[Music] today's topic is cardiovascular system in cardiovascular system we will discuss five main topics these are hypertension congestive heart failure anginas Arias and anti-lipidemic trugs we'll start uh start with we'll discuss the topic of congestive heart failure so as the name tells heart failure means this is a condition characterized by inability of heart to do its function function of heart is to supply the blood to all parts of the body according to their requirement so when heart is not able to do that it is called heart failure now if we see we have four chambers of the heart right atrium right ventricle left atrium left ventricle now left ventricle pump the blood all over the body through Iota all over the body on the other hand right ventricle it pump the blood mainly into the pulmonary circulation hes the lungs now from the lungs the blood will reach the left at from there it reach the left ventricle again it is pumped all over the body Superior and inferior vava bring the blood into the right so the circulation we all know Suppose there is left ventricular failure that means left ventricle is not able to pump the blood so when left ventricle is not able to pump the blood the first of all body parts will not get the blood second blood will accumulate in the left ventricle left ventricle get the blood from the left atrium so it will start accumulating here left atrium get the blood from the lungs so it will start accumulating here so left ventricular failure will result in pulmonary Ed similarly if right ventricle FS the blood will accumulate in the right ventricle it leads to accumulation of blood the right at right atrium takes the blood from inferior and Superior Vaga it will accumulate the inferior vava take the blood from the lower part of the body like liver so blood will accumulate in the liver leading to hpom again congestive homic superior vena take the blood from the jugular vein so blood will accumulate here resulting in increase in jugular Venus pressure so basically what is happening is when blood is not pumped that means when the heart fails it will lead to accumulation of blood in the areas from where it was getting the blood in case of left ventricular failure there is pulmonary edem whereas in right ventricular failure there is accumulation of blood in the liver and jugular veins so that will lead to homic Alley and increase in jugular venous pressure and we all know accumulation of fluid is known as congestion so that's why the term used in heart failure is congestive hpom so due to failure of heart to pump the fluid accumulates in different parts of the body this is called as congestive heart failure So based on this pathogenesis the simple aim of treatment in heart failure or congestive heart failure are two aims we have two problems so we have to treat those two problems the first problem is the blood is getting accumulated in the different parts of the body so we have to remove the excessive flu second heart is not able to pump so we need to increase the pumping activity of the heart are the two main AIMS in the treatment of congestive heart failure the drugs which are used to remove the fluid from the body are diuretics and the drugs which increase the pumping activity of the heart they are called as inotropics diuretics and inotropics are the two main drugs which are used in congestive heart failure we will discuss these one by one we'll start from diuretics now diuretics in congestive heart failure we mainly use two type of diuretics one are called Loop Diuretics like fosite second are called thides the basic difference between these two group of diuretics are Loop diuretics are very strong diuretics they are called as high sealing diuretics High sealing diuretics means they have high efficacy that means they can remove large amount of fluid from the body large amount of sodium and water can be removed from the body on the other hand thides are relatively weak diuretics that means they can remove little bit of sodium and water from the body but not large amounts but most of the Loop diuretics are short acting whereas most thides are long acting so based on these two differences we will prefer Loop Diuretics in case of congestive heart failure or most cases of Edema because Loop Diuretics can remove large amount of fluid from the body on the other hand thides are weak diuretics so they are not very effective in conditions like congestive heart failure but because of their long action they are preferred in hypertension which will cover later so in congestive heart failure we use Loop Diuretics now both Loop Diuretics and thides have some common side effects and these side effects are side effects of Loop and thides common they remove sodium from the body we all know they cause loss of sodium and water loss of sodium can lead to hypon now not only sodium they can remove most of the ions from the body they can remove potassium they can remove hydrogen they can remove magnesium so both Loop and haides they can result in hyponatremia hypoc calmia metabolic alkalosis and hypo magnesia similarly both of them they cause increase in metabolic substances like they can cause increase in blood sugar increase in serum lipids increase in uric acid so both Loop Diuretics and thides can result in hyperglycemia hyper lipidemia and hyper UD these are the common side effect of both Loop Diuretics and thides and you need to remember only one difference between the two and that difference is effect on calcium one diuretic increase calcium and one diuretic decrease calcium and this you can remember from the simple word Loop loses calcium Loop loses calcium that means Loop Diuretics will cause loss of calcium that means Loop diuretic can result in hypocalcemia on the other hand thides are opposite so they will result in hypercalcemia that is the only important difference you need to remember Loop Diuretics cause hypocalcemia thyes cause hyper calmia so diuretics particularly Loop Diuretics they are used in congestive heart failure so first group of drugs we have covered in congestive heart failure these are diuretics they will remove the fluid and give symptomatic relief to the patient the second problem was body is not able to pump the blood so we need to give a drug which can make the heart pump the blood and these drugs are called inotropic drugs so inotropic drugs we going to discuss now inotropics normally on the heart we have beta 1 receptors we know beta 1 will stimulate the heart so if a drug stimulate the beta 1 receptor then it can be used as an inotropic and we discussed in the autonomic nervous system there are several drugs which can stimulate beta 1 and used in congestive heart failure these drugs include dopamine dobutamine nor adrenaline isoprenaline so all of them can stimulate beta 1 receptors and can be used in congestive heart failure now quick recap of these drugs dopamine stimulate three receptors in the body in sequence D1 beta 1 and Alpha doamin is primarily beta 1on nor adrenaline we discussed at not all so it stimulate the sympathetic receptors but not all it stimulate alpha 1 Alpha 2 and beta 1 seps but does not act on beta 2 I prolin mainly act on beta 1 and beta2 receptors if you see carefully all of these drugs the common point is they can stimulate beta 1 receptors and in case of inotropic effect we want beta 1 action so any of these can be used in congestive heart field if we discuss in detail how V one stimulate the heart so we'll need to discuss that if this is a cell we know beta 1 is a g protein coupled receptor so this is a beta 1 receptor and this is a g protein so when we give any of the drugs which stimulate beta 1 receptors it will bind to the receptor receptor will stimulate the G protein G protein breaks into two components one is inactive and one is active and this active component in case of beta 1 receptors act by increasing cyclic so basically it is cyclic amp which will stimulate the heart that means if we increase cym by any other method that should also stimulate the and the second method we employ is we inhibit the metabolism of cyclic so normally cyclic is metabolized by an enzyme called phosphodiesterase phosphodiesterase metabolize cyclic so if we give a drug which inhibit this metabolism then cyclic EMP level will increase and when cyclic level increase it will stimulate the heart so inotropic effect can be produced so these type of drugs are called phosphodiester inhibit and they can also be used as inotropic drugs and the drugs in this category are phoso diester Inhibitors they are Amino and milino am known and Miller known these are phoso diester Inhibitors they act by increasing cyclic amp bya inhibition of the enzyme phosphor diges if you see we discussed drug stimulating beta 1 like dopamine doam they also increase cyc and we discussed drugs inhibiting phosphor Diest like and milon they also increase cyclic a so what will be the difference between these two drugs so basic difference will be beta 1 Agonist will increase hycm only at that place where beta 1 is present and we know beta 1 is mainly present in heart so they will increase cylic amp mainly in heart so their predominant effect will be inotropic on the other hand phosphor diester Inhibitors they will increase cylic a in all the places where phosphor Diest is and phosphor Diest is present in both heart as well as blood vessels that means phosphor destr Inhibitors they will increase hym in heart as well as blood vessels when they increase hym in the heart they will produce inotropic effect but when cyclic M increase in the blood vessels it result in VOD dilation so phosphor digest Inhibitors have one extra effect apart from beta Agonist and that extra effect is VOD dilation so if we see the effect of phosphor Diest Inhibitors so this include inotropic effect as well as VOD effect so we combine these together so fos for Diest Inhibitors they are known as inodilators IOD dilators phosphor digest inhibitor group of drugs are called inodilators they will produce inotropic as well as vasodilator effect in case of right sided heart failure the predominant action required is Vaso dilation so if they ask which is the inotropic drug of choice for right sided heart failure so it will be phoso diestra inabit or simply IOD dilators okay so these are the second drugs which can be used in congestive heart faure which increase the contractility that means inotropic effect now third group of drugs used in congestive heart failing now first we'll discuss the disadvantage of the first two drugs we discussed beta 1 Agonist can produce inotropic effect we discussed phosphor Diest inhibit can produce inotropic effect but the problem is both of these groups they act by increasing cyclic amp and cyclicamp cannot differentiate between different activities of the heart means heart has three main activities one is heart rate second is conduction from Atrium to V and third is contractility so in congestive heart failure we will like to increase the contractility because heart is not pumping so we like to increase the contractility but these drugs both of these groups they increase all the three things that means not only they increase contractility which is required but they also increase heart rate and conduction which is not required so we will want such a drug which increase only contractility which do not increase heart rate or conduction what is the disadvantage of increasing heart rate so it is obvious that if heart will contract more number of times it will have to do more work and we already discussed heart is failing heart is not doing its normal work and this extra work will be detrimental for heart so we will want a drug which do not increase heart rate which increase contractility so in search of such a drug we found the next group of drug which is called as dexin group of the drug is called as digitalis other name of this group is cardiac glycosites cardiac glycosites dexin or cardiac glycosites now first of all how dexin Works before going to mechanism of dexin we'll discuss first how normally the ventricular fibers contract if you see this is the cell this is a ventricular muscle cell like every cell in the body it also has same pump which is called sodium potassium pump and we all know the function of this pump is sodium goes out in exchange potassium comes in now in the cardiac muscle there is one more pump present which is called as ncx ncx means sodium calcium exchanger so as the name tells sodium and calcium will be exchanged that means if one comes in second will go out they will be exchanged now you can remember the direction of this pump from the direction of sodium pottassium pump now we know that from sodium potassium pump sodium is going out so when sodium is going out means it will be less inside so when sodium is less inside sodium will enter from here now as the calcium has to exchange so it will go out so through the ncx sodium enters and calcium goes out of the cell now how the normal muscle contracts we know when normal muscle has to contract we want depolarization so depolarization occur that lead to opening of the L Type calcium channels in the cells calcium channel opens and this will lead to entry of calcium so calcium will enter inside the cell we know for muscle contraction we require calcium so calcium has entered so it should cause muscle contraction but this does not happen the reason is amount of calcium entering the cell is very small for muscle contraction we require large amount of calcium but this is very small so example take we consider suppose only 10 molecules of calcium enters but for muscle contraction we want around 1,000 molecules of calcium so these 10 molecules will not be able to produce muscle contraction so what we do we know that there is a storehouse of calcium in the cells and that is called endoplasmic reticle so this is the endoplasmic reticulum of the cardiac muscle endoplasmic reticulum of the muscle cells is called as sarcoplasmic reticulum sarcoplasm reticulum is already storing the 1,000 molecules of calcium which we want for muscle contraction but we want this calcium in the cytoplasm to cause muscle contraction so these 10 molecules of calcium what they will do is they will request the endoplasmic reticulum to release calcium and how they request is they will stimulate a receptor present on the endoplasmic reticulum and this name of this receptor is rhodin receptor so they stimulate a receptor called as rhodin receptor when rhino receptor is stimulated the calcium which is stored in the endoplasmic reticulum it will be liberated out so 10 1,000 molecules of calcium they come outside so when this 1,000 calcium comes out now it can cause interaction of actin with myosin and that lead to muscle contraction so calcium enters from outside small amount it stimulate the Rodin receptor on the sarcoplasm reticulum that lead to release of calcium from the sarcoplasm reticulum so now this will cause muscle contraction now after some time the muscle has to relax so when the muscle relax this calcium will become free again so now what we do we will return this calcium back to endoplasmic reticulum and how it is returned is there is presence of another pump here and the name of this pump is cira this pump is named as cira cira is sarcoplasmic endoplasmic reticulum calcium ATP so in simple language it is calcium atpa the abbreviation is cira so this calcium atpa it will take back its 1,000 molecules of calcium so sarcoplasmic reticulum has provided 1,000 molecules of calcium to cause muscle contraction and the same thousand comes back in the sarcoplasm reticulum through cira now what about these 10 molecules of calcium which have entered from outside so these 10 molecules of calcium which has entered during the depolarization they will go out through the sodium calcium exchange so basically the calcium which has entered from outside will go out and the calcium which has come from the endoplasmic reticulum will go back into the endoplasmic reticulum so that means the cell will again become as earlier normal cell so the same thing will repeat in the next depolarization that means again depolarization occur small amount of calcium enters it will stimulate the rhodin receptor on the endoplasmic reticulum more calcium will be liberated from the endoplasmic reticulum it will cause muscle contraction and when the muscle relax endoplasmic reticulum calcium will be returned and the calcium entering from outside will go outside is it clear so this is the normal muscle contraction now how digitales work how digital is work is digial is act by inhibiting this sodium potassium pump digitales inhibit sodium potassium pump so when we give digitales this pump is not working so when this pump do not work means sodium cannot go out and when sodium is not able to go out it will accumulate en so when sodium is more inside the cytoplasm more sodium is not required so entry of sodium from the ncx stops so indirectly sodium calcium exchanges stop working so that means when this sodium is not coming so in exchange calcium is not going out so when calcium is not able to go out what will happen to this 10 molecules of calcium instead of going out because it cannot go out so this will also start going inside the endoplasm reticulum so dexin inhibit sodium potassium pump that lead to increase in intracellular sodium as sodium is more inside so ncx stop working so when ncx is not working calcium cannot go out so that calcium which has to go out now will start going inside the endoplasmic reticulum but will you expect that just 10 extra molecule in the endoplasm reticulum will increase the contractility significantly obviously no but what is happening is instead of th000 molecules of calcium now we have 1,10 molecules of calcium inside the endoplasm reticle so when the next depolarization occur 10 molecules of calcium come they will stimulate the Rodin receptor and now the endoplasmic reticulum it will release 1,0 calcium is it clear but 110 kium will not significantly increase contraction but in this bit also same thing happen so those 10 molecules which have entered from outside cannot go out because ncx is not working so this will again enter the endoplasmic reticulum so now the endoplasmic reticulum contains 1,20 Calcium in next weed it will contain 130 calcium and after several weats it will contain 2,000 calcium and when 2,000 calcium are released it will lead to significant increase in contractility so digital is canot produce immediate effect it will gradually increase the calcium in the endoplasmic reticulum and after some time there will be significant increase in contractility is it clear so now just revising the mechanism of action of digitales digitales inhibit sodium potassium pump inhibition of this pump will indirectly result in inhibition of sodium calcium exchange so when calcium is not able to to go out there will be increase in calcium in the plasma sorry not plasma increase in calcium in the cytoplasm when calcium increase in the cytoplasm finally it will go more inside the endoplasm reticulum more calcium in the endoplasmic reticulum and more calcium in the endoplasmic reticulum will lead to increase in contractility because that calcium will be released and cause contraction so this is the mechanism of action of digitalis in congestive heart field now as compared to other inotropic drugs digitales do not increase the heart rate so it will not increase the work of art but rather than this digitalis has one more mechanism digitalis has Veo mimetic effect Veo mtic effect Veo mtic means it will have parasympathetic effect remember vus is a parasympathetic nerve to 10th kinian and we know parasympathetic system depress the so due to its Veo mtic action rather than increasing it actually decrease heart rate and decrease conduction from Atrium to ventricle digitalis decrease heart rate and decrease conduction but do you want to decrease rate and conduction in ch obviously no so as such this is not of any use in case of congestive heart failure but unlike Other Drug this is not of disadvantage because it do not increase the work of heart but this action of decrease in rate and conduction we utilize in another disease which is called as atrial fibrillation atrial fibrillation atrial fibrillation is a condition in which atrial rate is very high when we say heart rate of a person is 80 beats per minute so what do we mean what is Contracting 80 times in one minute it is it Atrium or is it a ventrical yes it is both so 80 beats a minute means S node gives 80 impulses every minut and all these 80 are passed to Atrium Atrium contracts 80 times in one minute and all these 80 are passed to ventricle now ventricle contract 80 times every minute so that means every part of the heart is Contracting same times per minute now when we say Atrium or ventricle to contract 80 times in 1 minute so they have enough time that means they have to contract 80 times in 60 seconds so they can completely contract and relax contract and relax that means they can effectively pump the BL they can do that 80 times in 60 seconds now in atrial fibrillation we the heart rate is very high the atrial rate in this condition is around 400 to 500 beats per minute that means Atrium or ventricle have to contract 400 times every minute so when Atrium has to contract 400 times in 1 minute 500 times in 1 minute so how it will do so it will start Contracting relaxing but then it realizes that it cannot do like this for 500 times in 60 seconds so what it does instead of complete contraction and relaxation it just start fibrillating slight contraction relaxation contraction relaxation contraction relaxation that means it cannot completely contract it just complete its number just complete its number so it does it 500 times in 1 minute but the contractions are ineffective so those ineffective contractions are called fibrillations so in atrial fibrillation the rate is very high but all the contractions are ineffective the question is if Atrium do not contract completely that means if Atrium do not pump the blood will it be of severe significance severe consequences the answer is no reason Atrium has to give the blood just to ventricle so even if it do not contract completely even then the blood can go by gravity also so in atrial fibrillation there is not significant hemodynamic compromise but problem is normally we discuss that all 80 contractions will pass to ventricle if all 500 are passed to ventricle then ventricular contractions will also become ineffective that means ventricular fibrillation can and if ventricle do not pump the blood it will lead to heart failure and all the problems so in atrial fibrillation our major aim is we do not want ventricular fibrillation so most of the drugs which are used in atrial fibrillation they are targeted to prevent the increase in ventricular rate so same is done by digitales also so digitalis what it do is it decrease the conduction from Atrium to ventricle digitales decrease the conduction from Atrium to ventricle that means out of four or five atrial beats only one will go to ventricle so if one beat out of four go to ventricle so even if Atrium is Contracting at 400 times only 100 will be passed to ventricle so that means ventricle will beat at 100 times per minute so when it beats 100 times in 1 minute it can pump the blood so the major problem will will not occur so digitales can be used in atrial fibrillation but the major mechanism is decrease in conduction from Atrium to ventricle so digitales has two main uses first is congestive heart failure where major mechanism is inhibition of sodium potassium pump whereas it has second mechanism in atrial fibrillation where it decrease the conduction from Atrium to ventricle now coming to drugs digitalis is name of of the group of drugs the only drug which is available available now is dexin dexin is name of the drug whereas few years earlier one more drug is present in the digitalis Group which is digitoxin now digitoxin has been withdrawn only dioxin is available but commonly the question is asked between the difference between these two drugs what is the difference between dexin and digitoxin and you can easily remember one of them is metabolized by liver one of them is mainly excreted by kidney and that you can remember is dig toxin the name start with toxin so when the name contains Toxin and we know all the toxins are metabolized in liver so this will also be metabolized in liver so digitoxin is mainly metabolized by liver whereas dexin is mainly excreted by kidney so due to this reason digitoxin was contraindicated in renal failure liver failure digitoxin was contraindicated in liver failure whereas dexin is contraindicated in kidney failure remember now only dioxin is available digoxin has been withdrawn now and dexin is contraindicated in renal failure another important thing to remember digitalis group or in fact dexin is the only drug which is used in congestive heart failure act as inotropic drug and can be given orally remember among all the inotropic drugs only drug that can be given orally is dexin adverse effects of dexin what are the most common adverse effect like every drug most common adverse effects of digitalized group of drugs is also nausea and vomiting so git side effects are most common side effects of deoxy now apart from G dexin can cause Arias if you discuss the mechanism of action of dexin we discussed two mechanisms one it increase calcium so when calcium increases it will try to stimulate the heart but the same time dexin also decrease the conduction from Atrium to ventri that means it has Veo mtic effect and due to Veo mtic effect heart get the information that I have to get depressed so vtic effect will inhibit the so dejection is doing two things one it is stimulating the Heart by increasing calcium second it is inhibiting the Heart by vtic effect so when we give dexin the heart gets confused what to do so in this confusion heart will start doing its own work so that means it can undergo arithm so any type of arhythmia can occur techmas as well as bready arhythmia depending upon which is more okay the question asked on digitales induced arithm are what is the most common ariia caused by digitales the answer to this is ventricular bmin ventricular bmin is the most common ariia caused by digitalis but read the McQ very carefully because sometime the question is asked what is the most common adverse effect of digitalis and they give first option as ventricular byin which is not the answer remember overall most common side effects are git side effects like nausea and vomiting but among the Arias most common is ventricular Byam second question asked is what is the most specific arhythmia caused by digitalis most specific arhythmia or also called as most characteristic arhythmia caused by digitalis first of all what is the difference between these two questions most common ariia means whenever digitalized overdose occur it is likely to occur but this is not caused only by digitalis ventricular by can be caused by 10 other drugs also so when ventricular bmin is present we are not 100% sure that it is caused by digitalis but it is commonly seen in digitalis overd but on the other hand when we say most specific or most characteristic it means that although it is not common but if this arthia is present we are almost 100% sure that it is caused by digitalis so that means it is characteristic of digitalis other drugs are not able to cause this ariia and the most specific arthia caused by digitales is non paroxysmal atrial teic cardia nonparoxysmal atrial teic cardia with atrio ventricular block nonparoxysmal atrial teic cardia with atrio ventri vular block is the most characteristic arhythmia caused by digitalis remember most common arhythmia is ventricular bin but most specific arhythmia is nonparoxysmal atrial teic cardia with AV then third important question asked is which Arias are not seen in digitalized toxicity this is just theoretical that till now these Arias have not been found in overdose of the italis and these Arias are one is atrial flutter atrial flutter and second is mbits type two heart block mbits type two heart block so these two Arias are not seen in digitalis poisoning so three important questions one most common arhythmia second most specific ariia and third which Arias are not seen in digitalis poisoning so most common adverse effect of digitalis are git side effects then it can cause arithm apart from these digitalis can cause gyesa gyom mestia gyom mestia is development of male breast so digitalis long-term use can result in gyom mestia development of male breast and another important thing to remember which other drugs are commonly associated with gynecomastia and these drugs you can remember as disco drugs drugs causing gyom mestia you can remember as disco drugs disco drugs you can remember di for dexin we just discussed dexin can cause gyom s for sponcon spyon lecton is a potassium sparing diuretic it can also result in gyom C for cadin cadin is a drug used in peptic ulcer it can also cause gyacom o are estrogens and obviously we know estrogens are female hormones so it can cause female symptoms gyy so disco drugs they can result in gyy so digitalis third side effect is gyom lastly digitalis can cause color vision defect which is called xanthopsia xenopsi the other term for xanthopsia is yellow vision so digitalis can result in color vision defects called as yellow vision defect xanthopsia xanthopsia so these are the main adverse effects of deox now one question which is very commonly asked and very very important from McQ point of view is interactions of digitalis and more important than the interactions we can say which factors increase the risk of digitalis toxicity which factors can precipitate dexin toxicity to remember these we'll divide into three categories first metabolic factors second drugs some drugs can increase the risk of digitalis toxicity and third pathological factor or disease factors so among the metabolic factors you need to remember three important these are hypercalcemia hypo Calia and hypo magnesium you can remember dexin increases calcium we know mechanism of dexin is to increase calcium so if calcium is already more dexin will work more that can lead to toxicity similarly if potassium or magnesium are less remember potassium and magnesium are inhibitory whereas calcium is stimulatory so if potassium and magnesium are lesser then heart will be stimulated more so that can cause dexin toxicity so this is just a way to remember it is not the reason actually what happens is the sodium potassium pump which is present which transport sodium outside and potassium inside this pump where the potassium binds to this pump at same place dexin binds so dexin and potassium has same place where they bind so if potassium is more extra cellularly then dexin has a more competition so that means if potassium is more binding of dexin will be less so dexin binding is inhibited by extracellular potassium so that's why if there is less potassium in the blood hypokalemia there will be no competition more dexin can Bine and that can lead to toxicity this is one thing but you need to be very careful if toxicity occurs in case of severe toxicity when dexin has already blocked this pump what happens is potassium will not able to enter when potassium is not able to enter it will stay in the blood so that lead to hyper caline so read very carefully these are two opposite things hypokalemia will precipitate dexin toxicity but in toxicity there will be presence of hyper calmia okay hypercalcemia hypokalemia and hypomagnesemia they increase the risk of digitalis poisoning hypercalcemia hypokalemia hypom magnesia then which drugs increase the risk of digitalis toxicity these include quinin Verapamil Amon and thides when these drugs are co-administered with detoxin there is increased risk of toxicity quinin Verapamil amiodaron and thides thides they cause hypoc calmia hypomagnesemia and Hyper calmia and we know all these factors they can precipitate detoxin toxicity so thide precipitate detoxin toxicity by pharmacodynamic interaction this is phod damic interaction because thides do not change the plasma level of detoxin so plasma level is same but same amount of dexin become more toxic so that is called pharmacodynamic interaction on the other hand Verapamil and amoon they increase the plasma concentration of dioxin and when plasma concentration is more obviously the toxicity will occur so this type of interaction is called as pharmacokinetic interaction so thides have pharmacodynamic interaction to cause toxicity whereas Amon and Verapamil they have pharmacokinetic interaction to cause detoxin toxicity now pathological factors we already discussed there is increased risk of digitalize toxicity if there is renal failure there is risk of dexin toxicity and in case of liver failure there is a risk of digitoxin toxicity now question is how to remember these these are very important so to remember this this is just for remember not the reason so you can remember digitalis mechanism is to increase calcium so if calcium is already more it will work more so that will lead to toxicity so hyper calcemia we can explain then we know that potassium and magnesium are inhibitory ions whereas calcium and sodium are stip ions so if we inhibit the inhibitory ions that means if inhibitory ions are less it will lead to more stimulation so that will lead to toxicity so you can remember hypo calmia hypomagnesemia and Hyper calcemia increase the risk of digitalis toxicity now the drugs you can remember if you just study it in Hindi so in Hindi you can remember that if we give dein Queen so dexin que so Quin veram Amon and thides now pathological Factor we already discussed if there is toxin in the name toxins are metabolized by liver so there will be toxicity in case of liver failure so other drug that means dexin will become toxic in renal failure so these are the important points regarding the digitalis toxicity lastly how to manage digitalized poisoning or digitalized toxicity so first and most important thing is to correct these interactions we have discussed so many interactions so all these if we correct them like if the person is taking some drug like Amon or thide we will stop that if there is metabolic abnormality like hypokalemia we will correct that so most of the time we can treat digital as poisoning but if still Arias are present even after correcting these then we need to give anti- arhythmic drug and the drug of choice for digital induced arhythmia is liin lignin is drug of choice for digitalis induced arhythmia the alternative to liin is phin fenin or lignin they are drug of choice for digitales induced arthas they are mainly used for ventricular arthas but as we already discussed the most common arithm in digitalis poisoning are ventricular so mostly lioc like drugs can be used but depending upon the arhythmia we can choose the anti- arhythmic drug now if the arithm are not controlled even with anti- arhythmic drugs then we will need to give one more drug which is called as d G bind DG bind it is indicated in severe digitalis po severe dexin po dig bind so as the name tells it will bind digitales and remove it so dig bind is a monoclonal antibody against digitalis dig bind is an antibody against digitalis it will bind digitalis and remove it indicated in dexin poisoning so these are the important inotropic drugs so in case of congestive heart failure we use two type of drugs one are called inotropic drugs which we just finished and Other Drugs were diuretics which are for symptomatic Improvement so the type of heart failure we have discussed so far it is called acute congestive heart failure so that means the patient will present acutely in emergency with symptoms so we need to give two type of drugs one in the drug increasing contractility and second the drug which remove the fluid from the body now suppose a person develop congestive heart failure but this person that means this person is having low cardiac output cardiac output is less but this person do not go to any doctor that means the person do not take treatment so if the person do not take treatment for heart failure what will happen contrary to our expectations that this person will die this does not happen the reason is our body has compensatory ability for everything if anything goes wrong in the body body will automatically correct that but we know that we have only two arms for compensation one is sympathetic system second is parasympathetic system so if a person's cardiac output is low which arm will be activated for compensation yes it will be sympathetic system so when cardiac output is low there will be stimulation of sympathetic system when sympathetic system is activated means cacola means like adrenaline nor adrenaline will be released and when they are released they will stimulate beta 1 receptors in the heart and when beta 1 receptor is stimulated in the heart they will increase cardiac output we know beta 1 stimulate the heart so cardiac output is increased now the question is when the body can automatically manage it automatically increase cardiac output then why to give the drugs we have discussed so many drugs with so many side effects when the body can automatically manage then what is the requirement of drugs the reason is when sympathetic system is activated will it stimulate only beta receptors obviously no so it will stimulate Alpha receptors also and we know stimulation of alpha receptors will cause Vaso constriction constriction of veins as well as construction of arteries when the veins contract it will increase work of heart which is called preload when the arteries contract it will increase the work of heart which is called after Lo so visoc constriction will increase work of the heart called as preload and after load now before going into further details we'll quickly discuss what is the meaning of preload and afterload we know that left ventricle pump the blood into the iot left ventricle pump the blood in the iota now suppose this Iota is contracted so when the Iota is contracted then left ventricle has to pump more forcefully only then the blood can go that means left ventricle has to do more work after the blood has come to left ventricle it has to work more to remove the blood if there is contraction of the arteries so that means if the arteries are contracted the work increases and this work is called as after load so the name tells after load means after the blood has come to Heart how much work is done to remove that blood so after load depends upon arteries so if there is contraction of arteries after load increases similarly if more blood comes to heart through inferior and Superior vinegar huh if more blood comes into heart it has to pump more blood so that work increases and this work is called as preload preload and we know when the veins contract the blood will come toward remember veins have one way walls only so when the veins contract more blood will come to heart when more Blood come to heart heart has to pump more blood so work increases so that work is preload so that means contraction of veins will increase preload and contraction of arteries will increase after Lo so we discussed when sympathetic system is activated it will cause visoc constriction that will cause increase in preload and increase in after load work of heart increases heart is not able to do normal work and we have given heart extra files to do the work so that is detrimental for heart so first problem with increasing sympathetic activity is work of heart increases second problem when sympathetic system stimulate the beta receptors beta 1 receptor is not only present in heart but it is also present in GG cells of kid so beta 1 sceptor will also be stimulated in the gtra glomular cells of kidney and when beta 1 is stimulated here what will happen yes there will be secretion of renin so beta 1 will help in release of renin and we know function of renin it convert inot enogen toot tensin first inot tensin first is converted to inot tensin second with the help of enzyme inot tensin converting engine inot tensin converting engine andot tensin second will work on its receptors mainly they are 81 receptors Angiotensin second stimulate 81 receptors and when 81 receptors are stimulated it produce three effects 81 receptors are present at three places mainly one 81 receptors which are present in the blood vessels they result in Vaso constriction stimulation of at1 receptors cause Vaso constriction so this Vaso constriction will further increase pre-load and after as discussed earlier so work of heart increases further second 81 re are also also present in adrenal medula and stimulation there it result in release of cacol that means adrenaline nor adrenaline Etc will be released from the adrenal medula so that means they will further cause Vaso constriction so that will further increase the work of and third and most important thing is 81 receptors are present in the adrenal cortex where they secrete oston aldosterone so 81 receptor will result in release of aldosterone and we know function of aldosterone is to increase sodium and water retention so oston cause retention of sodium and water simultaneously oston also cause removal of pottassium and hydrogen so when sympathetic system remains active for long periods there is increase in aldosterone and that cause sodium and water retention and when sodium and water is retained that will lead to edema again so another problem apart from increase in work there is edema now these are just two problem but most dangerous is still left and that is if aldosterone remain elevated for prolonged periods it result in left ventricular hypertrophy left ventricular hypertrophy so when aldosterone increased for prolonged periods it result in left ventricular hypertrophy which is also called cardiac Remodeling and it is this left ventricular hypertrophy which will result in death of the person person do not die from acute CHF person develop compensatory mechanisms and finally the death occur mainly because of left ventricular hypertrophy or cardiac remodeling so this type of situation in which cardiac output is almost normal but the patient is having totally different type of problem this type of heart failure is called as chronic CHF chronic CHF the other name of chronic CH is CHF is compensated CHF compensated CHF as the name tells it is due to compensatory mechanisms so aim of treatment in acute CHF and chronic CHF are totally different in acute CHF the major aim was to increase the contractility whereas in chronic CHF the cardiac output is already normal so the inotropic drugs do not have major role in chronic CHF so what are the aim of treatment in chronic CHF so three main aims of treatment in chronic chfr first is to reduce the work of heart we discussed the work has increased preload after load has increased so we want to decrease that work second aim is to remove the fluid because of sodium and water retention the fluid has accumulated so we want to remove that fluid and third and most important aim is to reverse the left ventricular hypertrophy which result in death of the person so we want to reverse the left ventricular hypertrophy so remember the main aim of acute CHF was to increase contractility this is not the aim in chronic CHF because contractility is already normal so we'll discuss one by one how we can achieve these aims the first aim is to reduce the work of heart and we know work was increased because of visoc constriction so we can reduce the work by causing VOD dilation so VOD dilators are used to reduce the work of heart and we have three types of VOD dilators one which dilate mainly veins second which dilate mainly arteries and third which can dilate both veins and arteries if a drug mainly dilate veins it will decrease preload if a drug mainly dilate arteries it will decrease after load if a drug dilate both it will decrease both preload and after Lo the main Veno dilator we have is nitrate group of drugs so nitrates are predominant Veno dilators so their major aim is to decrease preload main arterial dilator is hydrin hydrin so hydras mainly decrease after load on the other hand drugs dilating both veins and arteries they include sodium nitr sodium nitrite AC Inhibitors AC Inhibitors and ensin receptor blockers so sodium nitrite AC Inhibitors and ensin receptor blockers they dilate both veins and arteries so they can reduce both preload and after so first aim was to reduce work which we can do by giving Vaso dilators now the second aim is to remove fluid and fluid we already know they can be removed by diuretics and we discussed two type of diuretics Loop and thides so in case of congestive heart failure we will prefer Loop Diuretics because we have to remove large amount of fluid from the body so Loop Diuretics which we have already covered now third and most important aim is to reverse the left ventricular hypertrophy and we discussed left ventricular hypertrophy occurs left ventricular hypertrophy occurs because of aldosterone so if we see the pathway left ventricular hypertrophy pathway starts from here so beta 1 which is present in the GG cells secrete renin that will activate inot tensin noen to inot tensin 1 2 that will stimulate at 81 that will release elderone that will cause left window hypertrophy which result in death this is the problem so if we stop this pathway we can prevent the death of the person we can decrease the mortality so what are the drugs that can decrease mortality so right in the beginning we can give beta blockers so when we block beta 1 renin will not be released so this pathway will not start so beta 1 blocker can be used for decreasing left ventricular hypertrophy second we can inhibit AC so inot tensin converting enzyme Inhibitors thirdd we can use at1 receptor blocks inot tensin receptor blocks and lastly we can use aldosterone antagonis so four type of drugs beta blockers AC Inhibitors ensin receptor blockers and aldosterone antagonist these are used to reverse left ventricular hypertrophy so they can decrease mortality so it's very important to remember all the drugs used in congestive heart failure cannot decrease mortality mortality is decreased mainly by those drugs which decrease left ventricular hypertrophy and these are the four drugs include the drugs decreasing left ventricular hypertrophy they are beta blockers AC Inhibitors enot tensin receptor blockers and aldosterone antagonist so four type of drugs they can decrease left ventricular hypertrophy beta blockers their name end with LOL so the main beta blockers which are used in congestive heart failure the most commonly used one is carvol carvol and two more are indicated in congestive heart failure these include metoprol and bizol so only three beta blockers are approved in congestive heart failure these are carvol metoprolol and bisoprolol and these are these can decrease mortality but very important to remember beta blockers are contraindicated in acute CHF remember in acute CHF we want to increase contractility and beta blocker can decrease contractility so they are contraindicated in acute CHF but they can be used in chronic CHF because they decrease left ventricular hyper however the dose of beta blocker should be gradually increased in congestive heart failure if we start the full dose on the first day it will block the beta receptor in the heart also and that can lead to decompensation so person which is well stabilized will suddenly go into decompensation or we can say acute heart failure so whenever beta blockers are started they are started at very low dose around one/ tenth of the final dose and this dose is gradually increased every 2 weeks to reach the final dose in around 2 to 3 months if we give in this manner then they will prevent the mortality by preventing the left ventricular hypertrophy and at the same time they will not cause decompensation also so beta blocker should always be started in Low Dose and gradually the dose should be increased the elderone antagonist which is useful is sponcon sponcon one new drug in this category has been formed which is called appon appone so spon electon and appone these are the two aldosterone receptor antagonist so if we block The oston receptors so the function of oston will be reversed whatever oston is doing that will not help so function of oston one was to cause left ventricular hypertrophy so these drugs will reverse left ventricular hypertrophy second important thing elderone cause retention of sodium and water and removal of pottassium and hydrogen so oston antagonist will stop this function so that means sodium and water cannot be retained so that result in diuretic effect whereas potassium cannot be removed so potassium will be retained so these drugs are called as potassium sparing diuretics so elderone antagonist are potassium sparing diuretics potassium sparing diuretics and we already discussed sponcon is one of the Disco drugs disco drugs means this can cause gyesa spon electon can cause gyom but this side effect is absent in appon appon do not cause gyo mestia so now we are left with AC Inhibitors and inot tensin receptor blockers now if you see if we give eitas inot tensin converting enzyme Inhibitors so that means this acce is not working so when acce does not work means inot tensin first cannot be converted to inot tensin second that means ensin second is not produced when inot tensin second is not produced it cannot stimulate the at1 receptors so when at1 receptors are not stimulated we get mainly three effects first Vaso constriction will not occur second catac colomines will not be released and third aldosterone will not be released so veso constriction cacam and aldosterone so all these three will stop on the other hand if we give ensin receptor blockers that means if we antagonize 81 receptor ensin second continue to be produced that means ensin second production continues but in spite of its production it cannot work because the receptors are blocked so the final effect will be same that means there will be no Vaso constriction no cacam and no ostero so final effect of AC Inhibitors and otens and receptor blockers are same so due to this reason AC Inhibitors and arbs they have same uses they have same side effects and they have same contraindication so clinically they are similar drugs the only important difference between AC Inhibitors and arbs are that AC e has one more function and that function is to break breinin AC also cause metabolism of breinin breinin metabolism is also done by acce so that means when we give AC inhibitor they inhibit the conversion of inot tensin first to second which result in same effect as produced by inot tensin receptor blockers but in addition it will inhibit the conversion or metabolism of Bine so when this pathway is stopped the level of breinin increases so you see nitas will increase the level of bikine and when breinin increases significantly it can result in two side effects increase in brein it result in two important side effects one is dry cuff and second is Ino increase in breinin can result in dry cuff andio edema these two side effects are present in AC Inhibitors but they are not present in Angiotensin receptor blockers so that is the major clinical difference between AC Inhibitors and ensin receptor blockers so now we can discuss more important points about the AC Inhibitors first the name of AC nibas it end with pill AC nibas the name end with pill any drug ending with p is acit the examples are capto lizo inel Ramy PR parindo [Music] moil and many more pills are present so any drug which end with pill is an AC inhibitor drugs ending with pill are AC Inhibitors and all the important points regarding the AC Inhibitors we can remember from the first drug captopril so captopril is used to remember all the important points regarding AC Inhibitors so we'll write captopril captop C for cuff dry cuff and a for NGO edema so AC Inhibitors they can result in Dy cuff and Ango edema this side effect is not caused by enot tensin receptor blockers these are the main clinical difference between AC Inhibitors and Arps then P for pro drugs Pro drugs prod drugs means AC Inhibitors are themselves inactive they are metabolized to produce some compound which will result in inhibition of acce except the first two drugs all other pills are inactive that means inel is inactive it is metabolized to form inel prate so inala prate will inhibit AC similarly Remi is inactive it is metabolized to form Remi prate that will inhibit AC perindopril is inactive it is metabolized to parendo prate that will make inhibit AC so that means all the pills are pro drugs but prates are active except the first two so captopril and lioil are not pro drugs all AC inors are pro drugs but kopil and lioil are are themselves active so all acas are pro drugs except captopril and lioil which are themselves active and this also you can remember so we commonly study in anatomy anterior cruciate Li commonly say ACL so from the ACL or anterior cruet liment you can remember that active AC Inhibitors active AC Inhibitors are captopril and lioil active AC Inhibitors are captopril and lioil all other AC Inhibitors are pro drugs so Pro drugs all AC Inhibitors except captopril and lenil then t for Taste alteration acas can cause disturbance of taste and the technical term for that is disia so AC Inhibitors can result in disia or alteration of taste then o is orthostatic hypotension orthostatic hypotension also called postural hypotension so AC Inhibitors can cause postural hypotension which is highest with captopril among acors highest risk of postural hypotension is noted with captopril and the risk of this side effect increases if a person has volume depleted State volume depleted State means if a person is taking some other drug which can lead to less volume fluid overload that can lead to orthostatic hypotension so if we combine AC Inhibitors with diuretics the risk of postural hypotension increases the next three are the contraindications of AC Inhibitors P for pregnancy AC Inhibitors are contraindicated in pregnancy R is renal artery stenosis renal artery stenosis particularly when it is Bilal so bilateral renal artery stenosis AC are contraindicated and I for increased potassium increased potassium means hyper calmia so AC neas are contraindicated in pregnancy bilateral renal artery stenosis and patients with Hyper calmia then L it says AC Inhibitors lower the risk of diabetic complications like diabetic nephropathy so in simple language AC neas are good drugs for diabetic patients they lower the risk of diabetic nephropathy so ac nitas they are remembered as captopril now ensin receptor blockers we discussed clinically they are similar drugs as compared to AC Inhibitors the only clinical difference is they do not cause cuff and angio edema so you can remember that apart from cap rest all points also appli to inot tensin receptor blockers that means inot tensin receptor blockers can also cause disia they can also cause orthostatic hypotension they're also contraindicated in same three situations mean pregnancy bilateral renal arter stenosis and Hyper calamia and they are also very good drug for diabetic patients so the only thing which we need to know now is the names of ensin receptor blockers ensin receptor blockers or at1 receptor blockers the name of these drugs end with Satan any drug whose name end with San is inot tens and receptor blocker the examples are Lo B tell me sat IO Satan candy sat and some more also are present so any drug whose name end with San is Angiotensin receptor blocker and actually you can remember the Satan stand for S means selective a means at1 RT means receptor and a means antagonist so Sans are selective at1 receptor antagonist selective 81 receptor antagonist now among these heartens one special point of remember is talison apart from inhibiting The inot tensin receptors tan also stimulate an enzyme called as PP gamma peroxisome proliferator activated receptor gamma is also stimulated by Tartan and the drugs which stimulate PPA are gamma we will discuss in diabetes glazon are the drugs like Rosy glazon pazon like drugs so telmisartan also have similar action and it is also used to reverse insulin resistance so tell me Satan has additional action to reverse insulin resistance because it stimulate an a receptor called PP AR GMA so tell me the name of an ARB which can decrease insulin resistance I'm not asking I am telling I am telling you tell me tell me means tell me Satan so tell me Satan is a ARB which has PP gamma agonistic activity and it decreases insulin resistance clear now another important drug in this category which is losartan losartan can cause decrease in uric acid remember most of the drugs used in hypertension like beta blockers or thides they have problem of causing hyper uremia so they are avoided in gout but losartan can cause lowering of uric acid decreases uric acid from the name you can remember it says l o means lower uric acid so lartan will decrease the serum uric acid so these are the important points regarding the enot tensin receptor blockers also so that means we have completed drugs for chronic CHF the aim of treatment in chronic CHF was number one to decrease work which we do by vasod dilus number two to remove fluid which we give by diuretics and number three to reverse left ventricular hypertrophy which can be done by beta blockers AC Inhibitors ensin receptor blockers or aldosterone antagonist so now we'll move to some new drugs in congestive heart failure and among the new drugs the most important thing that we will discuss is the new strategy and that strategy is to Target a compound called as BNP BNP is netri uretic peptide so as the name tells it cause netri uresis netri uresis means loss of sodium in the urine netri uresis apart from netri uresis all the netri urtic peptides they are powerful vasodilates so the function of BNP is it cause netri uresis and vasod dilation after production brain netri uretic peptide is metabolized and the enzyme which metabolize this is called neutral Endo peptidase neutral endopeptidase the other name of this enzyme is neyin nein or neutral endopeptidase it breaks brain nettic peptide now what you do you want to do to BNP in patient with congestive heart failure will you like to increase BNP or you like to decrease BNP obviously we will like to increase BNP because we want to remove sodium we want waso dilation so if we increase BNP we can treat CHF and how to increase BNP is one option is to give vnp from outside if we give vnp from outside it will produce same function second thing we can do is we can inhibit the metabolism of BNP if BNP is not broken its level will increase so same function will be produced so we have two type of drugs one which is BNP given from outside and second which is neyin inhibitor or NE inhibitor so starting with first drug BNP given from outside the name of the drug is nazer Tite nazer Tite nazer Tite is nothing but recombinant brain netri uretic peptide recombinant brain netri uretic peptide the main problem with this drug nerti is the name says it is a peptide and what is the problem of being a peptide any peptide cannot be given orally the reason there are lot of peptidases present in the git we have pepsin Trin chot triin and many more enzymes present in the git so they can break peptides so no peptide is effective orally so so is BNP so nazer tide need to be given by intravenous R not effective orally so it has to be given IV second problem with the nazer tide is it is BNP because it is BNP so it can be metabolized by neyin or neutral Endo peptides so because it is broken by endogenous enzyme it is very quickly metabolized so it is short acting so NZ tide is given IV and it is short acting so it is indicated only in acute cases it cannot be used for long term only used for acute cases so the first drug is nazeri di second thing we can inhibit NEP or Ney so in if we inhibit neyin the BNP cannot be metabolic so BNP level will increase so that will treat the congestive heart failure and the drug which are neyin inhibitors NE Inhibitors their name end with Trill just like we discussed the drug inhibiting AC end with pill similarly TRS in a bit n ep the example is Saku tra Saku tra and EAD Trail Saku Trail and EAD Trail remember Prill inhibit Ace and Trill inhibit NEP now these drugs are effective orally Naz tide was injectable but trills can be given orally then we developed one more group of drugs which are called vasopeptidase Inhibitors vasopeptidase Inhibitors are those drugs which can inhibit two enzymes they can inhibit AC e as well as NE that means vop pepti Inhibitors have properties of both PS as well as trills so the drug having both the property that means property of pill as well as Trill that means AC inhibitor plus neyin Inhibitors they are called vasopeptidase Inhibitors and the drug in this group is we have drugs like omop Petri let and Sam battery om petet and Sam petet they are vop days inhibits that means AC inhibits plus NE inhibits and again from the name you can remember these drugs you can find that In The Name They contain Trill so when Trill is present in the name means they are NEP Inhibitors now if we see the name again carefully we will find that the name contains at at two places at is present here and at is present here also so these two ATS will cancel each other so if we cancel at with at this at cancels this at so what is the remaining his P so you can find in the name it is containing P also in the name it is containing Trill also so p means AC neitor and Trill means NP inhibitor so these have both the properties now because they are AC Inhibitors so they will have same two side effects that means they can cause cuff andio edema cuff andio edema are the side effects of vasopeptidase Inhibitors also another new drug in CHF are called as Arnie the full form of AR is Angiotensin receptor Block Plus neyin inhibitor so just like we discussed that in case of uh omop petet like drugs the drug has combination of two things that means they are inhibiting neyin as well as they are inhibiting acce but because of AC inhibition they can cause cuff andem so if a person develop cuff and Ino edema then we cannot use AC inhibitor so if we want to use similar combination we wanted that the drug should have combination of inot tensin receptor blocking property so that cuff and inoda do not occur and along with that NE ination property but we were not able to create such a drug a single drug which has both of these properties so what we do is we give two separate drugs to produce this effect means one of the drug is inot tensin receptor blocker and second drug is NEP or NE Lin inhibitor and what is the combination is inot tensin receptor Blocker we use is Val and Neil inhibitor we use is Saku Trill so this combination of Val sartan and Saku Trill is known as AR ensin receptor blocker Plus neyin inhibitor so this is important drugs which are targeting the BNP pathway that means increasing the brain nitrog netic peptide by by inhibiting the metabolism through NEP inhibition clear now apart from the BNP pathway the another method of uh treating the congestive heart failure is a drug called As Eva Breen Eva [Music] breaden this is a drug as the name tells which act by causing bre cardia we know when we decrease the heart rate then the work of heart decreases in ch of the work is more so we can use this drug to produce bre cardia and it act by blocking a current known as funny current the symbol of current is I there is a funny current in the heart in SE node it acts by blocking the sodium channel in SA node which carries the funny current more detailed mechanism you will see later on in treatment of angina this drug is also used in angina the major side effect of Eva brein is VA means visual acuy it cause decrease in visual ACU so from the name itself you can remember everything evab readin I means if blocker means funny current blocker VA means visual ACU is reduced it is side effect and bready means it is bready cardiac agent it decrease the heart rate so principle mechanism in CHF is causing the decrease in work of Heart by decreasing the heart rate okay then the last group of new drugs they are vop pressin [Music] antagonist now before going into details we should know the basic things what is the other name of vasopressin yes the other name is ADH so vop pressin the other name is anti-diuretic hormone now why I am talking about two names because it has two major functions which are written in the name itself so vop pressin says it cause Vaso constriction and anti diuretic says it decreases urine but these actions are mediated by different receptors so when vasopressin it stimulate V1 receptors which are present in the blood vessels it result in Vaso constriction when vasopressin act on V2 receptors which are present in the kidney it decreases urine so vasopressin has two actions one Vaso constriction second decrease in urine so which action you want in CHF none of them we do not want Vaso constriction rather we want Vaso dilation we want to decrease the work and second already there is edema so we will not want to decrease urine we will want to increase urine so what we will do we will block these receptors so if a drug block these receptors by blocking V1 it will cause VOD dilation and blocking V2 it will increase UR so that drug can be used in CHF and these drugs are called as vaptans the drugs which block the vasopressin receptors are called vaptans two important drugs in this group are con vaptan and tall vpon conpon and tall vpon from the name itself you can remember it is saying VA means veso p means pressin veso pressin and if we put the T here it will become a n means antagonist so vaptans are vasopressin antagonist vaptans are vasopressin antagonist the major difference between the two vaptans is Con vaptan is given IV whereas toall vaptan is given orally toall vaptan is given orally con vaptan is given intravenously now this tall vaptan recently it has also been approved in autosomal dominance adult polycystic kidney disease tall vaptan is recently approved for autosomal dominant adult polycystic kidney disease so these are the important new drugs which are used in congestive heart fi okay