Provision and assessment of pharmacology and pharmacotherapy education across an integrated medical school curriculum

The papers presented here detail the approach to provide pharmacology and pharmacotherapy education at the Leiden University Medical Center. First it was decided to use the ability-based education model as the educational method and to have consistent outcomes and assessments throughout the curriculum. Pharmacology materials were moved to the TRC Pharmacology Database, a computer self-study program. Students__ acceptance of the Database is demonstrated in their utilization. In effort to measure students__ learning when using the TRC Pharmacology Database, we correlated the students__ time spent using the database and the grade they ultimately achieved in each course. There was no standard model for pharmacotherapy, so a survey of local physicians ability to report a therapeutic plan to one another was done. The results determined the competencies the local physicians most needed to improve to communicate an appropriate therapeutic plan. A new learning strategy was developed for students to address the deficient competencies. Students__ abilities were assessed after repeatedly developing a therapeutic plan using the new learning strategy. Lastly, incorporating initiatives across the curriculum is not easy. Change management skills were used to liaise with colleagues, departments, and committees. Both successful and unsuccessful techniques are presented.This thesis was financially supported by the foundation ‘Centre for Human Drug Research’, in Leiden, The NetherlandsUBL - phd migration 201

Clinical Pharmacology Research Internships at the Interface between Academia and Industry: Students' Perceptions and Scientific Output

The Centre for Human Drug Research (CHDR) is a non-profit clinical research institute at the interface between academia and the pharmaceutical industry. CHDR hosts a research internship programme for undergraduate (bio)medical students. The aim of this study was (i) to investigate the student perceptions of the undergraduate research internship and (ii) to quantify the scientific output related to these internships. We surveyed former interns at the CHDR from the year 2007 to 2014 and quantified their scientific output with a PubMed search. There was a response rate to the survey of 61%, with a good overall rating of the internships. Many students considered their internship at CHDR to be (much) more broad (55%) and with a (much) stricter planning (48%), compared to previous internships at academic research groups. In turn, there were many aspects reported to be similar to academic research internships such as focus on research methodology and 'outcome-drivenness'. Twenty-four per cent of the internships resulted in a co-authorship on papers published in peer-reviewed journals with an average impact factor of 3.3. In conclusion, with appropriate management and supervision, effective research electives are possible in the more commercial environment of a clinical research organization.Pharmacolog

Central nervous system effects of the interaction between risperidone (single dose) and the 5-HT6 antagonist SB742457 (repeated doses) in healthy men

UNLABELLED WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: • Several lines of evidence suggest a possible role of 5-HT(6) receptor antagonists in dementia or cognitive dysfunction of schizophrenia. SB-742457 is a potent 5-HT(6) antagonist and has shown efficacy in different animal models of cognitive impairment. It is currently in development as a cognitive enhancer. Risperidone, commonly used to control agitation and psychotic features in both schizophrenia and Alzheimer's disease, is a D(2)/5-HT(2A ) antagonist with low affinity for 5-HT(6) receptors and limited effects on cognitive parameters. WHAT THIS STUDY ADDS • As the combination of risperidone and SB-742457 may constitute a reasonable combination in cognitively impaired patients, pharmacodynamic interaction effects were investigated in this study. The only significant drug-drug interaction was a small increase of electroencephalogram (EEG) alpha and beta bands, which might suggest mild arousing activity of SB-742457 on the central nervous system-depressant effects of risperidone. The clinical relevance of these findings in patients remains to be established. Additionally, this study provided an extensive multidimensional pharmacodynamic profile of risperidone in healthy volunteers, showing that this antipsychotic suppresses motor performance (eye-hand coordination, finger tapping and postural stability), alertness, memory and neurophysiological functions (saccadic eye movements and EEG power spectrum). AIM Several lines of evidence suggest a possible role of 5-HT(6 ) receptor antagonists in cognitive dysfunction of schizophrenia. Atypical antipsychotics, such as risperidone, are currently used in these disorders. Therefore, the pharmacological interactions between the 5-HT(6) antagonist SB-742457 and risperidone were investigated in the light of possible co-medication. METHODS A randomized, double-blind, two-way crossover design was used to study the interaction between multiple doses SB-742457 50 mg and a single dose risperidone 2 mg in 18 healthy subjects. RESULTS Treatment was well tolerated. The most common adverse event was somnolence in 83% during the combination vs. 50% of subjects after risperidone, 32% after placebo and 11% after SB-742457. Combination treatment produced a statistically significant increase in the maximum plasma concentration of risperidone and had no effect on SB-742457 pharmacokinetics. Risperidone decreased saccadic peak velocity, finger tapping, adaptive tracking, subjective alertness, delayed word recognition and body sway and increased electroencephalogram (EEG) theta power and prolactin. The only pharmacodynamic interaction of risperidone and SB-742457 was an increase of absolute EEG alpha (ratio = 1.25, 95% CI = 1.11, 1.40, P= 0.0004) and beta power (ratio = 1.14, 95% CI = 1.03, 1.27, P= 0.016). No significant effects of SB-742457 alone were found. CONCLUSION The pharmacokinetic interactions between SB-742457 and risperidone detected in this study were not clinically relevant. The increase in EEG alpha and beta power is incompatible with enhanced risperidone activity, but could point to mild arousing effects of the combination. Most pharmacodynamic changes of risperidone are consistent with previously reported data. The potential cognitive effects of SB-742457 remain to be established.Stress-related psychiatric disorders across the life spa

Psychomotor and cognitive effects of a single oral dose of talnetant (SB223412) in healthy volunteers compared with placebo or haloperidol

Central Nervous System (CNS) effects of talnetant, an NK-3 antagonist in development for schizophrenia, were compared to those of haloperidol and placebo. The study was randomised, double-blind, three-way crossover of talnetant 200 mg, haloperidol 3 mg or placebo. Twelve healthy males participated and EEG, saccadic and smooth pursuit eye movements, adaptive tracking, body sway, finger tapping, hormones, visual analogue scales (VAS) for alertness, mood and calmness and psychedelic effects, left/right distraction task, Tower of London and Visual and Verbal Learning Task were assessed. Haloperidol showed (difference to placebo; 95% CI; p-value) decreases in EEG alpha power (-0.87microV; -1.51/-0.22; p = 0.0110), saccadic inaccuracy (2.0%; 0.5/3.6; p = 0.0133), smooth pursuit eye movements (-7.5%; -12.0/-3.0; p = 0.0026), adaptive tracking (-3.5%; -5.4/-1.7; p = 0.0009), alertness (-6.8 mm; -11.1/-2.4; p = 0.0039), negative mood (-4.6 mm; -8.6/-0.6; p = 0.0266), the ability to control thoughts (1.2 mm; 0.2/2.3; p = 0.0214), and an increase of serum prolactin (ratio 4.1; 3.0/5.6; p < 0.0001). Talnetant showed decreased alpha power (-0.69 muV; -1.34/-0.04; p = 0.0390), improved adaptive tracking (1.9%; 0.1/3.7; p = 0.0370) and reduced calmness on VAS Bond and Lader (-4.5 mm; -8.0/-1.0; p = 0.0151). Haloperidol effects were predominantly CNS-depressant, while those of talnetant were slightly stimulatory. The results suggest that talnetant penetrates the brain, but it remains to be established whether this dose is sufficient and whether the observed effect profile is class-specific for NK3-antagonists.Stress-related psychiatric disorders across the life spa

Early stage development of the glycine-1 re-uptake inhibitor SCH 900435: central nervous system effects compared with placebo in healthy men

Stress-related psychiatric disorders across the life spa