipril causes angioedema. So don't mistake on that for ankle edema or peripheral edema. Um which is what amLODIPine will cause. Um So that's all the questions I have. Uh these are some of my references and, and what I took most of these um most of the information from and then this is a QR code to the feedback form if you'd want to fill that out and then you get your certificate um for attendance at the end. I hope you all enjoyed uh the talk and learned something from that. If you have any questions, feel free to put them in the chat um or email me um and we'll get back to you. Thank you very much. Thank you for, for delivering in that lecture. Sorry I II before today, apologies. So thank you very much for that. Uh Thanks everyone for attending. Um The feedback form is in the form in the QR code as Ravena is very kindly put it up there and also in the chat. So please make sure to give us some feedback and uh get you a certificate as well. So thanks very much for joining. Um Next week we have another lecture I think on ECG. So looking forward to hopefully seeing all of you there and uh yeah, enjoy the rest of your week. Thank you very much, George has asked why we're still prescribing ace inhibitors not going straight for Arbs. Good question George. Um I don't know if I can give you a good comprehensive answer on that. Um But I think ace inhibitors have been proven to have um still quite good efficacy and while they have um side effects that can be severe or intolerable in some patients, I think it's good to try that first and then see if we can go for the RBS. But I'm not sure if that totally answers your question. There might be another reason that I have no idea about. Um But I think um my my knowledge of, of pharmacology is still at a medical students level So you might be better asking somebody a bit more qualified than me about that. And do you have anything to add on that? No, no, absolutely not. That's something I don't really know. I think it's to do probably with the guidelines, as you said and a CRP Ace inhibitors being a bit more efficacious, but I'm really not sure either. Excellent. Yeah. Ok. So I'm gonna go ahead and end the call here. Um Thanks very much. Thanks very much again, Ravena and um hopefully see everyone next week. All right. Thank you, Cheers bye-bye.