Colinrgicos y Anticolinrgicos

FUNCIONES DEL SNA

AutonmicoSomticoInervacin simptica glndula suprarrenalSimpticaParasimpticoSin ganglioAcetilcolinaAcetilcolinaAcetilcolinaGlnd. suprarrenalAdrenalina(liberada a la sangre)NoradrenalinaAcetilcolina Acetilcolina Msculo estriado Receptornicotnico Receptormuscarnico Receptoradrenrgico Receptoradrenrgico Neurona preganglionarTransmisorganglinicoTransmisorNeuroefectorrganos efectores

PASOLIMITANTENEUROTRANSMISION COLINERGICA

Sntesis: AcetiltransferasaAlmacenamiento: Captacin en vesculas, protege la AcH de la degradacin.Liberacin: bloqueada por la toxina botulnica, el veneno de araa la induce.Unin al receptorDegradacin por la Acetilcolinesterasa (AcHE) rpidamente en la hendidura sinpticaReciclaje de colina.

ACh (5ug)ATROPINA (1mg)ACh (5ug)ACh (5mg)EFECTOMEFECTONTAM

Receptores ionotrpicos(Nicotinico)Receptores metabotrpicos(Muscarnico)

ReceptorPoroCanalNeurotransmisorCara extracelularCara citoplasmtica

NeurotransmisorReceptorProteina GCanalPoroCara extracelularCara citoplasmticaRECEPTORES COLINRGICOSMUSCARINICOSEfectores autonomicos parasimpaticos.Tejidos sin inervacion colinergica (ej: endotelio).Ganglios autonomicos.Neuronas del SNC.Terminaciones nerviosas simpaticas y parasimpaticas.Celula cromafin.NICOTINICOSPlaca mioneural.Placa terminal.Ganglios autonomicos.Celula cromafin.Terminaciones nerviosas colinergicas y noradrenergicas.TIPOESTRUCTURALOCALIZACINAGONISTASANTAGONISTAS

Ganglionar o neuronal

4 subunidades: 2 alfa, 1 gamma y1 beta

Ganglios autnomos y medula suprarrenal

Dimetilfenil-piperazinio Epibatidina Nicotina/AcH

Trimetafn Hexametonio

Musculo estriado

Placa motora

Feniltrimetil-amonio Nicotina/AcH

- D-tubocurarinaNICOTINICOSMUSCARINICOSReceptorLocalizacin principalSistema de 2 mensajerosAntagonistasAgonistasM1Neuronas del SNC, neuronas postganglionares simpticas, sistema digestivo, algunos sitios presinpticosFosfolipasa C. IP3 y DAG. Ca++ citoslicoAtropina, telenzepina y PirenzepinaAcetilcolina y esteres sintticos de la colina:MetacolinaCarbacolBetanecol

Alcaloides Sintticos:PilocarpinaMuscarinaArecolinaM2Miocardio, msculo liso, SNCInhibicin de la adenilciclasa y AMPc y apertura de canales de K+Atropina y MetoctraminaM3Tejido glandular, vasos (msculo liso y endotelio)Fosfolipasa C. IP3 y DAG. Ca++ citoslicoAtropina y HexahidrosiladifenidolM4SNCInhibicin de la adenilciclasa y AMPc y apertura de canales de K+ AtropinaM5SNCFosfolipasa C. IP3 y DAG. Ca++ citoslicoAtropina

Agonistas colinrgicosEstimulantes colinrgicos de accin directa Estimulantes colinrgicos de accin indirecta

Estimulantes colinrgicos de accin indirecta:

Estimulantes colinrgicos de accin directa: Agonistas colinrgicos

Estimulantes colinrgicos de accin directa:

Estimulantes colinrgicos de accin indirecta:ACh + EAECCh + EAE + AH2OIrreversibles

XPX + E XEPX X + EPX E + PX

Reversibles (sustratos de la enzima)

AX + E EAX X + EA E + A

Reversibles (NO sustratos de la enzima)

Irreversibles

ReversiblesPATOLOGA TRATAMIENTOMiastenia GravisNeostigmina, Piridostigmina, previa atropinizacionGlaucomaFisostigmina 0.5% + Pilocarpina 4% Mecanismo: La pilocarpina acta directamente sobre el receptor y la Fisostigmina acta inhibiendo la enzima AChE. leo paraltico/ atona de la vejiga urinaria Neostigmina va oral y parenteral.Pero en este caso lo que mas se utiliza es el Betanecol; por afinidad por el subtipo de receptor en el tracto GI y GU Intoxicacin por atropina Fisostigmina IV de 0.5-2 mg o Eserina. Importante recordar. Si el txico en este caso la Atropina (otros como antihistamnicos , fenotiazinas, antidepresivos tricclicos) en dosis muy altas puede producir intoxicacin, atraviesa barrera y produce efectos txicos centrales (Sndrome Anticolinrgico Central), es necesario:Fisostigmina:Frmaco que revierta este efecto txico. Frmaco que atraviesa barreras. Enfermedad de AlzheimerTacrine: es un inhibidor que atraviesa la barrera hematoenceflica y aumenta la disponibilidad de Ach en la va central con la mejora temporal. Es un tratamiento coadyuvante al cuadro de Alzheimer.

Estimulantes colinrgicos de accin indirecta:

Estimulantes colinrgicos de accin directa: Agonistas colinrgicos

Antagonista muscarnicos no-selectivosAntagonista muscarnicos selectivosAntagonistas colinrgicos

Estimulantes colinrgicos de accin directa Estimulantes colinrgicos de accin indirecta Antagonistas

?Y sigue la tortura!!Y si el finde largo les cuesta caroFarmacologa de los sistemas AdrenrgicosSntesis del neurotransmisor adrenrgicoAlmacenamiento de NALiberacin del mediador qumicoEstimulacin de los receptoresTerminacin de la actividad del neurotransmisorLa Neurotransmisin Adrenrgica en 5 etapas fundamentales.Sntesis de catecolaminas

L-Fenilalanina

L-Tirosina

L-Dopa

Dopamina

Noradrenalina

AdrenalinaFenilalanina hidroxilasaTirosina hidroxilasaDopa descarboxilasaDopamina HidroxilasaNoradrenalina N metil transferasaRepaso de bioqumica de sntesis de catecolaminas y receptores acoplados a protenas GEfecto de la droga dependiente del receptor.TIROSINADOPADADANANADopa decarb.Tirosina OHasaDHDOPEGVaricosidad de neurona adrenrgicaH+H+H+DANA NANA ATP NA NADHReserpinaGuanetidina-Almacenamiento VesicularATPADPMg2+TiraminaAnfetaminasEfedrinaGuanetidinaCromograninasCitosolVesculaH+Liberacin de NoradrenalinaNA2OpM2ATIIN2Muscarnicos pre-sinpticos en Cx +-IECAAng II-AChAChACa2+Ca2+OpiceosATPCromograninasFalsos NTNASinaptobrevinaSinapsinaCa2+Receptores Adrenrgicos11223GqGiGsGsGsI3P DAG + Ca2+FosfodiesterasaAMPcAdenilato CiclasaAMPcAdenilato CiclasaAMPcAdenilato CiclasaAMPcGq. PLC. IP3 y DAG. Aumenta Ca2+.A>NA>>IsoAg Selectivo: FenilefrinaAtg Selectivo: PrazosinGi. Inhibe adenilato ciclasa. Abre canales de K+.Cierra canales de Ca++A>NA>>IsoAg Selectivo: ClonidinaAtg Selectivo: yohimbina Msculo liso: vascular, genitourinariointestinal Corazn HgadoReceptorVa metablicaLocalizacin Neuronas Msculo liso Clulas pancreticas Plaquetas12*Ver lista completa en pgina 15 de la bibliografa de CtedraGs. Activa adenilato ciclasa. Iso>A=NAAg Selectivo: DobutaminaAtg: Propranolol, AtenololGs. Activa adenilato ciclasa. Iso>A>>NAAg Selectivo: ProcaterolAtg: PropranololGs. Activa adenilato ciclasa.Iso=NA>AAg Selectivo: BRL 26830AAtg: PropranololReceptorVa MetablicaLocalizacin123 Corazn NS Clulas yuxtaglomerulares

Corazn NAV Msculo liso BronquialMsculo liso Hgado Msculo esqueltico

Liplisis

*Ver lista completa en pgina 15 de la bibliografa de CtedraTerminacin de la accin del NTEliminacin de la biofaseDifusinCaptacin NeuronalCaptacin ExtraneuronalMetabolismoLa captacin neuronal es el mecanismo principal.Proceso activo (contra gradiente de concentracin. Co-transporte con Na+) y consumo de ATP asociado a Na/K ATPasa Saturable y dependiente de Temperatura. Acoplado a MAOInhibido selectivamente por Cocana y Antidepresivos triciclicos.

Captacin ExtraneuronalCarece de estereoespecificidad. No inhibido por cocana. Satura a mayores concentraciones (mayor capacidad) Clulas y elementos NO neuronales. Acoplado a COMTRecaptacin de NA

Inhibida por Beta-Haloalquilaminas (Bloqueantes alfa no selectivos no competitivos)MetabolismoMAOCOMTComplejo de enzimas mitocondrial

Desaminacin oxidativa

AminasAldehidosAlcoholesEnzima Citoplasmtica

Transfiere grupo metilo de S-adenosilmetionina al Hidroxilo meta

Requiere Mg++

Puede actuar antes o despus de la MAO

La estimulacin Adrenrgica y Colinrgica en el Ojo

Muscarnicos en Esfnter circular del Iris y Msculo Ciliar

Abran la pgina 24 del terico de ColinrgicoIrisMsculo radial (1)MIDRIASISMsculo liso circular del Esfnter (M3)MIOSIS

Estimulo estos receptoresBloqueo estos receptoresBloqueo estos receptoresEstimulo estos receptoresEn pacientes con Glaucoma de ngulo estrecho la MIDRIASIS produce elevacin de la presin intraocular

Inervacin del Msculo Ciliar1: Relajacin (Visin Lejana) HAY QUE CORRER!!M1: Contraccin (Acomodacin) Leemos tranquilosLos procesos Ciliares poseen receptores 2 La Contraccin de los msculos ciliares disminuye la separacin entre ellos y el cristalino y por lo tanto la zonula de Zinn (fibras conectivas que sostienen el cristalino) pierden tirantez permitiendo al cristalino esferizarse mejorando la conveccin de los rayos para la visin cercanaPor ende los Frmacos Midriticos simpaticomimticos producen midriasis SIN Ciclopja (parlisis de la acomodacin)Mientras los Bloqueantes muscarnicos producen midriasis CON ciclopeja

Production and drainageAqueous humour is secreted into the posterior chamber by theciliary bodyAqueous humour is secreted into the posterior chamber by theciliary body, specifically thenon-pigmented epithelium of the ciliary body(pars plicata)Aqueous humour is secreted into the posterior chamber by theciliary body, specifically thenon-pigmented epithelium of the ciliary body(pars plicata). It flows through the narrow cleft between the front of the lens and the back of the iris, to escape through the pupil into the anterior chamber, and then to drain out of the eye via thetrabecular meshworkAqueous humour is secreted into the posterior chamber by theciliary body, specifically thenon-pigmented epithelium of the ciliary body(pars plicata). It flows through the narrow cleft between the front of the lens and the back of the iris, to escape through the pupil into the anterior chamber, and then to drain out of the eye via thetrabecular meshwork. From here, it drains intoSchlemm's canalAqueous humour is secreted into the posterior chamber by theciliary body, specifically thenon-pigmented epithelium of the ciliary body(pars plicata). It flows through the narrow cleft between the front of the lens and the back of the iris, to escape through the pupil into the anterior chamber, and then to drain out of the eye via thetrabecular meshwork. From here, it drains intoSchlemm's canalby one of two ways: directly, via aqueous vein to theepiscleralAqueous humour is secreted into the posterior chamber by theciliary body, specifically thenon-pigmented epithelium of the ciliary body(pars plicata). It flows through the narrow cleft between the front of the lens and the back of the iris, to escape through the pupil into the anterior chamber, and then to drain out of the eye via thetrabecular meshwork. From here, it drains intoSchlemm's canalby one of two ways: directly, via aqueous vein to theepiscleralvein, or indirectly, via collector channels to the episcleral vein byintrascleral plexusAqueous humour is secreted into the posterior chamber by theciliary body, specifically thenon-pigmented epithelium of the ciliary body(pars plicata). It flows through the narrow cleft between the front of the lens and the back of the iris, to escape through the pupil into the anterior chamber, and then to drain out of the eye via thetrabecular meshwork. From here, it drains intoSchlemm's canalby one of two ways: directly, via aqueous vein to theepiscleralvein, or indirectly, via collector channels to the episcleral vein byintrascleral plexusand eventually into theveinsAqueous humour is secreted into the posterior chamber by theciliary body, specifically thenon-pigmented epithelium of the ciliary body(pars plicata). It flows through the narrow cleft between the front of the lens and the back of the iris, to escape through the pupil into the anterior chamber, and then to drain out of the eye via thetrabecular meshwork. From here, it drains intoSchlemm's canalby one of two ways: directly, via aqueous vein to theepiscleralvein, or indirectly, via collector channels to the episcleral vein byintrascleral plexusand eventually into theveinsof theorbit.

GlaucomaEs una afeccin ocular en la que se produce dao al nervio ptico asociada (pero no siempre) con el incremento de la presin intraocular.Se lo puede dividir en dos grandes gruposGlaucoma de ngulo abiertoGlaucoma de ngulo estrecho

Glaucomais an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye(s) and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye (aqueous humouris an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye(s) and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye (aqueous humour).[1]is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye(s) and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye (aqueous humour).[1]The term 'ocular hypertension' is used for cases having constantly raisedintraocular pressure(IOP) without any associated optic nerve damage. Conversely, the term 'normal' or 'low tension glaucoma' is suggested for the typical visual field defects when associated with a normal or low IOP.The nerve damage involves loss ofretinal ganglion cellsThe nerve damage involves loss ofretinal ganglion cellsin a characteristic pattern. There are many different subtypes of glaucoma, but they can all be considered a type ofoptic neuropathyThe nerve damage involves loss ofretinal ganglion cellsin a characteristic pattern. There are many different subtypes of glaucoma, but they can all be considered a type ofoptic neuropathy. Raised intraocular pressure is a significant risk factor for developing glaucoma (above 21 mmHg or 2.8kPa). One person may develop nerve damage at a relatively low pressure, while another person may have higheyeThe nerve damage involves loss ofretinal ganglion cellsin a characteristic pattern. There are many different subtypes of glaucoma, but they can all be considered a type ofoptic neuropathy. Raised intraocular pressure is a significant risk factor for developing glaucoma (above 21 mmHg or 2.8kPa). One person may develop nerve damage at a relatively low pressure, while another person may have higheyepressure for years and yet never develop damage. Untreated glaucoma leads to permanent damage of theoptic nerveThe nerve damage involves loss ofretinal ganglion cellsin a characteristic pattern. There are many different subtypes of glaucoma, but they can all be considered a type ofoptic neuropathy. Raised intraocular pressure is a significant risk factor for developing glaucoma (above 21 mmHg or 2.8kPa). One person may develop nerve damage at a relatively low pressure, while another person may have higheyepressure for years and yet never develop damage. Untreated glaucoma leads to permanent damage of theoptic nerveand resultantvisual fieldloss, which can progress toblindness.Glaucoma can be divided roughly into two main categories, "open angle" and "closed angle" glaucoma. Closed angle glaucoma can appear suddenly and is often painful; visual loss can progress quickly, but the discomfort often leads patients to seek medical attention before permanent damage occurs. Open angle, chronic glaucoma tends to progress at a slower rate and patients may not notice they have lost vision until the disease has progressed significantly.

Tratamiento Glaucoma- Mdico:Betabloqueantes (Timolol, betaxolol)Miticos parasimticomimeticos (Pilocarpina)- QuirrgicoTopicalbeta-adrenergic receptor antagonists, such astimolol,levobunolol(Betagan), andbetaxolol, decrease aqueous humor production by theciliary body.Alpha2-adrenergic agonists, such asbrimonidine(Alphagan) andapraclonidine, work by a dual mechanism, decreasing aqueous humor production and increasing trabecular outflow.Less-selectivesympathomimetics, such asepinephrine, decrease aqueous humor production through vasoconstriction of ciliary body blood vessels. Epinephrine's mydriatic effect, however, renders it unsuitable for closed angle glaucoma.