J. Simaan

Using team-based learning to teach pharmacology to second year medical students improves student performance

Background: Team-based learning (TBL) is an innovative instructional method that fosters active learning. It has been shown to improve student performance in some health care education courses. Aim: To examine the effect of teaching pharmacology using a TBL approach on second year medical students’ satisfaction and performance. Methods: A modified TBL method was used in two case-based discussion sessions of the second year pharmacology course: a relatively easy drug metabolism/pharmacogenetics session and a more challenging pharmacokinetics/pharmacodynamics (PK/PD) session. Individual and group answers to all questions were recorded, and an evaluation form was collected for each session. Class performance on a summative quiz was compared to previous years. Results: Students provided positive feedback. Group performance was better than individual performance during the TBL exercises. TBL was less successful when the questions were very difficult, with a difficulty range of 30–70% being the most appropriate. Performance of the class on the pharmacology summative quiz showed significant improvement over that in previous years in the PK/PD part, but was unchanged in other topics taught traditionally. Conclusion: The results suggest that TBL provides a better outcome for students, and provide insight into appropriate design of TBL exercises.

Using Team-based Learning to Teach Clinical Pharmacology in Medical School: Student Satisfaction and Improved Performance

Formal teaching in clinical pharmacology was never part of the curriculum at the American University of Beirut Faculty of Medicine. Based on feedback from students and on recommendations of academic bodies, we have introduced, since June 2008, twice‐monthly “rational prescribing” sessions during the required internal medicine rotation in year 4 of medical school. All sessions were designed according to the innovative Team‐based Learning format and concluded by having the students practice prescription writing and personal formulary development based on the World Health Organization criteria. Our 18‐month experience showed that students were very satisfied with the course and the teaching approach, and that their performance on prescription writing and formulary development had improved. Although further studies are needed to explore the impact of team‐based learning on additional performance measures, we recommend it as an effective alternative for teaching clinical pharmacology in medical schools.

Teaching clinical pharmacology using team-based learning: a comparison between third- and fourth-year medical students.

The purpose of this study was to formulate evidence‐based recommendations on whether to deliver the team‐based learning (TBL)‐designed clinical pharmacology course at the American University of Beirut Faculty of Medicine (AUBFM) during the third year instead of the fourth and final year of the medical curriculum. Between June 2010 and May 2011, AUBFM offered the course to both classes simultaneously to compare their performance. The findings of this endeavor supported the introduction of the course during the third year, first because fourth‐year students did not outperform third‐year students despite having the advantage of an additional year of clinical experience, and second, third‐year teams seemed more likely to develop into better functioning teams. The findings also suggested that simultaneous delivery of TBL sessions to both third‐ and fourth‐year teams was less favorably recommended because of the varying learning pace of both student groups.

Comparison of the cardiodynamic and metabolic effects of dobutamine with those of norepinephrine and dopamine in the dog isolated heart

SummaryA comparative study of the cardiodynamic and metabolic effects of norepinephrine, dopamine and dobutamine was carried out on the isolated heart-lung preparation from dogs, modified to measure coronary outflow and myocardial oxygen consumption. Infusions of the three sympathomimetic drugs which increased myocardial contractility, as reflected by maximal rate of rise of left ventricular pressure, dpldt, by 24%, produced comparable increases in heart rate of 5 to 7% with the three drugs, comparable increases in myocardial oxygen consumption of 11% with dopamine and 19% with dobutamine and a decrease in mechanical efficiency of 13% with dobutamine. At higher doses which increased dp/dt by an average of 68%, heart rate increased by 9%, 19% and 26% following norepinephrine, dopamine and dobutamine, respectively, the increase produced by dobutamine being significantly higher than that produced by norepinephrine. Myocardial oxygen consumption increased significantly following dopamine by 39% and dobutamine by 46% but not following norepinephrine. Mechanical efficiency decreased following dobutamine by 24%. At average increases in dp/dt of 123% and 166%, there were further increases in heart rate and myocardial oxygen consumption and decreases in mechanical efficiency, the changes in each parameter being similar for all three drugs. The increase in coronary outflow was compared with the spontaneous increase which is regularly observed with time in the isolated heart-lung preparation. Only dobutamine was found to increase coronary outflow by 49%, 117% and 137% at increases in dp/dt of 71%, 118% and 173%, respectively. It may be concluded from this study that, in the isolated heart, only norepinephrine can increase dp/dt by 57% without a concomitant increase in myocardial oxygen consumption and decrease in mechanical efficiency. Only dobutamine increases coronary outflow significantly above the spontaneous increase which is expected in the isolated heart-lung preparation, probably due to a more prominent direct relaxant effect on the coronary vascular bed. There is no significant difference in the arrhythmogenic effect of the three sympathomimetic drugs.

The effect of endogenous catecholamines and norepinephrine administration on the performance of the isolated canine heart

SummaryThe effect of endogenous catecholamines on the ability of the isolated canine heart to handle a volume load was studied in the Starling heart-lung preparation, modified to measure coronary flow and myocardial oxygen consumption. The isolated hearts were subjected to progressively increasing volume loads, and total left ventricular output and oxygen consumption were measured. Four groups of preparations were compared; controls, preparations from reserpine-pretreated dogs (0.5 mg/kg intraperitoneally 48 hrs and again 24 hrs prior to experimentation), preparations treated with 20 mg of pronethalol and preparations infused with norepinephrine (1 Μg/min for the duration of the experiment). The results show that the isolated heart depleted of its catecholamine content, or treated with pronethalol is capable of handling the same maximal volume load as a control heart. Similarly the isolated heart subjected to an infusion of norepinephrine of 1 Μg/min does not handle a bigger maximal volume load than a control heart. One may conclude from these results that in the isolated dog heart, augmentation of myocardial function, which accompanies an increase in volume work, is neither dependent on release of endogenous catecholamines, nor is it promoted by exogenously administered catecholamines.

The effect of ouabain-induced contractility on myocardial oxygen consumption.

SummaryThe present study was undertaken to explore the relationship between various doses of ouabain, myocardial contractility as reflected by the maximal rate of rise of left ventricular pressure and oxygen consumption, in the canine, nonfailing Starling heart-lung preparation modified to measure coronary flow. Concentrations of ouabain, previously found to be within “therapeutic” limits, as tested in the failing preparation, namely those attained 20 min and 30 min from the start of an infusion of ouabain (5μg/min), increased the maximal rate of rise of left ventricular pressure by an average of 13.4% and 24.2%, respectively, with no concomitant measurable increase in myocardial oxygen consumption. Changes in left ventricular work, left ventricular circumference, left ventricular end-diastolic and left atrial pressures were neither significant nor consistent. Concentrations of ouabain which induced ventricular tachycardia increased the maximal rate of rise of left ventricular pressure and myocardial oxygen consumption by an average of 205.2% and 81.4%, respectively. It may therefore be concluded from these results, that at constant aortic pressure and left ventricular dimensions an appropriate dose of ouabain induces in the isolated nonfailing heart an increase in contractility unaccompanied by a measurable increase in myocardial oxygen consumption.

In-vivo evidence of a role for nitric oxide in regulating the activity of the norepinephrine transporter.

We examined the role of nitric oxide (NO) in the regulation of neuronal uptake of norepinephrine (uptake-1) in rats under anesthesia. The effect on systolic blood pressure of two pressor drugs that work by different mechanisms, norepinephrine and angiotensin II, was explored in anesthetized rats under control conditions and after prevention of NO synthesis with Nw-nitro-L-arginine (L-NNA). The results showed that whereas the pressor effects of increasing doses of norepinephrine were potentiated by L-NNA, those of angiotensin II were not affected, which implied that NO was selectively involved in modulating the pressor effect of norepinephrine. To explore the mechanisms involved in this potentiation, we examined the effect of L-NNA on the pressor effect of tyramine, a purely-indirectly-acting sympathomimetic amine which enters nerve terminals thorough uptake 1 and liberates norepinephrine from storage vesicles. Increasing doses of tyramine produced pressor effects which, in contrast to those of norepinephrine, were significantly attenuated by pre-treatment with L-NNA. Similarly, pretreatment with cocaine, the classical inhibitor of uptake 1, significantly decreased the pressor effect of tyramine; however, the response to tyramine was then restored when L-NNA was administered, thus reversing the effect of cocaine. We conclude that NO plays a major role in the adrenergic system by enhancing the activity of uptake 1 in sympathetic nerve terminals. Blockade of uptake 1 by cocaine is also partly dependent on NO. The stimulus for the mobilization of the NO synthase pathway in adrenergic neurons and the subsequent steps involved in modulating uptake 1 deserve further exploration.

The effect of theophylline alone and in combination with ouabain on the isolated dog heart.

SummaryA comparative study of the inotropic effects of theophylline and ouabain as well as a study of the interaction between the two pharmacological agents were carried out in the nonfailing Starling heart-lung preparation modified to permit metabolic studies. Single doses of theophylline ranging between 100 to 200 mg added to the venous reservoir produced consistent increases in myocardial contractile force, as gauged by the maximal rate of rise of left ventricular pressure, dp/dt, 73%; systemic output, 28%; coronary output, 277%; total cardiac output, 41%; heart rate, 27%; left ventricular work, 45% and myocardial oxygen consumption, 43%. In addition, systolic time decreased consistently by 15%. 20 min and 30 min after the onset of an ouabain infusion of 5μg per min, which was started 15 min after the addition of theophylline, there was further increase in dp/dt to 87% and 107%, respectively, with no significant change in the remaining parameters from the levels attained 15 min after the administration of theophylline. As compared to ouabain administered alone, ouabain administered at peak effect of theophylline led to an earlier occurence of ventricular arrhythmias and death. It may be concluded from this study that maximally effective doses of theophylline brought about an increase in dp/dt which is greater than that brought about by maximal “therapeutic” doses of ouabain. Secondly, ouabain administered after the peak effect of theophylline was exerted led to an additional increase in dp/dt implying that the mechanisms underlying the inotropic action of each drug are different. Thirdly, at constant aortic pressure, heart rate, left ventricular enddiastolic and left atrial pressures, ouabain in the presence of theophylline brought about an increase in myocardial contractility, as gauged by an increase in dp/dt, without a concomitant increase in myocardial oxygen consumption, thus confirming earlier results obtained with ouabain alone. Fourthly, ouabain administered at peak effect of theophylline led to an earlier occurrence of ventricular arrhythmias and death.

The cardiodynamic and metabolic effects of glucagon

SummaryThe cardiac effects of a continuous infusion of glucagon at the rate of 10 μg/min were studied in the Starling heart-lung preparation, modified to measure coronary flow and myocardial oxygen consumption. A maximal increase in myocardial contractility, as reflected by maximal rate of rise of left ventricular pressure, dp/dt, of 31% was observed at a total dose of glucagon of 50 μg and was accompanied, by an increase in heart rate and in myocardial oxygen consumption of 59% and 57%, respectively. At a total dose of glucagon of 100 μg, there was an additional and comparable increase only in heart rate and myocardial oxygen consumption of 11.2% and 6.4% respectively. Similarly, at a total dose of glucagon of 150 μg, only heart rate and myocardial oxygen consumption increased additionally by increments of 2.6% and 2.9% respectively. These effects occurred at constant aortic pressure and left ventricular volume. Further infusion of glucagon led to an additional increase only in myocardial oxygen consumption of 4.2%. When the increase in heart rate was largely prevented by prior treatment with veratramine, an increase in dp/dt, not significantly different from the maximal increase obtained with glucagon alone, was accompanied by much lower and closely comparable increases in heart rate and in myocardial oxygen consumption of 15% and 19%, respectively. Coronary flow increased more markedly when glucagon was administered alone and it paralleled the increase in myocardial oxygen consumption. It may be concluded from this study that, in the isolated dog heart preparation, glucagon increases contractility, heart rate and myocardial oxygen consumption and that the increase in myocardial oxygen consumption is related more closely to the increase in heart rate than to the increase in contractility, but a minor increment is referable to a calorigenic action. The increase in coronary flow is of a secondary nature, resulting from the increase in myocardial metabolic demands.

ON THE MECHANISM OF THE PRESSOR ACTION OF TYRAMINE.

SummaryThe infusion of small amounts of noradrenaline for short periods of time into reserpinized dogs restores the pressor action of tyramine if the latter is given during the infusion but not immediately thereafter. These findings are consistent with the hypothesis that tyramine acts on its own but requires for its action the presence of noradrenaline at the receptor sites, for under these circumstances there are no stores from which noradrenaline can be released. In the normal animal, or in a reserpinized animal after repletion of the stores by prolonged noradrenaline infusion, tyramine is envisaged to act by releasing from the stores a sufficient amount of noradrenaline which in turn “catalyses” the action of tyramine at the receptor sites. These results do not support the view that tyramine, like guanethidine, acts solely by virtue of the amount of noradrenaline it releases.