Use and abuse of psychoactive drugs in the elderly.

The elderly are susceptible to many psychiatric symptoms caused by the vast array of drugs they may take. Therefore, history-taking demands a very careful look at all their medicines. In this paper some dangers of over-the-counter drugs are described, and the paradox of psychotropic drugs sometimes causing psychiatric side effects is discussed. Several types of drugs and their side effects are outlined, and suggestions are made for appropriate drug treatment in this age group.     

In thrombin stimulated human platelets Citalopram, Promethazine, Risperidone, and Ziprasidone, but not Diazepam, may exert their pharmacological effects also through intercalation in membrane phospholipids in a receptor-independent manner

Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processes according to the drugs’ intercalation capability. We investigated effects of Promethazine, Citalopram, Ziprasidone, Risperidone, and Diazepam on phospholipase A₂ (PLA₂) and polyphosphoinositide (PPI) metabolism in thrombin-stimulated human platelets. We also examined effects of the drugs on monolayers of glycerophospholipids using the Langmuir technique. Diazepam did not influence PLA ₂ activity, had no effects on PPI cycle, and caused no change in mean molecular area of phospholipid monolayers. The remaining psychotropic drugs affected these parameters in different ways and levels of potency suggesting that they act by being intercalated between the molecules of adjacent membrane phospholipids, thus causing changes in substrate availability for phospholipid-hydrolyzing enzymes (PLA₂ and Phospholipase C). We show that several psychotropic drugs can also have other cellular effects than receptor antagonism. These effects may be implicated in the psychotropic effects of the drugs and/or their side effects.     

Perspectives on genetic animal models of serotonin toxicity

Serotonin syndrome, or serotonin toxicity, is a serious disorder attributable to exaggerated serotonergic function in the brain, most commonly after antidepressant overdose or after combining several psychotropic medications. Similar condition (serotonin syndrome-like behavior) can be evoked in animals experimentally, following administration of serotonergic drugs. In addition to pharmacological stimulation, some genetic and other factors may contribute to serotonin toxicity, prompting the need for new experimental genetic models relevant to this disorder. Here we discuss current problems and perspectives regarding genetic animal models of serotonin-related syndromes, and outline the potential utility of these models in experimental neurochemistry and clinical research.     

The interaction of psychotropic preparations with immunocompetent targets as the basis for their future nontraditional use

Published data on interactions of some psychotropic drugs with immunocompetent target cells has been reviewed. The observed immunosuppressive, immunostimulating, and immunomodulating activities of the drugs are considered nontraditional. The necessity of more detailed study of mechanisms of such interactions is outlined. Possible use of psychotropic drugs as immunomodulators is proposed.     

Dysfonction érectile d’origine médicamenteuse: effet indésirable sous-estimé en pharmacovigilance

Some drugs can induce erectile dysfunction (priapism or impotence) due to their pharmacological properties. Some adverse effects (ADRs) are only detected after marketing of the drug with a low frequency (unexpected ADRs). Pharmacovigilance and pharmacoepidemiologic studies collect data about real drug use and contribute to a better evaluation of the benefit/risk ratio. Data about cases of erectile dysfunction spontaneously reported to the French Pharmacovigilance system were collected over a 5-year period (2000 to 2004). 39 cases of drug-induced priapism were identified, 25 of which were classified as serious (62.5%), mainly due to anticoagulants (12 cases), psychotropic drugs (8 cases), phosphodiesterase inhibitors (8 cases) and beta-blockers (2 cases). During the same period, 214 cases of impotence either isolated or associated with ejaculation dysfunction were reported, mainly with antiretroviral drugs, fibrates and HMG CoA reductase inhibitors, psychotropic drugs and beta-blockers. Our data indicate that some ADRs, such as erectile dysfunction, are severely under-reported. Spontaneous reporting and pharmacoepidemiologic studies could contribute to a better knowledge of drugs and their rational use.     

Specificity of the action of piracetam, encephabol and Cleregil on the transcallosal evoked potential

The influence of some drugs having nootropic effect on transcallosal evoked potential was studied in the experiments on non-anesthetized rabbits. Pyracetam, pyritinol and cleregil have been established to increase the amplitude of transcallosal evoked potential. Each of these drugs was found to exert specific effects on this neurophysiological phenomenon. The authors suggest that transcallosal evoked potential can prove helpful in the detection of new drugs with possible nootropic effect.     

Elimination of F'lac plasmid by different psychotropic drugs and some related compounds.

Desipramine, trimipramine, protriptyline, noxiptyline, promazine, trimeprazine, triflupromazine and chlorprothixene methoiodide eliminated the F'lac plasmid of Escherichia coli, while thiazinanum, toluidine blue, lidocaine and procaine were ineffective in this respect. The plasmid eliminating action of the drug ceased in the presence of 0.05 M magnesium sulphate. Methylene blue did not inhibit plasmid elimination by the psychotropic drugs, and in presence of the dye even lidocaine and procaine became effective. Based on plasmid elimination in the presence of methylene blue and on the selective effects of the lon- mutant, the plasmid eliminating mechanism of psychotropic drugs seems to differ from that of acridine orange.     

Cocaine and central monoaminergic neurotransmission: a review of electrophysiological studies and comparison to amphetamine and antidepressants

Psychomotor stimulants (e.g. cocaine and amphetamine) and many antidepressants are believed to elicit their psychotropic actions by interacting primarily with central monoaminergic neurons. The acute central neuronal effects of amphetamine and antidepressants have been extensively investigated in rats utilizing extracellular single unit electrophysiological and microiontophoretic techniques in vivo. In recent years the chronic effects of these compounds on the above neuronal systems have also been reported. Such investigations have proliferated because of the realization that the mechanisms underlying the psychotomimetic effects (e.g. amphetamine and cocaine) and mood elevation (i.e. antidepressants) observed with the administration of these drugs are more accurately reflected in chronic studies. For many years it has been assumed that cocaine and amphetamine produce very similar if not identical psychotropic effects through their actions on central monoaminergic neurotransmission. In terms of effects on single monoaminergic neurons, this assumption had gone by untested until two years ago, when the first report of the electrophysiological effects of cocaine on central monoaminergic (locus ceruleus) neurons appeared in the literature (61). This review discusses recent electrophysiological studies with cocaine at the level of single identified monoaminergic neurons and compares such data with that previously reported for amphetamine and antidepressants. In addition to identifying some of the similarities and differences between these compounds, this review also highlights some of the gaps in our knowledge regarding the effects of these drugs on central monoaminergic neurotransmission.     

Histone Modifications Are Associated with Δ9-Tetrahydrocannabinol-mediated Alterations in Antigen-specific T Cell Responses

Marijuana is one of the most abused drugs due to its psychotropic effects. Interestingly, it is also used for medicinal purposes. The main psychotropic component in marijuana, Δ⁹-tetrahydrocannabinol (THC), has also been shown to mediate potent anti-inflammatory properties. Whether the immunomodulatory activity of THC is mediated by epigenetic regulation has not been investigated previously. In this study, we employed ChIP-Seq technology to examine the in vivo effect of THC on global histone methylation in lymph node cells of mice immunized with a superantigen, staphylococcal enterotoxin B. We compared genome-wide histone H3 Lys-4, Lys-27, Lys-9, and Lys-36 trimethylation and histone H3 Lys-9 acetylation patterns in such cells exposed to THC or vehicle. Our results showed that THC treatment leads to the association of active histone modification signals to Th2 cytokine genes and suppressive modification signals to Th1 cytokine genes, indicating that such a mechanism may play a critical role in the THC-mediated switch from Th1 to Th2. At the global level, a significant portion of histone methylation and acetylation regions were altered by THC. However, the overall distribution of these histone methylation signals among the genomic features was not altered significantly by THC, suggesting that THC activates the expression of a subset of genes while suppressing the expression of another subset of genes through histone modification. Functional classification of these histone marker-associated genes showed that these differentially associated genes were involved in various cellular functions, from cell cycle regulation to metabolism, suggesting that THC had a pleiotropic effect on gene expression in immune cells. Altogether, the current study demonstrates for the first time that THC may modulate immune response through epigenetic regulation involving histone modifications.     

The effect of newly synthesized psychotropic preparations on the "open field" behavior of rats]

The results of effect of some new synthesized psychotropic drugs of nootropic series on rats' behavior in "open field" are given. The increase of locomotive activity and decrease of emotional tension correlated with the rise of rats' ability to learning during working-out of avoidance reaction in shuttle-box, e.i. conditionally reflectory memory. It has been concluded that the study of dynamics of behavioral reactions in "open field" may be used for testing of new synthesized psychotropic drugs of nootropic series.     

Role of drugs in traffic accidents.

Serum samples from 201 drivers who presented at emergency departments within six hours after being injured in a road accident and 325 control drivers selected randomly at petrol stations were screened for drugs by combined thin-layer and gas chromatography. Blood alcohol concentrations were also measured, and a questionnaire on the subjects'' state of health and use of drugs administered. At interview 30 patients (15%) and 44 controls (13%) said that they had taken drugs in the previous 24 hours. Four patients (2%) and six controls (2%) said that they had taken psychotropic drugs, but serum analysis detected psychotropic drugs in 10 patients (5%) and eight controls (2.5%). Diazepam was found in 16 of the 18 subjects in whom psychotropic drugs were detected. Alcohol was detected in 30 patients (15%) and three controls (1%). Drug use appeared to be somewhat lower in Finland than in other Western countries, and illness to be a more important traffic hazard than drugs in general. Interview was not a reliable method of establishing whether drivers had taken psychotropic drugs. Taking diazepam may increase the risk of being involved in a traffic accident, but alcohol was the most powerful risk factor.     

Medicating children: the case of Ritalin

In response to recent concerns about the overmedication of children, this paper considers ethical and conceptual issues that arise in the issue of when children who are diagnosed with attention deficit hyperactivity disorder should be given stimulants such as the psychotropic drug Ritalin as part of their treatment. There is considerable resistance and worry about the possibility of overmedication. This is linked to the worry that the diagnosis of ADHD is overused, and the paper considers some reasons to worry about the overuse of the diagnosis itself. The paper then focuses on the resistance to the use of drugs, which is particularly strong for children in the gray area of diagnosis, where it is dubious whether the children really meet the strict diagnostic criteria. The reasons behind such resistance are often not well articulated, so part of the task of the paper is spell out what they might be. The reasons are given the following labels: side effects, unnaturalness, profit motives, thought control, competitiveness, and doctors' power. The paper ends in taking the polemical position that while there is some legitimate concern about possible short and long term side effects of children taking psychotropic drugs, the other reasons for resistance are not well-founded.     

Variation de la flore levuriforme de la cavité buccale entre sujets témoins et sujets soumis aux psychotropes

The yeasts of buccal cavity were studied in a group of seventy-five subjects treated by psychotropic drugs in a psychiatric hospital, in a group of fifty-one subjects treated by psychotropic drugs at home, and in a basis group (100+50). It is found yeasts on 84% of treated subjects in a psychiatric hospital and only 40% in the other populations.     

Medicating Children: The Case of Ritalin

In response to recent concerns about the overmedication of children, this paper considers ethical and conceptual issues that arise in the issue of when children who are diagnosed with attention deficit hyperactivity disorder should be given stimulants such as the psychotropic drug Ritalin as part of their treatment. There is considerable resistance and worry about the possibility of overmedication. This is linked to the worry that the diagnosis of ADHD is overused, and the paper considers some reasons to worry about the overuse of the diagnosis itself. The paper then focuses on the resistance to the use of drugs, which is particularly strong for children in the gray area of diagnosis, where it is dubious whether the children really meet the strict diagnostic criteria. The reasons behind such resistance are often not well articulated, so part of the task of the paper is spell out what they might be. The reasons are given the following labels: side effects, unnaturalness, profit motives, thought control, competitiveness, and doctors' power. The paper ends in taking the polemical position that while there is some legitimate concern about possible short and long term side effects of children taking psychotropic drugs, the other reasons for resistance are not well-founded.     

Ontwikkeling van algoritmes voor oordeelkundig gebruik van psychofarmaca bij ouderen met verhoogd valrisico

Psychotropic drugs (hypno-sedatives, antidepressants and antipsychotics) are commonly used in the older population. On the long term, psychotropic drug use in older persons is associated with several negative functional outcomes such as an increased risk of falls. Gradual withdrawal of psychotropic drugs in older persons is feasible and leads to a significant reduction of falls. Both withdrawal of psychotropic drugs as well as the initiation of appropriate treatment with psychotropic drugs requires knowledge, consultation and cooperation between disciplines and a mentality change among healthcare professionals. In order to inform and support healthcare professionals, the Centre of Expertise for Fall and Fracture Prevention Flanders developed three clinical practice algorithms for the appropriate use of psychotropic drugs in older persons with high risk of falls and a fact sheet with background information.     

In vitro effect of 1,2-dihydro-3H-1,4-benzodiazepine-2-one derivatives on the platelet aggregation and lipid peroxidation in rats]

There were discovered the anti-aggregative properties of some psychotropic drugs as gidazepam, phenazepam and its derivatives 3-oxyphenazepam, esters of 3-oxyphenazepam, with IC50 values of 8.19-11 x 10(-4) M. On their anti-aggregative effects they exceed of the acetylsalicylic acid (IC50 = 21.3 x 10(-4) M). Only gidazepam, containing in its chemical structure hydrazide fragment, caused significant decrease in the content of MDA. The possibility of involvement of lipid peroxidation in mechanism of its anti-aggregative effect is discussed.     

Chemiluminescent analysis of the antioxidant and immunomodulation effects of several psychotropic drugs on peritoneal macrophages.

The present study describes the application of several chemiluminescent (CL) methods for evaluation of antioxidant and immunomodulation effects of psychotropic drugs upon phagocytes: KO2-induced luminal-dependent CL for detection of superoxide anion radicals in a pure chemical system; PMA- and A23187-induced CL of peritoneal macrophages for detection of free radicals in cell suspension; and CL, produced by the luciferase-catalyzed luciferin + ATP reaction, for evaluation of cell viability before and after drug application. These methods provide also a way to investigate the location of drug action. It was found that the psychotropic drugs in fluence the 'oxidative burst' of macrophages through two mechanisms: by expression of drug antioxidant properties and/or by a direct immunomodulation effect.     

The "sensory" safety of drugs: photosensitizing damage to the structures of the eye]

Phototoxic side effects of a number of different drugs and natural photosensitizers [correction of photosensors] (psoralenes, psychotropic phenotiazines, anti-malaria drugs, porphirines, adriamycine, etc.) have been analyzed. The ways of study of sensory harmlessness of drugs have been discussed.