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1 number 10 Done by Mohammad Shatnawi Corrected by Doctor Alia Shatnawi
2 Agonist: a drug or a molecule that binds to a receptor and causes the activation of the receptor, exp: adrenaline is an agonist for the adrenergic receptor. -for a drug to be able to give a response it needs to bind to its receptor and cause a conformational change. -to see how effective a drug is we devised experiments that link the concentration of a drug in a certain tissue and the seen response to that drug. -for example this is a muscle tissue which has 10 mascarinic receptors on it, and we wanted to measure the effect of a drug on this tissue, so we start with low concentrations of the agonist then we start increasing it. So the action of the tissue is going to increase until we reach a certain concentration ( in the picture above it's c=20). When the action of the tissue doesn t increase alot by increasing the concentration of the drug this is called-- Emax --and it happens because all of the drug s receptors are saturated with the drug so increasing the concentration won't increase the action of the tissue.
3 Determinants of Emax: 1-number of receptors: the more you increase the number of receptors the more Emax (efficacy) is going to increase, because more drug molecules are allowed to bind. 2-the concentration of the drug. 3-intrinsic ability: ability to fully or partially activate and produce a response. EC50:the concentration of a drug needed to reach 50% of the maximum drug s effect. The relationship between the concentration of the drug and receptor-bound drug molecules This curve helps in understanding how much affinity the drug has to its receptor, and we see that at a certain concentration the number of drug receptor complexes stops increasing; that is because all the receptors are saturated. This state is called Bmax.
4 **Bmax determines Emax of the drug but they are not the same number. ** we don't have to reach Bmax to get the full response, that is because of the activation mechanisims inside the cell. Exp: G-protein coupled recptor which has a cascaded event trait so activated receptors may give an elongated response. Spare recptors: when we have unused receptors but we reached the maximum response.(receptor is active even in the absence of an agonist) **intrinsic ability of the drug means the ability of a drug to activate receptors and cause a response. Determinants of Bmax: 1-concentration of the drug. 2-number of receptors. 3-affinity between the drug and its receptor. Kd: a term used to understand the affinity of a drug to its receptor which means: the concentration of a drug needed to reach 50% of the total drugreceptor complexes. **so if we are comparing two drugs we want to take the one with less Kd because it's more effective. **the higher the Kd the lower the affinity so it's an inverse relationship. Receptor occupancy (B/Bmax)=(D)/(D+Kd) B:bound drug. Bmax: total number of receptors. D: drug concentration.
5 Kd:discussed earlier -from this equation we know that the efficiency of the drug depends on the drug s concentration and its affinity. Determinants of drug effectiveness: 1-Kd 2-number of bound receptors. 3-concentration of the drug. Potency: the concentration of a drug that is going to give a particular effect. EC50: concentration of the drug which produces 50% of the maximum effect & determines the potency. ***the lower the EC50 the more potent the drug is (which is better). ***all of these terms are used to compare drugs. ***if we are given a curve comparing the drug dose and the receptor binding and we were given the KDs of those drugs we can conclude the potency of these drugs. **** we can't say Kd is the same as EC50; they may both give an indication of potency but they are not the same number(they only indicate each other). ****so if a drug has more affinity to its receptor we might say it has lower Kd and EC50 and higher potency.
6 -we can compare two drugs by all of these terms for example: We have two pain killers X and Y. drug X gives 100% blockage of pain while drug Y gives 50% blockage so we say drug X has more efficacy than drug Y, however X and Y have the same efficacy since they have the same Emax.
7 Efficacy: the maximum effect of a drug ( Emax). -we don't have to reach Emax to treat someone. -efficacy depends on: 1-maximum number of drug-receptor complexes response(intrinsic ability) 2-how much the drug is able to give me a Exp: aspirine and morphine are both painkillers but have different efficacy levels, morphine has higher efficacy than aspirine (no matter how much the concentration of aspirine is it will never reach the Emax of morphine.) We don't use morphine all the time because while it would kill the pain, at the same time it has serious side effects, that is why we commonly use it in surgery. Important points: 1-we want to know how to calculate EC50 and Emax and what they indicate.
8 2-the smaller the EC50 the greater the potency. 3- efficacy is determined by the hight of the log curve. **** a drug might be more efficient than another but has a higher EC50 **** ****the type of drug receptor also effects efficacy ***** --if we wanted to compare the potency of two drugs we do it in relation to the same receptor, exp: (aspirine,paracetamol) which both work on cyclooxygenase. The effect of a drug at a particular dose is calculated by this equation: E: the effect at a particular dose. Emax:the maximum effect of a drug. C: concentration of the drug. EC50: discussed earlier. E=(Emax*C)/(C+EC50) Spare receptors:when we get the maximum response whithout reaching Bmax because we reached saturation in the cell s signalling mechanisims. ***we don't use a drug rather than another based on its potency or efficacy but on the patient s condition. *** a question that the Dr said is important : which drug is better? A- The one with higher efficacy. B- The one with higher potency. C- Non of the above. Answer: C EC50 is potency when the effect reaches 50%, so potency is the concentration at any effect percent, but EC50 is the concentration at 50% of the effect
9 this video is very useful A life led by your mind.. is much better than a life led by the words of people. Thank you.
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