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0:05
Welcome to nonstop neuron dot com where learning medical concepts is as easy as watching cartoons. From this lecture, we will start studying pharmacodynamics. In previous lectures, we talked about pharmacokinetics. That was a study of what the body does to the drug. It included absorption, distribution, metabolism, and excretion of the drug by the body. Opposite to this, pharmacodynamics is the study of what a drug does to the body. So here we have a totally different
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set of concepts to learn. First, let's briefly overview what is studied under pharmacodynamics. Pharmacodynamics answers FOUR broad questions regarding the drugs. How the effects of the drugs are produced. What type of effects are produced? How much of an effect is produced at different doses? And how these effects are modified. As an answer to the first question, we will study different mechanisms of action of drugs. The effects are broadly categorized into
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desirable effects, and undesirable effects (or adverse drug reactions). The quantitative aspect is studied under the dose-response relationship. And factors that modify drug actions are broadly biological factors and other drugs. We will go into the details of all these broad answers over multiple lectures. In this lecture, we will talk about HOW the effects are produced. Or in other words, we will see all the different types of mechanisms of action by which a
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drug can act on the body. So let's get started. While talking about how the drug WORKS, you will come across two terms frequently. Action, and effect. So first let me make it clear what these terms mean. Action is the initial combination of the drug to its target molecule, and CHANGES that are caused in that molecule. Whereas effect means the final change in the biological function that occurs as a consequence of action through a series of intermediate steps. In simple words,
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action is about how the drug works at the molecular level. And effect is the final result of that action at the physiological level. Thus action is identified, whereas effects can be measured and quantified. For example, captopril inhibits the angiotensin-converting enzyme in the lungs. This causes vasodilation and eventually fall in blood pressure. Here inhibition of angiotensin-converting-enzyme is the action. And fall in blood pressure, is the effect.
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Now, knowing only about the final effects is not sufficient. We must also know HOW that effect is produced. Because the same effect may be produced by different actions. For example, a different drug called chlorthalidone also causes a fall in blood pressure, but by a different action. It inhibits sodium chloride cotransporters in the kidney. This leads to an increase in urine output, which eventually causes a fall in blood pressure. One more drug called propranolol does it by yet
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another action. It inhibits β1 receptors in the heart. This decreases the heart rate, which also causes a fall in blood pressure. You see, same effect can be produced by different actions. So knowing only the final effect is not enough. You need to know the action too. So now let's see the different mechanisms of action. Drugs can target a wide range of biomolecules in our body. The majority of the drugs target functional proteins. This includes
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enzymes, transport proteins, and receptors. You have learned in biochemistry that proteins are of two types. Structural proteins, and functional proteins. If structural proteins are like building blocks of the body, the functional proteins are like the working force of the body. And most of the drugs, target this working force of the body. However, there are a few drugs that target OTHER biomolecules, like tubulin, DNA, etc. Finally, some drugs act purely by physical or chemical
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means. So these are the targets of the drugs. Now we will see what a drug can do with each of these targets. We will start with the enzymes. Almost all the biochemical reactions in our body are catalyzed by enzymes. By modulating their activity, the rate of biochemical reactions can be modulated. So enzymes are very important targets of the drugs. Technically speaking, a drug can do two things with enzymes. It can either stimulate it or inhibit it.
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But stimulation of an enzyme by a truly foreign substance is rare. That is because the activity of most of the enzymes is already optimally set. In simple words, the enzymes are active by default. So there is no scope for stimulation. How do you awaken a person who is already awake? So the drugs don't have much scope on this side. It's the inhibition that the drugs mostly do. Broadly, there are two types of inhibition. Competitive inhibition, And noncompetitive
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inhibition. The competitive inhibition can be further divided into equilibrium type and nonequilibrium type. To understand these types better, first, let's quickly revise some basics of enzyme kinetics. Here this scissor is an enzyme. Its blades make the catalytic site. And this is an endogenous substrate for this enzyme. When substrates bind at the catalytic site the reaction is carried out. Now at any given location, we have many enzyme molecules. This dial shows the
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velocity or rate of the reaction. In simple words, it shows what percentage of enzymes are active. At low concentrations of the substrate, fewer enzymes are active. As the substrate concentration INCREASES, more and more of it comes in contact with the enzyme. The concentration at which HALF of the enzymes are active is called the rate constant of the reaction (or kM for short). Let me repeat. kM is the concentration of substrate at which HALF of the enzymes are occupied. With
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the increasing concentration of substrate, all the enzymes become active eventually. So the velocity of the reaction reaches its maximum level. This maximum rate is called Vmax. Please note: the Vmax is equivalent to the MAXIMUM FIGURE in this speedometer (not the position of the needle). This was all without inhibition. Now let's see what happens in different types of inhibition. In competitive inhibition, the drug is structurally similar to the endogenous
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substrate. So it binds with the same catalytic site where endogenous substrate also binds. In short, the drug and substrate both compete with each other for the same binding site. So in the presence of an inhibitor the substrate needs to be in higher concentration to engage with the same number of enzymes. Or in technical words, the kM is increased. This is common to both types of competitive inhibition namely: equilibrium and nonequilibrium type. In short, kM is increased in
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both, equilibrium as well as nonequilibrium type of inhibition. The difference is in the Vmax. If the bond between the drug and enzyme is weak, an increased concentration of substrate can displace the drug. So maximum velocity can be achieved. Thus with a weakly binding drug, Vmax remains the same. This type of inhibition is called the equilibrium type of inhibition. For example, inhibition of cholinesterase enzyme by physostigmine is of equilibrium
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type. Physostigmine makes a weak bond with the enzyme. So its effect can be surmounted by increasing the concentration of acetylcholine. However, if the drug makes a strong covalent bond, the substrate cannot displace it, even at higher concentrations. In simple words, the enzymes bound to the drug are lost forever. As these enzymes can never contribute to the activity, the maximum rate of reaction cannot be achieved. Or in technical words, the Vmax is decreased. In
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such cases, Vmax is usually restored only after the synthesis of fresh enzymes. And this takes time. This type of inhibition is called the nonequilibrium type of inhibition.
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For example, inhibition of cholinesterase by ORGANOPHOSPHATES is of nonequilibrium type. Organophosphates bind with the enzyme so strongly, that it's not displaced even with an increased concentration of acetylcholine. In such cases, normal cholinesterase activity is restored only after the synthesis of new enzymes. So this was competitive inhibition. The key point in competitive inhibition is that the inhibitor is structurally similar to the substrate,
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and it competes for the same catalytic site. But in noncompetitive inhibition, the drug is not a structural analog of the substrate. And it does not compete with the substrate for the same catalytic site. Instead, it binds with a different site. This binding induces conformational changes in the enzyme that make it incapable of carrying out its catalytic activity. In this case, the binding of the substrate at the catalytic site is not affected. So the kM remains the same. However,
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the enzymes bond to the inhibitor do not contribute to the reaction regardless of the substrate concentration. So the reaction cannot reach the maximum velocity. Thus the Vmax is reduced. For example, inhibition of cyclooxygenase by aspirin is of non-competitive type. If you are confused by all these details, let me summarize important points from enzyme inhibition. In competitive inhibition, the drug binds with the same catalytic site.
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Whereas in noncompetitive inhibition, it binds with a different site. In equilibrium type of inhibition, the binding is weak, so it can be reversed. But in the nonequilibrium type, the binding is strong. So it cannot be reversed. So this is ALL that drugs can do with enzymes. Next among the targets for drugs are transport proteins. So let's see what drugs can do with THEM. As you have learned in physiology, transport proteins are involved in transport
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across the cell membrane. They may be bringing the substances from outside of the cell to inside, or sending them from inside to outside. Some drugs target these transport proteins and interfere with their activity. For example, lignocaine blocks voltage-sensitive sodium channels in neurons, digoxin inhibits the sodium-potassium ATPase pump in the heart, furosemide inhibits sodium-potassium-2-chloride cotransporters in the kidney, fluoxetine blocks the serotonin
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transporter in the brain, nicorandil OPENS ATP sensitive potassium channels in blood vessels, etc. Thus drugs can interfere with the activity of transport proteins. This checks off one more functional protein in our list. Next, we have receptors. Receptors are the most common targets of the drugs among all these molecules. So this discussion is going to be a bit longer. Here I will assume that you don't remember much about receptors from physiology. So
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first we will quickly see some basics regarding receptors. Then we will come back to see what a drug can do with them. So let's go back to physiology. There in cell-to-cell communication, you learned that if a cell wants to say something, it says it by releasing a chemical messenger. That messenger is then identified by other cells. Following this identification, a series of reactions is carried out inside the receiver cell. And at the end of it, there is a target protein
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that initiates the ultimate response by the cell. Here the messenger that brought the signal from the distant cell is called the first messenger. The molecule that identifies this messenger is the receptor. The series of molecules that follow are second messengers. And finally, we have a protein that initiates the ultimate response. For example, different hormones and neurotransmitters are first messengers. As receptors, we have ligand-gated ion channels,
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G-protein-coupled receptors, catalytic receptors, and nuclear receptors. In the second messenger system, we have many pathways: like the cAMP pathway, IP3-DAG pathway, and many more. The final target protein can be a transport protein, gene regulatory protein, metabolic enzyme, cytoskeletal protein, or cell cycle protein. Taking the signal from the receptor to the final protein is also called intracellular signaling or signal transduction.
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Please note that this is a general theme. The exact combination of the first messenger, receptor, signal transduction pathway, and target protein is different for different physiological functions. Let's take an example of cells in the SA node that generate impulses for heartbeats. Here sympathetic nerve terminal releases noradrenaline. It acts on β1 type of adrenergic receptors on the cells of the SA node. This receptor activates the cyclic AMP pathway of
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intracellular signaling. In the end, there is an increased opening of sodium channels. So the frequency of impulse generation increases. Or in simple words, there is an increase in heart rate. Thus in this process, only THESE proteins are involved. This is just one example. In the body, we have a huge variety of such processes going on. But this is the general theme behind all of them. If you understood the overall position of receptors in cell-to-cell communication,
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now let's see them in detail. If you look at the real structure, receptors come in all kinds of complex and boring shapes. But to keep it simple, you can think of it as a mailbox. As we just saw, they receive the signal from an external messenger and transduce it into a response. Accordingly, they have two domains. A ligand-binding domain, and an effector domain. The ligand-binding domain recognizes a specific ligand molecule.
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And the effector domain initiates the downstream events. By the way, if you don't know the meaning of ligand, any molecule that can bind with a receptor is called a ligand. So all the endogenous messengers like hormones, neurotransmitters, etc, as well as drugs that bind with receptors are ligands. Now… a specific receptor can bind with a specific ligand only. This is determined by the STRUCTURE of the receptor and ligand. They bind with each other only if their structure is
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complementary. If their structure does not fit into each other they don't bind. For example, adrenaline binds with adrenergic receptors only, insulin binds with tyrosine kinase receptors only, etc. So these were some basic points regarding the STRUCTURE of the receptor. Now let's see how they operate. The basic thing here is that the receptors stay active only as long as the messenger is bound to them. That means they activate the
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second messenger pathway only as long as the messenger is bound. As the messenger leaves, they become inactive. So the activation of the second messenger system stops. This is similar to how some taps work. Do you remember the tap that you used to get drinking water in that garden? It stays open only as long as you keep the button pressed. When you release the button the tap closes. Here the hand is like a messenger, the button is like a ligand-binding domain,
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the part from where water comes out is like the effector domain, and pouring of water indicates that second messengers are being activated. The reason I am bringing up this analogy is because various actions of drugs on receptors can be easily understood with this analogy, rather than on realistic diagrams. So, we will be using this analogy a lot when discussing the effects of drugs. And that brings us back to our main discussion
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(what a drug can do with the receptors?). For a drug to do anything with a receptor, it should be able to do two things. First, it should be able to bind to the receptor. And second, it should be able to trigger the response. In fact, these two abilities have got names also. The ability of a drug to bind with the receptor is called affinity. And the ability to bring about changes in the receptor is called intrinsic activity. The intrinsic activity
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is denoted from 0 to 1, where 0 means no activity and 1 means full activity. Based on variations in this property, drugs can be broadly classified as agonists, partial agonists, antagonists, and inverse agonists. So now let's see what they exactly do to the receptor. An agonist has an affinity for the receptor. And its intrinsic activity is maximum. That is, it can bind with a receptor, and activate it to the maximum. As activation is maximum,
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the intrinsic activity is said to be one. This produces a response similar to that produced by physiological signal molecules. For example, morphine is an agonist for mu opioid receptor. A partial agonist has affinity but submaximal intrinsic activity. That means it activates the receptor, but not fully. There is only partial activation. Thus its intrinsic activity is between 0 to 1. So the response is also partial. For example, buprenorphine
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is a partial agonist at mu opioid receptor. It is worth noting that if an agonist is also present, the partial agonist prevents its action. That is because as long as the partial agonist occupies the receptor, the agonist cannot act on the receptor. For example in this case, although the buprenorphine has partial action, it prevents the full action of morphine on this receptor. Next, we have antagonists. They have affinity but no intrinsic activity. They cannot induce any
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conformational changes in the receptor. So they do not initiate any response. Thus their intrinsic activity is 0. However, if agonists or partial agonists are around, they prevent their action, by not allowing them to bind with the receptor. For example naloxone at mu opioid receptor. It just sits there and does nothing. And if morphine or buprenorphine is around, it neither lets it do anything. Lazy guy! Next, we have inverse agonists. They are seen
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only for constitutively active receptors. See some receptors in our body are active even without agonists. That means they activate the second messengers at some baseline level, even in the absence of an agonist. They are like leaky taps. Inverse agonists can exist for such types of receptors only. Here the drug binds with the receptors and stops the baseline activity. It's like pulling the button to stop the lea/akage. Here you can say that the intrinsic
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activity of the drug is with a minus sign, (that is, from 0 to -1). This produces an effect that is opposite to what the receptor normally does. This is called inverse agonism. For example, benzodiazepine receptors are constitutively active. This constitutive activity keeps a person CALM! However, an inverse agonist called β carboline prevents this constitutive activity. And this makes the person anxious! Thus inverse agonist produces an opposite effect.
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As a quick summary, you can look at the size and direction of the arrows here. Agonist activates the receptor fully, partial agonist activates it partially, the antagonist does not do anything, and inverse agonist inactivates constitutively active receptors. To keep all this simple, you can think of the agonist as a strong man who can press the button fully, a partial agonist as a kid who can press the button only partially,
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antagonist as a butterfly (who can sit on the tap but cannot press it), and inverse agonist as a plumber who closes the leaky tap. When any of them has occupied the tap, the other cannot work on it. Like partial agonist prevents the action of full agonist, antagonist prevents the action of partial as well as full agonist. So this is what drugs can do with the receptors. But the story doesn't end here. Because in response to the effect of the drug,
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the cells also regulate the activity of receptors. And that brings us to the other side of the story: receptor regulation by the cell itself. There are two possibilities here. Desensitization, and super sensitivity. As their names suggest, in de-sensitization, the cell becomes less sensitive to the stimulation, and in super sensitivity, it becomes more sensitive. First, let's see desensitization. In this, initially with strong or prolonged stimulation,
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the response reaches a high level. But over seconds to minutes, the response decreases in spite of the presence of an agonist. This is called desensitization. This can happen by multiple mechanisms. One is the impaired coupling of the receptor to the transducer mechanism. For example on prolonged activation, some G-protein-coupled receptors are phosphorylated by enzymes called GPCR kinases. This diminishes the ability of the receptor to initiate the response.
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Upon the removal of the agonist, a different set of enzymes called phosphatases causes de-phosphorylation. This restores the sensitivity and allows the receptor to respond upon the next encounter with an agonist. Another mechanism is the endocytosis of receptors. In this, the receptors on the cell membrane, are taken inside the cell by the process of endocytosis. So the drug cannot access the receptor, and therefore cannot act on it. In endocytosis
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and decoupling, the refractoriness develops and fades quickly over seconds to minutes. Apart from this, desensitization can occur by receptor downregulation also. This happens by endocytosis of receptors followed by their destruction, and reduced synthesis. So again the number of receptors available for the drug decreases. Along with receptors, the second messengers and target proteins may also be decreased. In contrast to previous mechanisms
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(which are quick) Downregulation takes weeks or months to develop. Receptor desensitization is a self-defense mechanism of the cell, to protect itself from excessive stimulation. So this is how desensitization occurs. Next is super sensitivity or upregulation. We saw that desensitization occurs in response to excessive agonists. In contrast to this, super sensitivity occurs due to excessive antagonists. As we have seen earlier, the antagonist has no
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activity of its own. Moreover, it prevents the activity of agonists also. So under the influence of an antagonist, the receptors stay inactive. If such a situation persists for a long time, cells become super sensitive. This happens by increasing the number of receptors. The mechanism behind this is exocytosis of stored receptors and also increased synthesis. This is also called upregulation. There is an upregulation of second messengers too. So this is how super
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sensitivity develops. The super sensitivity can sometimes create a trouble called withdrawal reaction. So what happens is: that if you continue to give an antagonist after super sensitivity, most of the extra receptors also stay inactive under its influence. But if you suddenly stop giving the drug, the agonist will now have a huge number of receptors to work on. And their activity will cause a sudden rise in whatever activity the cell normally performs.
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Such types of reactions (after the withdrawal of drugs) are called withdrawal reactions. For example, prolonged use of β blockers in angina patients causes super sensitivity of β receptors. If β blockers are abruptly withdrawn in such patients, there will be a sudden increase in the activity of natural agonist noradrenaline. The resultant increase in heart activity can even precipitate a heart attack. So this is all that drugs can do with receptors.
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That completes all the major targets for the drugs. So as I told you in the beginning, the most common targets for the drugs are functional proteins. But we also have other types of biomolecules in our body. And some drugs target them to produce their effect. For example, vincristine binds with tubulin, which is a STRUCTURAL protein. This binding in turn prevents cell division during mitosis. Busulfan binds with DNA and interferes with the
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replication. Thus Drugs may target biomolecules other than functional proteins as well. Finally, we have actions purely by physical or chemical means. In simple words, here the immediate action of the drug includes pure physics or chemistry, rather than biology. Of course, biology comes in eventually, but the direct action is more like a physical or chemical process. Let's see some examples.
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The first is neutralization. For example neutralization of gastric acid with antacids. This is useful for acid-peptic diseases. The second is chelation. In this, a chelating agent traps heavy metal and forms water-soluble complexes. These complexes are easily excreted in urine.
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This is useful in poisoning. For example chelation of calcium by EDTA. Third is sequestration. For example, cholestyramine sequesters bile acids in the intestine. This increases their excretion and helps reduce cholesterol levels. Next is osmosis. For example, mannitol holds the water in the lumen of the renal tubule by osmotic pressure. This helps increase urine output. Next is adsorption. For example, activated charcoal adsorbs many poisons. Obviously, this would be helpful in
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poisoning. Next, action by physical mass. Yes, we also have things that work just by being present! For example use of ispaghula as laxative. Very presence of food material in the intestine triggers peristaltic movement. So ispaghula by being present in the intestine, increases peristaltic movement. Next is lubrication. For example, liquid paraffin lubricates the content of the intestine. This makes passing stool easy, which is helpful in constipation. Next
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is the absorption of UV rays. For example, para-aminobenzoic acid absorbs UV rays and protects the skin from the damaging effects of sunlight. Last in our list we have radioactivity. For example, iodine 131 emits radio particles that destroy thyroid tissue. This is useful in hyperthyroidism. So these are the mechanisms where the drug acts by chemical or physical means rather than directly interfering with biological processes.
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So this completes everything we wanted to see in this lecture. Now let's have a quick summary of what we have studied in this lecture. Pharmacodynamics is the study of what a drug does to the body. In this, we learn how the drugs produce their effects, what kind of effects do they produce, how much of an effect is produced, and how the effects are modified. The term effect refers to the type of response produced by the drug. And the term action refers
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to how the effect is produced. So the action comes before the effect. The same effect may be produced by multiple actions. So knowing only about the effect is not sufficient. We need to know the exact action as well. The most common targets for the drugs are functional proteins like enzymes, transport proteins, and receptors. But apart from them, they may act on other biomolecules as well. And some agents act by purely physical or chemical means. Enzyme stimulation by a truly
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foreign substance is very rare. But inhibition is very common. In competitive inhibition, the drug competes with the substrate for the same catalytic site. If the bond is weak, the inhibition can be reversed by increasing the concentration of substrate. But if the bond is a strong covalent bond, it cannot be reversed. In noncompetitive inhibition, the drug binds at a different site. Coming to the receptors, the ability of a drug to bind with a receptor is called affinity. And
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ability to trigger a response is called intrinsic activity. Agonist activates receptors to the maximum level. Partial agonist does it partially. antagonist does not cause any change. And inverse agonist stops constitutively active receptors. If the binding site on the receptor is the same, they all prevent the activity of each other. Overstimulation of receptors can cause desensitization. And prolonged inactivity can cause super sensitivity.
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The main description of transport proteins, other biomolecules, and action by physical and chemical means was already like a summary. So I won't repeat the same in summary again. You can re-watch that part of the video if you want. This completes the lecture, but only for first-time learners. First-time learners can leave the video because extra detail can confuse you at present. But for those who are revising, I have so many bonus points to share with you. First, we will
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cover the bonus points related to receptors. Here I want to introduce you to a few interesting terms regarding receptors. First spare receptors. We have seen that receptors activate the transducer pathways inside the cell, and thereby initiate the response. Now it seems that to produce maximum response, ALL the receptors must get activated, doesn't it? But this is not always true. With some
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receptor types, activation of only a FEW receptors can initiate the maximum response. In such cases, the extra receptors are called spare receptors. Now you might be thinking why do the cells waste resources in synthesizing extra receptors? The answer is, that extra receptors reduce the need for a high quantity of first messenger. Let me explain. Imagine the receiver cell needs two active receptors to respond fully. And it has just that many receptors on the surface.
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In such a case, if the sender cell secretes the messenger in small quantities, there will be a very slim chance that the messenger will contact the receptor. So the communication will fail. For effective communication, the sender cell will need to secrete the messenger in large quantities. And that means the sender cell will need to synthesize it in large quantities. That may not be economical as a whole for the body. But if the receiver cell keeps a high number of receptors,
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a low concentration of the messenger would do the job. So the sender does not need to secrete large quantities. And this can be more economical as a whole. An example of spare receptors is insulin receptors. 90% of insulin receptors on the cells are spare. However please also note that not all the receptor types have spare receptors. So this was about spare receptors. The next term is silent receptors. So we have seen that when a drug binds to a receptor,
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it activates it and initiates some response. But there are sites in the body where drugs can BIND… but it does not initiate any kind of response. There is only silence. For example plasma proteins. Such sites are called silent receptors, non-specific binding sites, or inert binding sites. So this was about SILENT receptors. Next, we have three related terms. We have seen that hormones and neurotransmitters in our body, relay their message to receptors. Receptors
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for such endogenous messengers are called physiological receptors. Usually, the drugs also act on the same receptors. But apart from them, there are some receptors in the body where only drugs act. We don't know the physiological ligands for such receptors yet. Such receptors are called drug receptors. For example benzodiazepine receptor, sulfonylurea receptor, etc. We don't know the physiological ligands for these receptors yet. And finally, we also have receptors for whom
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we don't know ANY ligand. Neither endogenous nor exogenous. Such receptors, whose ligands are unknown, are called orphan receptors. So these were a few terms related to receptors. Next, I want to talk about the TWO-STATE receptor model. It explains how receptors WORK. According to this theory, receptors exist in two interchangeable states. Active and inactive. Usually in the absence of any ligand, the equilibrium is more toward the
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inactive state. So there is no activity. Agonist preferentially binds with the active state of the receptor and shifts the equilibrium to active side. So the activity increases. The antagonist binds to both the conformation. So it does not affect the equilibrium. That is it keeps the normal shift towards the inactive state as it is. So there is no increase in receptor activity. They also prevent the agonist from binding to the active state. So the action of
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the agonist is also prevented. Now, our tap analogy is very close to it, but it's not an exact representation of this model. I think for most of the learners, this much detail is not only unnecessary but also confusing. So I used the tap analogy in the main discussion to keep it simple, and explained more detail only as a bonus point. Next, remember we talked about receptor regulation? It doesn't happen only under the influence of drugs. They occur in physiological
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and pathological conditions too. For example, during the third trimester of pregnancy, the number of oxytocin receptors in the uterus is increased under the influence of estrogen. And after denervation, muscle cells become super sensitive due to the prolonged absence of agonists. So these were the bonus points related to receptors. Now to the enzymes. During the discussion of enzymes, I told you that enzyme stimulation is very rare,
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remember? However, there are a few situations where we can see an increase in enzyme activity. First is by natural biomolecules. For example, pyridoxine is a natural cofactor for enzyme decarboxylase. So in the pyridoxine deficiency, the activity of decarboxylase enzyme decreases. If we administer pyridoxine in such cases, the activity of decarboxylase increases and comes back to normal. Apart from this, a drug may stimulate enzymes indirectly. For example, dobutamine
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stimulates β1 receptors. This leads to increased cAMP, which in turn stimulates the activity of protein kinase A. Thus here, dobutamine is increasing the activity of enzyme protein kinase A indirectly. Yet another situation (where we see an increase in enzyme activity by the drug) is during enzyme induction. This is basically an increased synthesis of enzymes. Some drugs (for example rifampin) increase the synthesis of microsomal enzymes. Thus their activity is
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increased. So these are a few situations where we see an INCREASE in enzyme activity by a drug. Regarding enzyme inhibition also I kept one point secret. And that is apart from competitive and noncompetitive inhibition, denaturation of the enzyme also makes it inactive. You have learned about the structure of proteins and denaturation in biochemistry. For an enzyme to work properly, it must have a proper structure. But some agents destroy that structure. For example heavy metal
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salts, strong acids, alkalis, formaldehyde, phenol, etc. In the presence of these substances, the enzyme loses its tertiary structure and loses its activity. However, the problem with this is that it is not selective. That is, these substances destroy all the enzymes that they come in contact with. But in clinical practice, we don't want that. We want to target specific enzymes only. And that is not possible in this type of inhibition. So it has a limited
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medicinal value. What's more important for clinical practice is selective inhibition, as seen with competitive and noncompetitive inhibition. So this was about denaturation. In one more mechanism, drugs don't exactly inhibit the enzymes but rather keep them busy in useless activity. Let me explain. We know that normally the enzymes work on some substrate and produce some specific product. That product in turn serves some important function. Now some
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drugs work as a substrate for some enzymes. They undergo the biochemical reaction in the same way as normal substrates do. But the product produced is nonfunctional. So it does not serve any purpose. This way the drug keeps the enzymes engaged in purposeless activity. For example in some bacteria, the enzyme folate-synthase converts para-amino-benzoic acid to dihydrofolic acid. The dihydorfolic acid in turn plays some important role in them. But a drug called sulfonamide,
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behaves as a FAKE para-amino-benzoic-acid. So enzyme acts on it, but the product is a defective folic acid. This defective folic acid does not serve any purpose. So the normal metabolic activity of the bacteria is impaired. Thus some drugs fool the enzymes. Please note how it is different from genuine inhibition. An inhibitor stops the activity of the enzyme. So no product is produced. But here the activity has not stopped. Rather, useless products are produced
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during the activity. So this is the difference. This completes all the bonus points. With this, we have found the detailed answer of How the drugs produce their action in the body? In next lecture, we will talk about what effects are produced as a result of these actions.
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If you liked it please share it with your friends and colleagues too. And don't forget to visit the website. Thanks for watching, see you in the next lecture.
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