Medicinal Chemistry: The Basis of Drug Discovery

Video 1 -a challenge of oral drugs is maintaining a constant concentration in the body of drug -keep the conc. above the minimum effected dose -and below max tolerated dose -these windows make the therapeutic window -the graph is a repetition based on when you take your doses -when taking oral doses, the concentration ocellates, but should never go about the max tolerated dose or below the effective dose -make changes to dosing by frequency or by size of dose -this can make it less convenient for the patient Video 2 -an exciting lecture -clearance=.693/t0.5*volume of distribution -clearance is mL/min/Kg -vd is L/kg -half-life is the x in the y=mx+b -8 hour half life is the goal -to get the ideal half life of 8, you can change the Vd and CL -lipophilic drugs tend to want to leave bloodstream more and boosts Vd Video 3 -metabolism is actually two different ideas -one is chatabolism -the other is anabolism -when talking about metabolism on drugs, drugs are not bro...

My reaction to this new learning was some interest but more impressed as to the complexity of every single aspect of a drug, and how its modeled. Every possible thing that can be thought up must be considered, as you are dealing with human lives. The models made for how the drug moves throughout the plasma are very strange, yet important for dosing. considering dosing is one of the most important parts of medicine. Making sure you give enough active ingredient where it goes into the tissues and effects the proteins is important so it works, yet you also don't want to overdose. My question is about the elimination phase. does medicine get used up, or is the only way it leaves your body through metabolism or as waste?

There are two main models when trying to interpret data based on concentration of drug in the bloods plasma. Firstly, the one compartment model. This model treats the whole body as one compartment. the central compartment is some volume of plasma, depending on weight. then when the drug is injected in, the concentration is at max, and then as the body begins to remove the medicine through the kidneys or as waste or through general metabolism. The other model is the two compartment model. This has the circulatory system as the central compartment, and the rest of the places the drug could go in a body as the peripheral compartment. This includes muscles or tissues where the drug does what its supposed to. The different ways to model the circulatory system and concentration of drug in plasma shows the complexity of the effects of drugs on the body and how to control them. The dosage when using an IV can be changed in many ways, whether its more per minute or for longer amount of time. ...

Video 1 -volume of distribution is the amount of of plasma needed to contain the drug in the body -elimination constant determines half life -one compartment model is when using an IV bolus the drug resides in the central compartment  -central compartment defines some volume -initial concentration of plasma is a hypothetical number -Do is patient dose -with this, one wants to find the volume of plasma and a mass of the drug to find concentration  -volume using the equation Vd=do/cpo  -this is how to find size of central compartment -vol is more then 2.7L, bc 2.7 L is the amount of plasma a 70kg patient has -vol of distribution is a hypothetical number -it must be more so that the drug isn’t just in the bloodstream it’s going to the tissue  Video 2 -two compartment model -IV bolus puts drug into central compartment  -drug can leave the central comparment and go to a different compartment called the peripheral compartment -the ...

This week the videos were about clearance and pharmacokinetics which was pretty interesting. i think I'm realizing that I prefer biology that doesn't focus specifically on the molecules but is more anatomy based. This week was a lot more interesting to me as it focused on chemistry and blood and kidneys. My question this week is how long do drugs last in the body? What factors contribute to that rate? and is that why when taking medicine do you have different pills per day and time in between them?

An important part of how a medicine effects a patient is how long it lasts in the bloodstream. The study of the concentration of medicine in the plasma of the blood over time is called pharmakokinetics. This involves the kidneys filtering out the blood, similar to a public swimming pool. the kidneys take some of the blood, filtering out the impurities (like the drug) and then putting the clean blood back into the bloodstream. The rate that this can be done is modeled as an exponential decay graph. With any graph showing exponential decay, there is a half life that depends on the initial concentration of the drug, and the rate at which the kidneys can work. this rate is called clearance. Clearance is important to medical researchers because of dosing, as well as the efficacy of the drug. when learning about the molecule that has promise, you should be thorough and look at every single part of the drug. This includes how long it stays in the bloodstream and how it is removed.

 Video 1 -pharmacokinetics is study of relationship of plasma concentration over time -ties into ADME from last week -Plasma concentration is mass/vol -IV bolus is is a drug that is directly injected into the bloodstream of a patient. -as the drug is distributed through the body, the concentration goes down at a curve of exponential decay -Cp 0 is a hypothetical number, because the blood will already begin to be distributed before the blood has completely circulated the body -equation of graph is usually shown as Cp=(Cp0)(e^(-kel)(t) -ideal relationship for graph -kel is elimination rate constant -units of 1/time -slope depends on concentration of drug itself -elimination rate constant determines the half life of the drug -half-life is (ln2)/(kel) -to get it linear, it can be shown as ln(Cp)=-kel•t+ln(Cp0) -kel=CL/Vd -CL is clearance, which is volume of blood that contains a drug that is cleared per unit of time -Vd is apparent volume of distribution -Vd is a vo...

With every chapter it seems that there are more and more things that play into whether a drug will be safe and effective. Whether its which molecule or how the body will respond or if your targets is important to the disease. I am becoming more and more impressed with researchers and how they are able to create successful drugs and I also am gaining respect for these researchers. My question is about the methods that they test blood. Is this done in the first stage of clinical trials? or can it be done with blood taken out of the body?

An important part of medicine and targeting the desired protein is how the drug gets from outside the body to the specific site. This can be done in many ways, mainly orally or through an I.V. Either way, the drug must pass through the blood. "Whole blood" is regular blood that is made by the body. This contains 45% by volume red blood cells, 1% white blood cells and platelets, and 54% plasma. Plasma contains mostly water, with some proteins and hormones the body produces. when designing a molecule, one must consider how the molecules in the blood could alter the drug. another thing to consider is how the drug will do when the kidneys try to filter it out of the blood, or how the liver will try to destroy it if it enters the body orally. There are countless amounts of things one must consider when making a drug, at every step there are many things that can effect how your drug and make it ineffective or even toxic. even if you have a promising molecule, it may not respond w...

Video 1 -blood is the medium of which a drug moves throughout body -blood is taken to see drug concentration -not the tissue where the drug acts, because that is usually fragile -it’s easier to take blood then anything else -whole blood is water, cells, electrolytes, horomones, maybe some sugars, and maybe drugs -45% of volume of blood is red blood cells -1% of blood is white blood cells and platelets -water contains the proteins and drugs and horomones -54% of blood is water aka plasma -while blood is 8% by weight protein -the protein in water makes challenges for drug discovery -it affects how the drug is moved around the body, and how it binds to its intended target -to weed through your thousands of hits from the assay stage of discovery, you can see how well your molecules work when plasma is present -you don’t want your drug to bind to blood proteins Video 2 -ADME is for absorption, distribution, metabolism, and excretion -absorption-from point of...

My reaction to this weeks learning was that of confusion. the class is becoming very high level, and it is increasingly becoming harder to have a firm grasp on the content of the class.  The class is meant for chemistry students however should be for Biochemistry students or for Biology students. The material is still understandable however is becoming more the parts of  biology I was not very good at. The question I have is how much of medicine is analyzing with the graphs and equations and how much is testing and seeing which ones is best?

After talking about proteins and enzymes, one must also talk about receptors. A receptors main job is to accept and link to ions or other molecules and either transport them or transmit a signal to the cell to create a response. There are many different receptors that call fall into two categories. The first are the receptors that are on the outside of a cell. These are typically what are targeted by medicine as it is much easier to make contact with those receptors then the other kind, which are those that reside inside the cell. Receptors work in a similar way to enzymes with inhibiting molecules, and this is what medicines attempt to do in the body. This and the few chapters before it are all tied to picking a target for the cell, and designing a molecule that will stop the protein from doing its job. The idea is that the receptor will not be able to perform its job that it was created to do and halts the progress a disease is trying to make in the body.receptors accept...

Week 5 video 1 -Receptors are proteins that bind to a small molecule, like an enzyme -receptors act as a molecular switch, binding to molecules call ligands   -when ligands bond to a receptor, it causes a change in the protein which makes a cellular cascade and then a response in the cell -ligands can be in two categories. Either endogenous or exogenous -endogenous are natural molecules that interact with the receptors within the body -exogenous is what is dealt with in the drug industry, which are synthetic molecules -meant to interfere with receptors to give control of cellular processes and affect the disease state -receptors fall into categories as well -the first superfamily is the ligand-gated ion channels large membrane bound proteins.   -these receptors control the flow of ions across a membrane   -this is necessary to get ions in and out of a cell, this is pretty fast -the next super family is G-protein coupled receptors which are also ...