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Objetivo temtico
Describir la farmacodinamia, farmacocintica, indicaciones, efectos adversos y contraindicaciones de los frmacos que actan en el sistema nervioso central:
Estados de vigilia y sueo,
Estados de nimo y el comportamiento, Movimientos anormales y Farmacodependencia
Contenido temtico
continuacin
Neurotransmisores: - Aminocidos: GABA, GLICINA, GLUTAMATO - ACETILCOLINA - Aminas: NORADRENALINA, DOPAMINA, SEROTONINA, HISTAMINA. Receptores: GABAA, NMDA (N-metilDaspartato), colinrgicos (nicotnicos, muscarnicos), adrenrgicos (alfa 1 y 2, beta 2), dopaminrgicos, serotonrgicos, histaminrgicos. Canales inicos: de Na+, de Ca2+ (tipo T y dependientes de voltaje).
Contenido temtico
continuacin
Control farmacolgico del sueo y la ansiedad: Activadores de receptores GABAA: Benzodiazepinas ansiolticas: BROMAZEPAM, ALPRAZOLAM, DIAZEPAM. Ataques de pnico: ALPRAZOLAM Benzodiazepinas hipnticas: TRIAZOLAM,, CLONAZEPAM. Benzodiazepinas antiepilpticas: DIAZEPAM y CLONAZEPAM. Control farmacolgico del estado de nimo (antidepresores): Inhibidores de la recaptura de noradrenalina y serotonina con accin anticolinrgica: IMIPRAMINA, CLORIMIPRAMINA, AMITRIPTILINA. Inhibidores selectivos de la recaptura de serotonina: PAROXETINA, SERTRALINA, CITALOPRAM, ESCITALOPRAM. Inhibidores mixtos: DULOXETINA, VENLAFAXINA. Inhibidores de la recaptura de dopamina: BUPROPIN. Control farmacolgico de la psicosis (antipsicticos). Tpicos (antagonistas de receptores dopaminrgicos): HALOPERIDOL, CLOROPROMAZINA, LEVOMEPROMAZINA, PENFLURIDOL, TRIFLUPERAZINA. Atpicos (antagonistas de receptores serotoninrgicos): RISPERIDONA, CLOZAPINA, OLANZAPINA .
La neurona a travs de sus sinapsis. La sinpsis es una conexin especializada entre neuronas Entre una neurona y una clula efectora casi siempre glandular o muscular.
La ms comn
George Oliver and Edward Schfer's discovery of the cardiovascular action (efecto presor) of suprarenal extract. Se referan a Epinefrina
Concepto de Neurotransmisin. Thomas Renton Elliot Receptive Substances para Adrenalina y noradrenalina. John Newport Langley
Tradicionalmente para considerar una sustancia neurotransmisor Qu se requiere? Sntesis del neurotransmisor en la terminal presinptica. Almacenamiento del neurotransmisor en las vesculas secretorias. Liberacin regulada del neurotransmisor al espacio sinptico. Unin a receptor. Presencia de receptores especficos para ese neurotransmisor. Destruccin o recaptura. Un medio para terminar con la accin del neurotransmisor.
En base al efecto de incremento o disminucin de la transmisin neuronal cmo se clasifican los neurotransmisores?
Por el mecanismo de sealizacin Cmo se clasifican los receptores de los neurotransmisores ? Ionotrpicos Metabotrpicos
Si son metabotrpicos: A que protena G estn acoplados? y Cmo se llevaran a cabo los procesos de excitacin o inhibicin?
Gs Gq Gi Go
Sin son receptores ionotrpicos cmo se llevaran a cabo los procesos de excitacin e inhibicin?
Cmo se clasifican los potenciales postsinpticos? Cul es su consecuencia sobre el potencial de accin?
GABA is the main inhibitory neurotransmitter in the central nervous system. GABAergic inhibition is seen at all levels of the CNS, including the hypothalamus, hippocampus, cerebral cortex and cerebellar cortex. The activity of GABAergic neurones is decreased in generalised http://www.cnsforum.com/imagebank/item/Neu anxiety disorder. ro_path_GABA_GAD/default.aspx
Ventrolateral preoptic area (VLPA): A group of GABAergic neurons in the preoptic area whose activity suppresses alertness and behavioral arousal and promotes sleep. El dao de esta rea provoca insomnio total, coma y eventualamente la muerte (ratas).
Two molecules of GABA (squares) bind to the GABAA receptor to allow an influx of Cl-. One molecule of GABA binds to the GABAB receptor, which couples to the -subunit of the G protein. Gi inhibits adenylyl cyclase (AC) to open a K+ channel; Go delays the opening of a Ca2+ channel. (Reproduced with permission from Bowery NG, Brown DA: The cloning of GABAB receptors. Nature 1997;386:223.)
In the normal brain the prominent glutamatergic pathways are: the cortico-cortical pathways; the pathways between the thalamus and the cortex; and the extrapyramidal pathway (the projections between the cortex and striatum). Other glutamate projections exist between the cortex, substantia nigra, subthalmic nucleus and pallidum. Glutamate-containing neuronal terminals are ubiquitous in the central nervous system and their importance in mental activity and neurotransmission is http://www.cnsforum.com/imagebank/item/ considerable. Neuro_path_GLUT/default.aspx
http://www.accessmedicine.com/popup. aspx?aID=55823997
http://www.accessmedicine.com/ popup.aspx?aID=56261129
http://www.sciencedirect.com/science/article/pii/S00 91305711002747
Riluzol
Bitopertina: antagonista de glicina, modulador de la neurotransmisin glutamargica
http://www.cnsforum.com/imagebank/item/hrl_rcpt_sys _NMDA_antag/default.aspx
Memantina: ayuda en el control de la enfermedad de Alzheimer. Bitopertina: los 1os ensayos clnicos de fase III, reportan control de los sntomas positivos de la esquizofrenia (potenciador cuando antipsicticos no son suficientes). Riluzol: esclerosis lateral amiotrfica.
D) Cholinergic neurons in the basal forebrain complex project to the hippocampus and the neocortex and those in the pontomesencephalotegmental cholinergic complex project to the dorsal thalamus and the forebrain.
Acetilcolina: uno de los neurotransmisores ms importantes en el despertar Dos grupos de neuronas colinrgicas se localizan en el puente y ncleos basales. Cuando se estimulan producen desincronizacin cortical
LDT=Ncleo tegmental laterodorsal PPT= Ncleo tegmental pednculopontino
http://www.cnsforum.com/imagebank/section/Dementia_Cholinergic/default.aspx
Cuando un agonista acetilcolina activa el receptor se inician los http://www.cnsforum.com/imagebank/section/Dementia_Cholinergic/default.aspx mecanismos de sealizacin que finalmente dan lugar a la apertura de canales de potasio y la propagacin de un impulso nervioso.
Receptor activado por dos molculas de ACh, es un canal ionico con compuerta de ligando que permite la entrada de los iones sodio. http://www.cnsforum.com/imagebank/section/Dementia_Cholinergic/default.aspx
Neurotransmisin colinrgica
Gs Gq Gi Go
Gi
La enfermedad de Alzheimer se asocia con una disminucin de todas las neuronas colinrgicas en las reas subcorticales, reduciendo la biodisponibilidad de acetilcolina. RIVASTIGMINA, galantamina.
El sistema extrapiramidal incrementa actividad de tipo colinrgica debido a la falta de actividad dopaminrgica. Situacin que se manifiesta en la enfermedad de Parkinson y en el parkinsonismo secundario a medicamentos. BIPERIDEN, trihexifenidilo.
http://www.accessmedicine.com/popup.aspx?aID=5368477
B) Serotonergic neurons in the raph nuclei project to the hypothalamus, limbic system, neocortex, cerebellum, and spinal cord.
Serotonina (5-HT): casi todas se encuentra en el ncleo se encuentran en el nucleo del raf (comisura).
Sirve para facilitar la deteccin y respuesta ante estmulos externos y estn relacionados con el sueo y la vigilia. Su principal funcin es la de liberar serotonina al resto del cerebro. Otras: control del apetito, Raph: Raphe nucleus: conducta, alucinaciones, A group of nuclei located in the reticular formation of the medulla, pons, and conductas estereotipadas, midbrain, situated along the midline. percepcin del dolor, vmito
http://journals.psychiatryonline.org/data/Book s/scha4/scha4_c001f003.gif
En que enfermedades y que frmacos serotoninrgicos o antiserotoninrgicos se emplean? Depresin: Inhibidores de la recaptura de noradrenalina y serotonina con accin anticolinrgica: IMIPRAMINA, CLORIMIPRAMINA, AMITRIPTILINA. Inhibidores de la recaptura de serotonina :FLUOXETINA, PAROXETINA, SERTRALINA, CITALOPRAM, ESCITALOPRAM. Inhibidores mixtos: DULOXETINA, VENLAFAXINA. Migraa: sumatriptan Nusea y vmito: ondansetrn Antipsicticos atpicos: RISPERIDONA, CLOZAPINA, OLANZAPINA
C) Dopaminergic neurons in the substantia nigra project to the striatum and those in the ventral tegmental area of the midbrain project to the prefrontal cortex the limbic system.
A) Noradrenergic neurons in the locus coeruleus innervate the spinal cord, cerebellum, several nuclei of the hypothalamus, thalamus, basal telencephalon, and neocortex.
La norepinefrina: Neuronas noradrenrgicas situadas en el puente (cerca del piso del cuarto ventrculo), participan en el despertar y en el estado de alerta.
When a person smokes marijuana, the active ingredient, cannabinoids or THC, travels quickly to the brain. Point to the areas where THC (magenta) concentrates. The VTA, nucleus accumbens, caudate nucleus, hippocampus, and cerebellum are highlighted. THC binds to THC receptors that are concentrated in areas within the reward system as well as these other areas. Indicate that the action of THC in the hippocampus explains its ability to interfere with memory and actions in the cerebellum are responsible for its ability to cause incoordination and loss of balance.
http://www.drugabuse.gov/publications/teaching-packets/brain-actions-cocaineopiates-marijuana/section-iii-introduction-to-drugs-abuse-cocaine-opia-10
Endogenous cannabinoid system is its role in brain neuromodulation. Postsynaptic neurons synthesize membrane-bound endocannabinoid precursors and cleave them to release active endocannabinoids following an increase of cytosolic free Ca2+ concentrations: for example, after binding of neurotransmitters (NTs) to their IONOTROPIC (iR) or METABOTROPIC (mR) receptors. Endocannabinoids subsequently act as retrograde messengers by binding to presynaptic CB1 cannabinoid receptors, which are coupled to the inhibition of voltage-sensitive Ca2+ channels and the activation of K+ channels. This blunts membrane depolarization and exocytosis, thereby inhibiting the release of NTs such as glutamate, dopamine and -aminobutyric acid (GABA) and affecting, in turn, processes such as learning, movement and memory, respectively. The endogenous cannabinoid system might also exert modulatory functions outside the brain, both in the peripheral nervous system and in extraneural sites, controlling processes such as peripheral pain, vascular tone, INTRAOCULAR PRESSURE and immune function.
http://www.nature.com/nrc/journal/v3/n 10/box/nrc1188_BX1.html
http://onlinelibrary.wiley.com/doi/10.1111/j.1 755-5949.2010.00144.x/full
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647947 /
Cuando la histamina se une a los receptores H1, ste activa a una protena Gq que genera fosfatidilinositol y activacin del factor de transcripcin cFOS, resultando en vigilia, alerta y actitudes pro-cognitivas http://www.cnsspectrums.com/aspx/article_pf
.aspx?articleid=1916
Histamine: A neurotransmitter implicated in control of wakefulness and arousal; a compound synthesized from histidine, an amino acid. Antihistamines block H1 receptors and promote drowsiness.
TMN= ncleo tuberulomamilar. A nucleus in the ventral posterior hypothalamus, just rostral to the mammillary bodies; contains histaminergic neurons involved in cortical activation and behavioral arousal.
Caso clnico
Six months before presentation, a 35-year-old single woman began to complain that she occasionally saw double when watching television. The double vision often disappeared after she had some bed rest. Subsequently, she felt that her eyelids tended to droop during reading, but after a good night's rest she felt normal again. Her physician referred her to a specialty clinic.At the clinic, the woman said that she tired easily and her jaw muscles became fatigued at the end of a meal. No sensory deficits were found. A preliminary diagnosis was made and some tests were performed to confirm the diagnosis.What is the differential diagnosis? Which diagnostic procedures, if any, would be useful? What is the most likely diagnosis?
http://www.drugabuse.gov/sites/default/files/ rrmarijuana.pdf
http://www.sciencedirect.com/science/article/pii/S1 569733910701089