0:05 Hello everyone, today we are going to discuss the blockers, the autonomic blockers. We will dedicate this video and the following one to explaining the alpha blockers. But before we begin with the alpha blockers, I want to remind you of something important in physiology. Two types of reflexes related to our topic, and we will encounter them very often, so I want you to understand their bases whenever you hear about them. We have two types of something called baro, baroreflex, or baroreflexes. The first type of baroreflex states that when a human lies in supine position, while in supine position,
0:53 the body doesn't exert much effort regarding the distribution of blood. Why? Because blood is already distributed by gravity, therefore the body doesn't exert effort inducing vasoconstriction nor vasodilation, either way, blood is equally distributed. However, when you stay sleeping for a long period, then you change your position, from supine to the standing position abruptly, or if you stand up from the bed suddenly, blood becomes subjected to a state of pooling, pooling from the upper half of the body and descend to the lower half. This pooling process could markedly decrease your blood pressure. For the body to prevent this decrease in pressure brought up by this change, it induces a reflex
1:38 vasoconstriction, where? In the lower extremity, more in the lower extremity. So when it induces vasoconstriction and noradrenaline release, the blood doesn't fall or pool in the lower extremity, saving the pressure from the marked drop. Okay, now some people come to the clinics complaining like this: "Doctor, while I'm lying everything is ok, but once I get up from bed, once I stand up, I feel like everything is moving, I feel dizzy and I fall down to the ground." Here, this man is said to have a condition called postural, postural, or sometimes they call it ortho, orthostatic hypotension. Both postural and orthostatic are the same. This man who has this complaint has something wrong in the baroreflex that I mentioned.
2:24 When he is lying down in supine position for a long period, then suddenly changes his position, the body is incapable of inducing vasoconstriction in the lower extremities, in the veins, and the arteries down here. Accordingly, blood undergoes a state of pooling, and the pressure is decreased. The drop in the systole is around 20 mmHg. Because the diagnosis of this condition is made by ensuring there is a drop of the pressure more than 20 in the systole within three minutes, okay? What is the reason behind this condition? So many reasons. Maybe a disease like diabetes mellitus can cause such a condition. Maybe someone with a problem in his autonomic nerves, which means autonomic neuropathy - his nerves are damaged ,and the autonomic system is not functioning properly.
3:10 Maybe drugs can cause this condition, such as a family called tricyclic antidepressants. Tricyclic antidepressants are a class of drugs that we will study together in the CNS. Antidepressants sometimes induce this condition, as do alpha blockers that will be discussed today. The reason I'm explaining this part is that alpha blockers that will be discussed today induce this condition. Thus, one of the drawbacks of alpha blockers is blocking the alpha receptor, preventing the occurrence of this reflex. Therefore, a man who took an alpha blocker and went to sleep, say he took an alpha blocker at night, then he slept. Later, when he woke up, he felt his head spinning. What happened to him is something called postural or orthostatic hypotension. This condition
3:56 could be treated. Naturally, it is considered a medical problem and is very difficult to treat. However, you can help this patient by giving him something that induces vasoconstriction. Search for a drug from the ones we discussed before that causes vasoconstriction. They were three beside one another on one line. Do you remember their names? Phenylephrine, something called methoxamine, and something called midodrine. Look for one of these three that may help the patient, hoping to help induce vasoconstriction in the lower extremity, thus preventing this pooling. This is the first topic that I need you to understand. The second topic is one that we studied together. Let me refresh your memory and add a little more detail. Do you remember when I told you if the pressure is suddenly increased, suddenly exceeding 170 in systole? Here is the heart, and here is an aortic arch. Do you remember
4:45 when I told you that here in the aortic arch are receptors, or better called stretch receptors? When the pressure is elevated suddenly, stretch receptors send signals to the cardio inhibitory center in the medulla, and this reflex is vagally mediated, with the purpose of causing bradycardia. Do you remember this story? You must remember it well, as it will be repeated very often. And I told you then that this reflex is not related to any specific drug, any drug whatsoever that suddenly changes or elevates blood pressure, leading to a systole above 170, can trigger this reflex. Today, I'll add the opposite scenario. Let's switch the situation: if a drug is given or anything happens that leads to a sudden lowering of blood pressure, causing it to drop suddenly,
5:31 do you think if the pressure is lowered, these stretch receptors will also cause brady, bradycardia? Or does the opposite occur? The opposite occurs. These stretch receptors also send signals to the brain, but this time not through the vagus, as the vagus would cause bradycardia. Instead, they send signals to the sympathetic system. Therefore, the sympathetic system responds by triggering a reflex tachycardia. So remember from now on that a sudden change, a sudden rise in blood pressure, sudden rise, causes reflex bradycardia. A sudden drop causes reflex tachycardia. Look, what I've mentioned is the rule, however, what is the exception of this rule?
6:20 The exception might be that the drug causing this sudden change in the blood pressure is also the reason, the same drug that caused sudden rise may have a direct effect itself on the heart. It may stimulate or inhibit the beta receptors. If it happens that a drug affects the blood pressure either by elevating or lowering it, and it has itself a direct effect on the heart, then these reflexes don't occur, not bradycardia nor tachycardia. I'll give you an example with adrenaline. Do you remember adrenaline that was mentioned earlier? Do you remember when we mentioned that adrenaline causes hypertension? When we use adrenaline, do you remember it increasing the systolic blood pressure? However, if you are smart and well attentive, you would know that adrenaline can never cause bradycardia.
7:07 We never mentioned that using epinephrine causes reflex bradycardia. But it increased the pressure! What is the reason behind this? If someone asks? You'd tell him, look doctor, indeed epinephrine elevated the pressure and stretch receptors sensed it, yes, and they reached out to the higher centers crying for help. but when this reflex tries to help, it finds epinephrine standing here, in the heart, on the beta receptors stimulating them, therefore it can't cause bradycardia as the epinephrine itself is a direct stimulant for the beta receptors. Despite similar examples, consider contrasting cases. If you are using a beta blocker, a drug that lowers the pressure, it blocks the beta receptors. Do beta blockers – when they lower the pressure – trigger a reflex tachy? No, they never trigger a reflex tachy. Why?
7:54 Because when the pressure is decreased, stretch receptors send to the brain warning it against the lowered pressure and telling it to trigger a reflex tachy. When it triggers a reflex tachy, it finds that beta blockers are already blocking the beta receptors, so it can't cause tachycardia. To sum up, both reflex brady and reflex tachy appear with any change in blood pressure unless the drug responsible for it has a direct effect on the beta receptors in the heart. We're done with this point, and please don't forget it because it is very important, and you may be deceived in an MCQ and make a mistake. Let's move on to our main topic of today to which this video is dedicated, which is the alpha blockers. Let's classify the alpha blockers and illustrate them. I hope this video will suffice, or we may divide it into two videos. What are the alpha blockers that we have? Or to be more
8:41 exact, you can say alpha adreno receptor blockers. It's more accurate to say alpha adrenergic or adreno receptor blockers. What are they? We have four major alpha blocker classes or families, not drugs, not four drugs, no, but four families. The first family is the group of drugs that block alpha one and alpha two together. Thus, it is called non-selective alpha blockers. Let`s take an example by a drug called phenoxybenzamine , phenoxybenzamine , and its brother phentolamine. Both begin with P H , phen to la mine . okay There are drugs that block alpha one, only,
9:27 thus they are called selective , selective alpha one blockers, like what ? Such as a drug called prazosin and its sisters , what are its sisters ? Prazosin , doxazosin, terazosin , indoramin , tamsulosin , these are some names , however prazosin , it is the prototype. Do you remember the meaning of prototype ? remember it Okay , three , we have drugs that block alpha two ,only, so they are called selective alpha two blockers. It is just a single orphan drug , orphan , it has nobody else , through the whole curriculum. It is called Yohimbine , and I`ll tell you at the end of this video when we reach it
10:13 , I`ll tell you why didn`t they make another drug? Why did they suffice with one dug? And why is it orphan? The last family , number four , here , one , two , three, four , The last family that is related to alpha blockers, even though some may object to placing it in this classification. This family is called ergot , ergot alkaloids. We will dedicate a separate video to this family only. And it is better not to be classified with the alpha blocker but should have its own classification And you well know why when we reach it. Again , if you have an oral exam , and someone asks you if you know about alpha blockers You`d say ` I do If he asks you to mention their names ? tell him we have a family that blocks alpha one and two like a drug called pheoxybenzamine and phetolamine. a family that only blocks alpha one , like this. A family that only blocks alpha two like yohimbine
11:01 Then the ergot alkaloids. Now let`s delve into details and discuss them one by one in depth. I`ll start with the drug called phenoxybenzamine. phenoxy benzamine , first of all , phenoxybenzamine is from a chemical family called beta halo alkyl amine Don`t bother with the chemistry. But what is this phenoxybenzamine , what is its character ? They said this drug blocks alpha one and alpha two together. So it is a nonselective alpha blocker , and when it blocks them , it does it aggressively. Which means it makes a bond , a bond with the receptor called covalent bond. When you hear the term covalent bond you should know that it means a very strong bond, impossible
11:51 to be reversed, doesn`t get broken. Hence when the drug blocks alpha one and alpha two , it becomes irreversible. When we say irreversible it doesn`t mean for ever , it doesn`t mean an irreversible drug would last for ten years, no Irreversible means it won`t leave the receptor , until the body metabolizes the drug , eliminates it , brakes down the receptor, And synthesizes a new receptor. Okay, this story lasts about four days , when you swallow a tablet of phenoxybenzamine , it remains blocking the alpha receptors one and two For the period of four days. Within these four days your body destroys the receptor it undergoes endocytosis , eliminates the drug and synthesizes a new receptor. Because the receptor that was bound to the
12:37 drug is far gone or beyond repair , wasted. Okay , a drug with such a character , naturally we will use in in many cases , however after it lowers the pressure , I`ll give you a hint , When the pressure is lowered as it blocked the alpha , because when you block the alpha you prevent the vaso what? Blood vessels have alpha for vasoconstriction , when we block the alpha receptor , then the vasoconstriction is not going to occur in your body . So your blood pressure is lowered , and when your blood pressure is lowered , it is accompanied by what reflex? What ? reflex tachycardia So it is one of its drawbacks , it markedly lowers the pressure , and triggers your reflex tachycardia which we mentioned earlier. So what are the uses of this drug ? what is its major use ? We used to enumerate many uses of it the past
13:23 , however after we had a long discussion , we found out that most of the uses of phenoxybenzamine Don`t carry much significance for you when you become a general practitioner . After you graduate , you won`t get in touch with cases in which we need phenoxybenzamine. Thus we agreed to make the life of the student better and suffice with one indication that is explained in detail to be well understood. And that is what is required from you The rest of the indications were deleted from the past two editions of your book. they are no longer required from you , so if you encounter an outdated MCQ question in an outdated source , or in our book but ten years ago , then don`t bother with it . you are only required to study this one indication . phenoxybenzamine is used for treating a case that you know , I mentioned it before, called phenochromocytoma. Phenochromocytoma , do you remember when I told you that some people have a certain type
14:11 of tumor that arises from the suprarenal gland ? This tumor is usually unilateral , arising from one side , and mostly is not malignant but benign. The problem of this tumor is that it releases too much adrenaline , which takes its toll on the alpha receptors and also on the beta receptors. So the patient who has a phenochromocytoma complains of symptoms exactly as if he were receiving external adrenaline. He has a vasoconstriction due to the alpha His pressure is always elevated , he always has palpitations , palpitations means the sensation of your heart pounding or racing As if the heart was shaking , palpitations , tachycardia , arrhythmia and tremors . okay . In this condition , you have many treatment options , there is a surgical option , if you have the ability to surgically remove
14:58 it , that`s great. But if you cant interfere surgically , then what is the next step ? In this situation I have to block both alpha and beta together. Why ? because the patient has too much adrenaline in his blood , and alpha and beta are on the loose So you can`t block only one of them . okay, if I ask you which one would you prefer to block alpha one or two ? You`d say I want to block both alpha one and two together. And also block beta one and two together. Because this too much adrenaline is making chaos. That`s great , here it is , here we have a drug called phenoxybenzamine , my friend . It even starts with PH and phenochromocytoma also stats with PH , so they both make a tune . This drug blocks alpha one and alpha two and it has long duration as I mentioned , as one tablet lasts for four days in your body.
15:46 So here is the solution to the problem , because this drug helps us with the problem of both alpha one and alpha two. Now this too much adrenaline won`t be able to harm you like before , yet something is still missing Don`t you ever give this alpha blocker alone , you must add another drug , I`ll write it in red. It is called propranolol , this propranolol is a beta blocker , it blocks both beta one and two , and I told you , You can`t use a single drug . you must use two blockers , the alpha and the beta , at the same time , simultaneously. If someone asks you in the exam , in the oral exam for instance , asks you what would happen if we used alpha blocker alone? If a patient had a pheonochromocytoma and you gave it alpha blocker only ?
16:32 Tell him ok , if I use alpha blocker alone then it means it blocks the alpha while the other one is still active , the beta And when the beta remains active then all of the adrenaline in the patient`s body shifts to it , and all of the symptoms That are attributed to the beta are going to increase , such as tachycardia , arrhythmia and tremors. That`s why I can`t use alpha blocker alone. he may reply : then can you use a beta blocker alone ? Tell him it would be a catastrophe if I gave him beta blocker alone . he may then ask for an explanation Tell him : it means that we block the beta , alone , and leave the alpha active ?! Then all adrenaline would go to alpha causing severe vasoconstriction . And the pressure would change from 170 or 180 and exceed 200 and 300 causing cerebral hemorrhage.
17:20 So it is prohibited in the treatment of phenochromocyoma that you use a single drug. You must use the two together. An examiner may try to catch you out by making mistakes and tell you that he agrees to using both drugs, alpha and beta blockers together, but which one should be used first? If, for any reason, you have to begin with one drug at first, should you start with the alpha blocker or the beta blocker? Tell him: "I'd start the treatment plan with the alpha blocker But why ? because the main concern in this patient is the hypertension , so you are afraid of the hypertension , it is the major problem. First of all correct the hypertension by an alpha blocker , then when the situation is under control add the beta blocker to it . If you open the book you can see there is a dark square on the right , in which there is a brief explanation of the phenochromocytoma
18:08 and this treatment . it says we use phenoxybenzamine in a daily dose of 100 milligrams plus 50 milligrams of propranolol daily. None will ask you in these doses , don`t bother with numbers , all what you need to know is the name of the drug , why do we use it? And can we use it alone or not ? This is all about phenoxybenzamine and I told you remember only this one use and don`t concern yourself with any other uses , This was in the past and we removed them. Lets move on to its adverse effects , what are its problems? Now I hope that you can enumerate them before me, while you are watching me try to open your book and tell them to me . Number one , this drug lowers the pressure , naturally, being an alpha blocker. However, there is a reflex , don`t forget about it , Reflex tachy, reflex tachycardia. We discussed
18:54 it. Two, in men , it can cause failure of ejaculation , ejaculation in men is mediated through alpha one, when you block the alpha receptor for three or four days Some men may complain of this side effect . Three, do you remember when I told you about the eye, and here around the iris is something called radial muscle, and radial muscle contains alpha, Which is responsible for mydriasis , do you remember this , during the physiology introduction. Okay , now you are blocking this alpha for a prolonged time , for three or four days , what is the result? Absence of this mydriasis , so what happens ? The other muscle called constrictor pupallie dominates the area , causing myosis , as you are stopping the muscle responsible for mydriasis . Now we have three adverse effects , of course there are more . however, these three are
19:42 what we care about. Okay, that`s the phenoxybenzamine , we won`t give it more time , as there is nothing more that you need to know. Let`s now move to the next family , do you remember them ? they were just on the board . The second family is called , selective , needless to say that the term selective is music to our ears , selective alpha one blockers Selective alpha one blockers . the head of this family , the boss ,or the prototype is called prazosin pra zo sin However we derived from the prazosin other newer drugs like doxazosin , doxazosin , we made tamsulosin , we made indoramin
20:28 And we made many others that end with sin , you can find them in your book. However I want to draw your attention to something , if you want to forget , if you want to forget , forget! But don`t you ever forget the prototype , the prototype is extremely important to us , that`s why when questions are asked They either be about selective alpha one blockers ,or about Prazosin , as it is the head of this family , the others are up to you. Okay what is the story of this family ? let`s discuss their characters and illustrate which uses can they fit . First of all , this family blocks alpha one only , not alpha two , so it is selective and this means it would prevent the vasoconstriction . In your body ,It stops the vasoconstriction , thus your blood pressure is lowered , okay
21:14 ? great Here is an artery , this is a cross section of the artery , now we blocked the alpha one receptor , so the artery is now incapable of vasoconstriction . Not only this , but the drug also reaches the smooth muscles , let`s concentrate on this now , the drug reaches the smooth muscles Of the artery , inducing direct , direct relaxation. And direct means an effect that is independent of the receptor, as if the drug induces vasodilation through two methods Like a double kill in a game , it blocks the alpha receptor preventing the vasoconstriction , and also affects the smooth muscles inducing direct relaxation.
22:01 Through a mechanism that is independent of the alpha receptors, okay ? The result ? all of the arteries in your body get dilated , your pressure begins to be lowered , if you are a hypertensive patient , You will improve on this drug , okay my next question The pressure is lowered , is it for free or you must pay something in return ? of course there must be a reflex tachy Reflex tachycardia that we mentioned before . Why is the reason for this reflex tachycardia in our bodies ? It is some sort of compensation , when the pressure is lowered your body says ` I won`t stay still and helpless I`ll induce a reflex tachycardia hoping for some sort of compensation by the speeding heart. Therefore these drugs cause a reflex tachycardia , but not to the same extent that is caused by a non selective blocker It is written like this in the book , it is
22:48 a line in the book and I intend to explain it to you so you wouldn`t get confused As it may be a little difficult to understand . Any alpha blocker whatsoever when administered lowers the pressure and triggers a reflex tachycardia . However the book says that the reflex tachycardia that occurs with a selective alpha blocker is not as prominent as the reflex that occurs with a non selective alpha blocker. To clarify, non-selective alpha blockers lower blood pressure and trigger a reflex tachycardia more prominently, while selective alpha blockers lower blood pressure and trigger a reflex tachycardia, but not as prominently It is not as noticeable nor as annoying What is the reason of this ? Let's be fully present and focus on this now , you can repeat this part more than once until you understand it. Even if you don`t , no problem . After all
23:35 it is not written in the book and rarely required of you. I`ll explain it for you just to ease your mind. Let`s assume that this is an artery or a blood vessel and this is a nerve ending. Okay ? And it releases noradrenaline , the artery contains alpha one which causes vasoconstriction. The never ending contains alpha two which decreases the norepinephrine release. Correct ? This is physiology . Now when you administer a drug that blocks both alpha one and two together , a non selective alpha blocker , what is the result ? We blocked this thus the pressure is lowered , good . And when the pressure is lowered , it triggers which reflex ? a reflex tachy. Not only this my friend , you have also blocked
24:20 alpha two , and when alpha two is blocked…. ? This one decreases the norepinephrine , therefore by blocking it , norepinephrine starts to build up and when norepinephrine is increased, Don`t you ever forget that when norepinephrine is increased , it has a beta one effect about ten percent So it goes to the heart stimulating it , this beta one effect of the norepinephrine , it stimulates the heart . Now the tachycardia is triggered through two ways , by two mechanisms , once when the drug lowers the pressure triggering a reflex tachycardia exactly like any other pressure lowering drug. And once when it blocks the alpha two and when alpha two is blocked , norepinephrine starts to build up and goes to the heart Stimulating beta one in the heart , causing an additional tachycardia to the one that is triggered by the reflex.
25:11 As if you were trying to say that , when we administer a non selective alpha blocker , the tachycardia occurring in the patient is due to both a reflex and a direct effect as well. One time through the reflex and one time by the direct effect of increasing the norepinephrine . However when you use a selective alpha blocker , it lowers the pressure and causes a reflex tachycardia , only. It doesn`t increase the norepinephrine that stimulates the heart therefore it triggers a reflex tachycardia through a single component only. So this tachycardia becomes lower , lower than using a non selective alpha blocker . Please , be careful , take time to understand this point , repeat this video once or twice , and write it on the footnote to remember it. Okay, we are still discussing the selective alpha one blockers , illustrating their character
25:58 . I told you that they lower the pressure and trigger a reflex tachycardia but not that prominent as the non selective. What else ? they said , they also don`t change the renal blood flow , they don`t affect the renal blood flow nor the GFR, which is glomerular filtration rate . What?! You have just remembered a drug , right? You remembered a drug from the past video with the name of clonidine. We then mentioned that it lowers the pressure witout affecting the renal blood flow , and I told you than this drug is such a fantastic one to control the pressure in the renal patients. Today I`m discussing the selective alpha blockers which lower the pressure also without affecting the renal blood flow , no harm done.
26:43 therefore renal patients need not worry about these drugs. What`s next? Number three They said , these drugs lower the pressure and improve something called the lipid profile . What does lipid profile mean ? It means blood fat analysis , when a doctor ask you to perform a test for cholesterol and also for triglycerides Let`s check on them . This is called a lipid profile. Okay , these drugs lower the cholesterol and the triglycerides , they both get lowered. So not only the pressure is lowered but also blood fats are lowered , no way ! all of this benefits ! They lower the pressure nearly without triggering a reflex tachycardia , don`t affect the kidneys , don`t harm them and they Decrease blood fats , such a marvelous family of drugs !
27:29 Now the Doxazosin that I mentioned earlier , it is called Doxa zo sin It is considered the longest one of them regarding the duration , regarding the half life . It stays in your system for about twenty two hours . If you encounter an mcq in which there is five alpha blockers , selective that ends with sin sin sin . And asks you which one of these has the longest duration of action. Pick this one , doxazosin that starts with D like Duration So Doxazosin is similar Duration , D for D , so it has the longest duration. Now what are the applications of these drugs , my fiend ? The first use , you tell me The first use , you`d tell me ` for the hypertensive
28:15 patients , specially renal patients. And you already know why. Because they don`t change renal blood flow nor glomerular filtration rate. The second group of patients …. Are those who suffer from a condition called Acute Heart Failure Acute hear failure means sudden severe heart pump failure , because there is a chronic heart failure. Now we are talking about the acute heart failure , okay . This topic , in the cardio chapter , we will discuss the heart failure. Naturally we won`t discuss the whole topic of heart failure just to understand this use however I`ll give you an introduction , Two lines to help you until we reach the cardio , so when you study there is nothing left for later or left unclear that could annoy
29:01 you. I`ll give you only two lines about why we use these drugs in cases of acute heart failure. Look , here is the heart , the heart is supposed to be working with a certain rate and efficiency in all people . For some reason , for example If this is the aorta and here are the superior and the inferior vena cava , both are opening in the right atrium . If for any reason , the venous return markedly increases , or if the systemic circulation or the systemic resistance markedly increases If one of these two occurs , either a sudden vasoconstriction and the systemic resistance is markedly increased resulting in obstructions. Or the blood is returning excessively in a manner that exceeds the ability of the heart
29:49 to pump it . In this case the heart collapses , it says good bye , I`m incapable , you`re giving me too much work, the venous return is too much , and I can`t push all of this amount ! Here , this venous return is called preload , pre load , pre install And also the other way round If the preload is excess , the heart tells you No , I simply can`t push all of this! Or if the systemic resistance is suddenly increased , the left ventricle tries to push the blood but the routes are obstructed and the resistance is increased. It tells you same thing , I can`t Now should this resistance called pre or after ? it is called afterload Therefore you have two types of loads , preload and afterload. What is the preload ? preload is figuratively
30:34 called the venous return The volume of blood that is arriving to the heart in order to be pumped by it . And the afterload ? it is the resistance that the left ventricle faces during the systole. Okay , now if there is a sudden increase in the preload or in the afterload . The heart tells you it can`t , which is called acute heart failure . The patients becomes drowsy all of a sudden , can`t breathe normally , and four people are about to carry him to the hospital now Such a case is called acute heart failure In this situation , my friend, what is the immediate response ? Of course we are going to treat it , but before we treat it , this is some sort of emergency , you must quickly induce a vasodilation To the systemic side to decrease the afterload , so the pathways in front of the left ventricle return patent and the heart can dispose of the blood .
31:20 And we want this venous return to be decreased , okay . This family or these alpha one blockers , in addition to causing arteriolar dilation ; they dilate the arterial side , They also cause dilation of the venous side . Please , focus on this . When you induce a dilation of the venous side , don`t you ever think that when you induce a dilation of the venous side the blood increases , NO! When you dilate the veins , these veins were called in physiology capacitance vessels , they swallow the whole volume of blood , And the venous return decreases , When you induce a veno dilation , blood becomes swallowed within the peripheral veins. Your five or six liters gets swallowed in the venous side and the venous return decreases.
32:07 Because in this condition , when the patient has an acute heart failure , and you are giving him prazosin or this family. You are in fact decreasing both the preload and the afterload. These are the two lines written in the book , but this explanation is not their , when we reach the cardio You will find all of this detailed information discussed in depth. The third application of the family of selective alpha blocker , I hope you still remember it . Do you remember when I told you that people with enlarged prostate , elder people , elder males sometimes have enlarged prostates , And it is called benign prostatic hyperplasia or hypertrophy . Prostate when enlarges , this alpha receptor suffocates the urine flow , thus these people always tend to complain of urine retention. They suffer from urine retention due to this
32:54 alpha , this foolish alpha is the lock ! so let`s unlock this… situation using an alpha blocker . when we use alpha one blocker , this alpha receptor becomes blocked decreasing the resistance to urine outflow , urine flows downwards , thus the condition improves ! But there my friend , the patient may complain of some sort of dizziness , I explained this once , during the introduction videos of physiology. Why is he dizzy ? because the drug which blocked alpha one here , also blocked it in the blood vessels thus the pressure is lowered And the patient becomes dizzy. That`s why for this purpose we used to use Prazosin , which is the godfather of this family , the prototype. Prazosin had this bad quality of lowering the blood pressure and making patients dizzy.
33:43 So we no longer use Prazosin for this purpose . Scientists then decided to pray for god that they might invent a drug that can block the alpha receptor in the prostate only, Without affecting the blood vessel , without making patients dizzy . They conducted researches for so long till they discovered that the alpha one in the prostate is mainly alpha one A and alpha one D. A and D , so they said ` Bingo! , that`s it . BTW most of the blood vessels are the type of alpha one A and alpha one B , A and B, however in the prostate it is A and D . So they decided to design an alpha blocker that blocks these two with main effect on the D as it is the one present in the prostate So they designed a drug within the family
34:33 of the alpha blockers called tamsulosin Thus Tamsulosin has become the official sponsor for treating the enlarged prostate worldwide ! And if someone asks why only tamsulosin , we have many other alpha blockers , tell him because Tamsulosin is the only one that selectively acts on the prostate. Why ? how is that ? it is because it blocks the alpha one A and D , A and D , and this D is not commonly present in the blood vessels . Hence it improves the urine flow with minimal change on the standing blood pressure . It doesn`t change the standing blood pressure. Okay , we have mentioned the three uses of the alpha blockers with all their related details Now is the time of the downsides , the drawbacks , there is nothing without drawbacks .
35:20 Here the drawbacks are called adverse effects , adverse effects of this family. When you reach their adverse effects , my friend , you can notice that they all start with the letter F , as follows . Okay , now the first F stands for , First dose syncope . syncope means sudden drop in the pressure , the patient loses consciousness. First dose means with the first tablet , with the first dose . For instance , the first time for a patient in his whole life to use an alpha one blocker , the first time his body deals with it . So with the first tablet , the pressure suddenly drops , and when it suddenly drops he go through a syncope , he faints. This effect commonly occur in the people who suffers from salt and water depletion , depletion means the ratio of water in their body is
36:05 low. Or thin people , when someone is very thin and his body water content is low , this effects becomes more prominent on him. And this effect appears within 60 minutes, 60 minutes is the average , it ranges from 30 to 90 minutes after swallowing the tablet. That`s why the clever doctor , when he prescribes an alpha blocker for the patient , he asks him if it is the first time to use this dug. If he confirms , the doctor tells him to avoid using a whole tablet at the first time , instead lets divide it to four quarters. And only take one quarter , which means a small dose at bed time . when you are going to sleep. Avoid using it in the early morning . why ? as we are worried that it may be the first time for the patient to use this alpha blocker when going to work , so he may fall on the stairs , or fall in the street and people send him to a hospital .
36:52 Se we advice him that until your body gets used to it , take a quarter tablet at first when you are going to sleep. Okay and tomorrow ? tomorrow we can use a half tablet , and the day after ? three quarters of the tablet . We are gradually increasing the dose daily , hoping for the body to go through an adaptation , and starts to recognize this new guest Which is the drug thus this syncope becomes less likely to occur . This is the first side effect , and the first F is first does syncope . The second F here is something called fluid retention , fluid retention was mentioned before , we explained it during the discussion Of a drug called Clonidine, which was an alpha stimulant , and do you remember when I said that we have a rule , I`ll remind you of it because I know you are forgetful. Do you remember when I said that we have a rule stating that any drug that lowers the pressure for long periods is confronted by
37:40 a reaction from the body. But for long periods , not a day or two , say for a month or a month and a half , and the pressure remains low , The body says it won`t stand still , this is too much , the pressure is low for too long , so the body starts to trigger a reflex sympathetic stimulation That go to the kidney asking her majesty to activate something called renin angiotensin aldosterone system . This aldosterone holds your body water , an effect called fluid retention , or salt and water retention , hoping that this salt and water retention May balance the drop that occurred in the pressure. This is a rule , any drug that lowers the pressure leads to fluid retention. And it is better to prescribe an adjuvant diuretic , a drug that induces diuresis or urine flow so the water won`t be trapped in the body. Okay , this third F is false positive test
38:30 for anti nuclear factor , Hello there! Hello there , new terms! False positive test for antinuclear factor , so it may be thought that the patient has rheumatoid arthritis. Easy , easy there my friend . every thing is so simple , I promise you that there is nothing simpler than pharmacology , nor more beautiful. Easy now , my friend , we have a disease that will be explained thoroughly , and to the last detail , called rheumatoid arthritis. A disease that occurs in the joints , it has a long story , being an autoimmune disease , it will be explained in depth in a following chapter. I won`t discuss it now , however I can tell you that this disease called rheumatoid arthritis is diagnosed through some lab tests. Some maneuvers performed in the labs , among
39:16 these maneuvers diagnosing it , is that we search in the patient`s blood for something called antinuclear antibodies , antinuclear antibodies , if we see them the patient is thought to have rheumatoid. Then we look for other signs to confirm it . Now imagine that people on prazosin specifically , this one , this selective alpha one blocker , their bodies form these antibodies that are called antinuclear antibodies. But they don`t have rheumatoid , these people aren`t patients with rheumatoid , but when you take a sample of their blood , you see these antibodies elevated, Thus you think , think that they have rheumatoid , so it is called false positive It is not positive , this man doesn`t have
40:02 rheumatoid , no , the test result is false positive . Therefore this drug causes false positive test for antinuclear factor for rheumatoid arthritis. I hope it is clear now . The fourth side effect , that you may predict to occur with these , we say that opposites attract each other , This drug improves the urine retention , these drugs treat urine retention , as they block the alpha . So it is very reasonable to assume that it worsens the cases of urine incontinence. Please discriminate between the terms retention and incontinence. Retention means keeping the urine back , use an alpha blocker , it will improve. However , incontinence means drippling of urine without any control , the patient complains that while he is standing still , the urine pass down and I can`t preserve my
40:50 ablution for one hour , I can`t pray two prayers with the same ablution. Because whenever I cough or something , urine flows out . This condition is called this time , urine, urine incontinence , in conti nence Okay ? good Here in this incontinence we want to activate the alpha , this condition of incontinence means that the alpha isn`t working properly. So you want to activate it , thus it is reasonable to say when you use an alpha blocker , this case , this incontinence worsens. And who are the most people suffering from incontinence ? minutes ago I told you that most people who complain of retention are the men And most people who suffer from incontinence -for none is better than the other - are the females , the women Why ? due to pregnancies , with repeated pregnancies , the pelvic floor muscles are weakened , making
41:36 it harder to control the urine, So the woman with repeated , three or four times , vaginal deliveries , sometimes complains to her gynecologist from incontinence . As a result of this pelvic floor pathology , pelvic floor muscle damage . Therefore if this woman receives prazosin or an alpha blocker , her incontinence increases or gets worse. These are the four adverse effects . Now this family has come to an end , lets move on to the next family , the orphan drug , this poor lonely drug without any siblings Which is the selective alpha two blocker This selective alpha two blocker is an impoverished and an orphan drug called yohimbine , yohimbine BTW , when there is a single lonely drug with no siblings , it is called an orphan drug
42:24 , don`t cry please . So this yohimbine is an orphan drug. Why is it orphan ? let`s look at how it was discovered at first , it is an alkaloid , a natural substance extracted from a tree grows in the middle of Africa. Countries In middle Africa has a tree there called yohimbe , it has this alkaloid called yohimbine . When they studied it , they found that this drug blocks alpha two Do you remember where was this alpha two ? Remind me as I`m forgetful , alpha two was presynaptic , it`s function was to decrease the noradrenaline . So when you block the alpha two , supposedly when you block alpha two , norepinephrine increases. Yet truth to be told it didn`t happen , why ? because there is a difference between the
43:11 theoretical ideas on paper and when they are carried out on people. There is always something unexpected. This drug on papers is an alpha two blocker , on papers , and theoretically it is supposed to increase the norepinephrine release. And it is supposed to be applicable in many diseases , however on trial , it didn`t increase norepinephrine nor it was used in any disease or anything else. They say ` The unfortunate always draw the short straw Look where it is found ! it originates from countries in middle Africa , so when Africa finally gives us a drug which is globally known to be the only alpha two blocker … it turns to be useless , we don`t know how to use it So we started to spread some rumors , when a drug turns to be like this , we use rumors The rumor was spread to make this drug appear desirable and generate profits from this drug
44:01 despite the fact that it had no practical benefit . Nor any clinical use. So drug companies decided to spread a rumor that this drug is an aphrodisiac , aphrodisiac. Aphro is derived from the word Aphrodite , Aphrodite is the goddess of fertility and love in the Greek mythology Desiac from desire , aphrodisiac , this term means it enhances the sexual desire . So they decided to spread a rumor that it enhances the sexual desire , and once people from everywhere hear about this rumor They will start to buy this drug . However it is a rumor , and rumor in our terms means : without clinical evidence
44:47 So there is no evidence that supports this rumor . So when someone tells you that yohimbine enhances the sexual desire being an aphrodisiac . Tell him do you have any medical evidence ? any scientific bases ? he`d say no I don`t Tell him then it is just a rumor These are the works of rumors and gossip To sum up , yohimbine is an alpha two blocker ,we didn`t make any similar drugs as it turned to be extremely worthless . It didn`t have any uses , it didn`t increase the norepinephrine nor it had any clinical use. And if someone tells you that it is an aphrodisiac tell him no problem let`s go along with these rumors , without a clinical evidence
