0:00 Hello everyone … let`s continue the rest of sympathomimetics …we are still talking about direct acting sympathomimetics In the past video, we illustrated adrenaline in detail …because it is the prototype And I told you after we are done with adrenaline we will begin discussing the rest of the family in brief. The second drug we have after epinephrine…. Look … in this video we are going to explain the following drugs Number one noradrenaline or norepinephrine number two we will talk about dopamine … we will talk about dobutamine we will discuss beta two agonists whether they are selective or not number five we have dopamine receptor agonists but before them, we have alpha agonists
0:52 then we will discuss dopamine receptor agonists these are the drugs we are going to talk about in this video …so let`s begin with noradrenaline or norepinephrine when we talk about norepinephrine .. it is typically the cousin of adrenaline both of them share nearly the same structure … they contain the same ring the catechol ring when you want to talk about the chemistry or pharmacokinetics of noradrenaline it is exactly the same as adrenaline … not absorbed orally .. does cross the blood brain barrier can`t be taken orally as tablets it must be given by injection and so on also, it shouldn`t be exposed to the air for so long, or else it is oxidized turning into the substance that you
1:40 saw .. the dark substance called adrenochrome however, the core difference between adrenaline and noradrenaline is the mechanism of action when you read about norepinephrine you can see it acts on alpha one alpha two and beta one however, it doesn`t have beta two or beta three ….these are not present ..it acts on these okay .. and I told you in the past video …there is no drug acting on the receptors that has an apparent effect on alpha two except … by the way when you want to induce an effect on alpha two then design a drug for it design drugs called selective alpha two stimulants or agonists .. however, most of the drugs affecting more than one receptor .. when they reach alpha two it is hidden so the effect is not prominent and if you want to be more accurate ... then
2:29 noradrenaline acts mainly on alpha one between you and me … we can consider that ninety percent of its action is on alpha one and you know that alpha one causes vasoconstriction thus the main effect of norepinephrine is vasoconstriction regarding its effect on beta one ..it has some effect but not as much as it has on alpha one so between us both … we can consider it ten percent or even less than ten percent in conclusion , when you administer noradrenaline , its effect is prominent only on alpha one and beta one a drug with such a character , being very short acting exactly like adrenaline and is also destroyed by MAO and COMT within minutes what is the uses of a drug with such a character ? a drug which says I`m devoted to
3:16 alpha , my function is vasoconstriction that`s why the main use of norepinephrine is to induce vasoconstriction , we use it for this purpose but for who ? for people with acute hypotensive states … a patient who is in the ICU not for a normal person complaining of some hypotension … we don`t give anyone with hypotension norepinephrine …. No … it is for the acute hypotension . when he is in the ICU so not for any usual case Norepinephrine , being highly aggressive , it is prohibited … again it is prohibited to be administered by direct injection It is present as boluses exactly like adrenaline however it is prohibited to be given subcutaneously
4:03 Do you remember adrenaline , we could administer it by subcutaneous or intramuscular injection Here it is prohibited … thus it can`t be administered orally nor subcutaneously nor even intramuscular Then how can we use it ? the only way to administer noradrenaline , when it is indicated , It is by bringing a bag of saline or glucose five hundred milliliters .. Here like this one , this is a blue saline bag of five hundred milliliters … hang it to the patient And add to it the bolus of norepinephrine here is a device called intravenous set or dripping set , It attaches here Then you can give the drug to the patient by dripping , drop by drop to the vein
4:50 So you don`t administer the bolus directly … you don`t give this bolus itself by IV Why are we saying this ? because if you give this bolus by direct subcutaneous injection It cases severe vasoconstriction that can lead to something called tissue necrosis The area where you injected norepinephrine dies – if you injected it concentrated like this directly subcutaneous - This area dies … It turns blue then undergoes tissue sloughing and the drug won`t be delivered and so many problems occur due to this sever vasoconstriction That`s why it should only be added to an intravenous fluid … and here is a controller and a wheel in order to adjust the rate , twenty drops per minute or thirty as you like And tell the nurse to measure his blood
5:37 pressure every fifteen minutes , because it is probable that Norepinephrine highly elevates blood pressure suddenly …. And if the pressure is highly elevated without control It could lead to cerebral hemorrhage So keep focused on the precautions of using norepinephrine If an examiner asks you how do we administer adrenaline Tell him it can be given subcutaneously or by intramuscular injection and sometimes by inhalation But if he asks about noradrenaline administration Never tell him subcutaneous nor IV nor even intramuscular Tell him the only way is to add it to the intravenous fluid then give it by something called intravenous dripping This method is called intravenous infusion … there is a difference between saying IV IV like this means giving a syringe directly into the vein … but if you add an I the it
6:28 becomes intravenous infusion Which means the drug is added to these five hundred milliliters of solution then it flows very slowly to the vein This is called intravenous dripping We have an important note in physiology Take care of it because it is the subject of so many questions which we like to confuse you with We have some laws in physiology among them is the law of baroreflex , you studied it before Baro … reflex …. What is this baroreflex ? This law states that any reason elevating the blood pressure suddenly If the blood pressure is elevated suddenly say from one hundred twenty over eighty into higher values This elevated blood pressure must send to the brain to cause a reflex bradycardia
7:16 The heart must slows down … but what are the components of this reflex ? This is the aorta arising from the heart … here in the aortic arch there is something called stretch receptors Once the pressure is highly elevated … these stretch receptors must send to the cardio inhibitory center present in the medulla Telling it , watch out … the blood pressure is highly elevated and if the heart keeps this degree of activity with this elevated pressure it could lead to a problem called acute heart failure It could lead to aortic avulsion … the aorta is ripped out of the heart It could lead to something called aortic dissection … intimal dissection … the aortic intima is teared longitudinally and is cut Why ? because this bumping heart can`t withstand to keep this degree
8:05 of activity with an elevated pressure That`s why god is blessing you with a protective mechanism called baroreflex Once the blood pressure is elevated … these stretch receptors in the arc feels this elevation and sends to the cardio inhibitory center which then sends to the heart causing bradycardia This reflex arc is carried out by the vague never … that’s okay ? But there is an important condition for this reflex to occur This elevated blood pressure must be elevated suddenly … suddenly Not chronic …. Not from something about two or three years If someone has elevated blood pressure since two years … this elevated blood pressure won`t cause bradycardia For this reflex to occur … blood pressure must be elevated say from one hundred twenty Suddenly
8:53 exceeding one hundred seventy and systolic blood pressure must exceed one hundred seventy below this value this reflux doesn’t occur so I have two conditions for this baroreflex to occur the first one is the rise in the blood pressure must be sudden the second one is the value of systolic pressure which must exceed one hundred seventy because by time … when the pressure is elevated and the patient leaves it like this for years yes bradycardia occurs at first but by time adaptation sets in this reflex begins to disappear and fades away so the patient`s pressure could be one hundred ninety and the heart is working normally with its normal rate where did the reflex go ? it underwent adaptation now there is a drug called atropine …we will discuss together this atropine in the parasympathetic where you will learn that it is a muscarinic blocker
9:41 … it blocks the vagus nerve so it is a catastrophe to give noradrenaline or anything elevating the pressure not noradrenaline alone but any thing that could elevate the blood pressure it is a catastrophe if the blood pressure is suddenly elevated while the patient is atropinized why ? because now he doesn`t have this reflex … this baroreflex is broken since you blocked it by atropine so a drug like norepinephrine would suddenly elevate the pressure while this reflex is blocked causing aortic dissection or acute heart failure or whatever happens to the patient we like to ask students about this concept in MCQ exams so keep focused we might ask you about this reflex … this reflex bradycardia is caused by the answer would include any drug that elevates the blood pressure by the way this reflex bradycardia isn`t inclusive for norepinephrine alone … it is a physiological reflex that occur in
10:28 response to any sudden elevation in the blood pressure … whatever the cause either a drug or emotion or whatever it is linked to sudden elevation in blood pressure exceeding one hundred seventy be also aware that it is mediated by the vagus nerve and blocked by atropine which is very dangerous in this situation this is what you need to know about norepinephrine …. We updated and removed many parts from your old textbook so don`t confuse yourself with unnecessary information from old sources we are giving you the most recent concepts that you need to know in order to eliminate the burden of unnecessary information now lets shift to the next drug called dopamine dopamine is also a member of the same family … if you remember from the past video I told you we have something called tyrosine … this tyrosine turns into something called dopa
11:18 Dopa turns into dopamine do you remember … and then dopamine into noradrenaline then adrenaline And I told you all of these have the catechol ring and they all obey the same rules They are not absorbed orally don`t cross blood brain barrier and so on Accordingly dopamine is originally one of these catecholamines … It contains this catechol ring and obeys the same rules If we want to talk about dopamine regarding physiology , functions in your body , sites and so one Ten hours wouldn’t be enough thus we are not going to discuss physiological properties of dopamine We won’t discuss right now the functions of dopamine in your body on the other hand we are going to discuss The bolus which we invented from dopamine in other words how does external dopamine affect your body Very briefly … and when we reach dopamine during
12:05 CNS chapter then we will explain it thoroughly But for now all you need to know is that the drug called dopamine is already a natural compound and we turned it into a drug exactly like what we did with adrenaline And it is a catecholamine which means it is member of the same family Now be aware that regarding its mechanism dopamine is slightly different from adrenaline and noradrenaline Where does the difference come from ? That`s because dopamine acts in your body according to the dose that enters your body The amount used …. The amount of dopamine that enters your body is what determines its actions So when this dopamine is given in a low dose , a small one , in the past we used to determine its value but we removed this number because for you
12:53 it doesn`t matter , we will never ask you about this dose or how it is calculated This information is of no significance for you All what you need to know is when you use a low dose of dopamine it enters your body and act on a receptor called dopamine type one Dopamine has different types of receptors in your body , five types of receptors , dopamine type one , wo , three , four and five , five types Thus this low dose that you use - and I`ll tell you how to use It – goes to D1 stimulating D1 now The place that has the most dopamine type one receptors in your body and the first one to be affected by
13:38 this dopamine Is the renal vasculature and the mesenteric blood vessels you already know renal , so mesenteric means the blood vessels in the mesenteric area mesenteric area is the abdomen … those are the blood vessels supplying the spleen , the pancreas , the liver or the intestine … all of those are called mesenteric vascular bed all of these are filled with dopamine type one receptors … and when dopamine type one receptor is activated it causes vasodilation again dopamine in a small dose causes vasodilation in the renal and mesenteric vascular bed , and we will see the benefit of this however if it is slightly increased , now called intermediate dose which is a moderate dose , a
14:23 little bit more than before again for the second time , we removed the value of this dose the intermediate dose goes to the beta one present in the heart increasing the cardiac output we will also state its benefit soon furthermore increase which is now a high dose , now dopamine starts to swing at alpha one causing vasoconstriction increasing your blood pressure so dopamine acts according to the dose low dose , how much is low does , it doesn`t matter , it acts on dopamine receptors in renal and vascular bed causing vasodilation and it may increase the urine out put because when you induce vasodilation in the renal artery and renal blood vessels you increase the urine output intermediate dose activates beta and high dose activates alpha one
15:11 note that they all have one …. one one one no tows D1 B1 alpha1 all in the same order exactly like the name So you may never forget it during the exam It is called dopamine the first litter is D thus at first in the small dose it goes to dopamine receptors This P consider it b which refers to beta , so it later goes to beta , And this a is for alpha So at first it goes to dopamine then beta then alpha This is according to the order of the receptors Now lets see how can we use dopamine and take advantage of its properties And how can we administer the dopamine when it is indicated ? Firstly this dopamine which we invented and is externally administered .. is made almost for a single purpose It is almost exclusively made for patients in
15:57 something called shock state Shock state in medicine When you say shock it means sudden upsetting or surprising event However to be more scientifically accurate regarding the medical definition What is shocked patient ? shocked patient means a patient with hypotension … low blood pressure But this is not the core of it … instead you must add to it Impairment of tissue perfusion Blood is not sufficiently reaching the internal organs There is a huge difference between a patient who is just hypotensive … just low blood pressure And a patient who is shocked … this one is far more dangerous Why ? because blood is not reaching the internal organs like kidneys mesenteric
16:43 vascular bed liver or pancreas This could lead to ischemia and tissue damage if you don`t interfere But how can we identify a shocked patient ? When a patient goes to a hospital to chick his blood pressure Either if his blood pressure was just low or if he is shocked In both cases the patient looks drowsy or somewhat disoriented However you can identify the shocked patient by asking him When was the last time you urinated .. he might say a moment or a short time ago This means the blood is reaching the kidneys and they are forming urine thus most probably this patient is not shocked But then another patient may tell you that he didn`t go to the bathroom since two days Here you should start doubting , observe the patient , look at his hands they would be pale … pale and cold
17:28 We all have pink color on the palm of our hands reflecting the state of the circulation Blood color is always reflected in the palmer side of the fingers Shocked patient in addition to oliguria , oliguria which means little urine output Or sometimes anuria which means no urine at all Anyone of us when he press in his finger like this it turns white this whitish color is because of the blood running from these pressurized areas and then the blood fills it again this is called capillary refilling capillary like this capillary refilling this process is natural in any human when you release the pressure from the finger capillary refilling occurs
18:16 but in the shocked patient since the blood is not capable of reaching internal organs and he has impairment in the tissue perfusion then when you press on his finger like this it turns white due to the pressure however this time the circulation doesn`t come back or it comes back very slowly … and in addition to cold hands he may also be sweaty and he tells you he didn`t go the bathroom since yesterday so he has oliguria or anuria no urine at all oliguria means urine less than five hundred milliliterss per day the bare minimum of daily urine output is half a liter lesser than this is called oliguria no urine at all is called anuria all of these point the shocked patient out now if I ask you during an oral exam or whatever
19:02 in a shocked patient what is your goal of therapy , what is the aim of the treatment a student may tell me the aim is to restore the blood pressure , this is a mistake this is not the main aim of the treatment restoring blood pressure is not a problem however our main purpose is to restore tissue perfusion firstly to ensure that blood is reaching the internal organs because this is where the danger comes from the problem arises from this point so answer me like this shock state means hypotension associated with impairment of tissue perfusion my goal of therapy is to restore tissue perfusion firstly , at first … rather than correcting hypotension after this we fix the hypotension , now I explained
19:48 to you what does it mean to have a shock so let`s see what are the benefits of dopamine imagine if this patient came to you at the hospital , a shocked patient You`d give him dopamine , exactly like norepinephrine we bring five hundred milliliters bag of solution like this bag Bring the dopamine vial which has about four hundred milligrams or two hundred milligrams whatever Add it to this solution and hang it to the patient as intravenous infusion We give it to him slowly by dripping .. the wheel or the controller present here controls the rate of dripping Okay .. now this dopamine is dissolved in the solution and you are giving it slowly t patient after adjusting the rate to about ten drops per minute
20:34 try this at first don`t rush it … give him ten or fifteen drops per minute at first this little amount of dopamine is a small dose and to where does the small does go ? I`ve just told you that small dose will go to dopamine type one receptors which are present in the renal and mesenteric area causing vasodilation after inducing vasodilation urine output increases thus you ensure to restore firstly the tissue perfusion for the kidney and the mesenteric area with the first amount of the drug you ensure restoring the tissue perfusion with the fist amount of dopamine the after a while .. after the dopamine enters his body and starts to build up the amount is increased … then it goes to beta one increasing the cardiac out put this is very good because increased cardiac
21:23 out put contributes in further correction of tissue perfusion after sometime when the dopamine is highly increased … it goes to the alpha one causing vasoconstriction and starts to fix the blood pressure do you see in what order does dopamine fix the patient ? we always say that dopamine is a smart drug , it may sometimes understand the situation better then the doctor who is giving it because the dopamine understands the case and knows how to manage it once you administer the dopamine by intravenous infusion , firstly it goes to the renal and the mesenteric area opening them because there is a problem in them … there is tissue ischemia that`s why dopamine acts on them before anything to ensure hem then it increases the cardiac output and then it suffocates the blood
22:09 vessels controlled by alpha because the are of no use right now where is this alpha ? it is mainly present in the skin and the sub mucus blood vessels thus when it suffocates these two then the cardiac output goes to the opened areas which are ? the only opened blood vessels are those of the renal mesenteric and other vital organs thus all of the blood shifts to them leading to an increase in the urine output and ensuring that the patient don`t develop renal failure many of you guys make this mistake because you are rushing for example a patient with hypotension comes to the hospital and when you measure his pressure you find him hypotensive and you consider him an ordinary case of hypotension and prescribe any drug elevating the blood pressure I could raise the pressure by noradrenaline for instance , instead of this dopamine I could use noradrenaline
22:57 However noradrenaline wouldn`t fix the shock , norepinephrine only corrects the hypotension superficially After fifteen minutes of norepinephrine his blood pressure begins to normalize so you think you treated him so you shake hands and tell him congrats , good bye , go home He goes home and in the next day he comes back to you with renal failure Why ? because you corrected his blood pressure superficially however organs are still deprived from blood Thus the patient went home with tissue ischemia and stayed like this for a day or two until he developed renal failure That`s why dopamine is the best option for shock You may encounter a question in the final asking you to mention the mechanism of action With the names of five or six drugs asking you to mention the mechanism of action of each one In the following conditions
23:42 And beside each drug is a case say , dopamine for shock What does dopamine do in shock If you are a smart student Always remember when I ask you about the mechanism of a drug in a certain case at first show me two lines illustrating this case , show me you understand it for example , dopamine in shock tell me about it then tell me its mechanism don`t go directly for the mechanism firstly tell me what does shock mean tell me shock is a state of hypotension associated with impairment of tissue perfusion this is the first line … the second line … to show me you understand my goal of therapy is to correct tissue perfusion at first rather than to correct blood pressure firstly this then we correct the blood pressure then shift to the dopamine and tell me what does it do tell him the effect of dopamine in small dose on D 1 in renal and mesenteric
24:31 then it increases the cardiac out put then it induces vasoconstriction correcting the blood pressure this is how dopamine fixes the case , starting from the most important point which is vasodilation until it corrects the blood pressure not the other way round look at this mistake made by some people he hangs dopamine to the patient and gives him maximum rate , a doctor or a nurse in rush may add dopamine in a rate of sixty drops per minutes sixty drops per minute is a very high dose … this is called alpha dose what does alpha dose mean ? it means all of this amount enters directly to alpha bypassing B1 and D1 causing vasoconstriction which corrects the blood pressure instantly so you think the patient has improved and discharge him
25:21 while the blood hasn`t yet arrived to the renal sufficiently and mesenteric vessels that`s why you shouldn’t rush while using dopamine add the dopamine to the solution then give it at first by a rate of ten drops per minute and then when you see the urine begins to be corrected and the patient circulation begins to be fixed when you find the normal capillary refilling he is no longer sweaty his temperature improved the disorientation is subsiding and he starts to wake up then you aim for the blood pressure and do whatever you like because you are now sure he won`t develop renal failure and so on this is the dopamine .. and again no one will ask you about the dose at all all what you need to know is its effects in a small dose intermediate dose and in large dose
26:08 don`t bother with numbers or any calculations , at all the next drug we have is dobutamine .. dobutamine is the little brother of dopamine it is also synthetic .. by the way dobutamine is a catecholamine but it is synthetic look here … instead of wasting our time explaining dobutamine , lets just compare it to dopamine this is the dopamine … dopamine and here is its little brother dobutamine you may find this comparison in you exam paper .. a small comparison for a one mark or two asking you to state the difference between two drugs this dopamine is a natural cat … natural cat means natural catecholamine
26:54 while this one is a synthetic cat which means it is a synthetic catecholamine that’s why dopamine takes the letter b for book while this has P for pen why is that ? because this one is natural originating from dopa .. this is a natural compound in your body originating from dopa thus it is natural while this one is a man made , it is not originating from dopa but from other chemical compounds so if we had named it with P for pen you would have thought it is originating from dopa and it is natural that`s why the global council for drug naming gave it the letter B for book in order to avoid this confusion draw a line
27:42 the next point is … as we know from its name dopamine acts on D1 then B1 then alpha 1 while dobutamine is almost exclusively acting on beta 1 so it acts one cardiac beta one only accordingly its function is to increase the cardiac out put and you can also say heart rate however it mainly increases the contractility rather than the heart rate don`t bother with this at least note that dobutamine don`t act on D1 nor alpha 1 it doesn`t have vascular effects draw a line , what did you use dopamine for ? I told you in cases of shock and by the way we will explain all types of shock in cardiology chapter in detail
28:28 but as I told you here I`m giving you a general idea about the sympathomimetics any case of shock specially the septic shock … septic shock means a hypotensive patient with insufficient blood supply for the internal organs because of severe infection it is called septic shock and we will discuss it later in detail while this one … this dobutamine which only acts on beta one as you know it’s effects are only on the heart that`s why it is used when the sock is due to a cardiac cause which is called cardiogenic shock what does cardiogenic shock mean ? again … I told you cardiogenic shock means low blood pressure and blood is not reaching the internal organs and I told you it has so many causes which we will discuss it later when we reach the cardio but you should know that one of its main causes is
29:16 cardiac insult .. a major problem in the heart lowering the blood pressure and blood supply for example , patients with myocardiac infarction .. infarction is a dead part in the heart this all of sudden dead part was due to a coronary insult or whatever it led to sever myocardial depression .. so the heart went down , now its not capable of contraction and a not contracting heart means no blood supply for the internal organs accordingly the patient is hypotensive with impairment of the tissue perfusion so he is shocked what do we call this type of shock that`s caused by the heart it is called cardiogenic shock and since you know the reason assuming that you could correctly diagnose that the cause of this shock is something cardiac related specifically
30:01 so instead of using dopamine it is better to use dobutamine , why ? because it is the specialist in beta one since the cause is in beta one , something in the heart we call pump failure , then give him a beta one stimulant such as dobutamine which increases the contractility and wakes the heart up and of course we administer it by the same way ….. it is also prohibited to be given like this to give dopamine or dobutamine directly , no .. they must be added to a fluid so if it is a cardiogenic shock then it is the dobutamine then if you are asked to compare between dopamine and dobutamine we have three differences only … dopamine is a natural cat , this is synthetic dopamine acts on three receptors according to the concentration used on the other hand dobutamine in
30:46 a small or a large dose only acts on beta dopamine can be used in any shock case generally … any shock case whatever the reasons are , use dopamine however dobutamine is only used for single type of shock cases which is caused by the heart and called cardiogenic shock that`s okay … and I don`t want to repeat again that these are catecholamines only last for short periods of time and must be given by intravenous infusion … again and again for you to remember the next drugs after dobutamine are going to be beta receptors related I`ll tell you about a class of drugs called beta two agonists Beta two means they are going to stimulate beta two receptors Now let`s divide beta two agonists , and
31:36 we are generally talking about drugs acting on beta receptors There are some drugs that stimulate beta two receptors and called selective beta two agonists And there are some drugs that stimulate beta one and two Now if I may trick you and ask you, is there are drugs stimulating beta one ? Yes , there are drugs stimulating beta one only , like what , I have just told you Two minutes ago , dobutamine , it acts on beta one Thus if you are asked about drugs acting on beta receptors Tell him there are drugs acting on beta one like dobutamine as I told you a minute ago There are drugs acting on beta two , we will discuss them in a minute And there are nonselective drugs that stimulate both beta one and two We have explained the dobutamine , right ?
32:24 So let`s shift to beta two agonists , these drugs which act on beta two are important And they are a wide class of drugs with so many names , so be patient with us Number one a drug called salbutamol , another drug is called ritodrine Third drug is called terbutaline , there is salmeterol , formoterol , bamboo bambuterol and so on They end with terol tero terol Let`s separate this one ritodrine and mark it with red color , although it is one of them I want to distinguish it a little it What are beta two agonists
33:12 again ? salbutamol , ritodrine , terbutaline , salmeterol , formoterol , bambuterol First of all , these are non cat , non cat means they are not catecholamines So forget about what you know about the catecholamines , accordingly these drugs can be given orally They are absorbed , and their duration of action is long , they are not destroyed by MAO nor COMT They don`t obey the previous rules Okay , some of these drugs like this salbutamol lasts for about four hours in your body ; it is not destroyed by MAO nor COMT but by the liver And there are other drugs like this salmeterol that lasts for twelve hours
33:59 So among them there are drugs with relatively ,short duration and others with relatively long duration Okay … these drugs that are no catecholamines and you can use them as pills inhalers and syringes , however you like And they stimulate beta two … and I say beta two only because they are selective on beta two When you stimulate beta two , what do you think can happen to your body ? Remember with me , where was the kind beta two ? and all what you know from the video in which we explained beta two is going to occur For example , if I choose blood vessels , what would you say ? you`d tell me it causes vasodilatation But where ? you`d tell in the skeletal muscles blood vessels Not only in there but also in the coronary artery because the coronary also has beta two
34:48 Okay and what else ? the uterus , I has beta two as I told you , it causes relaxation What else ? you`d tell me and this , tremors , tremors of the hand , they are caused by beta two What else ? you`d tell me they enter the live and melt the glycogen elevating blood sugar level , this is also cause by beta two What else ? they go to blood potassium , these drugs draws the potassium out of the blood transferring it into the muscles What else ? they go t the lug , the bronchi and causes bronchodilation All of these effects are caused by beta two All of these drugs cause all what I mentioned on the board However, are you going to use all f them in all of these situations ? of course no We mostly use them only for two indications , two situations or two indications for the
35:37 use of the selective beta two these are the most well known The first one of them where we use these drugs in and one of the most well known use is in bronchial asthma Bronchial asthma is chest allergy , why ? there is a long chapter dedicated only for the bronchial asthma It is not the time now to discuss bronchial asthma in detail But at least you know bronchial asthma patients suffers from bronchoconstriction Thus you want to induce bronchodilation , very simple And you have these specialized drugs , they specialize in beta two And they are present as tablets inhalers whatever the form that the patient desires So the first indication of them is the bronchial asthma , with all of its types that we will discuss in detail when we reach the respiratory system
36:24 Okay ? the second indication is when you wat to induce uterine relaxation during pregnancy Some women when they get pregnant , they experience repetitive abortions This is called habitual abortion , habitual abortion means repetitive abortions Her uterus is weak , so whenever she gets pregnant , for any reasons , some uterine contractions occur And she undergoes abortion One time when she is pregnant , she goes to the obstetrician , the obstetrician tells her to rest and not to exert any effort In addition I`ll give you external drug that causes uterine relaxation This drug stimulates beta two within the uterus Which one of them ? of course they all can be used , those five or
37:10 six drugs I mentioned before can be used Salbutamol terbutaline ritodrine salmeterol bambuterol formoterol albuterol All of these drugs could be used However then one that we chose specifically for the uterus and the one most well known for this effect it Is the one among them which I marked with red a while ago to distinguish it The one called ritodrine , so this ritodrine is a beta two stimulant and its function is on the uterus , to relax the uterus Thus it is given to delay premature labor or to prevent an abortion Delay premature labor is the same as this …. If you are afraid that some woman would give birth at six or seven months She is a pregnant woman at seven months but her uterus is not able to carry on So the doctor describes her a beta two in order to cause some uterine relaxation to extend this pregnancy
37:58 Instead of giving birth after seven it could be after eight or nine months This is called premature labor , accordingly we use the ritodrine either to prevent an abortion or to delay a premature labor Okay , now allow me to ask you what are the downsides of these drugs ? collectively as a class These drugs called beta two agonists , what are their downsides , or the adverse effects that you expect ? The adverse effects you expect , and I want you to add some more to your textbook We have three T letters and on H letter Three T and one H , I`m taking about the adverse effects or the disadvantages of this class The first T is for tachycardia , tachy cardia and arrhythmia What ?! are you saying tachycardia ? why ?! Doctor , didn`t you tell me they act on beta two
38:49 I`ll tell you yes . .. so you would ask me ….. then where does this tachycardia come from ? I know tachycardia is caused by beta one , I`ll tell you : you are right However you didn`t notice when I told you these drugs stimulate beta two , I hid something from you They can lose their selectivity and swing at beta one , but when does this happen ? When you increase their dose , if their doses are increased they lose their selectivity They start to act on bet two and beta one causing arrhythmia and tachycardia So that some people with bronchial asthma who take these drugs His breathing is heavy .. so he takes the inhaler constantly .. but he is not relieved so he increases the dose more and more and more until at one moment he complains of tachycardia and his hands starts to be shaky thus he calls his doctor Complaining from his heart and rapid
39:37 pulse and then the doctor reassure him that these drugs only act on beta two This is wrong ! these drugs act on beta two however when you increase their dose , they start to lose their selectivity And go to beta one causing tachycardia and so on This is the first adverse effect you should be aware of The second adverse effect as I mentioned before is tremors and you know that this shaky hands make sense due two beta two effects The third T is for tolerance … to le rance , like this What does tolerance mean ? this term tolerance will be explained more thoroughly in general chapter But for know you should know that tolerance means the body starts to be accustomed to the drug Day after another , the usual dose is no longer producing the desired effect And the patient must increase the dose in order to get the desired effect
40:23 Day after another the patient keeps increasing the dose until he suffers from the side effects This is Tolerance , and it has many causes We have a rule stating that the more you target receptors with a selective drug and stimulate them day after another the less their numbers become If this is a cell like any cell in your body , if it contains one hundred receptors , and each day I stimulate these receptors with a drug Day after another they become ninty , they become eighty and so on This is called down regulation , down regulation of the receptors Which means their numbers and their sensitivity begin to be decreased as long as you continuously use the drug day after another This is called tolerance and it always occurs with beta two receptors specially The most receptors that get mad at you when you keep stimulating them everyday
41:11 are beta two receptors in your body because they experience tolerance quickly from these drugs Okay .. I mentioned the three Tees tachycardia tremors and tolerance The H , now I want you to say it … what for does this H stand ? It stands for hypokalemia , blood potassium starts to be decreased Why ? because I told you whenever anything stimulates beta two , beta two shifts the potassium from blood into the tissue this is called potassium shift and it causes hypokalemia okay now we have finished the selective beta two agonists in the past we had a drug that no one would tell you about these days we used to explain in the old textbook thoroughly , later we removed it because
41:57 it is no longer important for the students this drug is called isoprenaline , isoprenaline have another name, in MCQ exams they may instead use the name isoproterenol isoproterenol , so isoprenaline or isoproterenol are the same drug this drug was a synthetic cat , catecholamine but synthetic why are we no longer using this drug more often ? because it stimulates both beta one and beta two thus it was termed nonselective beta agonist , and the term nonselective is always undesirable in pharma
42:45 we don`t like any nonselective drug , unless it has a certain indication of course but in most case we like to use more selective drugs now we have a drug that acts only on beta one , do you remember it ? it is called dobutamine and used for cardiogenic shock as I told you and I have drugs acting only on beta two , do you remember them ? the five or six drugs that I mentioned before what is the reason for using a drug that acts on the two types of receptors with each type of receptors come another adverse effects why would you use it ? to stimulate beta two ? you have these to stimulate beta one ? you have this and so on that`s why In your new textbook there are no information about this isoprenaline except for being a nonselective drug and we mentioned that it is rarely used I repeat again , so don`t you add
43:31 twenty pages about isoprenaline I see students add completely non significant texts about it , we removed this for you In order not to fill you head with nonsense and because it is not commonly used So if you find and old mcq question in an outdated textbook from more than ten years ago You may find a question about isoprenaline , indeed from ten years ago we used to discuss it in detail Now we don`t , because it is no longer significant Thus if you encounter such a question don`t burden yourself with further outdated information We no longer ask about this drug … the only information you may need to know is that it stimulates both beta one and beta two That`s it we won`t ask you anything more , because it is rarely used Lets shift to the next family which is drugs stimulating alpha receptors Don`t forget that we are taking it step by step
44:21 until we finish a family called sympathomimetics I started with adrenaline , we specified a whole video for it , and now we are explaining the rest of the drugs , other direct sympathomimetics Me and you are illustrating drugs that stimulate the receptors Now let`s see those stimulating the alpha receptors You can either stimulate alpha one or alpha two Because you have two types of alpha receptors Thus if you say alpha agonist .. which receptor of these do you mean ? or do you mean both of them ? Okay .. lets see the available drugs that are called alpha agonists You will find that the first drug of the family stimulating alpha is called phenylephrine… Phenylephrine And it is an important one … beside it a drug called methoxamine , methoxamine
45:13 Beside it a drug called midodrine …. all in one line The three of them phenylephrine , methoxamine , midodrine Naturally the three of them are non catecholamines ,okay ? So they are absorbed orally and so on … they stimulate alpha one and have relatively long duration Because they last for about two hours in your body … when they stimulate alpha one they case vasoconstriction Okay .. so what for do we them ? you`d tell me exactly like noradrenaline What did we use noradrenaline for ? didn`t we use it to elevate the blood pressure ? Then phenylephrine methoxamine and midodrine are also used as vasopressors to elevate the blood pressure via induction of vasoconstriction They are present as tablets to be given
45:58 orally , they are present as eye drops And they are present as syringes … all forms are available Okay .. tablets are given orally three times per day to stimulate alpha one and elevate the blood pressure But why are they present in the form of eye drops ? sometimes they are even present as nasal drops So why are there eye drops and nasal drops ? Because some people complain of red eye … red eye means his eye is always congested Or he always complain of blocked nose from common cold or whatever and he can`t sleep that`s why we make them in the form of eye drops and nasal drops to produce vasoconstriction if you are using them for red eye .. apply these drops to the red eye and it become clear
46:50 nasal decongestants are used when you have a blocked nose from congestion to relieve this congestion but there is an important observation when we use these drugs indeed they cause vasoconstriction , clearing the red eye and relieving the nasal congestion however they cause something called rebound can you tell me what does rebound mean ? rebounds means that after two hours these symptoms will return to you worse than before thus after exactly two hours … if you used them for red eye firstly I`ll tell you something funny .. once upon a time during a wedding the bride was nervous for some time she couldn’t sleep well and during the wedding day her eyes turned red so she used this eye drops
47:37 in order to have a clear eye for the photo session by the time she arrived home , rebound congestion ensued the red eye returned worse than before , the groom was terrified and the wedding was cancelled same scenario occurs in the nose … when you have a nasal congestion and you can`t fall asleep you use these drops then you have peace for two hours two or three hours later and the congestion returns worse than before … this is called rebound why is that ? what is the explanation of this phenomenon ? in case someone asks you if someone asks you why do these drugs cause this rebound ? tell him look at this blood vessel .. here is a cross section .. it was congested , dilated and causing problems but when I used the drug the blood vessels were suffocated due to vasoconstriction from the prolonged vasoconstriction the blood vessels become like this
48:27 from the prolonged vasoconstriction metabolic waste starts to accumulate , you studied this in physiology and you know that this metabolic waste causes vasodilation however as long as the drug is present it doesn`t appear as the drug is causing vasoconstriction and once the drug effect disappears after two hours … these metabolites takes over this blood vessels causing sever vasodilation and the patient experiences congestion worse than before this is the explanation of the word rebound okay this is the first class of drugs acting on alpha … exactly like the three drugs I mentioned are two drugs from a family called imidazoline derivatives a drug called xylometazoline and oxymetazoline … xylometazoline oxymetazoline
49:16 from a family called imidazoline …these two are exactly like the ones before however the difference is they stimulate both alpha one and two and they are considered non selective what are their uses ? I told you alpha two effects are not prominent unless you target it with a specialized drug thus their effects are like the ones before they also act on alpha one causing vasoconstriction and their main use .. their main use is as nasal decongestant and eye drops exactly like those I mentioned before … they differ in names but they are treated the same way like the previous drugs now let`s see the next group of drugs … but before we leave this part I still have some notes in here glad you reminded me … I want to tell you about some notes under the title of
50:06 if you wish call it adverse effects , that`s okay also if you want to call it precautions , no problem and be aware they are important for the exams these drugs , nasal decongestants or eye drops , this family of drugs and the previous one are used so often without restrictions , people go to pharmacis and buy these drugs as if they were candies people with common cold get these drugs over the counter without any prescriptions and when it comes to the exams we always give much attention to such drugs because they can be dangerous if people use them carelessly , that`s why we have a holly question that you can expect to see in any exam it is the precautions of nasal decongestants , or the group of drugs called nasal decongestants
50:57 which are drugs stimulating alpha one what are the precautions ? we have one , two , three a question for three marks and it is very often present the first precaution , I told you that most of these drugs frequently cause rebound what does this mean ? it means that when you are going to use them don`t take a high dose because any way once the used dose wears off you get a congestion worse than before so try to use minimal , the minimal effective dose , and try not to repeat it often so you don`t experience this rebound effect number two , some unfortunate people , when he apply these drops locally in the eye or in the nose they undergo systemic absorption ,
51:47 he was hoping for a local effect but unfortunately the drug is absorbed into the systemic circulation causing systemic vasoconstriction which highly increases the blood pressure , probably into dangerous levels there is still more to it , even some people went through a stroke due to these drugs stroke means bleeding in the brain , a bleeding in the brain is called stroke or hemorrhagic stroke to be more accurate some people experienced this , he applied the drops and went to sleep without knowing that they could be absorbed systemically , they caused sever hypertension and caused a stroke that`s why I advise you to avoid using them frequently not anyone suffering from some nasal problems or congestion should use these drugs
52:34 number three , these drugs , people who use them every now and then and get used to them whenever they use them they cause vasoconstriction this prolonged vasoconstriction may lead to something called atrophic rhinitis , atrophic rhi ni tis rhinitis means something related to the nose , atrophy in the mucosa why ? due to the prolonged vasoconstriction … you are inducing vasoconstriction for days and months it is not for free … this mucosa will die from this prolonged vasoconstriction after awhile you may complain of anosmia , you can no longer smell , okay ? and after some time you may have a chronic allergy , polyps or many other problems so these drugs shouldn`t be used for a
53:21 duration longer than three weeks , longer than this they could be dangerous they could cause atrophic rhinitis to summarize , the three precautions that you should never forget about are these drugs could always cause rebound , and I told you what causes it and how it originates two , they could be absorbed systemically causing systemic hypertension three , prolonged use of them more than three weeks could lead to atrophy of the nasal mucosa which is called atrophic rhinitis that`s why you shouldn`t use them longer than three weeks let`s see the next group of drugs which stimulates alpha two this time drugs stimulating alpha two do you remember when I told you that alpha two effect can`t be prominent except when you specifically target it with a drug here we have two drugs , they are specifically
54:07 alpha two agonists , the first one is called clonidine , clonidine the other , or its little brother : tizanidine , okay , now step by step clonidine , when you study the autonomic , you can notice that it is mentioned later in the autonomic chapter there is only one line about it but it tells you that it is explained later in detail in the page sixty two of our book what is the story of this clonidine ? this clonidine . in brief , a drug that functions by stimulating alpha two , this is its function and since it stimulates alpha two , can you tell me where was it present ? we said it is presynaptic .. do you remember what did it do ? it decreases norepinephrine release this alpha two here
54:54 when clonidine reach this alpha two and binds to it , it decreases the norepinephrine in your body it is decreased both peripherally and centrally since this drug cross the blood brain barrier as it is a non catecholamine and when norepinephrine is decreased then we can say this drug decreases the central sympathetic outflow focus on this term , so clonidine decreases the central sympathetic outflow hence your blood pressure is decreased and you calm down , the patient calms down , the patient who is nervous hypertensive and anxious all of this goes down the drug relives the patient from these in addition to this , when the blood pressure is decreased the renal blood flow is not affected the drug decreases the blood pressure without affecting the renal blood flow
55:40 why are we saying this ? because there are too many drugs when they decrease the blood pressure they also decrease the renal blood flow and the GFR GFR is glomerular filtration rate this also starts to be decreased thus urine output is also decreased and this is dangerous ! That`s why we are assuring you that this drug is acting centrally , it is acting on the nerve ending It decreases the norepinephrine without affecting the tissue itself like kidney, liver or other This encourages me to tell you that it is such a fantastic drug , as you can lower the elevated blood pressure of the hypertensive patient especially if he was also a renal patient if he has a renal problem like renal failure for example a patient with renal failure who is also hypertensive can benefit from this amazing drug which decreases the blood pressure without
56:28 affecting the renal blood flow here you have this clonidine the second use which we need this drug for … , I told you once when I was explaining the introduction something about drug addicts The Aunti Emma is termed opium , this family of substances is called opioids , opioids means substances related to this Aunti Emma drug addict uses these substances to get high , ask him why do you take this ? he tells you : to get high High on what , you don`t know but any way he is high Okay , now when he tries to stop , what is the problem ? He tells you : I can`t , I don`t bear it , I get nervous and vengeful That`s why there are designed programs for them , and I can help him with this nervous part Because when he stops using drugs he gets nervous and vengeful
57:17 and to get rid off this nervous and anxious behavior , I give him this clonidine Clonidine decreases norepinephrine release in the nerve endings and in the central nervous system So the patient calms down …. Or this addict calms down As if this clonidine has tow major indications … one of them , the first indication of it Is to reduce the blood pressure or to treat hypertension specially in the renal patients , patients with renal failure Two , to help with opiate withdrawal , opiate withdrawal or to prevent opiate withdrawal Which means when the addict stops the opiate or other opioid drugs it prevents the effects that accompanies cutting the drugs off , and which we call withdrawal symptoms , like nervousness anxiety and so on these are its uses , so what are
58:03 its adverse effects ? we should always try to remind ourselves by using mnemonics adverse effects of clonidine are three Esies , the first S is sedation sedation , the term sedative means tranquillizer , sedation means the patient becomes sleepy all day that is okay , no problem , why ? when the drug addict stops using a drug and takes his medication he becomes calmer and sleepy in Egypt we say "The sleep of the tyrant is a worship" so this is beneficial and it is due to the decrease in the norepinephrine it also causes dry mouth dry mouth means his throat has little saliva , his throat is dry and this is irritating but be aware that this dry mouth is not a peripheral effect it is not a outcome
58:49 of the peripheral effect of the drug but the central , and it is not well know , why ? if you ask me what is its explanations ? I`ll tell you that it is a central effect , however how exactly does this drug causes dry mouth , we don`t know . okay , the second S is for sudden withdrawal of this drug , sudden withdrawal means stopping the drug abruptly it causes seveeeeeeeeeeere hypertension the most popular question about clonidine in , is this point one of the most well known drugs that should never be stopped suddenly sudden withdrawal means stopping the drug abruptly which causes sudden sever hypertensive crisis look here my friend , nerve ending , norepinephrine … and you are giving
59:37 this drug for years and this alpha two is working to decrease the norepinephrine , now the body is accustomed to this at some moment you stop this drug by mistake inducing a sudden withdrawal what happens ? what happens is that alpha two stops working thus norepinephrine starts to be increased returning to its normal value and more and more so that patient could suffer from sudden sever hypertension and the most common question about clonidine that we ask student in , is this point when we tell you , one of the following drugs is very famous … of not being suddenly withdrawn which means one of these five drugs is very well known that it mustn’t be suddenly withdrawn
1:00:23 shouldn`t be stopped abruptly , then you must blindly choose clonidine this last S is salt and water retention … it causes your body to hold on to water and by the way salt and water retention is such a large topic that will be explained in the cardio however I`ll tell you two lines about it to help you until we reach the cardio we have a rule , my friend which states that any drug what so ever that decreases the blood pressure if you continue to use it for period about a month or longer the body starts to induce a reflex , reflex sympathetic activation the body starts to release something called renin angiotensin system , you may remember it from physiology thus any drug that lowers the blood pressure for
1:01:11 long periods , after a month , the body starts to confront it with renin angiotensin system to be more accurate it was called renin angiotensin aldosterone system here in the middle something called aldosterone , which causes salt and water retention so we will state a rule , a rule which says that any drug what so ever that lowers the blood pressure for long periods and you intend to keep the patient on it , the body starts to confront you , with what ? the body tells you it won`t abide your rule , I won`t let you control me you are lowering my blood pressure day after another , then I`ll let you face my renin angiotensin system or renin angiotensin aldosterone which induces salt and water retention why is the body doing this ? the body does this as a form of reaction you are lowering the pressure so the body is trying to react , he is trying to fix what you are doing the body doesn`t understand what you are doing
1:01:58 you keep lowering the pressure by a dug , okay , then I`ll hold onto the water to limit this decrease in the blood pressure accordingly we are to use this term salt and water retention with any drug that lowers the blood pressure from now , from this moment till the end of the curriculum , once you hear a drug lowers the blood pressure then be sure that after a while not a day but after a while it will cause salt and water retention now the clever doctor is the one prepared for this so if he prescribes a pressure lowering drug ha adds to it a diuretic .. diuretic means something increasing the urine , in order to get rid of the water and prevent its retention again , clonidine is a very well known drug, and it is also popular in exams it stimulates alpha two ? what for are you going to use it ? I use it to lower the blood pressure , specially in the renal patients
1:02:45 two , it can help the addict to cut off his drugs , if he decides to stop his abuse then I can calm him down with clonidine as it decreases the central sympathetic outflow what are his drawbacks ? 3S first one is sedation , sedation means the patient feels sleepy all day and dry mouth which is not explained as I told you it is central but its exact mechanism is still unknown two , sudden withdrawal of the drug , if you stop the drug abruptly it causes sudden severe hypertension three , it causes salt and water retention and I told you how does it happen , in brief until we reach the cardio , and its treatment is to give a diuretic beside it The next drug after clonidine , its little brother which is called tizanidine Tizanidine is a recently added drug to your textbook , it wasn`t present in the previous edition Tizanidine is exactly similar to clonidine
1:03:34 it also stimulates alpha two however this time tizanidine chooses to stimulate alpha two in ? Can you imagine where ? in the spinal cord Here is the spinal cord and as you know here are something called anterior horn cells which give rise to the motor nerve supplying the muscles , like this Tizanidine stimulates alpha two - exactly like clonidine - however this time it chooses to stimulate alpha two only on the level of the spinal cord Only , what does only mean ? it means it doesn`t act on the nerve endings nor it acts on the brain It only acts on the middle part which is the spinal cord When it acts on the spinal cord , on this alpha two here You know that alpha two is always inhibitory , so when you stimulate alpha two in the spinal
1:04:21 cord , it decreases the neuronal transmission The neurotransmission , or the signal that is coming from the brain , when it descends to the muscle It is blocked , and when the signal that`s going to your body muscles is blocked , your body muscles starts to relax That`s why this tizanidine is a
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