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Mechanisms of Drug Actions

Fall 2005

Pharmacogenetic determinants of the metabolism and anti-ulcer activity of omeprazole.
Three sets of brain scans from a young adult given a placebo (top) and two different doses of methylphenidate (bottom), showing the ability of methylphenidate to block the transporter "gates" by which the brain chemical dopamine returns to its home cell after sending a pleasure signal. (Image courtesy of the Brookhaven National Laboratory.)

Course Highlights

This course features a complete set of assignments.

Course Description

This course covers the chemical and biological analysis of the metabolism and distribution of drugs, toxins and chemicals in animals and humans, and the mechanism by which they cause therapeutic and toxic responses. Metabolism and toxicity as a basis for drug development is also covered.



This course covers the chemical and biological analysis of the metabolism and distribution of drugs, toxins and chemicals in animals and humans, and the mechanism by which they cause therapeutic and toxic responses. Metabolism and toxicity as a basis for drug development, metabolic polymorphisms and biomarkers of exposure are also covered.



 Golan, David E., Editor-in-chief; Armen H. Tashjian, Deputy Editor; Ehrin J. Armstrong, et al., eds. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. Baltimore, MD: Lippincott Williams & Wilkins, 2004. ISBN: 9780781746786.


 Klaassen, Curtis D., ed. Casarett and Doull's Toxicology: The Basic Science of Poisons. 6th ed. New York, NY: McGraw-Hill Medical Pub Division, 2001. ISBN: 9780071347211.

The Biochemistry you need to know or learn for this course

  • Structures and Functional Groups
    • Carboxylic Acids
    • Aldehydes
    • Ketones
    • Aromatic Molecules/Heterocycles
    • Esters
    • Amides
    • Thiols (Sulfhydryls)
    • Epoxides
  • Nucleophiles/Electrophiles
  • Bonding
    • Covalent Bonds
    • Coordinate Covalent Bonds
    • Ionic Bonds
    • Hydrogen Bonding
    • Van Der Waal's Interactions
  • Reduction/Oxidation
  • Thermodynamics and Equilibria
  • Acid/Base Chemistry
  • Reaction Kinetics and Mechanisms
    • Zero-, First- and Second-Order Reaction Kinetics
    • SN1 and SN2 Nucleophilic Substitution Mechanisms
    • Michael Acceptors
  • Enzymes
    • Kinetics
    • Cofactors: NAD+/NADH; FAD/FADH; FMN; Coenzyme A/acetyl CoA; UDP-Glucuronic Acid; ATP; GTP; cAMP; cGMP; PAPS (3'-phosphoadenosine-5'-phosphosulfate); s-adenosylmethionine (SAM); Glutathione
  • Lipids
    • Membrane Structure
    • Types of Lipid: Fatty Acids (Arachadonic Acid); Triglycerides; Cholesterol; Phospholipids
  • Mitochondrial Structure and Function
  • Metabolism and ATP Generation
  • DNA Structure
    • Bases, Nucleosides, Nucleotides
    • Primary, Secondary Structure
  • Proteins/Peptides
    • Amino Acid Structure and Side Chain Chemistry
    • Peptide Bonds
    • Glutathione


There will be a recitation session offered throughout the term. Several of these sessions will consist of seminars presented by scientists from local pharmaceutical and biotechnology companies. The other sessions will be run by the TA and will entail answering questions relating to the lecture material, homework assignments, and projects and providing background help with concepts in several areas, including elements of chemistry and biochemistry.

Homework Assignments and Readings

Additional assignments will include:

  1. specific papers and book chapters;
  2. problem sets associated with the reading; and
  3. problem sets relevant to lecture material.

The homework is due as noted in the lecture schedule. There is a 20% reduction in the grade for each day the assignment is late.


There will be two quizzes during the term. All are non-comprehensive, in-class quizzes given during the regular lecture period. There is no final examination.

Team Projects

The class will be divided into groups of 3-5 students (depending on class size) to work as a team on a project to investigate a drug. The investigation will center on concepts developed during the term, with emphasis on understanding drug mechanisms and the successful development of drugs.

Grading Policy

Percentage contributions to the final grade are as follows:

Quizzes (30% each) 60%
Paper 10%
Final Team Presentation of Project 10%
Homework Assignments 10%
Class Participation 10%


PCD = Prof. Peter Dedon
SRT = Prof. Steven Tannenbaum

1 Introduction and Principles PCD  
2 Chemistry/Biochemistry Review    
3 Overview of Drug Development Guest: Dr. Robert Rubin Homework 1 due
4 Uptake/Transport/Distribution of Drugs PCD  
5 Drug Transporters Guest: Dr. Keith Hoffmaster Homework 2 due
6 Bioethics Seminar    
7 Drug Transporters (cont.) Guest: Dr. Keith Hoffmaster  
8 Introduction to Drug Metabolism SRT  
9 Liver Lecture   Project teams assigned
10 Drug Metabolism 2 SRT  
11 Drug Metabolism 3 Guest: Dr. Sean Harriman  
12 Drug Metabolism 4 Guest: Dr. Sean Harriman  
13 Quiz Review   Homework 3 due one day after Lec #13
  Quiz 1 SRT  
14 Oxygen Radicals in Drug Toxicity SRT  
15 Drug Toxicities SRT  
16 Drug Toxicities (cont.) SRT  
17 Bioethics Seminar    
18 Pharmacokinetics PCD

Project summaries due

Homework 4 due

19 Pharmacokinetics (cont.) PCD Homework 5 due
20 Receptors and Case Study - Omeprazole PCD  
21 Case Study - Omeprazole PCD  
22 Case Study - Omeprazole (cont.) PCD  
23 Case Study - Acetaminophen SRT  
24 Case Study - Acetaminophen (cont.) SRT  
25 Case Study - Statins SRT/PCD Presentation schedule ready
26 Case Study - Statins (cont.) SRT/PCD Papers due
27 Drug Industry Seminar Guest: Mark Trusheim (Massachusetts Biotech Council)  
28 Case Study - Statins (cont.) SRT/PCD  
29 Student Presentations    
30 Quiz Review    
31 Student Presentations (cont.)    
  Quiz 2   Tell A Friend