Medicinal Chemistry: The Basis of Drug Discovery

Week 10 video 1 -phase 1 metabolic reactions specifically oxidation -sp3 hybridized carbons includes dealkylation and alcohol oxidation -sp2 hybridized carbón mostly alkenes and aromatic rings in videos mostly aromatic rings -heteroatoms (non carbon) -starting in nitrogen dealkylation oxidation -visualized as a removal of a carbon group from a nitrogen atom -used with small alkyl groups, and carry prefix nor- -same can happen on oxygen atoms, the carbon Group is removed -involves small alkyl groups and uses prefix desmethyl -alcohol oxidation is very common -primary alcohols oxidize to a carboxylic acid -secondary alcohols to a ketone -sp2 hybridization ex benzene -when nitrogen are oxidized form a n-oxide -sulfur also is very easily oxidized -forms sulfoxide which can turn to sulfones Video 2 -phase 1 covers oxidation, reduction, and hydroleses -reductions are the opposite of oxidations -ketones/aldehydes to alcohols -the ketone of warfarin is reduced to provide ...

My reaction to the learning was interest. I realized that the majority of this class has been math, which I find boring. However, learning about metabolism was very interesting. The topics i find interesting is the real chemistry and biology, not so much the math and graphs. I also learn the things that I want to learn better. The part about the graphs and the concentration limits was somewhat interesting, and the equations and calculations part was pretty boring. My question for this week is about overdosing. When someone overdoses, what is happening in their body? why does that much of a substance make your body stop functioning?

When creating a drug that will be administered orally, the window between the minimum required for a proper effect and the maximum to avoid adverse effects must be considered. When this drug is swallowed, the concentration in the plasma rises, then as metabolism begins to take effect, it decreases again. This continues for each time the drug is taken, slowly adding up until the max begins to plateau. The goal is to always be above the minimum efficacy and below the maximum amount to not feel adverse effects. Another consideration is to the half-life of the drug. The goal for the half-life is 8 hours, and changes can be made to the molecule to effect the half-life. When talking about metabolism, most people think about calories. When talking about drugs, however, it has to do with the process of getting the drug out of the body. This can be done through two phases. In phase one, the single molecule undergoes a chemical change that makes it easier for the kidneys to filter the blood. In ...

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 ...