Medicinal Chemistry and Toxicology

Preliminary syllabus for first two weeks:

Update for September 14: Room numbers have been added to the weekly schedule. Note that the Monday start time has been moved to 10 AM!
Update for August 13:
The daily schedule listed below is correct. Some texts have been chosen:
Foye's Principles of Medicinal Chemistry 5th ed.,  by Williams, Lemke, & Foye, published by Lippincott Williams and Wilkens 2002   ISBN: 0683307371
Studying a Study and Testing a Test: How to Read the Medical Evidence 5th ed. by Richard Riegelman published by Lippincott Williams and Wilkens 2004   ISBN: 0781745764
The Discovery of Insulin by Michael Bliss University Of Chicago Press; Reprint edition (October 15, 1984)
ISBN: 0226058980  Any printing of this should be fine This will be the first seminar book
Testosterone Dreams by John Hoberman University of California Press 2005 ISBN: 0520221516

On you bookshelf you should also have a fairly current organic chem text and a biochemistry -cell biology reference.

We will probably also do 1-2 of the recent critiques of the drug industry. I am still undecided and am reading through the following three: Powerful Medicines by Jerry Alvorn, The Truth About Drug Companies by Marica Angell, and Overdose by Jay Cohen. Each is slightly different but there is also a lot of overlap. I'll let you know when I decide.

INFORMATION AS OF MAY 23 2005
Medicinal Chemistry and Toxicology: Information for Academic Fair May 11, 2005
Fall 2005
Faculty: James Neitzel, Lab I room 1022, 867-6463, neitzelj@evergreen.edu

Enrollment options: 16 or 12 credits. (The 16 credit option includes a laboratory component. The 12 credit option does not.)
Course Equivalencies likely given in medicinal chemistry, toxicology, and statistics
Required Student Preparation: Jr/Sr status, completion of at least 2 quarters organic chemistry, 2 quarters biochemistry, some molecular or cell biology useful.
Texts: Have not yet been finalized. Will include medicinal chem text, biostatistics, and possibly a toxicology text. You should have access organic chemistry and biochemistry texts.

Program summary:
This program will examine the interactions between chemicals and animals, particularly focusing on events at the cellular and molecular level. A major emphasis will be on common cellular signaling pathways altered by drug action. In addition, the importance of structure-function relationships in examining the biological activity of chemicals will be a common theme.  Mathematical models for the absorption, distribution, and elimination of pharmaceuticals will be covered.
Toxic reactions to drugs and other chemicals will be examined, and the biochemical mechanisms for the transformation and elimination of foreign compounds will be covered. Current trends in research that are allowing rapid drug discovery and testing will be included. The statistical methods used to examine biomedical hypotheses will be taught to assist in the understanding of primary research papers in this field. Finally, historical case studies on the discovery, development and regulation of selected drugs will be studied. Program time will include lectures, seminars, laboratories, and student presentations. This is an upper division program assuming students have completed organic chemistry and biochemistry

Proposed Weekly Schedule:
Monday: 10-12 Lecture/Workshop Seminar 2 E2107
Monday: 1-3 Computer Lab Lab 2 1223 A
Tuesday: 10-12 Seminar; 1-3 Workshop Lab 1, 1040
Wednesday: 9-12 Lecture/Workshop Lab 1, 1040
Thursday: off
Friday: 9-12, 1-4: Laboratory Lab 1, 2040/2046 (In addition, students will need to use other time for instrument instruction.) Also, at least one all-program Friday field trip (medicinal herb garden, biotech company.)
 
Proposed topics to be covered:
Effects of physical properties of chemicals (solubility, partition coefficients, acid/base) on their biological effects.
Structure-activity relationships (configuration, conformation, polarity)
Adsorption, distribution, metabolism and excretion of xenobiotic compounds
Mechanisms for toxicity (acute, carcinogenesis, developmental, genetic)
Pharmacokinetics
Endocrinology and physiology as needed
Historical origins and key experiments in the development of ideas about drugs and toxins
Statistical methods commonly used in biomedical research, as used in examples drawn from primary literature.
Current topics in drug development and toxicology, production processes, economic/political linkages, regulations.

Examples of planned class case studies:
Anesthesia
Pain control (opiates, NSAIDS, selective COX inhibitors)
Adrenergic/cholinergic receptors and autonomic nervous system
Antibiotics
Antiviral and antiparasitic compounds
Steroid hormones, oral contraception, estrogen mimics
Cardiac glycosides
Fungal toxins
Insecticides
Validation and interpretation of drug screen results.

Each student will also research and present an individual case study on a particular compound.

What will be done in the lab portion?
1. More advanced use of GC-MS. New topics would include sample prep and cleanup from complex matrices, (esp. solid phase microextraction), derivatization, quantitative methods, selective ion mode.
2. Measurement of drug affinity to a serum protein.
3. Conversion of organic compounds by an enzyme system (cytochrome P450 oxidation or monoamine oxidase) commonly seen in biotransformation processes
4. Simple toxicology model system (brine shrimp/bacteria) or Ames test for mutagenesis.


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