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PubMed2005

Progress and dilemma of contemporary clinical pharmacology.

Owing to the great progress in clinical chemistry connected with utilization of applied mathematics, pharmacokinetics came into being. The unknown objective methods of research of drugs in human were discovered, among them controlled clinical trials (CCT). These new methodologies generated a new clinical discipline called clinical pharmacology (CPH) which has its roots in basic pharmacology but was applied in clinical specialties. This field is very young, recognized by World Health organization in 1970. Up to the 90s several enthusiasts developed quickly CPH. The scope and development of this discipline is presented in the first part of this article. At the end of the 20th century the science on drugs performed in humans was in the center of interest of the public as well as an object of great pressure of pharmaceutical industry, politicians, and the public. These phenomena started to influence CPH, practiced and taught in medical university faculties and patients care, unfavourably. Government, university authorities, non-profit organizations are not interested in supporting objective research in CPH on the highest academic level. The industry considers the mentioned studies as a threat for its profit. CCT was elaborated for objective comparison of effectiveness and efficacy of old (standard) drugs with the new approved substance. The main purpose of this type of study is a rejection of null hypothesis. Since 1990, these trials caused a strong movement toward evidence-based medicine. A few years ago trials were performed in independent academic centers. These studies were in experienced hands of the teams consistent of highly competent specialists of several fields of medicine. These centers contributed to the quality, intellectual rigor and impact of such clinical trials. But as economic pressure increases, this may belong to the past. Actually pharmaceutical companies curtailed the participation of academic centers in CCT to 40%. According to EU Parliament decision the pharmaceutical industry adopted the whole control of CCT. Politicians and society demand the instant application of new observations and discoveries into practice. Then new drugs approved in 2003 are mentioned. At the end, the general proposition to improve the Status of academic CPH and creditability of CCT is suggested: to develop essential studies on mechanisms of drugs on human being. The highest academic authorities, who understand the importance of CPH, have to discuss the necessity of funding of this type of research with university authorities, non-profit organizations and the Ministry of Health. To soften unavoidable conflict of interests, laborious discussions between academic scientists, pharmaceutic company authorities and governmental authorities are necessary. There is also an urgent necessity of new legislative acts. These proposals are very general and deficient. They were presented here to conclude this article on the present status of clinical pharmacology with the statement that the real threat for this discipline exists.

Biomedical Research↗
PubMed1991

Citation analysis of selected clinical pharmacology journals.

Perceptions of pharmacy and medical journal quality vary widely. One objective measure of the quality of a scientific journal is the impact factor that can be defined as "a measure of the frequency with which the 'average article' in a journal has been cited in a particular year." The purpose of this study was to evaluate the clinical pharmacology journals available through the Science Citation Index and determine those that have the greatest impact. From these data, it appears that the premier primary literature journal in clinical pharmacology is Clinical Pharmacology and Therapeutics while the premier review journal has been Clinical Pharmacokinetics. Possible explanations for impact factor fluctuations over time are also discussed.

Abstracting and Indexing↗
PubMedDate not supplied

[Note on the epistemology of clinical pharmacology: comparison with the approach of Karl Popper].

Is clinical pharmacology a science or only an application of science? Karl Popper suggested a method to identify science and to sort it out from other logical activities such as metaphysics, whereby the falsification criterion he proposed can apply to the theory in such a way that the theory could be refuted. The clinical pharmacologist's approach requires the build-up of a therapeutic model on the basis of two other models: the physiopathologic and the pharmacological. The three-model construct is a theory. Is it scientific in the Popperian sense? From the therapeutic model, one can predict the efficacy of a drug, and the corresponding statement is tested by a clinical trial. Whatever the original statement, it is modified into a refutable one because of the use of the statistical approach in clinical trials. Furthermore, the predicate represents a hypothesis of the model validity, which will then be confronted with 'reality' through clinical experiment. As the therapeutic model is refutable, clinical pharmacology is a science in the Popperian sense.

Drug Therapy↗
PubMed1999

[Clinical pharmacological drug information. Well over one year's experience].

Clinical pharmacology was established quite recently in Denmark as a medical specialty. It comprises--among other items--clinical pharmacological drug information service, the primary aim of which is to provide service to health personnel with clinical responsibility involving drugs and specific patient-related questions. Questions forwarded to the clinical pharmacological drug information service at two Copenhagen hospitals have been summarized. The questions were categorized according to the profession and the affiliation to the health care system of the inquirer as well as the nature of the question. At the two hospitals, 118 and 77 questions were answered from January 1st 1997 to June 1st 1998, respectively. Physicians employed at hospitals were responsible for the majority of the questions. Most questions concerned adverse drug reactions, choice of therapy/drug, and therapy during pregnancy or breast feeding.

Denmark↗
PubMed2000

International union of pharmacology. XXII. Nomenclature for chemokine receptors.

Chemokine receptors comprise a large family of seven transmembrane domain G protein-coupled receptors differentially expressed in diverse cell types. Biological activities have been most clearly defined in leukocytes, where chemokines coordinate development, differentiation, anatomic distribution, trafficking, and effector functions and thereby regulate innate and adaptive immune responses. Pharmacological analysis of chemokine receptors is at an early stage of development. Disease indications have been established in human immunodeficiency virus/acquired immune deficiency syndrome and in Plasmodium vivax malaria, due to exploitation of CCR5 and Duffy, respectively, by the pathogen for cell entry. Additional indications are emerging among inflammatory and immunologically mediated diseases, but selection of targets in this area still remains somewhat speculative. Small molecule antagonists with nanomolar affinity have been reported for 7 of the 18 known chemokine receptors but have not yet been studied in clinical trials. Virally encoded chemokine receptors, as well as chemokine agonists and antagonists, and chemokine scavengers have been identified in medically important poxviruses and herpesviruses, again underscoring the importance of the chemokine system in microbial pathogenesis and possibly identifying specific strategies for modulating chemokine action therapeutically. The purpose of this review is to update current concepts of the biology and pharmacology of the chemokine system, to summarize key information about each chemokine receptor, and to describe a widely accepted receptor nomenclature system, ratified by the International Union of Pharmacology, that is facilitating clear communication in this area.

Animals↗
PubMedDate not supplied

[Safety pharmacology: central nervous system].

Some of the results formerly included in the dossiers under the heading of 'General Pharmacology: Central Nervous System' were intended to document most of the information now covered by the CNS Safety Pharmacology. This paper allows to point out some general experimental conditions relating to the choice of (1) suitable animal species whose use should be advocated, (2) the route by which the effects of the drugs should be studied and (3) the controls of the experimental context (surroundings, temperature, schedules of the trials, interference with food-intake episodes, influence of noises and smells, expertise of the experimental staff) likely to optimize the predictive value of the trials. Besides the core of investigations recommended by most of the regulatory authorities (changes in gross behaviour, motor coordination, locomotor activity, interaction with hypnotics, convulsant potential), the need to include or not some investigations such as EEG studies and the prediction of adverse events, such as anxiolytic and amnesia potentials, is considered. The place, within the scope of CNS Safety Pharmacology, of studies intended to document the potential for drug abuse and dependence is mentioned and some information given about the methods generally used.

Animals↗
PubMed1995

[The integration of Greek pharmacology into Arabic world].

The paper is a first study of the assimilation of ancient Greek pharmacology in the Arabic world. In a first part, it inventories the Greek works in the field, with their relative importance (tables 1 & 1). The second part is a study of the translations of these treatises, with, first, an inventory of their various Syriac and Arabic versions and, second, a reconstruction of the dynamic of this enterprise (table 3). The third part studies more specifically the integration of the most important work in that field, the De materia medica of Dioscorides. From the methodological point of view, the study is conducted on the Arabic sector, as well on the Greek one, with a special attention to the various aspects of the phenomenon, pharmacological, textual, artistic and others. The conclusion is that the integration of Greek pharmacology in the Arabic world reproduced the general tendencies of the Byzantine world, with an association of both Dioscorides' and Galen's works in the field.

Arab World↗
PubMed1992

[Use of pharmacological data in the choice of antipsychotic drugs].

The choice of antipsychotic drug should be based on experimental data from biochemistry and animal pharmacology, according to the targeted clinical effects. However, owing to the lack of good animal models of mental disease only the clinical approach can validate the antipsychotic efficacy of a drug. Within the theoretical frame of dopaminergic activity in schizophrenia a specificity of the various neuroleptics according to the four dopaminergic structure is evidenced through cellular electrophysiological studies. Classical provisional pharmacology of antipsychotics uses in animals on the one hand naturalistic observation tests, and on the other hand interactions vis-à-vis behaviours induced by stimulating dopaminergic agents, as amphetamine and apomorphine. Differential analysis of antipsychotic effects on each of those behaviours allows to discriminate between the various neuroleptics and to refine their pharmacological profile, specially to predict a disinhibitory action with some of them. Progress in the identification, localisation, number modification of target receptors of different neurotransmitters as well as the biochemical response to their stimulation by agonist or antagonist allows to delineate more precisely the neurobiochemical action of antipsychotic drugs. On top of antidopaminergic D2 effect, anti D1 effect begin to be investigated. More over the role of antiserotonergic 5-HT2 and central anticholinergic actions seems to be important in the "atypical" aspect of some neuroleptic drugs. More recently, contributions from molecular biology made it possible to clone and to synthetize five subtypes of dopaminergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Applicability of the principles of developmental pharmacology to the study of environmental toxicants.

Although nontherapeutic xenobiotics represent the vast majority of environmental exposures during childhood, study of these compounds in children has lagged behind drug studies. Some useful extrapolation can be made from the latter, however. An increased impetus for pediatric pharmacology studies resulted from evidence of shortcomings in algorithmic approaches to dosing and the recognition of differing efficacy and toxicity in children compared with adults. With some drugs, developmental differences resulted in increased toxicity or failed efficacy; however, in others, decreased toxicity has been demonstrated. Thus, pediatric patients may not be classified arbitrarily as a susceptible population but certainly a different one compared with adults. Better designed pediatric pharmacology studies use well-documented, nonlinear changes in body composition across childhood, as well as knowledge about the impact of physical growth, mediated by complex hormonal changes. Developmental differences in all components of drug disposition, including absorption, distribution, metabolism, and excretion, have been characterized. Of these, the ontogeny of metabolism, particularly tissue-specific metabolism, is the most complex. Many knowledge gaps persist within developmental pharmacology; however, recent Food and Drug Administration regulatory action likely will ensure continued accumulation of pediatric therapeutic data. Although these data can provide important a priori information for improved environmental study design, evaluation-specific toxicant disposition by pediatric patients is clearly needed.

Adult↗
PubMed1992

Three-dimensional view of pharmacology.

The relationship between the stereochemistry of drugs and their therapeutic and toxic effects is discussed. Molecular structures that have the same chemical constituents and are related to each other as an object and its nonsuperimposable mirror image are enantiomers. A molecule that has at least one pair of enantiomers is a chiral compound, and a 50:50 mixture of enantiomers is a racemic mixture. The enantiomers of a chiral drug may vary in their interactions with chiral or asymmetric environments such as enzymes and receptors. These variations may lead to differences in pharmacology, pharmacokinetics, therapeutic effect, efficacy, and toxicity. For example, dextropropoxyphene is an analgesic, whereas its mirror image, levopropoxyphene, is an antitussive agent. Enantiomers may have identical efficacy and toxicity. They may have the same therapeutic and toxic effects but differ in the magnitude of these effects; one may possess all the pharmacologic activity and the other may be biologically inactive, or both may be pharmacologically active but have qualitatively different therapeutic and toxic effects. Continued research into the stereochemistry of drugs may lead to the development of newer, safer, and more efficacious drugs and other chemical compounds.

Animals↗
PubMed2004

Teaching pharmacology to medical students in an integrated problem-based learning curriculum: an Australian perspective.

The world-wide move away from the didactic teaching of single disciples to integrated Problem-based Learning (PBL) curricula in medical education has posed challenges for the basic sciences. In this paper we identify two major challenges. The first challenge is the need to describe a core disciplinary curriculum that can be articulated and mapped onto the new structure. We illustrate how the British Pharmacological Society (BPS) Guidelines are used to evaluate the curriculum coverage in the medical course at The University of Melbourne. The second challenge is to ensure that foundational concepts are given adequate emphasis within the new structure, and in particular, that students have the opportunity to pursue these concepts in their self-directed learning. We illustrate one approach to teaching important pharmacological concepts in an integrated curriculum with a case study from the first year curriculum at The University of Melbourne. Finally, we propose the features of an integrated curriculum that facilitates the learning of basic pharmacology in a situation where PBL and integration sets the curriculum framework.

Australia↗
PubMed2004

Teaching of pharmacology in Universiti Malaya and the other medical schools in Malaysia -- a historical perspective.

Traditional pharmacology teaching has focused more on drug instead of therapeutics, such that although pharmacological knowledge is acquired, practical skills in prescribing remain weak. In Malaysia many new medical schools (both public and private) have been set up in the last 12 years due to a change in government policy, resulting in a wide spectrum of medical curricula. Universiti Malaya (UM) being the oldest medical school in Malaysia was deep set in its traditional way of teaching-learning, since its inception in 1962, until a visit from the General Medical Council of the United Kingdom in 1984 triggered off a change of tide. Since then the medical curriculum in UM has undergone two major revisions. The first revised curriculum (1988) aimed to inject more clinical relevance into basic science teaching, through introducing clinical lectures and skills in the paraclinical year. Professional behaviour was also addressed. The second revised curriculum (1998) sought to improve further the integration of knowledge as well as to produce a holistic doctor, viewing the patient as a person instead of a clinical entity. The teaching-learning of pharmacology has gradually moved from factual regurgitation to more clinical reasoning, from lab-based to more patient-oriented approach. As more new medical schools are being set up in Malaysia, exchange of experience in this area of learning will hopefully help us find a happy medium between "the old is best" and "the new is better" type approach so that a pedagogically sound and yet logistically practical curriculum can be found in our local setting, to help produce doctors with good prescribing practice.

Curriculum↗
PubMed2004

Pharmacology teaching and its reform in China.

The general situation of pharmacology teaching in China was introduced and the educational reform in China in recent decade is summarized. The aim of the article is to provide those who are interested in teaching of pharmacology to be acquainted with the teaching of pharmacology, including the teaching of both principles and practice, in China.

China↗
PubMed2004

Problem-based learning in pharmacology: a survey of department heads in Taiwan, China.

Problem-based learning (PBL) requires active student participation and the use of clinical cases as a trigger to learn within a given area. It has gained much attention as a pedagogic alternative in the course of reform in medical education due to information overload. From discipline-based consideration, it is interesting to understand the views of department heads of pharmacology about implementing PBL for their medical students. According to a general survey from the heads of the department of pharmacology across medical schools in Taiwan, we found that although serious reservation about the approach remains, many departments indeed look forward to including PBL component in their pharmacology curriculum.

Education, Medical, Undergraduate↗
PubMedDate not supplied

[Historical Archives of Italian Nephrology. The form, evocative of function. A short historical review about the discovery of drugs from the most remote times to new trends in pharmacological sciences].

The image, the imaginary and the imagined are more than ever the guide in pharmacological research, and predominate in the expectations of discovering, designing and producing a potential drug. The concept of ""form"" is now corroborated and implemented by the most recent and astounding acquisitions on the existing relationship in biology between form, structure and function. This article is a brief historical reconstruction of how the ""form"" has represented, from the most remote times, a fundamental guiding criterion in the choice of potential pharmacological remedies, and how in times of biotechnology and informatics the design and development of new drugs is based on the assumption that the form-function requisite is among the most promising trends in pharmacological sciences and drug discovery, in the nephrology field too.

History, 18th Century↗
PubMed1991

[Molecular pharmacology--the road to selective pharmacotherapy?].

The intensive research in molecular pharmacology over the past few years has provided completely new insights into the mechanisms underlying pharmacological specificity. At the molecular level, signal transmission from the receptor to the cellular effector mechanism manifests far greater diversity than formerly supposed. In part, this diversity is due to the combination of separate molecular entities into a pattern specific for a given cell type. An added complication is the frequent crosstalk between different receptor signal transmissions. Thus, where specificity is concerned, only rarely is it a question of a specific molecular entity that can be targeted for the action of pharmacological agents. Moreover, disease may be due to an imbalance in signal transmissions that can only be combated by a multiple targeting approach. Accordingly, although the techniques of molecular biology are invaluable in generating new understanding of the mechanisms underlying drug specificity, they may prove disappointing as applied to actually tailoring specific drugs for the treatment of such major human ailments as hypertension or schizophrenia.

Animals↗
PubMed1991

[Recent past years of the Network of Clinical Pharmacology-- contradictions, central measures, possibilities].

Problems in connection with the activity of Clinical Pharmacological Network, the debate conferences of the recent past and measures taken recently put the Network i.e. the clinical pharmacological activity in the center of attention of the professional public opinion. It appeared therefore necessary that a short and possibly objective summary be prepared of the problems of the recent past and measures taken for their solution and last but not least of the present situation and ways planned for the future. Presenting these problems to the wide public is all the more worth as a high-level clinical pharmacology-activity in Hungary may be regarded as a key-issue of the pharmaceutical research. The development of the pharmaceutical industry in Hungary cannot be indifferent either from the viewpoint of economy or of a public health care on appropriate level.

Drug Industry↗
PubMed1987

[Postgraduate training in veterinary pharmacology].

The system of postgraduate training of veterinary pharmacology in the European countries is different--in some countries it is connected mainly with the intensive research work and with the obtaining of academic ranks (Ph. D., Dr. Sc.), in others--with attendance at special courses, with nonobligatory research work and with the obtaining of certificates (diplomas); in more countries are organized short-term courses for qualification and refreshment of the knowledge of the pharmacologists. There are no special forms of post-graduate work of pharmacologists for the pharmaceutical industry. Proposals are brought forward for postgraduate work of veterinary pharmacology in the range of European Association of Veterinary Pharmacology and Toxicology (E. A. V. Ph. T.)--unified system of special courses (long-term and middle-term) for specialization of the higher graduates and forms of education, connected with the obtaining of academic rank. There are recommended definite courses, including international, for raising the qualification and for refreshment of knowledge of the working veterinary pharmacologists, also courses, organized with the help of outstanding guest-scientists, invited in definite countries, and mutual visits of institutes and laboratories. For pharmacologists, in the pharmaceutical industry is recommended preliminarily 2-years education in universities or academies, and after that a special education in the research laboratories of the pharmaceutical firms. It is usefull for all courses to use not only the classic forms of education--lectures, but as well films, videos, computers etc.(ABSTRACT TRUNCATED AT 250 WORDS)

Education, Continuing↗