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.

Influence of pretreatment with phenytoin, lidocaine and quinidine on the cardiodynamic and electrophysiological effects of ouabain in the cat heart-lung preparation.

The effect of pretreatment with phenytoin (diphenylhydantoin), lidocaine, and, for comparison, quinidine, on the doses of ouabain which produce a maximal inotropic effect, onset of arrhythmias and cardiac arrest, was explored in the cat heart-lung preparation. Ouabain was administered as an infusion (0.5 micrograms/min) either alone or after treatment with phenytoin (0.095 +/- 0.012 mM), lidocaine (0.090 +/- 0.004 mM) or quinidine (0.028 +/- 0.006 mM) and the cardiodynamic and electrophysiological changes monitored. Phenytoin, lidocaine and quinidine were administered in doses which were maximally tolerated by the preparations to ensure full effect, as evidenced by early cardiac depression. Ouabain alone produced a maximal increase in contractility prior to the development of arrhythmias at a blood concentration of 0.212 +/- 0.014 microM, onset of arrythmias at 0.227 +/- 0.015 microM, stable ventricular tachycardia at 0.269 +/- 0.010 microM and cardiac arrest at 0.342 +/- 0.014 microM. Pretreatment with phenytoin or lidocaine did neither modify these values nor change the pattern of the arrhythmias or the terminal cardiac event. Pretreatment with quinidine prevented the development of ventricular extrasystoles and aberrant ventricular conduction, which were the earliest arrhythmias in all other series. It also made the preparations develop stable ventricular tachycardia at an ouabain blood concentration of 0.246 +/- 0.007 microM, which was not significantly different from the concentration at which early arrhythmias were noted in the other series. In addition, quinidine decreased the dose of ouabain producing cardiac arrest by 13% but did not modify the terminal event. Pretreatment with phenytoin, lidocaine and quinidine did not affect the electrocardiographic pattern, but at the maximal increase in contractility with ouabain prior to the development of arrhythmias, the PR interval increased to comparable limits with ouabain alone and ouabain after quinidine and lidocaine. However, with ouabain after phenytoin, this increase was 61% less than that with ouabain alone and 31% less than that with ouabain after quinidine. Ouabain given alone or after phenytoin, lidocaine or quinidine produced comparable maximal effects on dp/dt, -dp/dt and left atrial pressure. It may be concluded that pretreatment with phenytoin and lidocaine does not modify the maximal inotropic dose of ouabain prior to the development of arrhythmias, the arrhythmogenic dose or the dose producing cardiac arrest, and that phenytoin partly counters the ouabain-induced depression of AV conduction. Quinidine has an additive effect on the ouabain-induced depression of AV conduction, prevents the ouabain-induced increase in idioventricular rhythm responsible for extrasystoles but not that responsible for ventricular tachycardia, and reduces the dose of ouabain producing cardiac arrest.(ABSTRACT TRUNCATED AT 400 WORDS)

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

A 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, dp/dt, 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.(ABSTRACT TRUNCATED AT 250 WORDS)

The cardiodynamic and metabolic effects of carbochromen and propranolol on the isolated dog heart.

In the isolated canine heart-lung preparation modified to measure coronary outflow and myocardial oxygen consumption, an infusion of carbochromen of 1 mg/min produced an increase in coronary outflow of 120.0% and a decrease in myocardial oxygen consumption of 11.0% at a cumulative dose of 28.0 +/- 3.8 mg, resulting in an increase in efficiency of 22.4%. At a total dose of 40 mg, the corresponding figures were +181.0%, -15.0% and +38.0% respectively. No change in heart rate was observed. An infusion of propranolol of 1 mg/min, on the other hand, was characterized by decreases in myocardial contractility and heart rate starting with cumulative doses of 20 mg and 40 mg respectively. At a cumulative dose of 62.9 +/- 3.0 mg a marked degree of myocardial failure occurred (peak failure) characterized by a decrease in cardiac output (-53.3%), dp/dt (-50.8%), heart rate (-18.5%) and myocardial oxygen consumption (-25.5%). In a separate series exposed to the same infusion of propranolol but in which the decrease in heart rate was prevented by pacing, identical changes were observed except that myocardial oxygen consumption decreased only by 7.7%. It may be concluded from this study that carbochromen, in confirmation of reports by other investigators, increases coronary outflow markedly. Carbochromen decreases myocardial oxygen consumption by a direct effect on myocardial metabolism as is evident from the fact that this decrease is not accompanied by changes in any of the parameters which are known to influence myocardial oxygen consumption such as heart rate. Propranolol has no effect on myocardial oxygen consumption unless it is given in a dose which produces myocardial failure and a decrease in heart rate. The decrease in heart rate following propranolol bears a close relationship to the decrease in myocardial oxygen consumption.

The cardiodynamic and metabolic effects of glucagon.

The cardiac effects of a continuous infusion of glucagon at the rate of 10 mug/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 mug 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 mug, 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 mug, 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.

A comparative study between the cardiovascular effects of cetiedil, a new vasodilator, and papaverine and aminophylline.

The cardiovascular effects of progressively increasing infusions of papaverine hydrochloride, aminophylline and cetiedil, a new vasodilator, were studied and compared in the anesthetized intact dog preparations. Papaverine and aminophylline had qualitatively the same effects on the various parameters, but in general the maximal effects of papaverine were of a greater order of magnitude. Cetiedil exhibited a different pattern of cardiovascular activity characterized by initial decrease in mean pulmonary arterial flow of 16% accompanied by an increase in systemic vascular resistance of 28% and in pulmonary vascular resistance of 19%, a stage of restoration of mean pulmonary arterial flow to control level accompanied by decrease in dp/dt of 25% and increase in pulmonary vascular resistance of 27% and a final stage of decrease in mean pulmonary arterial flow, representing toxic effects and accompanied by decrease in mean aortic pressure of 26%, dp/dt of 54% and heart rate of 27%, and an increase in pulmonary vascular resistance of 84%. These results indicate that cetiedil is devoid of cardiac stimulant activity. In another group of experiments devoted to measurement of vascular resistance of the hind limb, the results indicate that cetiedil, like papaverine and aminophylline, increased femoral blood flow through a decrease in resistance of the hind limb vasculature. This increase in flow could have been brought about only by redistribution of the cardiac output through differential effects on different vascular beds, since unlike papaverine and aminophylline, cetiedil does not increase cardiac output. The lesser maximal increase in femoral blood flow following cetiedil as compared to that following papaverine is probably referable to the relatively limited capacity of redistribution of the cardiac output to augment femoral blood flow. Superimposition of cetiedil and aminophylline on maximal effects of papaverine led to an additional decrease in mean femoral perfusion pressure, probably implying differences in basic mechanisms by which the three agents bring about their smooth muscle relaxant action.

Hemodynamic effects of aerosol propellants. III. Vascular resistance in the canine hind limb.

The question as to whether or not the hypotension observed as part of the effect of tricholorofluoromethane (FC11), dichlorofluoromethane (FC 12), dichlorotetrafluoroethane (FC 114) and methyl chloroform was due to a vasodepressor component of action, in addition to the previously documented depression in myocardial contractile force, was answered by testing these agents in an anesthetized dog preparation in which one hind limb was perfused at constant flow through the femoral artery. 5% FC 11, 20% FC 12 and 20% FC 114 decreased vascular resistance of the perfused limb, as reflected by decrease in mean femoral arterial perfusion pressure, in vagotomized but not in intact preparations. Methyl chloroform decreased vascular resistance even in intact preparations. Spontaneous blood flow in the intact femoral artery decreased following FC 11 and methyl chloroform administration in vagotomized preparations and was associated with marked decrease in mean aortic pressure. Blockade of alpha and beta adrenergic receptors with phentolamine and propranolol in the vagotomized preparation had no modifying influence of the effect of FC 11 and methyl chloroform. It may be concluded from this study that FC 11, FC 12 and FC 114 exhibit a vasodepressor activity on skeletal muscle vascular bed which is readily overcome by the hypotension-induced activation of the sympathetic system but which becomes evident when reflex activity is prevented by vagotomy. Methly choloroform exhibits a vasodepressor effect even in intact preparations probably because of concomitant depression of reflex activity through its general anesthetic action. A decrease in spontaneous femoral blood flow following FC 11 and methyl chloroform administration is referable to the accompanying severe hypotension notwithstanding concomitant vascular relaxation. Neither FC 11 nor methly chloroform directly liberate catecholamines from their sites of storage.

Hemodynamic effects of aerosol propellants. I. Cardiac depression in the dog.

The inhalation of fluorocarbons caused a depression of myocardial contractility, aortic hypotension, a decrease in cardiac output and an increase in pulmonary vascular resistance. The minimal concentrations that elicited these changes are as follows: 1% trichlorofluoromethane (FC11); 2.5% dichlorotetrafluoroethane (FC114); and 10% dichlorodifluoromethane (FC12). Inhalation of 20% octafluorocyclobutane (FC318) and difluoroethane (FC152a) did not influence these hemodynamic parameters. As in previous comparisons, the most widely used aerosol propellants are potentially cardiotoxic in the anesthetized dog.

Hemodynamic effects of aerosol propellants. II. Pulmonary circulation in the dog.

The inhalation of trichlorofluoromethane (FC11), dichlorotetrafluoroethane (FC114) and dichlorodifluoromethane (FC12) caused a reduction in mean aortic blood pressure but only FC11 and FC114 caused a reduction in mean pulmonary arterial pressure. The primary cause of the fall is a decrease in pulmonary blood flow. When blood flow to a lobe is kept constant and the adrenergic alpha receptors are blocked by injection of phentolamine, the inhalation of FC11 caused vasodilation. In the intact circulation, the vasodilation is masked by release of catecholamines which constrict the pulmonary blood vessels.