Second lecture 29/9/2008

By the end of this lecture you have to:
* Understand why there is a difference between the in vivo and in vitro results of biological activity.
* Understand that variation in biological activity is not always a matter of drug-receptor affinity or intrinsic activity.
* Know that bioavailability of the drug is a key factor in determining the therapeutic efficacy of the drug.
* Correlate between drug solubility, pKa, logP and its pharmacokinetic profile (site of action, duration of action,...etc.).
* Know how to, structurally, modify a drug so as to change its physicochemical properties and hence change or improve its therapeutic use.

Here are some T/F questions from previous exams:
1- The physicochemical properties of I.V. general anesthetics are important in that they affect ADME of the drug.
2- Micronized griseofulvin has better dissolution and absorption than regular griseofulvin.
3- High molecular weight dugs are absorbed by convective absorption.
4- Barbital and secobarbital have similar absorption rates since they have similar pKa values.
5- It is always required that drugs have high partition coefficient to ensure better absorption from GIT.
6- Neutral fat, unlike plasma protein, is regarded as a storage site for hydrophobic drugs.

Answers will be:
1- (F) because IV drugs are not absorbed through membrane barriers.
2- (T)
3- (F) it is only low MW drugs that are absorbed by convective absorption.
4- (F) because they differ in their part.coeff.
5- (F) because some drugs are required to act locally in the GIT eg. succinyl sulfathiazole.
6- (T) storage in neutral fat depends on the lipophilicity of the drug but plasma protein binding depends on the structure of the drug not lipophilicity.

First lecture 22/9/2008

Click the following link about the discovery of Captopril
http://en.wikipedia.org/wiki/Captopril

Here are some examples of true/false questions from previous exams:
1- Mechanism-based drug design is a rationale drug design.
2- 5-FU inhibits DNA biosynthesis in cancer cells because of its structure analogy to deoxyguanosine.
3- Mevalonic acid is the natural substrate of HMG-CoA reductase enzyme in cholesterol biosynthesis.
4- The mechanism of the antidiabetic effect of rosiglitasone is not a receptor mediated process.
5- The molecular lead of captopril is the nonapeptide ‘teprotide’.
6- Although, cimetidine is not structurally related to histamine, yet it is a potent H2-receptor antagonist.
The answers are : T, F, F, F, T, F.

After studying the lecture you should:
* Be able to differentiate between traditional and rationale drug design.
* Differentiate between pharmacological action of a drug and its therapeutic application.
*Notice the mimicry (resemblence) between natural metabolites or endogenous components and their antagonists.
*Be able to identify the biological targets (enzyme or receptor) for each drug.
*Know how to modify lead compounds to improve binding of the drug molecule to its target protein. (Example of Captopril,..).
*Relate between the physicochemical properties of a drug (E.g. polymixin) and its mechanism of action.

Welcome to 4th year pharmacy students

Welcome to fourth year pharmacy students. I wish you a happy fruitful academic year. Your are first-time students of pharmaceutical and medicinal chemistry. This is an interesting chemistry science that deals with the study of the chemical structures of drugs. The importance of this study lies in that the relation between structure and biological activity is intimate; so that you can predict the activity of an unknown compound just from its chemistry. Also, you can know which structure will be more active than the other. In addition, you can explain many pharmacokinetic and pharmacodynamic properties based on the chemical stucture of the compound. You will also study the principles of drug design and discovery in traditional and in computer-assissted processes. Another important topic in your study includes the understanding and pathways of drug metabolism. Moreover, you will study the methods of synthesis and analysis of different drugs.

Regarding my course, we will enjoy together the study of mechanism-based drug design, computer-aided drug design, physicochemical properties of drugs in relation to their action, and quantitative structure-activity relationships.

You are invited to visit my blog at the end of each week during the course of my lectures as you can find helpful things that will assisst your knowledge and understanding of the course I will teach to you.

Best wishes.