Pharmacogenomics instruction in US and Canadian medical schools: implications for personalized medicine.

AIMS: To determine the extent of pharmacogenomics instruction at US and Canadian medical schools, characterize perceptions of curricular coverage, identify curricular resources and compare responses with similar studies conducted in US pharmacy schools and British medical schools. MATERIALS & METHODS: A survey was sent to the pharmacology department chairs of US and Canadian medical schools accredited by the Liaison Committee on Medical Education or the American Osteopathic Association's Commission on Osteopathic College Accreditation. Data were collected from July 2009 to February 2010. RESULTS: A total of 56% of eligible medical schools responded (90 out of 160). Of these schools, 82% (74 out of 90) incorporated pharmacogenomics into their curriculum. However, only 28% (21 out of 74) had more than 4 h of the required didactic pharmacogenomic coursework, and only 29% (22 out of 75) were planning to increase the number of pharmacogenomic coursework hours in the next 3 years. Pharmacogenomics coursework was most often contained within a required pharmacology course (66%; 49 out of 74) taught in the second professional year (72%; 53 out of 74). A total of 57% (44 out of 77) considered pharmacogenomics instruction at their own school as 'poor' or 'not at all adequate' while 76% (54 out of 71) considered it 'poor' or 'not at all adequate' at most medical schools. CONCLUSION: Most US and Canadian medical schools have begun to incorporate pharmacogenomics material into their curriculum; however, the extent of instruction is less than that of US pharmacy schools. To adequately prepare physicians to practice in the era of personalized medicine, medical schools should be encouraged to incorporate greater pharmacogenomic material in their curriculum.

Development of an undergraduate pharmacogenomics curriculum.

Pharmacogenomic biomarkers are becoming increasingly common in medicine and drug development. However, there is a genuine concern that the healthcare workforce will be ill-equipped to translate this information to clinical practice. As a result, a major effort is underway to educate future healthcare professionals on pharmacogenomics. This paper describes the development of a year-long course that aims to instill the fundamental concepts of this rapidly growing field into the minds of undergraduate students. This course offers the advantage of exposing students to the concepts of pharmacogenomics prior to their enrollment in PhD, PharmD or MD/DO graduate programs.

Synaptically released and exogenous ACh activates different nicotinic receptors to enhance evoked glutamatergic transmission in the lateral geniculate nucleus.

The effects of activation of nicotinic acetylcholine receptors (nAChRs) on glutamatergic transmission in the ventral lateral geniculate nucleus (LGNv) were examined in chick brain slices. Whole cell recordings showed that monosynaptic postsynaptic currents (PSCs) evoked in LGNv neurons by optic tract stimulation were blocked by glutamate receptor antagonists. Exogenously applied nicotine (0.5 microM), choline (1 mM), or acetylcholine (ACh, 100 microM) markedly increased (>3-fold) these evoked PSCs. Potentiation by ACh was dose-dependent and did not desensitize during a 5-min application. In a second set of experiments, the effect of releasing endogenous ACh by stimulating the lateral portion of the LGNv through a separate conditioning electrode before optic tract stimulation was examined. Conditioning stimulation trains increased PSCs by an average of 5.2-fold, an effect dependent on both the intensity and number of conditioning pulses. This increase in PSC amplitude was most likely caused by released ACh activating alpha6- and/or alpha3-containing nAChRs because it was blocked by 100 nM alpha-conotoxin MII, 100 nM dihydro-beta-erythroidine (DHbetaE), and 0.1-1.0 microM methyllycaconitine (MLA). In contrast, exogenously applied ACh increased PSC amplitude by activating a pharmacologically different population of nAChRs because this effect was inhibited by 100 nM alpha-bungarotoxin, 50 nM MLA, and a high concentration (30 microM) of DHbetaE, indicating that alpha7- and/or alpha8-containing receptors were involved. The results are consistent with a model whereby alpha6- and/or alpha3-containing nAChRs on retinal ganglion cell nerve terminals are located preferentially at cholinergic synapses, whereas alpha7- and/or alpha8-containing receptors are primarily extrasynaptic.

Opioid receptor activation attenuates nicotinic enhancement of spontaneous GABA release in lateral spiriform nucleus of the chick.

We examined the effects of opioids on the nicotinic enhancement of spontaneous GABA release from presynaptic terminals in the lateral spiriform nucleus (SpL) of the chick. Whole cell recordings from SpL neurons in brain slices were used to monitor spontaneous GABA release. Nicotine (1 microM) produced an 8-fold increase in the frequency of GABA events without changing their amplitude, consistent with an increase of GABA release from presynaptic terminals. L-enkephalin (1 microM) blocked these effects of nicotine on presynaptic GABA release, and the opioid antagonist naloxone (100 nM) antagonized the actions of L-enkephalin. The selective mu agonist DAMGO (300 nM) also attenuated the nicotine-mediated enhancement of GABA release, and the mu selective antagonist CTOP (1 microM) blocked the actions of DAMGO. In contrast, the kappa opioid agonist U50488 (3 microM) and the delta opioid agonist DPDPE (1 microM) had no effect. The results demonstrate that presynaptic release of GABA in the SpL can be regulated by both nicotinic agonists and mu opioids. While mu opioids have little effect on GABA release by themselves, they are able to block the marked enhancement of GABA release normally produced by nicotine. Since both cholinergic and enkephalinergic nerves are present in the SpL, the interactions of these two neurotransmitter systems may serve to precisely regulate GABA release in this brain region.