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PubMed2003

Pharmacology education: a theoretical framework of applied pharmacology and therapeutics.

United Kingdom Government initiatives such as The NHS Plan (DoH 2000) identified the need for nurses to undertake multi-skilled professional roles. In the United Kingdom, the transition to a larger graduate nurse workforce continues, as Universities offer nurse pre-registration courses at diploma and degree levels. Concomitant with the change in educational standard is the need to teach student nurses the theoretical principles of medication management and to develop skills in clinical reasoning skills. Both elements are limited in current educational pre-registration nurse programmes, in order to develop the future, multi-skilled workforce such courses should incorporate the theory and skills of health assessment, physical examination, applied pharmacology and clinical reasoning. This paper aims to examine how knowledge of applied pharmacology and therapeutics can be integrated into an undergraduate pre-registration nursing programme. Discussion focuses on how this generic framework can provide educators with an outline of the theoretical constructs, their application, the teaching strategies involved and instruction on how to prepare nurses to clinically reason with regard to medication management issues. This framework can be adapted to accommodate nurses studying for all parts of the register.

Clinical Competence↗
PubMed2007

American Board of Clinical Pharmacology fellowship training and certification in clinical pharmacology: educational value and future needs for the discipline.

Currently, the training and education of young clinical pharmacologist who represent the future of our discipline rest almost entirely on institutions/organizations with established and productive fellowship training programs. Here, we discuss the role of the American Board of Clinical Pharmacology (ABCP) in accrediting fellowship training programs and certifying individual clinical pharmacologists. We also explore how ABCP certification adds value to both individual trainees and the discipline in the evolving world of clinical therapeutics and research in human pharmacology.

Certification↗
PubMed1991

[Pharmacology of the memory. Review of cognition activator pharmacology].

The pharmacology of memory is fraught with problems. For one thing, the lack of consensus on the definition of memory and the absence of reference compound create clinical validation problems for new drugs. Then, it is difficult to predict clinical effectiveness on the basis of animal experiments and data obtained from healthy subjects, and this is due to the lack of analogy between animal models and clinical situations. Finally, to this must be added the complexity and variety of the possible modes of action of the agents under study. Thus, the pharmacology of cognition activators is closely dependent upon both fundamental research and clinical research.

Animals↗
PubMed1990

[Cardiovascular pharmacology. An example of the need of clinically relevant pharmacological research].

Like all other scientific disciplines, preclinical pharmacological research is subject to permanent changes. New measuring devices and the possibility of continuous on line data acquisition have markedly influenced basic research in this field. Another aim of modern cardiovascular pharmacology is the testing of promising drugs in clinically relevant animal models of disease, particularly under conditions, referring to the everyday situation in patients, e.g. physical activity. Investigations carried out in this way allow an exact assessment of the clinical efficacy of new drugs, and are, thus, clearly indispensable, also from the ethical point of view, before primary evaluation of the drug in man.

Angina Pectoris↗
PubMed1990

The pharmacology and clinical pharmacology of defibrotide: a new profibrinolytic, antithrombotic and anti-platelet substance.

Defibrotide, a deoxypolyribonuclide, has been found to modulate endothelial cell function causing increase in t-PA and decrease in PAI levels and also increase in PGI2 production. In addition, it increases platelet c-AMP levels and decreases MDA and TXB2 formation in human. Defibrotide inhibits platelet aggregate formation in vitro experiments as well as end-to-end anostomosis in rats. So, defibrotide inhibits the activation of platelets. Besides an increase of protein C and S levels a synergic action of heparin was observed in animal experiments. A strong antithrombotic effect has been observed in animal models. The drug has a beneficial effect in the cases of DVT, POVD, stroke and thromboembolism. Through its action we may say that the drug acts in a novel fashion in contrast to the other drugs used in this area. Defibrotide is a single-stranded polydeoxyribonucleotide obtained from deoxyribonucleic acid of mammalian lungs by controlled depolimerization. Since 1981 in our laboratory and in the clinical department we have been investigating a newly developed agent defibrotide in vitro experiments, animal experiments, and also its clinical pharmacology and clinical application. Some of our findings are already published and compared with literature (40, 43, 46). Because of the limited space we are not going to review the literature in detail but we are going to summarize our observations on this compound in the following order. I--in vitro experiments, II--Animal experiments, III--clinical pharmacology in human.

Animals↗
PubMed1990

Pharmacology and clinical pharmacology of organic nitrates.

Current concepts and future aspects of pharmacological interventions in the treatment of coronary heart disease have been compiled. Especially new insights in the pathophysiology of coronary heart disease e.g. the dynamic pathology of coronary atherosclerosis, possible role of endothelin in vasospasm, as well as new pharmacodynamic and pharmacokinetic aspects of organic nitrates are discussed. Also the role of sympathetic nervous system as a pivotal question in pathophysiology and clinical pharmacology in the treatment of angina pectoris has been considered.

Adrenergic beta-Antagonists↗
PubMed1995

Review of the pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA or "Ecstasy").

3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") was first synthesised 80 years ago, but has recently received prominence as an illegally synthesised recreational drug of abuse. There is a widely held belief among misusers that it is safe. In the last 2-3 years there have been a number of reports of the drug producing severe acute toxicity and death and there are concerns that it may cause long term toxic damage to 5-hydroxytryptamine (5-HT) nerve terminals. There is a considerable literature on the acute pharmacological effects of MDMA in experimental animals, and this is reviewed. The drug produces both hyperthermia and the "serotonin syndrome", a series of behavioural changes which result from increased 5-HT function. Acute clinical toxicity problems following MDMA ingestion also include hyperthermia and the appearance of the serotonin syndrome. The hyperthermia appears to precipitate other severe clinical problems and the outcome can be fatal. In agreement with others, we suggest that the recent increase in the number of reports of MDMA toxicity probably results from the widespread use of the drug at all night dance parties or "raves". The phenomenon of amphetamine aggregation toxicity in mice was reported 40 years ago. If applicable to MDMA-induced toxicity in humans, all the conditions necessary to induce or enhance toxicity are present at raves: crowded conditions (aggregation), high ambient temperature, loud noise and dehydrated subjects. Administration of MDMA to rodents and non-human primates results in a long term neurotoxic decrease in 5-HT content in several brain regions and there is clear biochemical and histological evidence that this reflects neurodegeneration of 5-HT terminals. Unequivocal data demonstrating that similar changes occur in human brain do not exist, but limited and indirect clinical evidence gives grounds for concern. There are also data suggesting that long term psychiatric changes can occur, although there are problems of interpretation and these are reviewed. Suggestions for the rational treatment of the acute toxicity are made on the basis of both pharmacological studies in animals and current clinical practice. Cases presenting clinically are usually emergencies and unlikely to allow carefully controlled studies. Proposals include decreasing body temperature (possibly with ice), the use of dantrolene and anticonvulsant and sedative medication, particularly benzodiazepines. The use of neuroleptics requires care because of the theoretical risk of producing the neuroleptic malignant syndrome and the possibility of precipitating seizures. In rats, chlormethiazole antagonises the hyperthermia produced by MDMA and has been shown clinically to block MDMA-induced convulsive activity.

Animals↗
PubMed2006

Chronic headaches: pharmacological and non-pharmacological treatment.

Chronic headaches have increasingly become a focus within the field of head pain. The biological and physiopathological origins of chronic headaches probably reside in receptor physiology, but it is also probable that the initiation and sustaining dynamics of this pathological condition involve several other factors. Not all, but most patients with frequent headache eventually overuse their medications, and when this happens (approximately 1%), the diagnosis of medication-overuse headache is clinically important, because patients rarely respond to preventive medications while overusing acute medications. Properly treating medication overuse and preventing relapse require recognition of the different factors that contribute to its development and perpetuation, including some behaviours and psychological elements that are important in sustaining the overuse of medication. The problems concerning the diagnosis, classification and clinical aspects of chronic headaches are mentioned. Also the different therapeutical approaches, pharmacological and non-pharmacological, initial outcomes and long-term durability of treatment are discussed.

Headache Disorders↗
PubMed1998

Pharmacological effects of SA96 (bucillamine) and its metabolites as immunomodulating drugs--the disulfide structure of SA-96 metabolites plays a critical role in the pharmacological action of the drug.

SA96 (generic name, bucillamine) is a disease-modifying anti-rheumatoid arthritis (RA) drug with immunological effects. This compounds has two sulfhydryl groups in its molecule, and the differences and similarities between this drug and D-penicillamine, which is also a sulfhydryl group-containing anti-rheumatic drug, have frequently been discussed. To clarify the pharmacological differences between these two drugs, we examined the concentrations of the compounds and its metabolites in serum and synovial fluid, paying special attention to the metabolites of SA96 produced in vivo. SA96 was metabolized in a very short time to SA981 which is a disulfide compound formed by intramolecular binding of two sulfhydryl groups, and transferred to synovial fluid. In addition SA981 had significant suppressive effects on IL-6 and IL-8 production by synovial cells in vitro. These results demonstrate that SA96, which has two sulfhydryl groups, exhibits anti-rheumatic effects via a pharmacological action clearly different from that of D-penicillamine.

Adjuvants, Immunologic↗
PubMed2000

Adherence to pharmacological interventions. Current trends and future directions. The Pharmacological Intervention Working Group.

The complexity of adherence to pharmacological interventions is frequently underestimated. Consequently, little research has been done to understand, improve, or evaluate the effects of adherence to drug protocols. While efforts to better measure and increase adherence require dedicated resources, improved adherence in existing clinical research can potentially cut costs in trial size and length. This paper outlines strategies to facilitate research on adherence to pharmacological interventions including: reporting of adherence data, changing how we conceptualize adherence to pharmaceuticals, understanding issues unique to older adults' pill-taking behavior, and creating standardized methodologies to measure adherence. Further, we describe some promising research areas that may lead to effective interventions: adherence "typologies" and modality matching. Control Clin Trials 2000;21:218S-225S

Aged↗
PubMed2002

Synthesis and pharmacological activity of new carbonyl derivatives of 1-aryl-2-iminoimidazolidine. Part 3. Synthesis and pharmacological activity of 1-aryl-5,6(1H)dioxo-2,3-dihydroimidazo[1,2-a]imidazoles.

Synthesis and pharmacological activity of 1-aryl-5,6(1H)dioxo-2,3-dihydroimidazo[1,2-a]imidazoles (D) are presented. The title compounds were obtained from 1-aryl-2-iminoimidazolidines (1) by cyclization reaction with oxalic acid derivatives-ethyl ester (2) or chloride (3). They were tested for pharmacological activity in animal and binding assay tests. With moderate acute toxicity (LD(50) approximately 200 mg kg(-1), i.p.), they exhibited significant analgesic and serotonergic activities as results of the 'writhing' and the 'hot plate' tests indicated, and reduced number of 'head twitch' episodes after 5-HTP (5-hydroxytryptophan) administration. Reversion of the antinociception produced in the 'writhing' test by small dose of naloxon (5 mg kg(-1)) can suggest an opioid-like mechanism of their analgesic activity. The probable receptor inhibition mechanism of their analgesic and serotonergic activity was confirmed in the binding assay tests (by radioligand displacement) toward the opioid mu and serotonin 5-HT(2) receptors. Additionally, they exhibited affinity toward the benzodiazepine (BZD) receptor as well, although in behavioral tests compounds did not produce any clear depressive effect on the central nervous system (CNS) of mice. Simple chemical structure of the title compounds, in comparison to other carbonyl derivatives of 1-aryl-2-iminoimidazolidine presented in this series of papers, underline very important role both of a hydrophobic moiety (aromatic ring) and polar groups (hydrogen-bond acceptors) in the serotonin receptor interaction. The co-existence of opioid-like, serotonergic and BZD receptor inhibition activity can be very interesting and can lead to creation of the novel group of antidepressants.

5-Hydroxytryptophan↗
PubMed2001

Pharmacology and behavioral pharmacology of the mesocortical dopamine system.

The prefrontal cortex (PFC) has long been known to be involved in the mediation of complex behavioral responses. Considerable research efforts are directed towards refining the knowledge about the function of this brain area and the role it plays in cognitive performance and behavioral output. In the first part, this review provides, from a pharmacological perspective, an overview of anatomical, electrophysiological and neurochemical aspects of the function of the PFC, with an emphasis on the mesocortical dopamine system. Anatomy of the mesocortical system, basic physiological and pharmacological properties of neurotransmission within the PFC, and interactions between dopamine and glutamate as well as other transmitters within the mesocorticolimbic circuit are included. The coverage of these data is largely restricted to what is relevant for the second part of the review which focuses on behavioral studies that have examined the role of the PFC in a variety of phenomena, behaviors and paradigms. These include reward and addiction, locomotor activity and sensitization, learning, cognition, and schizophrenia. Although the focus of this review is on the mesocortical dopamine system, given the intricate interactions of dopamine with other transmitter systems within the PFC and the importance of the PFC as a source of glutamate in subcortical areas, these aspects are also covered in some detail where appropriate. Naturally, a topic as complex as this cannot be covered comprehensively in its entirety. Therefore this review is largely limited to data derived from studies using rats, and it is also specifically restricted to data concerning the medial PFC (mPFC). Since in several fields of research the findings concerning the function or role of the mPFC are relatively inconsistent, the question is addressed whether these inconsistencies might, at least in part, be related to the anatomical and functional heterogeneity of this brain area.

Animals↗
PubMed1989

Brain entry and direct central pharmacological effects of the nootropic drug oxiracetam. Oxiracetam: brain entry and pharmacological effects.

Oxiracetam administered systemically to rats as a 14C radiolabelled drug (200 mg/kg p.o. or 100 mg/kg intra-artery) enters the brain and is found unmetabolized above all in some of the brain areas functionally involved in the modulation of cognitive processes. Among the brain areas examined, the largest amount of compound was recovered in septum, followed by hippocampus; a smaller amount was found in cerebral cortex and striatum. 14C oxiracetam administered directly into the lateral ventricles of the brain presented a similar pattern of distribution, indicating that the tropism of the drug for the above brain areas does not depend on its route of administration. The amounts of oxiracetam that could reach the brain after systemically administered pharmacologically active doses were also estimated. These amounts (1.9 to 19 nmols/rat) were delivered through a permanently implanted cannula, into the lateral ventricles of the brains of conscious, freely moving rats. In this experimental condition oxiracetam dose-dependently antagonized the amnesia induced by scopolamine (0.66 mg/kg s.c.). The above findings clearly indicate that oxiracetam enters the brain and directly exerts its pharmacological activity there.

Administration, Oral↗
PubMed1987

Hormetic effects in pharmacology: pharmacological inversions as prototypes for hormesis.

A biological, physiological or biochemical response to a drug at a low dose may be completely opposite to that response when a larger dose is administered. Also, a response to a single dose of an agent may shortly afterwards be completely reversed. These observations are as old as the use of medicinal preparations or alcoholic beverages. The term "pharmacological inversions" can be used to describe these phenomena. A subset of the dose-response relationship is that of "hormesis." This term, "hormesis," is often used to denote the beneficial response of an organism to a low dose of a physical or chemical agent and a detrimental response to a much larger dose. Many, but not all, of the pharmacological inversions can serve as prototypes of hormesis. Examples of the dose-time effect or the dose-response relationship (which may include the phenomenon of hormesis) can be found among these agents: alcoholic beverages, anesthetic gases, barbiturates, some tranquilizers, many vitamins, caffeine, nicotine, salicylates, enzyme inducers and some toxic metals.

Animals↗
PubMed1979

[Pharmacological studies of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M73101). (3). General pharmacological actions (author's transl)].

General pharmacological actions of M73101, a new non-steroidal analgesic anti-inflammatory drug were investigated in mice, rats, guinea pigs, rabbits, cats and dogs. Intravenous administration of M73101 produced a slight transient fall in blood pressure, an increase in heart rate and a respiratory stimulation, but no remarkable change in the electrocardiogram. The contraction induced by epinephrine in the isolated ear vessels of rabbits relaxed by M73101. In the isolated trachea of guinea pigs, M73101 relaxed the contraction induced by histamine. Furthermore, M73101 inhibited the bronchoconstriction by histamine but not by bradykinin in guinea pigs. These properties of M73101 on the tracheal smooth muscle were similar to those seen with aminopyrine but different from those seen with aspirin which inhibited only the contraction by bradykinin in vivo, suggesting that M73101 is a compound with properties similar to basic non-steroidal anti-inflammatory drugs. M73101 inhibited the intestinal propulsion in mice and also the gastrointestinal movement in rats and dogs. Moreover, M73101 showed a spasmolytic activity on the isolated ileum of guinea pigs, but such was not due to any specific antagonistic action on the chemical mediators. On the other hand, M73101 had no effect on the isolated uterus and vas deferens of rats. M73101, unlike aminopyrine and phenylbutazone, slightly increased urine volume and electrolytes excretion in rats, indicating that this compound probably does not produced edema. M73101 showed no significant pharmacological activities on the blood sugar level, blood coagulation, platelet aggregation, methemoglobin formation and local irritation.

Animals↗
PubMed1981

[Pharmacological study of mequitazine (LM-209). (IV). General pharmacological action (author's transl)].

The general pharmacological actions of LM-209 were studied in rats, cats, dogs, guinea pigs and mice and the findings were compared with data on clemastine fumarate (CL). LM-209 but not CL produced a slight increase in pulse pressure and tachycardia. Inhibitory effects of LM-209 against contraction of the vas deferens and nictitating membrane, mainly dominated by sympathetic innervation, were remarkably less potent than CL. Inhibitory effects of LM-209 in the gastrointestinal tract were slightly more potent than CL. LM-209 accelerated norepinephrine-induced pressor reaction, while CL inhibited these effects at the dose level inhibiting histamine-induced depressor reaction. At the oral dose level showing anti-histaminic and anti-allergic actions, LM-209 but not CL had slight anti-tussive action, in an experimental model. Local anesthetic action of LM-209 was slightly more potent than that of lidocaine. LM-209 showed the same properties and potencies as CL, in most of the general pharmacological experiments.

Animals↗
PubMed1996

Ambulatory blood pressure monitoring: non-pharmacological and pharmacological treatment.

The main advantages of ambulatory blood pressure monitoring (ABPM) over clinic blood pressure measurements are the following: the lack of an alarm reaction and of observer bias; repeated readings during 24 h in the customary environment of the patient, instead of a single measurement in the doctor's office; superior reproducibility, allowing the sample size of study groups to be reduced substantially; and multiple data, likely to be analysed by several complementary methods. The different non-pharmacological interventions could be classified as follows: probably ineffective (sodium intake restriction, caffeine intake restriction, abstinence from alcohol consumption), probably effective (potassium supplementation, magnesium supplementation, weight reduction by overweight patients, cessation of smoking) and requiring further investigation (psychological interventions, physical activity, dietary lipid level modifications). The effects of pharmacological treatment may be accurately assessed by using ABPM: detailed information is given concerning the duration of action of the antihypertensive drugs; different regimens of the same treatment mayi be compared with each other or with placebo; and the trough: peak ratio can be determined for each drug. It is noteworthy that all of these subtle measurements have to be performed in patients the blood pressure of whom seems to respond adequately to the drug under evaluation. An additional key role for ABPM in clinical trials could be to establish selection criteria both for trial entry and for dose adjustment.

Journal Article↗
PubMed1986

Pharmacological effects of nalorphine and nalorphine-7,8-oxide (nalorphine-epoxide): interaction of the intrinsic activity, affinity and pharmacological responses.

We examined the relationship between the pharmacological effects and the interactions of the receptors of nalorphine and its epoxide. The abilities of nalorphine-epoxide to displace [3H]-dihydromorphine (mu-site) and [3H]-ethylketocyclazocine (kappa-site) were practically equal to those of the parent compound, nalorphine, using binding assay to the rat brain membrane preparations. Furthermore, the affinities of mu- and kappa-receptors are virtually uninfluenced by epoxidation of the 7,8-double bond of nalorphine using electrically stimulated mouse and rabbit vasa deferentia. The intrinsic activity of nalorphine, however, is considerably decreased by epoxidation. Moreover, the antagonistic effect of nalorphine to the morphine-induced antinociception (via mu-receptors) was little influenced by epoxidation, but the antinociceptive effect of nalorphine using the acetic acid writhing test was considerably reduced by epoxidation. These results suggest the presence of a higher receptor capacity for the antinociception mediated through kappa-receptors and that the differences between the pharmacological responses of nalorphine and its epoxide are due to the differences of their intrinsic activities.

Analgesics↗