hello in this video we're going to talk about anti-hypertensives so medication to lower blood pressure so the heart pumps oxygenated blood around our body the hot first pumps um this Blood through the arteries and this is in red here and then once the oxygenated blood is distributed around the body tissues the blood is then brought back to the heart via the veins here in blue focusing first on the heart the heart actually pumps a certain amount of blood each time it contracts and this is the cardiac output the cardiac output allows blood to flow through the arteries and deliver oxygenated blood to tissues before returning back to the heart via the veins the cardiac output it's itself has a big impact on blood pressure other organs responsible for or plays a role in regulating blood pressure include the liver lungs kidneys and the endocrine organ above the kidneys called the adrenal glands when we talk about blood pressure we are really talking about the arterial blood pressure so the mean arterial pressure and this mean arterial pressure can be calculated by um having cardiac output multiplied by the total peripheral resistance tpr and tpr is the resistance um of the vessels of the archery in this case to make things even more complicated the blood pressure we know has two numbers one on top called the systolic and one number on the bottom called the diastolic blood pressure the systolic blood pressure is essentially the pressure um of the arteries when the heart is pumping blood out and the diastolic blood pressure is the pressure in the arteries when the uh when the heart is filling back with blood normal blood pressure is about 120 over 80 hypertension means high blood pressure many things can cause hypertension persistent untreated or unmanaged uh hyper hypertension can have serious consequences and one way to treat hypertension is by using anti-hypertensives or medication to treat hypertension and these medications can be remembered by the alphabet so a b c d and e let's begin by looking at a so a includes ACE inhibitors Angiotensin receptor blockers and Alpha 1 receptor blockers now before focusing on these um let's just recap some physiology so the liver produces this molecule called angiotensinogen uh when there's a decrease in blood pressure in the arteries the kidneys will detect this and then produce a molecule called renin now renin enters circulation and is responsible for converting angiotensinogen produced by the liver into angot tensin one Angiotensin one will then circulate around the body and get in contact with a membranebound enzyme called Ace or angot tensin converting enzyme which mainly resides in the lung tissues so Ace converts Angiotensin one to Angiotensin 2 Angiotensin 2 is an important regulator of blood pressure and what it does is basically it increases blood pressure via a number of mechanisms Angiotensin 2 binds onto Angiotensin 2 receptors on many different types of cells around our body and depending on what cell Angiotensin binds to its effect on the body um differs so but essentially it will result in an increase in blood pressure so for example some of the effects of angiotensin 2 includes increasing sympathy itic activity vasoconstriction stimulating the release of aldosterone a hormone from the adrenal cortex and these effects all of them will lead to an increase in blood pressure ACE inhibitors or Angiotensin converting enzyme Inhibitors is a very common anti-hypertensive these medications can be remembered uh by the ending pill so for example captop Ram they all end in pears usually the mechanism of action of ace inhibitor is that it inhibits Ace the enzyme bound membrane bound enzyme and so it inhibits the conversion of angiotensin one to Angiotensin 2 and because you have less Angiotensin 2 means that you will decrease blood pressure because it's not working some side effects of ACE inhibitors include a dry cough a rash nausea vomiting diarrhea angio edema and headache there are contraindications to using ACE inhibitors or relative or absolute and these include being pregnant having bad asthma chronic cough being allergic to ACE inhibitors having a kidney disease particularly renal stenosis the other medication that starts with a is the Angiotensin receptor blocker and as the name suggests the mechanism of action it blocks The Binding of angiotensin 2 to its receptor and so thus it will decrease the activity of angiotensin 2 which will result in a decrease in blood pressure the side effects of angiotensin receptor blockers include headache nausea diarrhea dizziness and back pain some contrad indications include pregnancy renal stenosis bilaterally and if they are allergic to Angiotensin receptor blockers it's interesting to note that Angiotensin receptor blockers are usually used as an alternative to ACE inhibitors because people that use ACE inhibitors getting a chronic or getting a dry cough is quite common and so sometimes people change to the Angiotensin receptor blockers Angiotensin receptor blockers can be remembered because it us usually ends in sartan so for example La sartan the sartans anyway the final anti-hypertensives that begin with a are the alpha 1 receptor blockers and these guys aim is to work on the vessel epithelial cells so zooming into the blood vessels here is the Lumen of the blood vessel and surrounding the Lumen is the endothelial cells and the smooth muscle cells the smooth muscle cells can contract usually and this will make the Lumen of the vessel smaller or the smooth muscle cells can relax and this will dilate the Lumin quote making it wider so as you might suspect when the smooth muscle cells contract and the Lumen becomes smaller the blood pressure increases the smooth muscle cells that surround the vessels have alpha 1 receptors these receptors react to noradrenaline Adrenaline produced by the nerve fibers or from noradrenaline adrenaline in circulation noradrenaline and adrenaline is same same thing as epinephrine norepinephrine anyway nor adrenaline will uh can bind to the alpha 1 receptor and this will cause or stimulate contraction of the smooth muscle cells the contraction of the smooth muscle cells that around the vessel will cause the vessel to become more smaller will narrow the Lumen and this will lead to an increase in blood pressure alpha 1 receptor blockers they block alpha 1 receptors and thus the mechanism of action of alpha 1 receptor is that inhibits the adrenergic activity leading to the decrease in blood pressure alpha1 receptor blockers also have a role in decreasing total cholesterol in the body thus it's a good option for people who have both high blood pressure and cholesterol problems side effects include um it can lead to hypotension so a drastic decrease in blood pressure so they were the anti-hypertensives that begin with a let's look at the anti-hypertensives that begin with b b it's easy it's just beta blockers and beta blockers are very easy to remember because they end usually in all like metol andol or L anyway beta block is block uh what are called beta receptors and beta receptors are important in the sympathetic activity so by blocking the beta receptors you are blocking sympathetic activity essentially so there are beta receptors everywhere in the body we mainly we will mainly concentrate on the heart here so be beta blockers can be selective and work specifically on the heart or beta blockers can be non- selective and work on the periphery too such as the blood vessels but let's focus on heart the heart have these cells called pacemaker cells which make up the conduction system of the heart the pacemaker cells regulate the heart rate so how fast your heart is pumping the pacemaker cells can be influenced by many things including the parasympathetic nervous system and the sympathetic nervous system pacemaker cells of the heart they have receptors on them the beta one receptors adrenergic neurons which are part of the sympathetic nervous system Target these pacemaker cells and release adrenaline and noradrenaline which will bind onto these beta 1 receptors thus it will stimulate the pacemaker cells to fire more rapidly which will increase the heart rate and because you get an increase in heart rate you will get an increase in blood pressure by increasing the cardiac output further the heart itself is a muscular organ they are made up of cardiomyocytes which are basically the cardiac muscle cells the muscle cells of the heart the cardiomyocytes are the cells which contract and help eject blood out the hot muscle cells also contain beta one receptors so noradrenaline and adrenaline released by adrenergic cells the sympathetic nervous system can stimulate the beta 1 receptors of the cic muscle cells which will cause the codic muscle cells to contract stronger and to be exact it will lead to a more powerful contraction with a more powerful contraction the hot is able to increase cardiac output and because you're increasing cardiac output you will increase blood pressure beta blockers selective for the heart work by inhibiting beta 1 receptors the mechanism of action of beta blockers is that they block the sympathetic function on the Heart by blocking the beta one receptors and they do this by two ways first by decreasing the heart rate which will decrease cardiac output and then decrease blood pressure or they will decrease the myocardial contraction the strength and thus decreasing CTIC output which will subsequently decrease blood pressure side effects of beta blockers include bradicardia fatigue hypotension decrease in libido impotence and Bronco constriction contradiction include obstructive lung disease and peripheral vascular disease so that was the anti-hypertensives with B let's look at C anti-hypertensives and the C's uh are the calcium channel blockers most names um for calcium channel blockers they end in or sound something like deine um or like um Mill so for example Verapamil um but these guys are kind of hard to remember but hopefully you get the idea anyway in order to understand calcium channel blockers we need to understand calcium and its role in the body when you think of calcium think of muscle contraction think of excitability calcium channels are important channels in our body that allow the movement of calcium in and out of cells or uh cellular organel there are two main calcium channels we will talk about and these are the T type calcium channels and the L Type calcium channels but what these drugs do is that as the name suggests they block calcium channels more specifically they block ttype calcium channels and or L Type calcium channels so there are L Type calcium channel blockers or ttype calcium channel blockers or both and it's important to know this because these channels are found in different parts of our body for example in the hot going back to our past maker cells which control the hot rate there are ttype calcium channels calcium activity in the past maker cells causes the heart to pump faster and so contributes to increasing the blood pressure think of ttype calcium channels as time so t for time because the pace maker cells of the heart control the heart time the heart rate and so by using the T P type calcium channnel blockers it will block calcium activity and thus decrease heart rate decreasing CC output and then decreasing blood pressure this might get confusing but there are three types of uh T type calcium channel blockers these are the phenol alkaline such as Verapamil the benzoin such as delim and the dihydro paradine such as the ones that end in deine so they they are all different but to put it simply they just work differently and they also work on L Type calcium channels but anyway so for example um here is Verapamil a common calcium channel blocker which will block the ttype calcium channels of the pacemaker cells let's talk about the L Type calcium channels which are found on smooth muscle cells so here we have the blood vessel which as we know contain smooth muscles um and here is the limit of the vessel for example the ltop calcium channels allow influx of calcium into the muscle filaments which will cause contraction this will increase the blood pressure because it causes the vessels to contract and become more narrow but the L Type calcium channels are also found in the cardiomyocytes and thus they will increase the power of contraction of of the cardiomyocytes um which will further increase cardiac output and so blood pressure lype calcium channel blockers are the dihydropyrenes where that end in deine some of the drugs from dihydropteridine also block ttype calcium channels and so is also part of the ttype calcium channel category a common example of a l type calcium channel blocker is neopine side effects of the DI hydrop paradin like a lot of anti-hypertensives are flushing headache dizziness from hypotension palpitations and peripheral edema Contra indications of calcium channel blockers are congestive heart failure heart block hypotension and ventricular tachicardia and this is unique to calcium channel blockers because in heart failure the heart is trying to compensate by by Contracting a lot harder and so if you use a calcium channel blocker specifically an L Type calcium channel blocker you are weakening or you are reducing the strength of contraction of the heart and this is what you do not want to do in people who have hot failure so that was the C anti-hypertensive medication the calcium China blockless next is D for diuretics so when we think of diuretics we think of the kidneys diuretics works on the kidneys and what they essentially do is induce diuresis cause peeing so when we pee the water in our body it drops and this will then uh you know drop blood pressure so here is the kidneys with the adrenal glands above it and the functional unit of the kidneys or the main players of the kidneys are these things called nephrons and there are millions of nephrons in the kidneys and this is where diuretics work and it's important to understand that the nefron the functional unit of the kidneys they filter things from blood and they allow for secretion and reabsorption of things in and out of the blood vessel so here I'm just going to draw a a vessel a vein let's just say a vessel and so the mechanism of action of diuretics again is to increase urine output decrease fluid overload and this will decrease blood pressure and there are three types of diuretics three main ones these are the Loop Diuretics which is the strongest of the lot the thide diuretics and the potassium sparing diuretics the nefron is divided into different sections one of which is the loop of Henley in the loop of Henley in the ascending part there is this channel a symptom which transports one sodium molecule two chloride molecules and one potassium from the nefron back into circulation back into the blood vessel when sodium is reabsorbed in the blood water follows Loop Diuretics inhibit the transport of this this transporter by inhibiting the movement of chloride ions which will disrupt the whole transport and so you don't get sodium moving into into the blood vessel and so you don't get water following and so you don't get an increase in blood pressure thide diuretics work on the distal part of the nefron there is a transporter here which reabsorbs sodium and chloride together this will then draw water back into the blood as well which will increase the blood pressure in the body thide diuretics block this transporter and so block sodium reabsorption abortion and thus water reabsorption causing a decrease in blood pressure in the distal part of the nefron there's also this other transporter exchanger which reabsorbs sodium but secretes potassium and potassium sparing diuretics inhibit this uh transporter and by inhibiting this transporter you actually decrease the reabsorption of sodium which means you decrease the reabsorption of water which subsequently decreases blood pressure but you also prevent the secretion of potassium and this is why it is called a potassium sparing diuretic because you're sparing potassium and so all these diuretics they essentially um inhibit sodium from going into the blood and so you have more sodium being peed out which means that you have more water being peed out which means that you will decrease blood pressure side effects of Loop Diuretics and thide diuretics include hypo calmia hypo naturamia hypo vmia hypotension hyperemia which increases the risk of gout hyperglycemia hypercalcemia metabolic alkalosis and pancreatitis the side effects of potassium sparing diuretics is quite different in that they can cause hyperemia met abolic acid dosis and gynecomastia if you want to know more about diuretics I have a separate video on the pharmacology of diuretics finally e antihypertensives is for endothelium reor antagonist and these guys basically um relax the blood vessel causing Vaso dilation which will cause a decrease in blood pressure they work on the blood vessel um the smooth muscle cells contain endothelin one receptors which when endothelin a molecule produced by the blood vessel itself binds onto it it will cause contraction and narrowing of the blood vessel which will cause an increase in blood pressure of course well endothelin receptor antagonists as the name suggests inhibits this receptor which means you don't get contraction of the vessel which means that you will lower the blood pressure the side effects of endo othian receptor antagonists include headache peripheral edema nasal congestion nausea hypo tension and palpitations so that concludes the video on the anti-hypertensive medications we looked at um a b c d and e a for ACE inhibitors Angiotensin receptor blockers and um Alpha 1 Alpha receptor antagonists and we also looked at B for beta blockers C for calcium channel blockers D for diuretics and finally we just looked at e for endothelin receptor antagonists anyway I hope you enjoyed this video I hope it was helpful thank you for watching byy