Transcript Document

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 201- 2 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.
PHCO 201“Introduction to Molecu lar Pharmacol ogy”
2004
Mon day an d Wednesdays 9:00 - 9:50 AM
Bu i l din g
C ourse Directors: JoAn n Trejo an d David S iderovsk i
Topic
Lecture hours
I.
Genes to Protei n /Mole cu lar Biology 8
II. Re ceptors/Ion Ch an nel s
5
Re gu lation of Se con d Me ssenge rs
4
III. Principles of Drug/Re ceptor Interaction s 6
Metabol ism
4
Fall Se meste r
1102 Mary El len Jone s
Block Leader
S i de rovsk i
Rosenberg
Doh lm an
Harden
Graves
I. Genes to Protei n /Mole cu lar Biology
W
Augu st 25
Course Introduction (T rejo/Siderovski);
Central Dogma of Genet ic Information (R. Kole)
M
Augu st 30
RNA as a T herapeutic Target (R. Kole)
W
September 1 Introduct ion to Bioinformatics Part I (Siderovski)
M
September 6 (HOLIDAY) NO CLASS
W
September 8 Techniques of P rotein Purificat ion/Struct ure Determinat ion (Bet t s)
M
September 13 Introduct ion to Bioinformatics Part II (Siderovski)
(Assignment of Take-home Exam I - due Friday Sept. 24th, 5P M)
W
September 15 Structural Bioinformatics (Temple)
M
September 20 Techniques of Gene Manipulat ion/Macromolecular Therapeut ics
(Miyamoto)
W
September 22 Gene Therapy (Samulski)
M
Septembe r 27 Take u p session of EXAM I
II. Re ceptors/ Ion Channels an d Re gu lation of Second Messengers
W
September 29 Historical Perspect ive (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
Octobe r 18 Activation and i nactivation of G protei n s (includes RGS
protei ns)
In troducti on to effectors and second messen gers (H. Doh l man)
W
October 20
Act ivat ion and inactivation of ras-family GTP binding proteins
(C. Der)
M
Octobe r 25 Activation of PKA by cAMP, re gu lation of cAMP by cyclase
an d
PDEs.(L. Graves)
W
October 27 Act ivat ion of CaM kinase and PKC and PKC by PLC, DAG, IP 3,
and calcium second messengers (McCarthy/Harden)
M
Novem be r 1 EXAM II
III. Pri nci ple s of Drug/Re ceptor In te ractions and Drug Metabol ism
W
November 3 Drug receptor interact ions (K.Harden)
M
November 8
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W
November 10
“
M
November 15
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W
November 17
“
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)
Associating Disease
with Genomic DNA:
Karyotype analyses
p
CYTOGENETIC
MAP POSITION:
Tell me everything that’s
ever been found here…
q
www.ensembl.org
The Future of Chemotherapy Patient Profiling?
Chemical
library
SAR analyses
Don’t delay triage of
compounds that aren’t
“drug-like”
In vitro
ADME / Tox
HTS results
Proteins
Assign pharmacophore
Combi-chem
synthesis
ADME / Tox workup
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
 Protein Data Bank (PDB)
with > 22,700 structures
http://www.rcsb.org
 Cambridge Structural Database (CSD)
with > 250,000 structures
 Text or Sequence Similarity
Estrogen Receptor
PDB Molecule of the Month
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)
PHCO 202- 3 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.
Principles of Pharmacology
Mon, W ed Fri, 9:00-9:50, 1102 MEJ
Course Director: Leslie Parise (1021 MEJ; 966-2238; [email protected]
mic/autocoid/endocrine-- Ken McCarthy
W ed. Ken Harden
Anatomy & Physiology of Autonomic Nervous System
Fri.
Ken Harden
Synthesis, Storage, Release and Metabolism of Catecholamines
Mon
Holiday
W ed. Ken Harden
Alpha Adrenergic Receptors
Fri.
Ken Harden
Beta Adrenergic Receptors
Mon. Ken Harden
Ken Harden sick  
W ed. Ken Harden
Sympathomimetic Ag ents
Fri.
Shelly Earp
Pathogenesis/Pathophysiology and Treatment of Diabetes
Mon. Ken Harden
Adrenergic An tagonists
W ed. Ken Harden
Review session
Fri.
David Ontjes
Calcium Homeostasis and Associated Disorders
Mon. Ken McCarthy
Parasympathetic Nervous System
W ed. Ken McCarthy
Drugs affecting the Parasympathetic Nervous System
Fri.
Gary Johnson
Treatment of GI Disorders
Mon. Rudy Juliano
Autocoids, Histamine and An tihistamines
W ed. Rudy Juliano
Eicosanoids, Anti-inflammatory Drugs, Non-narcotic analgesics
Fri.
Exam
nal--Bob Rosenberg/Leslie Parise
Mon. Bob Rosenberg
CV Physiol review
W ed. Lee Graves
Antihypertensives
Fri.
JoAnn Trejo
Diuretics
Mon. JoAnn Trejo
Diuretics
W ed. Leslie Parise
Atherosclerosis and An tihyperlipidemics
Fri.
Leslie Parise
Anticoagulants and anti-platelet agents
Mon. Bob Rosenberg
Antiarrhythmics
W ed.
Fri.
Mon.
W ed.
Fri.
Mon.
W ed.
Fri.
Mon.
W ed.
Fri.
Mon.
Cam Patterson
Angina
Cam Patterson
Heart Failure (receive take-home exam on CV/Renal)
Richard Mailman and Clyde Hodge
Richard
Overview of Pharmacology of CNS (psychiatric and neurologic
Mailman
disorders)
Richard
Antipsychotic Drugs (dopamine and serotonin mechanisms):
Mailman
Holiday
Richard
Drugs for ParkinsonÕs and AlzheimerÕ
s Disease (dopamine, Ach, etc.):
Mailman
Richard
Psychostimulants & H allucinogens (dopamine & serotonin):
Mailman
Richard
Drugs for Mood Disorders (norepinephrine & serotonin):
Mailman
Clyde Hodge
Ionotropic Drugs & the CNS: Anxiolytics (GABA)
Clyde Hodge
Ionotropic Drugs & the CNS: Antiepileptics & Alcohol (GABA &
Glutamate)
Richard
CNS Analgesics & Drugs of Abuse (Opioids)
Mailman
CNS Exam
CNS Exam
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
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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):487-98.
Dual ACE and neutral endopeptidase inhibitors: novel therapy for patients with
cardiovascular disorders.
Tabrizchi R.
.
Drugs. 2003;63(20):2185-202.
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 InhibitorsGraves, Johnson.
4. Ras Superfamily and Signal Transduction- Der , Cox
5. Molecular Pharmacology of Cancer-Kole