CLINICAL PHARMACOLOGY & THERAPEUTICS VOLUME 73, NUMBER 2 American Society for Clinical Pharmacology and Therapeutics P 9 5

PDII-B-1 INCORPORATION OF ABILITY-BASED PHARMACOLOGY

EDUCATION IN AN INTEGRATED MEDICAL SCHOOL CUR- RICULUM. K.L . Franson, P h a r r f ~ E. A. Dubois, PhD, J. M. van Gerven, MD, PhD, A. F. Cohen, MD, PhD, CHDR, Leiden Univer- sity, Centre for Human Drug Research, Leiden, Netherlands.

Medical students need to learn how to appropriately select patient~ specific drug therapy. To meet this need, Leiden University Medical Center developed an ability-based approach to clinical pharmacology instruction during the introduction of a newly integrated curriculum. Four ability outcomes and the corresponding knowledge content were identified and assigned levels by the clinical pharmacology group. Learning strategies (see www.medfac.leidenuniv.nl/trc) and assess- ments by which the students could practice and evaluate their per- formance of the outcomes were developed. These were shared with course coordinators during the planning of each block. In the first year of implementation, the progress of successfully incorporating the outcomes into the curriculum was cataloged. Ten of the possible 24 (41%) blocks offered in years 1 - 3 incorporated at least one the outcomes. The lowest level outcome of the understanding of knowl- edge content was adopted in 100% of these blocks. Higher level outcomes and assessments, which include the ability to select and monitor drug fl~erapy based on pharmacotherapeutic principles was only incorporated in one block (10%). Student evaluations have been positive regarding the learning strategies and indicated a preference for higher level assessments and integration. Next year is expected to yield a higher percentage of pharmacology and level of content in the curriculum. Specific outcomes, knowledge content, and assessments will be shared.

PDII-B-3 TEACHING PHARMACOKINETIC LOGIC THROUGH EX

AMPLE: APPLICATION OF MODELING TO OBSERVATIONS FROM THREE PERPLEXING OVERDOSES. P. Pollak, MD. P ~ S. L. Shafer, MD, Dalhousie University, Stanford University, Halifax, Canada.

Basic concepts in human pharmacology are sometimes best con- veyed through example. A seminar we teach to pharmacology stu- dents steps them through exploration of unusual data from 3 cloza- pine overdoses. Students provide their first impressions as to the pharmacokinetic explanation for an observed 4-day plateau in serum concentrations. We then walk through a disciplined approach to this unusual data. Using mixed effects models, we objectively compare delayed absorption vs. impaired metabolism as potential causes of the observation. When considering both the parent (clozapine) and me- tabolite (norclozapine) concentrations, the model of delayed absorp- tion best explains the sustained clozapine concentrations. Students are reminded of their first impressions and learn that these may not hold true under critical examination.

Massive drug overdoses provide unique pharmacokinetic data not available in ethical human studies. Clozapine overdose produces a pattern of absorption fundamentally different than normal doses. Thoughtful application of clinical pharmacology can reveal unex- pected mechanistic implications from this data. In this case it has bearing on the management of clozapine overdose and therefore serves as an example to students of the importance of disciplined application of the principles of clinical pharmacology. They learn by example that logical exploration of unexpected pharmacokinetic data can produce answers that are not apparent on cursory examination.

PDII-B-2 ESTABLISHMENT OF A CLINICAL PHARMACOLOGY

CURRICULUM IN A COMMUNITY-BASED MEDICAL SCHOOL. D. K. Naritoku, MD, C. U Faingold, PhD, Southern Illinois University, Springfield, IL.

In institutions with full time Clinical Pharmacology (CP) faculty, concerns of inadequate knowledge of therapeutics is addressed by CP courses. Smaller institutions, such as ours, may not have critical mass of clinical pharmacologists or/or institutional awareness and interest to support. We brought together clinical and basic science faculty to create Advanced Therapeutics as a 30 hr senior medical student elective. Faculty included all 8 members of Dept. of Pharmacology, one clinical faculty with CP certification, and faculty from each clinical department with expertise in therapeutics. Content was se- lected from topics of greatest current interest in clinical pharmacol- ogy, per journals and meetings, expertise of faculty, and textbook of Melmon and Morrelli. Our approach involved one hour sessions jointly presented by a pharmacologist, who presented 30 miu of mechanistic evidence and a clinician who presented 30 rain of clinical evidence on use of therapies. General principles of CP (drug inter- actions, interpreting clinical trials, drug delivery and pharmacokinet- ics, clinical trial ethics) were presented by the Clinical Pharmacolo- gist. Therapeutic areas included gene therapy, integrative therapies, infectious diseases, cardiovascular, respiratory, gastrointestinal, en- docrine, neurologic and psychiatric diseases, weight loss, dermatol- ogy, imrnunosuppression, and cancer. Students were assigned a sem- inar and analyzed specific articles in journal club format. Performance was evaluated by assessment questions at end of each session. This course serves as a model for providing this important information to medical students and serves as mechanism to further develop CP curriculum in community-based schools.

PDII-B-4 DO DRUGS WITHDRAWN IN RECENT YEARS HAVE

GREATER RISK IN WOMEN? FINDINGS FROM POSTMAR- KETING REPORTING OF ADVERSE EVENTS DATA, M. Chen, MS RPh S. Huang, PhD, Food and Drug Administration, Rockville, MD.

Purpose. To evaluate adverse reaction reports in FDA for possible gender difference in the risks associated with ten recently withdrawn prescription drugs.

Method. The FDA Adverse Event Reporting System (AERS) was searched between 1994-1999 for all relevant adverse events associ- ated with the risks with the ten drugs that were withdrawn from the market between 1997-2000. Approved product labeling was reviewed for approved indications relevant to the gender exposure. Drug use data between 1994-1999 or during marketing years were obtained from 1MS Health.

Summary of Results. Eight of the ten prescription drugs appeared to post greater health risks for women than for men. For terfenadine, astemizole, cisapride, mibefradil and grepafloxacin, most of the se- rious, life threatening and fatal cardiac adverse events contributed to the withdrawals, such as Torsades de Pointes, ventricular fibrillation, arrhythmia or cardiac arrest, were reported proportionally more in women than in men. The risks may not be necessarily higher in women because they were prescribed more often to women than to men, except for mibefradil. There was more withdrawn related ad- verse event reporting in women for fenfluramine, dexfenfluramine and alosetron because these drugs were mainly used in women, such as for appetite suppressant (fenfluramines) and irritable bowel disease for women (alosetron), respectively. No similar patterns can be derived from the use or serious liver adverse event reporting trend for troglitazone or bromfenac.

Conclusion. Of the ten prescription drugs withdrawn from the U.S. market since Januaw 1997, there were no conclusive evidences that the risks leading to withdrawals were greater in women than in men. The higher adverse event reporting trend in women in eight drugs might be simply reflecting the higher prescription usages in women.