PSYCHOTROPIC DRUGS

Author: DORADO HERNÁNDEZ PEDRO.
Year: 2002.
University: EXTREMADURA [More theses of this university] [www.unex.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The cytochrome P-450 2C9 (CYP2C9) introduced genetic polymorphism and participates in drug metabolism of great therapeutic value as warfarin, tolbutamide, phenytoin, losartan and many NSAIDs, such as diclofenaco.La variability in the metabolism of diclofenac has not yet been studied in a sufficiently large population of individuals sanos.Tampoco has been analyzed the influence of environmental factors and the genotype CYP2C9 on the metabolism of this drug. The CYP2C9 presents three alternatives aléticas in povlaciones Caucasian and appears to be that option CYP2C9 * 3 is the most significant influences on the activity of CYP2C9 in vivo.También CYP2D6 is polimorfico and it is known that participates in the metabolism of many psychotropics , as well as other drugs of importance clínica.Evaluar the possible influence of genotypes CYP2D6 and CYP2C9 on concentrations plasméticas of haloperidos and tioridacina and those on the QTc interval, it could help prevent the occurrence of adverse effects not seseados as arrhythmias cardiacoas type Torsade de Pointes and sudden deaths in psychiatric patient. Therefore, the main objectives of the work of this thesis can be grouped into three: 1) Determine the frequency of variants aléicas CYP2C9 in healthy volunteers and patients psiqueátricos to compare between these two gurpao in turn with the frequencies of the populations of healthy volunteers previamente4 gonotipadas. 2) To evaluate the influence of factors genético on the metabolism of diclofenac and losartan in healthy volunteers. 3) To study the influence of genotypes CYP2C9 and CYP2D6 on the plasma concentrations of haloperidos.tioridacina and metabolitoas, on the QTc interval, in a population of patients in psychiatric treatment. Based on the results obtained in the five studies which consists thesis draws the following conclusions: 1) The allelic frequencies of CYP2C9 in healthy volunteers are no different from the rest of Caucasian populations previously studied, nor to those found the patient population psiqueátricos studied. 2) The PRESENCE OF ALELO cyp2c9 * 3 influences the metabolism of diclofenac and loartan to 4'-OH diclofenac and E-3174 respectively. 3) The genotype CYP2C9, does not seem to influence the plasma concentrations of haloperidol, but can not be ruled influence partial CYP2D6, the number of patients treated with haloperodol with QTc interval, is abnormally high but has not found any related factor. 4) The genotip CYP2D6 and not CYP2C9, seems to influence the concentrations plasméticas of tioidacina, and these in turn, on the QTc interval in patients in psychiatric treatment.

Author: DORADO HERNÁNDEZ PEDRO.
Year: 2002.
University: EXTREMADURA [More theses of this university] [www.unex.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The cytochrome P-450 2C9 (CYP2C9) introduced genetic polymorphism and participates in drug metabolism of great therapeutic value as warfarin, tolbutamide, phenytoin, losartan and many NSAIDs, such as diclofenaco.La variability in the metabolism of diclofenac has not yet been studied in a sufficiently large population of individuals sanos.Tampoco has been analyzed the influence of environmental factors and the genotype CYP2C9 on the metabolism of this drug. The CYP2C9 presents three alternatives aléticas in povlaciones Caucasian and appears to be that option CYP2C9 * 3 is the most significant influences on the activity of CYP2C9 in vivo.También CYP2D6 is polimorfico and it is known that participates in the metabolism of many psychotropics , as well as other drugs of importance clínica.Evaluar the possible influence of genotypes CYP2D6 and CYP2C9 on concentrations plasméticas of haloperidos and tioridacina and those on the QTc interval, it could help prevent the occurrence of adverse effects not seseados as arrhythmias cardiacoas type Torsade de Pointes and sudden deaths in psychiatric patient. Therefore, the main objectives of the work of this thesis can be grouped into three: 1) Determine the frequency of variants aléicas CYP2C9 in healthy volunteers and patients psiqueátricos to compare between these two gurpao in turn with the frequencies of the populations of healthy volunteers previamente4 gonotipadas. 2) To evaluate the influence of factors genético on the metabolism of diclofenac and losartan in healthy volunteers. 3) To study the influence of genotypes CYP2C9 and CYP2D6 on the plasma concentrations of haloperidos.tioridacina and metabolitoas, on the QTc interval, in a population of patients in psychiatric treatment. Based on the results obtained in the five studies which consists thesis draws the following conclusions: 1) The allelic frequencies of CYP2C9 in healthy volunteers are no different from the rest of Caucasian populations previously studied, nor to those found the patient population psiqueátricos studied. 2) The PRESENCE OF ALELO cyp2c9 * 3 influences the metabolism of diclofenac and loartan to 4'-OH diclofenac and E-3174 respectively. 3) The genotype CYP2C9, does not seem to influence the plasma concentrations of haloperidol, but can not be ruled influence partial CYP2D6, the number of patients treated with haloperodol with QTc interval, is abnormally high but has not found any related factor. 4) The genotip CYP2D6 and not CYP2C9, seems to influence the concentrations plasméticas of tioidacina, and these in turn, on the QTc interval in patients in psychiatric treatment.

Author: SERRATS VILAR JORDI.
Year: 2003.
University: BARCELONA [More theses of this university] [www.ub.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The modulaciÃÂ ³ n the activity of neurons sertonÃÂ © rgicas located in nÃÂ fourth cleos the raphe (mainly in the nÃÂ kernel and the dorsal medial) plays a very important role in regulaciÃÂ ³ n different aspects fisiolÃÂ ³ ments, as the cycle sueÃÂ ± o-vigilia, The presence of different neurotransmitter receptors in nÃÂ fourth cleos the raphe has proposed using tÃÂ © cnicas electrofisiolÃÂ ³ gicas, microdiÃÂ ¡lisis and, in some cases through tÃÂ © cnicas histoquÃÂmicas. With intenciÃÂ charges of giving validity anatÃÂ ³ mica in the presence of certain receptors in cÃÂ © lulas of raphe, and to try to determine the phenotype of cÃÂ © lulas expressing these receptors for neurotransmitter we intended: 1-Studying the colocalizaciÃÂ charges of different mRNAs that code to neurotransmitter receptors (5-HT1A, 5-HT1B, 5-HT2C, 5-ht5B, GABAB, alfa1B adrenoceptor) with the markers cellular serotonÃÂ © rgico (5-HTT mRNA) and / or GABAÃÂ © rgico (GAD mRNA) by tÃÂ © cnica of double hibridaciÃÂ ³ n spot at different levels shaft rostrocaudal of nÃÂ fourth cleos dorsal medial and the raphe. Studying the effect of the destrucciÃÂ ³ n selective of cÃÂ © lulas serotonÃÂ © rgicas on the mRNAs of neurotransmitter receptors mentioned above. 2-To study the effect of pindolol on recipients 5-HT1A pre - and postsinÃÂ ¡pticos at transuccional through studies autorradiogrÃÂ ¡Features of fijaciÃÂ charges of GTPgammaS marked with [35S]. To carry out this study estimulÃÂ ³ receiver with 5-HT (ligand endÃÂ ³ geno), and bloqueÃÂ ³ with an antagonist (pindolol). It determinÃÂ ³ the possibility that recipients pre - and postsinÃÂ ¡pticos have properties transduccionales different. 3-Characterize neuroanatÃÂ ³ micamente connectivity of a subzone of nÃÂ kernel medial the raphe, specifically the area ventral nÃÂ kernel. With these results we have a better and mÃÂ ¡s detailed visiÃÂ charges of architecture neuroquÃÂmica of nÃÂ fourth cleos the raphe.

Author: REY SÁNCHEZ PURIFICACIÓN.
Year: 2003.
University: EXTREMADURA [More theses of this university] [www.unex.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The antipsychotic medication is widely used in patients diagnosed with schizophrenia. Given the chronic use of the same, it is necessary to determine the safety and tolerance of these agents in pobláción, target of these drugs. It is described in the bibliography that one of the effects is hyperprolactinemia in women and increased risk crólúco osteoporosis, and thus an increased risk of fractures, among others. We have studied the áIteraciones that produces tratanliento chronic antipsychotic drugs on bone mass, through a study transversáI in 73 schizophrenic patients, 48 men and 25 women, mean age 60.45 years, treated with these drugs. It has also studied a group of 73 healthy subjects of similar characteristics with respect to age, sex, race and geographic area, considered normáles based on blood tests and medical history, included as controls. Both patients and controls were reálizó studies: anthropometric (weight táIla, body mass index and fat-free mass), densitométrico (using ultrasound fálanges) hormonál (vitanlina D PTH Yprolactina) and biochemical (basic biochemistry and also, creatinine, calcium, phosphorus, total protein, phosphatase alcálina, tartrate-resistant acid phosphatase, and a study coagulation). After reálizarestosestudiosse found that: l. Women esquízofrénicas in tratanliento with conventional antipsychotic drugs were less valued by ultrasound bone mass than women controls. 2. The decrease in bone mass is associated with a lack of vitamin D, which leads hiperparatiroidísmo, and also manifests itself with an increased bone turnover. 3. The effect of drugs antipsícótícos conventional bone mass in women can be produced by the hypoestrogenism secondary to hyperprolactinemia presented, and the inhibitory effect of this on the osteoblasts. 4. In women esquizofrénícas treated with drugs antipsícóticos is necessary tracking bíoquímico and densitométrico, and ensuring an adequate intake of vitamin D, in order to prevent bone loss and consequently the appearance of osteoporotic fractures. 5. In male schizophrenics treated with antipsychotic drugs, we have not found impairment of bone mass assessed by ultrasound.

Author: REY SÁNCHEZ PURIFICACIÓN.
Year: 2003.
University: EXTREMADURA [More theses of this university] [www.unex.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The antipsychotic medication is widely used in patients diagnosed with schizophrenia. Given the chronic use of the same, it is necessary to determine the safety and tolerance of these agents in the target population for these drugs. It is described in the literature that one of the effects is hyperprolactinemia in women and increased risk of osteoporosis chronic and therefore an increased risk of fractures, among others. We have studied the changes that produces chronic treatment with antipsychotic drugs on bone mass, using a cross-sectional study in 73 schizophrenic patients, 48 men and 25 women, mean age 60.45 years, treated with these drugs. It has also studied a group of 73 healthy subjects of similar characteristics with respect to age, sex, race and geographic area, which are considered normal based on blood tests: anthropometric (weight, height, body mass index and fat-free mass), densitométrico (using ultrasound phalanges), hormone (vitamin D, and prolactin PTH), and biochemical basic biochemistry, and in addition, creatinine, calcium, phosphorus, total protein, alkaline phosphatase, tartrate-resistant acid phosphatase, and a study coagulation). After conducting these studies it was found that: 1, schizophrenic - Women treated with conventional antipsychotics were less valued by ultrasound bone mass than women controls. 2 - The decrease in bone mass is associated with a lack of vitamin D, resulting in hyperparathyroidism, and manifests itself in addition to an increase in bone turnover. 3, - The effect of conventional antipsychotic drugs on bone mass in women can be produced by the hypoestrogenism secondary to hyperprolactinemia presented, and the inhibitory effect of this on the osteoblasts. 4-In women schizophrenic treated with antipsychotic drugs is necessary track and densitométrico biochemist, and to ensure an adequate intake of vitamin D, in order to prevent bone loss and consequently the appearance of osteoporotic fractures. 5, men - schizophrenics treated with antipsychotic drugs, we have not found impairment of ultrasonic bone mass values.

Author: PICHINI SIMONA.
Year: 2004.
University: AUTÓNOMA DE BARCELONA [More theses of this university] [www.uab.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: ESCUELA DE POSTGRADO.

Author: RIVERA LOPEZ TELLO ANTONIO JOSE.
Year: 2004.
University: REY JUAN CARLOS [More theses of this university] [www.urjc.es].
Place of defense: FACULTAD DE CIENCIAS DE LA SALUD.
Place of preparation: FACULTAD DE CIENCIAS DE LA SALUD.

Summary: In the first part of this doctoral thesis explored the changes that occur with age in the structure and neurons plexus mientérico of the guinea pig ileum. and downstream, motoneuronas excitadoras). In terms of the structure was observed that with age comes a reduction in the size of gangllos and an increase in the relative number of neurons extragangllonares. These results could indicate a process of dismantling gangllonar in plexus mientérico of the guinea pig ileum. In terms asus neural alterations observed a significant loss of neurons mientéricas with age. This indicates that notodas populations of neurons mientéricas affected the same way with the passage of age, and that age could be producing an imbalance between the role exciting and inibidora gastrointestinal tract, which might be related the most common gastrointestinal problems in old age: constipation, gastroesophageal reflux, etc.. In the second part of this dissertation was observed by electrophysiological recording in the rat diaphragm, comoalgunos cannabinoids can produce changes in neuromuscular transmission that takes place at the diaphragm, specifically noted as the delta nine resulted in a facilltación of thc neuromuscular transmission, to increase the amount of neurotrasmisor that is released into space in synaptic potential of each plate motor terminal (quantum increase in the content). The synthetic antagonist win 55212-2 produced no change in the electrophysiological parameters analyzed. The observed effect for the delta nine thc was weakly antagonizado by elantagonistnagonista reverse cannabinoid sr 141716, for which the observed effect could be mediated by a receiver other than the recipients cannabionoides described so far.

Author: AMARGÓS BOSCH MERCE.
Year: 2004.
University: BARCELONA [More theses of this university] [www.ub.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The prefrontal cortex (CPF) plays a crucial role in higher brain functions, such as cognition, which are altered in schizophrenic patients. The pyramidal neurons of the medial FPC (CPFm) comprise aferencias excitatorias the cortex and thalamus, and modulatorias of nuclei aminérgicos brain medium: the raphe nuclei (NR), the locus coeruleus and the ventral tegmental area. In turn, CPFm controls the activity of neurons of serotoninergic NR. Previous studies have shown that the group stimulation of the receptors prefrontales 5-HT2A or AMPa increases the frequency of discharge of pyramidal neurons and serotoninergic, and the release of serotonin (5-HT) in the CPFm. We use the release of 5-HT (techniques microdialisis intracerebral) as an indirect measure of the activity pyramid. In this Doctoral Thesis we examined the role of excitatory and inhibitory receptors in cortical circuit CPFm-NR, since both regions are involved in schizophrenia. Given the similar laminar distribution of receptors h-HT2A and alpha1-adrenérgicos in CPFm and its action on the excitatory activity of pyramidal neurons, we have hypotheses that alpha1-adrenoceptores could also modulate the release of 5-HT. The antipsychotic drugs have a high affinity for receptor expressed in pyramidal neurons as 5-HT2A and alpha1-adrenoceptores. For this reason, we have also studied the effects of antipsychotics, as well as those of antognistas selective for these receptors on the increase in 5-HT in CPFm induced 1) the cirazolina (agonist alpha1-adrenérgico), 2) IPR (agonist sertoninérgico 5-HT2A/2C) and 3) increased glutamatergic neurotransmission. Our results have shown that stimulation of alpha1-adrenoceptores and increased glutamatergic transmission (through 1. Exogenous stimulation of AMPA receptors, 2.la desinhibición of aferencias talámica towards CPFm or 3.de Acute administration of non-competitive antagonists of the recipients glutamatérgicos NMDA) activates the aferencias pyramidal neurons serotoninergic upward toward (measured as an increase in the release of 5-HT in the NR and CPFm) possibly in a manner similar to that observed for receivers 5-HT2A. This effect was reversed by receptor antagonists exictatorios located in the pyramidal neurons, as well as by antipsychotic drugs. The CPFm contains a high density of receptors for serotonin 5-HT1A (inhibitory) and 5-HT2A (excitatory). Our studies have shown how the activation of receptor 5-HT1A cortical reverses the increase in the local release of 5-HT induced cirazolina DOI and S-AMPA. Finally, our studies suggest that antipsychotics exercise their therapeutic action by reducing the increased excitability of pyramidal neurons prefrontales. The effect of genetic conventional antipsychotics (haloperidol and chlorpromazine) involve blocking the alpha1-adrenoceptores, whereas that of the atypical (clozapine and olanzapine) would also blocking receptors receptors sertoninérgicos 5-HT2A.

Author: GARCÍA FUSTER M. JULIA.
Year: 2005.
University: BARCELONA [More theses of this university] [www.ub.es].
Place of defense: FACULTAD DE BIOLOGÍA.
Place of preparation: FACULTAD DE BIOLOGÍA.

Author: ALONSO-BARAJAS MARTINEZ RICARDO.
Year: 2005.
University: MÁLAGA [More theses of this university] [www.uma.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: Hypertension (ETS) and the metabolic syndrome (SM) is a public health problem. In many of the hypertensive patients and SM are common pathophysiological factors as increased insulin resistance, presence demarcadores proinflamatorios, protrombóticos presence of factors. The information available on the prevalence of SM in the hypertensive population in Spain is very low, especially when it comes to hypertension treated in hospital units, which makes it difficult to compare our population with other countries. The main objective of the study was to estimate the prevalence of SM, with criteria NCEP ATP III-2001 in hypertensive patients treated in a hospital unit of hypertension in Spain. And the Secondary objectives were to describe the cardiovascular risk factors, comorbidity, sintomatologia and laboratory parameters associated with the SM in the study population, describe the procedures followed in these study patients and treatments applied to them, analyze the prevalence rates obtained with the implementation of the new diagnostic criteria for SM, published recently. There has been an epidemiological study, transverse in a series of 720 hypertensive patients, treated in a hospital unit of ETS. It has collected family history and personal habits, co-morbilidad, treatments, etc., physical examination, and anthropometric data, laboratory tests (Total Cholesterol, cHDL, cLDL, triglycerides, uricemia, fasting glucose, insulin, HOMA index, creatinine Ratio algúmina-creatinina and PCR. rate SM found, using criteria ATPIII 2001 is 35.1% and increases with age. predominately diagnosis of abdominal obesity, followed by the elevation of fasting blood glucose and the decrease the shawl. 48.6% of patients remained well controlled PA figures, but 99.2% of the patients presented RCV added, 25.7% and 10.5% HVI microalbuminuria. Metabolic syndrome is associated a higher prevalence of obesity, abdominal obesity, and co-morbilidad HVO, as well as higher-PA, insulin, HOMA index, microalbuminuria and PCR. SM doubles the risk of events caridovasculares. The results of this study confirm the relationship between the SM and the assignment of target organs in the hypertensive, which is reflected in a significantly higher rate of HVI and microabluminuira in carriers of the syndrome. Criteria for the IDF and ATPIII 2005, which resulted in prevalence rates extraordinarily high discriminatory lose utility for identifying subjects at risk, which will hinder the adoption of intervention strategies.

Author: SORIA RODRÍGUEZ GUADALUPE.
Year: 2005.
University: POMPEU FABRA [More theses of this university] [www.upf.edu].
Place of defense: DEPARTAMENTO DE CIENCIAS EXPERIMENTALES Y DE LA SALUD.
Place of preparation: DEPARTAMENTO DE CIENCIAS EXPERIMENTALES Y DE LA SALUD.

Summary: Addiction is a chronic disorder characterized by the conduct of search and compulsive consumption of drugs, the loss of control to limit consumption, to emergence of a negative emotional state where access to drugs is prevented and relapse in the process even after long periods of abstinence. The dopaminergic system mesolímbico cortex has been proposed as the primary neurobiological basis of addiction, but there are other systems neurotransmission involved in the consolidation process addictive. The system endocannabionoide, via receptor CB1, is involved in the addictive properties of different drugs of abuse such as delta9-tetrahidrocannabionol, nicotine and morphine. However, so far to begin this work, we study a few have shown a clear implication of the system endocannabionoide in reinforcing properties of psychostimulants. Using mice VCB1 knockout, we demonstrated that the receptor CB1 participates in the effectiveness of fortifying cocaine. Furthermore, the presence of such a receiver is necessary for building processes operant behavior maintained by the self-administration of cocaine. This study demonstrates the importance of this receptor CB1 in the addictive properties of cocaine, confirming that the system endocannabionoide is a common substrate for addiction drug abuse. Moreover, the system purinérgico modulates many systems neurotransmission in the CNS. The close relationship at the cellular level and functional between adenosine receptors and dopamine receptors provides evidence that the system purinérigco could modulate the reward systems. Using different animal models, we have demonstrated that the receptor for adenosine A2A is necessary that the addictive properties of drugs of abuse as cannabinoids, opioids, nicotine and laos psychostimulants occur in a way completely. Our studies allow us to say that the two systems, cannabionoide and purinérgico could assume the existence of new modulation systems common processes addictive. Thus, it would be important to develop new strategies receptor blockade A2A and CB1 to mitigate or even prevent the development of addiction.

Author: BARRONDO LAKARRA SERGIO.
Year: 2005.
University: PAÍS VASCO [More theses of this university] [www.ehu.es].
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: The work done in this thesis has sought to fill two key objectives: first, to study thoroughly the receptor pharmacology be tonérigco 5-HT1A, valuing the pharmacological modulation exerted on the receiving both endogenous compounds (zinc cation) as a different antidepressant drugs (MAOIs and SSRIs): and on the other hand, study the regulation exercised by the chronic treatment with antidepressant drugs on the levels of receptors serotonérgicos 5-HT1A and their proteins transductoras, G protein subtype Gi / o. The results cover after the first goal of this work show that the cation Zinc is able to modulate alostéricamente setting ligands to the recipient serotonérgico 5-HT1A concentrations of order microMolar, within the range of concentrations of zinc that can be achieved under certain physiologically synapse. These results are of great interest because they point to the ability of zinc for ctaur as a modulator alostérico endogenous receptor serotonérigco 5-HT1A, indicating the possibility that such cation print a certain hue regional central nervous system to the transmission serotonérgica mediated the receiver 5-HT1A. Likewise, different antidepressant drugs tested in this study show ability to interact so alostérica with the receiver serotonérgico 45-HT1A also concentrations of order microMolar, thus proving an additional biochemical mechanism that may be contributing to the overall net effect observed after Chronic treatment with these drugs. In the second paragraph of this dissertation is assessed the effect of chronic treatment with fluoxetine on the levels of expression of receptor serotonérigoc 5-HT1A and their proteins transuctoras in two different regions, hippocampus and cortex. Interestingly, prior to this assessment is a detailed study of plasma levels of cortical and fluoxetine and its metabolite norfluoxetina that are reached after chronic treatment with different doses of fluoxetine, which enables you to choose, for comparison with data bibligoráficos, fluoxetine dose administered in a manner that chronic experimental animals reproduced more accurately the chronic treatment with this drug in humans. This will set the dose of 5 mg / kg of fluoxetine as an optimal dose to reproduce the conditions of chronic treatment in humans, and it is shown that there is a huge accumulation of brain drug that exceeds by several orders plasma concentrations. Additionally valued-dose 5mg/kg- sharing of individual enantiomers of fluoxetine and norfluoxetina both in plasma and in cerebral cortex. After making these determinations are studying the effect produced by chronic treatment with fluoxetine on the levels of expression of the receptor serotonérigo 5-HT1A and their proteins transductoras both bark like hippocampus, observed two in a significant decrease in the levels of expression and receptor subunit alfai2 in cortex, hippocampus while there are variations in the runlevels receptor expression and there is a decline in the levels of expression of the subunit alfail, demostrándose therefore, a regulatory region selectively.

Author: CÁCERES LEÓN MACARENA CELINA.
Year: 2006.
University: EXTREMADURA [More theses of this university] [www.unex.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The introduction of new generation antipsychotics (atypical) for the treatment of schizophrenia appears to advantage as compared to the classics (typical) greater effectiveness and fewer side effects, but its cost is much higher. Another controversy is the prescription of antipsychotics in mono or politerapia, which could be relevant for potential drug interactions causing adverse effects and possible hospitalization of these patients. One of the problems associated with the treatment of schizophrenia is the wide variability in response to antipsychotic medication. This can be explained by interindividual variation in metabolism due to the involvement of enzymes (cytochrome 450) with polimórfismo genetic, which has been demonstrated in pharmacokinetic studies. Among them, CYP2D6 appears cytochrome more important in the metabolism of antipsychotic drugs, the basis of the treatment of schizophrenia. The overall objective was to analyze the relevance of factors associated with prescription (compared with atypical antipsychotics, monotherapy vs. politerapia), as well as factors pharmacogenetic (genotypes CYP2D6) in revenues and the number of hospital stays of patients with schizophrenia. The total use of antipsychotics with Primary Care in Extremadura has increased significantly over the study period. The most widely used antipsychotic in Primary Care were haloperidol and risperidone. In recent years the use of atypical antipsychotics has increased greatly. It was estimated that over 80% of prescriptions were with substrates of CYP2D6. There has been a relationship between the increased use of atypical antipsychotics in Primary Care and the decrease in the number of hospital admissions for schizophrenic patients in Extremadura. The results show that despite the general recommendations for use of monotherapy for the treatment of schizophrenia, it is very frequent use politerapia both antipsychotics as other substrates of CYP2D6, for what might be expected competitive inhibition of CYP2D6 with the potential for rapid transformation of individuals PMs. It has been shown that hospital stays minors occurred in patients treated with monotherapy antipsicóteicos with regard to those who were treated with politerapia. Patients treated with atypical antipsychotics presented stays lower than those who were treated with antipsychotics. It has been found frequently under Metabolizadores Lentos in schizophrenic patients. Therefore, CYP2D6 could be associated not only with interindividual variability wing response to antipsychotic treatment but also vulnerability to psychiatric disorders such as schizophrenia. Overall, the use of hospital services for patients treated with atypical antipsychotics was lower than those treated with typical both in Primary Care and Hospital. Similarly, patients on monotherapy presented stays lower than those treated with politerapia. The study of polymorphism of the CYP26 can help choosing treatment regimens for each patient group, identifying doses, mainly in patients alone. In this way it would be possible to prevent side effects and therapeutic failures, and therefore reduce the recovery time and the number of relapses of schizophrenic patients.

Author: GONZÁLEZ MARTÍNEZ IDILIO.
Year: 2006.
University: EXTREMADURA [More theses of this university] [www.unex.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: In clinical practice are frequently notes that the response to drug therapy varies widely among patients treated with the same doses, differences in the efficiency in the presence of adverse effects. Genetic and environmental factors can alter the activity of drug metabolising enzymes, and therefore be a cause of differences in plasma, which in turn may be determinants of interindividual variability and inter on the therapeutic response and presentation effects secondary. One major determinants of this variability is the genetic polymorphism of the enzyme system in the cytochrome P450 (CYP) including the most studied is CYP2D6 discussed in this thesis. The differences in the frequencies that are different allelic variants of the gene CYP2D6 in different populations could justify inter observed variability in the response to drugs. The study of the variability in the inter-activity and genotypes CYP2D6 in the Cuban population is the main objective of this Doctoral Thesis. This is justified by the existence of few studies on Latin American populations. The knowledge of the variability population could be very useful for the optimization and customization of the treatment regimens to each town. The main results of this study demonstrate the existence of genetic polymorphism of CYP2D6 in the Cuban population of healthy volunteers, with a frequency of 4.6 to MLs and a 3.8% URs. Moreover showed differences in metabolic capacity CYP2D6 between Cubans classified as white and mestizo, probably due to the different frequencies of allele CYP2D6 * 17 between the two groups, as well as a link between the ability of hydroxylation of debrisoquine and certain traits of personality, what has made the MLs are more prone to anxiety and less socialization that MRs of debrisoquine. It also shows that due to the widespread use of drugs metallized by CYP2D6 in the treatment of schizophrenia in Cuba, there is a potential risk of adverse effects for these patients pharmacokinetic interactions.