challenges of teaching pharmacology in the 21st century
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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 UNCBasic Structure/ Core CoursesFall-1st YearPHCO 201- Introduction to Molecular PharmacologyPHCO 331- Pharmacology Seminar Spring-1st YearPHCO 202- Principles of Pharmacology
Fall-2nd YearPHCO 220- BiostatisticsPHCO 330-Current Topics in Pharmacology
Spring-2nd YearPHCO 330- Current Topics in PharmacologyPHCO -Electives/ Special Topics
Pharmacology at UNC
Some General Things We Do:
ComputersAll 1st year graduate students receive new lap top computerswith “wire-less” internet capabilities. Students can access WEB information during class, useful for teaching Bioinformatics, structural anaylsis and biostatistics.
CoursesCourses 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.
PHCO 201 “Introduction to Molecular Pharmacology” Fall Semester2004Monday and Wednesdays 9:00 - 9:50 AM 1102 Mary Ellen JonesBuildingCourse Directors: JoAnn Trejo and David Siderovski
Topic Lecture hours Block LeaderI. Genes to Protein/Molecular Biology 8 SiderovskiII. Receptors/Ion Channels 5 Rosenberg
Regulation of Second Messengers 4 DohlmanIII. Principles of Drug/Receptor Interactions 6 Harden
Metabolism 4 Graves
I. Genes to Protein/Molecular BiologyW August 25 Course Introduction (Trejo/Siderovski);
Central Dogma of Genetic Information (R. Kole)M August 30 RNA as a Therapeutic Target (R. Kole)W September 1 Introduction to Bioinformatics Part I (Siderovski)M September 6 (HOLIDAY) NO CLASSW September 8 Techniques of Protein Purification/Structure Determination (Betts)M September 13 Introduction to Bioinformatics Part II (Siderovski)
(Assignment of Take-home Exam I - due Friday Sept. 24th, 5PM)W September 15 Structural Bioinformatics (Temple)M September 20 Techniques of Gene Manipulation/Macromolecular Therapeutics
(Miyamoto)W September 22 Gene Therapy (Samulski)M September 27 Take up session of EXAM I
II. Receptors/ Ion Channels and Regulation of Second MessengersW September 29 Historical Perspective (K. Harden)M October 4 GPCRs (J. Trejo)W October 6 Nuclear Receptors (K. Korach)M October 11 Ion Channels (R. Rosenberg)W October 13 RTK’s (S. Earp)M October 18 Activation and inactivation of G proteins (includes RGSproteins)
Introduction to effectors and second messengers (H. Dohlman)W October 20 Activation and inactivation of ras-family GTP binding proteins(C. Der)M October 25 Activation of PKA by cAMP, regulation of cAMP by cyclaseand
PDEs.(L. Graves)W October 27 Activation of CaM kinase and PKC and PKC by PLC, DAG, IP3,
and calcium second messengers (McCarthy/Harden)M November 1 EXAM II
III. Principles of Drug/Receptor Interactions and Drug MetabolismW November 3 Drug receptor interactions (K.Harden)M November 8 “W November 10 “M November 15 “W November 17 “
The “Core” CoursesPHCO 201/202
PHCO 201- 2 credit hours
Course Objectives:To introduce basic and essential concepts of Pharmacology to preparestudents 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’sclipboard: ^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…
www.ensembl.org
The Future of Chemotherapy Patient Profiling?The Future of Chemotherapy Patient Profiling?
Proteins
Chemical library
HTS results
SAR analyses
Combi-chem synthesis
Assign pharmacophore
ADME / Tox workup
In vitroADME / Tox
Don’t delay triage ofcompounds 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. 43:2083-6.
Structure Databases
Estrogen ReceptorPDB Molecule of the Month
Protein Data Bank (PDB) with > 22,700 structures
Cambridge Structural Database (CSD) with > 250,000 structures
Text or Sequence Similarity
http://www.rcsb.org
Structural Neighbors Databases• Structural Neighbors Databases
CATH, SCOP, CE, VAST, FSSP
Horse liver alcohol dehydrogenase
Silverleaf whitefly ketose reductase
Gprotein beta subunit
Pharmacology 202 (Spring 2005)Principles of Pharmacology
Mon, Wed Fri, 9:00-9:50, 1102 MEJCourse Director: Leslie Parise (1021 MEJ; 966-2238; parise@med.unc.edu
mic/autocoid/endocrine-- Ken McCarthyWed. Ken Harden Anatomy & Physiology of Autonomic Nervous SystemFri. Ken Harden Synthesis, Storage, Release and Metabolism of CatecholaminesMon HolidayWed. Ken Harden Alpha Adrenergic ReceptorsFri. Ken Harden Beta Adrenergic ReceptorsMon. Ken Harden Ken Harden sick Wed. Ken Harden Sympathomimetic AgentsFri. Shelly Earp Pathogenesis/Pathophysiology and Treatment of DiabetesMon. Ken Harden Adrenergic AntagonistsWed. Ken Harden Review sessionFri. David Ontjes Calcium Homeostasis and Associated DisordersMon. Ken McCarthy Parasympathetic Nervous SystemWed. Ken McCarthy Drugs affecting the Parasympathetic Nervous SystemFri. Gary Johnson Treatment of GI DisordersMon. Rudy Juliano Autocoids, Histamine and AntihistaminesWed. Rudy Juliano Eicosanoids, Anti-inflammatory Drugs, Non-narcotic analgesicsFri. Exam
nal--Bob Rosenberg/Leslie PariseMon. Bob Rosenberg CV Physiol reviewWed. Lee Graves AntihypertensivesFri. JoAnn Trejo DiureticsMon. JoAnn Trejo DiureticsWed. Leslie Parise Atherosclerosis and AntihyperlipidemicsFri. Leslie Parise Anticoagulants and anti-platelet agentsMon. Bob Rosenberg Antiarrhythmics
Wed. Cam Patterson AnginaFri. Cam Patterson Heart Failure (receive take-home exam on CV/Renal)
Richard Mailman and Clyde Hodge
Mon.RichardMailman
Overview of Pharmacology of CNS (psychiatric and neurologicdisorders)
Wed.RichardMailman
Antipsychotic Drugs (dopamine and serotonin mechanisms):
Fri. Holiday
Mon.RichardMailman
Drugs for ParkinsonÕs and AlzheimerÕs Disease (dopamine, Ach, etc.):
Wed.RichardMailman
Psychostimulants & Hallucinogens (dopamine & serotonin):
Fri.RichardMailman
Drugs for Mood Disorders (norepinephrine & serotonin):
Mon. Clyde Hodge Ionotropic Drugs & the CNS: Anxiolytics (GABA)
Wed.Clyde Hodge Ionotropic Drugs & the CNS: Antiepileptics & Alcohol (GABA &
Glutamate)
Fri.RichardMailman
CNS Analgesics & Drugs of Abuse (Opioids)
Mon. CNS Exam CNS Exam
PHCO 202- 3 credit hours
Course objectives:To teach classicalmechanisms of drug actioncombined with currentresearch discoveries and directions.
Course parallels the MEDPHARM course taught to Med students. The differenceis the amount of mechanismand current research.
PHCO 202 Principles of Pharmacology
Example: My lecture on anti-hypertensive agents
1st-half- classical approaches to treat hypertensionMechanism of action of different drug classesStandard view of hypertension treatment
2nd- half- current research in anti-hypertensiveDogma 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 successesor 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):487-98.
Dual ACE and neutral endopeptidase inhibitors: novel therapy for patients with cardiovascular disorders.Tabrizchi R. .Drugs. 2003;63(20):2185-202.
ExamsStill test the basics!Multiple choiceand problem solvingQuestions
Course evaluationscollected- feedbacksought.
Implementing “smallGroup” strategies toteach 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
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