What Challenges? How do we prepare students for a career in Pharmacology? How do we combine elements of “traditional pharmacology with modern concepts and discoveries? Are students getting a solid foundation of the basics? How do we stay current as instructors and teachers? How do we determine if we are doing a good job?

Pharmacology at UNC Basic Structure/ Core Courses Fall-1st Year PHCO 201- Introduction to Molecular Pharmacology PHCO 331- Pharmacology Seminar Spring-1st Year PHCO 202- Principles of Pharmacology Fall-2nd Year PHCO 220- Biostatistics PHCO 330-Current Topics in Pharmacology Spring-2nd Year PHCO 330- Current Topics in Pharmacology PHCO -Electives/ Special Topics

Pharmacology at UNC Some General Things We Do: Computers All 1st year graduate students receive new lap top computers with “wire-less” internet capabilities. Students can access WEB information during class, useful for teaching Bioinformatics, structural anaylsis and biostatistics. Courses Courses organized into “blocks” with Block-heads organizing the block content, instructors, exams etc. Integrate required aspects of Physiology, Biochemistry and Genetics as needed to prepare students for Pharmacology.

The “Core” Courses PHCO 201/202 PHCO credit hours Course Objectives: To introduce basic and essential concepts of Pharmacology to prepare students for detailed mechanism of drug action covered in PHCO 202.

Introduction to Bioinformatics I “Machine-readable biological information” Dr. David P. Siderovski Department of Pharmacology Sept. 1st, 2004

The Entrez System

Use your computer’s clipboard: ^C & ^V (or command-C & command-V)

p CYTOGENETIC MAP POSITION: q Associating Disease with Genomic DNA: Karyotype analyses Tell me everything that’s ever been found here…

The Future of Chemotherapy Patient Profiling?

Proteins Chemical library HTS results SAR analyses Combi-chem synthesis Assign pharmacophore ADME / Tox workup In vitro ADME / Tox Don’t delay triage of compounds that aren’t “drug-like”

HTS for Absorption - Model membrane assay: Detect via UV spectroscopy (faster than LC/Mass Spec)

HTS for Absorption - SPR with liposome surface: Danelian, E. (2000) J. Med. Chem. 43:

Structure Databases Estrogen Receptor PDB Molecule of the Month  Protein Data Bank (PDB) with > 22,700 structures  Cambridge Structural Database (CSD) with > 250,000 structures  Text or Sequence Similarity

Structural Neighbors Databases CATH, SCOP, CE, VAST, FSSP Horse liver alcohol dehydrogenase Silverleaf whitefly ketose reductase Gprotein beta subunit

PHCO credit hours Course objectives: To teach classical mechanisms of drug action combined with current research discoveries and directions. Course parallels the MED PHARM course taught to Med students. The difference is the amount of mechanism and current research.

PHCO 202 Principles of Pharmacology Example: My lecture on anti-hypertensive agents 1st-half- classical approaches to treat hypertension Mechanism of action of different drug classes Standard view of hypertension treatment 2nd- half- current research in anti-hypertensive Dogma challenging research and re-evaluation of Status-quo. Mechanism of action of novel therapeutics

Antihypertensive Drugs Drugs Classes 1. Angiotensive converting enzyme inhibitors- Enalapril, Captopril 2. Angiotensive receptor antagonists 3. Aldosterone antagonists 4. Diuretics 5. Ganglionic blockers 6.  receptor antagonists 7.  receptor antagonists 8. Direct vasodilators 9.  2 receptor agonists in CNS 10. Noradrenergic neuron blockers

Renin/Ang System

PHCO 202 Principles of Pharmacology Incorporation of Current Research Topics Med line searches- updated analysis on drug successes or failures. Assign a manuscript to read: often a current review or research paper to prepare students for specific topics. The shift in the "paradigm" of the pharmacology of hypertension. Flordellis CS, Goumenos D, Kourounis G, Tsementzis SA, Paris H, Vlachojiannis J. Curr Top Med Chem. 2004;4(4): Dual ACE and neutral endopeptidase inhibitors: novel therapy for patients with cardiovascular disorders. Tabrizchi R.. Drugs. 2003;63(20):

Exams Still test the basics! Multiple choice and problem solving Questions Course evaluations collected- feedback sought. Implementing “small Group” strategies to teach key concepts

Electives- “Filling in the Gaps” Some examples: 1.Gene Therapy: Medicine for the 21st Century-Samulski 2.Discovery Biology and Pharmacogenomics- Siderovski, Sondek 3.Protein Kinases as Targets for Novel Pharmacological Inhibitors- Graves, Johnson. 4.Ras Superfamily and Signal Transduction- Der, Cox 5.Molecular Pharmacology of Cancer-Kole