DO NEUROTRANSMISSOR pré-sináptico IMPACTOS · apetite agressão Sistema ... Controle do impulso...

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Neurônio pós-sináptico Fenda sináptica Neurônio pré-sináptico Refs.: 21-35 METILFENIDATO LISDEXANFETAMINA INIBIÇÃO DA RECAPTAÇÃO DO NEUROTRANSMISSOR EM RECEPTORES PRÉ-SINÁPTICOS METILFENIDATO LISDEXANFETAMINA ESTIMULAÇÃO DA LIBERAÇÃO DO NEUROTRANSMISSOR NA PRÉ-SINAPSE www.shire.com.br Shire Farmacêutica Brasil Ltda. - Edifício Rochaverá Towers - Av. das Nações Unidas, 14.171, Torre Ebony - 5º andar - 04794-000 - São Paulo - SP - Brasil Material de distribuição exclusiva a profissionais da saúde prescritores, e/ou dispensadores de medicação. público leigo BR/C-ANPROM/LDX/17/0008 - Fevereiro/2017 [email protected] IMPACTOS TDAH e o CÉREBRO Dextroanfetamina Transportador de Dopamina (DAT) Transportador de Noradrenalina (NET) Dopamina Noradrenalina Receptor de Dopamina Receptor Adrenérgico á 2a Canal controlado por nucleotíideo cíclico ativado por hiperpolarização (HCM) Vesícula 1. Almeida, RM; Cabral, JC; Narvaes, R. . "Behavioural, hormonal and neurobiological mechanisms of aggressive behaviour in human and nonhuman primates". Physiology & Behavior. DOI:10.1016/j.physbeh.2015.02.053. Visitado em 2015. 2. Leight J. Pharmacological and optical methods of treatment for vestibular disorder and nystagmus. In: Herdman SJ, editor. Vestibular Rehabilitation. Philadelphia: F. A. Davis Company; 2007. p. 178-187. 3. Curthoys IS, Halmagyi GM. Vestibular compensation: clinical changes in vestibular function with time after unilateral vestibular loss. In: Herdman SJ, editor. Vestibular Rehabilitation. F. A. Davis Company: Philadelphia; 2007. p.76-97. 4. Shepard NT. Medical therapy for the balance disorder patient. In: Shepard NT, Telian AS, editors. Pratical manangement of the balance disorder patient. Singular Publishing Group: California; 1996. p. 187-192. 5. Baloh RW. The peripheral vestibular system. In: Baloh RW, Kerber KA, Clinical neurophysiology of the vestibular system. 4th ed. Oxford University Press: New York; 2011. p.25-62. 6. Baloh RW. Symptomatic treatment of vertigo. In: Baloh RW, Kerber KA, Clinical neurophysiology of the vestibular system. 4th ed. Oxford University Press: New York; 2011. p.405-418. 7. Shaw P, Lerch J, Greenstein D, et al. Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 2006; 63: 540-549. 8. Shaw P, Malek M, Watson B, et al. Development of cortical surface area and gyrification in attention- deficit/hyperactivity disorder. Biol Psychiatry 2012; 72: 191-197. 9. Nakao T, Radua J, Rubia K, et al. Gray matter volume abnormalities in ADHD: voxel-based meta-analysis exploring the effects of age and stimulant medication. Am J Psychiatry 2011; 168: 1154-1163. 10. Pavuluri MN, Yang S, Kamineni K, et al. Diffusion tensor imaging study of white matter fiber tracts in pediatric bipolar disorder and attention-deficit/hyperactivity disorder. Biol Psychiatry 2009; 65: 586-593. 11. Shaw P, Sudre G, Wharton A, et al. White Matter Microstructure and the Variable Adult Outcome of Childhood Attention Deficit Hyperactivity Disorder. Neuropsychopharmacology 2014. 12. Cortese S, Kelly C, Chabernaud C, et al. Toward systems neuroscience of ADHD: a meta-analysis of 55 fMRI studies. Am J Psychiatry 2012; 169: 1038-1055. 13. Snyder SM, Hall JR. A meta-analysis of quantitative EEG power associated with attention-deficit hyperactivity disorder. J Clin Neurophysiol 2006; 23: 440-455. 14. Loo SK, Makeig S. Clinical utility of EEG in attention- deficit/hyperactivity disorder: a research update. Neurotherapeutics 2012; 9: 569-587. 15. Arns M, Drinkenburg W, Leon KJ. The effects of QEEG-informed neurofeedback in ADHD: an open-label pilot study. Appl Psychophysiol Biofeedback 2012; 37: 171-180. 16. Economidou D, Theobald DE, Robbins TW, et al. Norepinephrine and dopamine modulate impulsivity on the five-choice serial reaction time task through opponent actions in the shell and core sub-regions of the nucleus accumbens. Neuropsychopharmacology 2012; 37: 2057-2066. 17. Volkow ND, Wang GJ, Kollins SH, et al. Evaluating dopamine reward pathway in ADHD: clinical implications. JAMA 2009; 302: 1084-1091. 18. del Campo N, Fryer TD, Hong YT, et al. A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment. Brain 2013; 136: 3252-3270. 19. Hannestad J, Gallezot JD, Planeta-Wilson B, et al. Clinically relevant doses of methylphenidate significantly occupy norepinephrine transporters in humans in vivo. Biol Psychiatry 2010; 68: 854-860. 20. Tomasi D, Volkow ND. Functional connectivity of substantia nigra and ventral tegmental area: maturation during adolescence and effects of ADHD. Cereb Cortex 2014; 24: 935-944. 21. Stahl SM. Mignon L. Stahl´s Illustrated: Attention Deficit Hyperactivity Disorder. New York, NY: Cambridge University Press, 2011. 22. Volkow ND, Wang GJ,Fowler JS, Gatley SJ, Logan J, Ding YS, Hitzemann R, Pappas N. Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry. 1998 Oct;155(10):1325-31. 23. Volkow ND, Wang G, Fowler JS, Logan J, Gerasimov M, Maynard L,Ding Y, Gatley SJ, Gifford A, Franceschi D. Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain. J Neurosci. 2001 Jan 15;21(2):RC121. 24. Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, Morin SM, Gehlert DR, Perry KW. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002 Nov;27(5):699-711. 25. Hannestad J, Gallezot JD, Planeta-Wilson B, Lin SF, Williams WA, van Dyck CH, Malison RT, Carson RE, Ding YS. Clinically relevant doses of methylphenidate significantly occupy norepinephrine transporters in humans in vivo. Biol Psychiatry. 2010 Nov 1;68(9):854-60. 26. Kahlig KM, Javitch JA, Galli A. Amphetamine regulation of dopamine transport. Combined measurements of transporter currents and transporter imaging support the endocytosis of an active carrier. J Biol Chem. 2004 Mar 5;279(10):8966-75. 27. Wall SC, Gu H, Rudnick G. Biogenic amine flux mediated by cloned transporters stably expressed in cultured cell lines: amphetamine specificity for inhibition and efflux. Mol Pharmacol. 1995 Mar;47(3):544-50. 28. Zhu MY, Shamburger S, Li J, Ordway GA. Regulation of the human norepinephrine transporter by cocaine and amphetamine. J Pharmacol Exp Ther. 2000 Dec;295(3):951-9. 29. Sulzer D, Rayport S. Amphetamine and other psychostimulants reduce pH gradients in midbrain dopaminergic neurons and chromaffin granules: a mechanism of action. Neuron. 1990 Dec;5(6):797-808. 30. Avelar AJ, Juliano SA, Garris PA. Amphetamine augments vesicular dopamine release in the dorsal and ventral striatum through different mechanisms. J Neurochem. 2013 May;125(3):373-85. 31. Daberkow DP, Brown HD, Bunner KD, Kraniotis SA, Doellman MA, Ragozzino ME, Garris PA, Roitman MF. Amphetamine paradoxically augments exocytotic dopamine release and phasic dopamine signals. J Neurosci. 2013 Jan 9;33(2):452-63. 32. Ramsson ES, Howard CD, Covey DP, Garris PA. High doses of amphetamine augment, rather than disrupt, exocytotic dopamine release in the dorsal and ventral striatum of the anesthetized rat. J Neurochem. 2011 Dec;119(6):1162-72. 33. Florin SM, Kuczenski R, Segal DS. Effects of reserpine on extracellular caudate dopamine and hippocampus norepinephrine responses to amphetamine and cocaine: mechanistic and behavioral considerations. J Pharmacol Exp Ther. 1995 Jul;274(1):231-41. 34. Pifl C, Agneter E, Drobny H, Sitte HH, Singer EA. Amphetamine reverses or blocks the operation of the human noradrenaline transporter depending on its concentration: superfusion studies on transfected cells. Neuropharmacology. 1999 Jan;38(1):157-65. 35. Bula do profissional de saúde – Produto Venvanse®. Saiba mais em: CONEXÃO FOCO Não metabolizado 35 pelo CYP 450 Duplo Mecanismo 21-35 de Ação 35 Pró-droga

Transcript of DO NEUROTRANSMISSOR pré-sináptico IMPACTOS · apetite agressão Sistema ... Controle do impulso...

Neurônio pós-sináptico

Fenda sináptica

Neurônio pré-sináptico

Refs.: 21-35

METILFENIDATOLISDEXANFETAMINA

INIBIÇÃO DA RECAPTAÇÃO DO NEUROTRANSMISSOR

EM RECEPTORES PRÉ-SINÁPTICOS

METILFENIDATOLISDEXANFETAMINA

ESTIMULAÇÃO DA LIBERAÇÃO DO

NEUROTRANSMISSOR NA PRÉ-SINAPSE

www.shire.com.brShire Farmacêutica Brasil Ltda. - Edifício Rochaverá Towers - Av. das Nações Unidas, 14.171,

Torre Ebony - 5º andar - 04794-000 - São Paulo - SP - BrasilMaterial de distribuição exclusiva a profissionais da saúde prescritores, e/ou dispensadores de medicação.público leigo

BR/C-ANPROM/LDX/17/0008 - Fevereiro/[email protected]

IMPACTOSTDAH e o CÉREBRO

Dextroanfetamina

Transportador de Dopamina (DAT)

Transportador de Noradrenalina (NET)

Dopamina

Noradrenalina

Receptor de Dopamina

Receptor Adrenérgico á2a

Canal controlado por nucleotíideo cíclico ativado por hiperpolarização (HCM)

Vesícula

1. Almeida, RM; Cabral, JC; Narvaes, R. . "Behavioural, hormonal and neurobiological mechanisms of aggressive behaviour in human and nonhuman primates". Physiology & Behavior. DOI:10.1016/j.physbeh.2015.02.053. Visitado em 2015. 2. Leight J. Pharmacological and optical methods of treatment for vestibular disorder and nystagmus. In: Herdman SJ, editor. Vestibular Rehabilitation. Philadelphia: F. A. Davis Company; 2007. p. 178-187. 3. Curthoys IS, Halmagyi GM. Vestibular compensation: clinical changes in vestibular function with time after unilateral vestibular loss. In: Herdman SJ, editor. Vestibular Rehabilitation. F. A. Davis Company: Philadelphia; 2007. p.76-97. 4. Shepard NT. Medical therapy for the balance disorder patient. In: Shepard NT, Telian AS, editors. Pratical manangement of the balance disorder patient. Singular Publishing Group: California; 1996. p. 187-192. 5. Baloh RW. The peripheral vestibular system. In: Baloh RW, Kerber KA, Clinical neurophysiology of the vestibular system. 4th ed. Oxford University Press: New York; 2011. p.25-62. 6. Baloh RW. Symptomatic treatment of vertigo. In: Baloh RW, Kerber KA, Clinical neurophysiology of the vestibular system. 4th ed. Oxford University Press: New York; 2011. p.405-418. 7. Shaw P, Lerch J, Greenstein D, et al. Longitudinal mapping of cortical thickness and clinical outcome in children and adolescents with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 2006; 63: 540-549. 8. Shaw P, Malek M, Watson B, et al. Development of cortical surface area and gyrification in attention-deficit/hyperactivity disorder. Biol Psychiatry 2012; 72: 191-197. 9. Nakao T, Radua J, Rubia K, et al. Gray matter volume abnormalities in ADHD: voxel-based meta-analysis exploring the effects of age and stimulant medication. Am J Psychiatry 2011; 168: 1154-1163. 10. Pavuluri MN, Yang S, Kamineni K, et al. Diffusion tensor imaging study of white matter fiber tracts in pediatric bipolar disorder and attention-deficit/hyperactivity disorder. Biol Psychiatry 2009; 65: 586-593. 11. Shaw P, Sudre G, Wharton A, et al. White Matter Microstructure and the Variable Adult Outcome of Childhood Attention Deficit Hyperactivity Disorder. Neuropsychopharmacology 2014. 12. Cortese S, Kelly C, Chabernaud C, et al. Toward systems neuroscience of ADHD: a meta-analysis of 55 fMRI studies. Am J Psychiatry 2012; 169: 1038-1055. 13. Snyder SM, Hall JR. A meta-analysis of quantitative EEG power associated with attention-deficit hyperactivity disorder. J Clin Neurophysiol 2006; 23: 440-455. 14. Loo SK, Makeig S. Clinical utility of EEG in attention-deficit/hyperactivity disorder: a research update. Neurotherapeutics 2012; 9: 569-587. 15. Arns M, Drinkenburg W, Leon KJ. The effects of QEEG-informed neurofeedback in ADHD: an open-label pilot study. Appl Psychophysiol Biofeedback 2012; 37: 171-180. 16. Economidou D, Theobald DE, Robbins TW, et al. Norepinephrine and dopamine modulate impulsivity on the five-choice serial reaction time task through opponent actions in the shell and core sub-regions of the nucleus accumbens. Neuropsychopharmacology 2012; 37: 2057-2066. 17. Volkow ND, Wang GJ, Kollins SH, et al. Evaluating dopamine reward pathway in ADHD: clinical implications. JAMA 2009; 302: 1084-1091. 18. del Campo N, Fryer TD, Hong YT, et al. A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment. Brain 2013; 136: 3252-3270. 19. Hannestad J, Gallezot JD, Planeta-Wilson B, et al. Clinically relevant doses of methylphenidate significantly occupy norepinephrine transporters in humans in vivo. Biol Psychiatry 2010; 68: 854-860. 20. Tomasi D, Volkow ND. Functional connectivity of substantia nigra and ventral tegmental area: maturation during adolescence and effects of ADHD. Cereb Cortex 2014; 24: 935-944. 21. Stahl SM. Mignon L. Stahl´s Illustrated: Attention Deficit Hyperactivity Disorder. New York, NY: Cambridge University Press, 2011. 22. Volkow ND, Wang GJ,Fowler JS, Gatley SJ, Logan J, Ding YS, Hitzemann R, Pappas N. Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry. 1998 Oct;155(10):1325-31. 23. Volkow ND, Wang G, Fowler JS, Logan J, Gerasimov M, Maynard L,Ding Y, Gatley SJ, Gifford A, Franceschi D. Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain. J Neurosci. 2001 Jan 15;21(2):RC121. 24. Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, Morin SM, Gehlert DR, Perry KW. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002 Nov;27(5):699-711. 25. Hannestad J, Gallezot JD, Planeta-Wilson B, Lin SF, Williams WA, van Dyck CH, Malison RT, Carson RE, Ding YS. Clinically relevant doses of methylphenidate significantly occupy norepinephrine transporters in humans in vivo. Biol Psychiatry. 2010 Nov 1;68(9):854-60. 26. Kahlig KM, Javitch JA, Galli A. Amphetamine regulation of dopamine transport. Combined measurements of transporter currents and transporter imaging support the endocytosis of an active carrier. J Biol Chem. 2004 Mar 5;279(10):8966-75. 27. Wall SC, Gu H, Rudnick G. Biogenic amine flux mediated by cloned transporters stably expressed in cultured cell lines: amphetamine specificity for inhibition and efflux. Mol Pharmacol. 1995 Mar;47(3):544-50. 28. Zhu MY, Shamburger S, Li J, Ordway GA. Regulation of the human norepinephrine transporter by cocaine and amphetamine. J Pharmacol Exp Ther. 2000 Dec;295(3):951-9. 29. Sulzer D, Rayport S. Amphetamine and other psychostimulants reduce pH gradients in midbrain dopaminergic neurons and chromaffin granules: a mechanism of action. Neuron. 1990 Dec;5(6):797-808. 30. Avelar AJ, Juliano SA, Garris PA. Amphetamine augments vesicular dopamine release in the dorsal and ventral striatum through different mechanisms. J Neurochem. 2013 May;125(3):373-85. 31. Daberkow DP, Brown HD, Bunner KD, Kraniotis SA, Doellman MA, Ragozzino ME, Garris PA, Roitman MF. Amphetamine paradoxically augments exocytotic dopamine release and phasic dopamine signals. J Neurosci. 2013 Jan 9;33(2):452-63. 32. Ramsson ES, Howard CD, Covey DP, Garris PA. High doses of amphetamine augment, rather than disrupt, exocytotic dopamine release in the dorsal and ventral striatum of the anesthetized rat. J Neurochem. 2011 Dec;119(6):1162-72. 33. Florin SM, Kuczenski R, Segal DS. Effects of reserpine on extracellular caudate dopamine and hippocampus norepinephrine responses to amphetamine and cocaine: mechanistic and behavioral considerations. J Pharmacol Exp Ther. 1995 Jul;274(1):231-41. 34. Pifl C, Agneter E, Drobny H, Sitte HH, Singer EA. Amphetamine reverses or blocks the operation of the human noradrenaline transporter depending on its concentration: superfusion studies on transfected cells. Neuropharmacology. 1999 Jan;38(1):157-65. 35. Bula do profissional de saúde – Produto Venvanse®.

Saiba mais em:

CONEXÃO

FOCO

Não metabolizado35pelo CYP 450

Duplo Mecanismo 21-35de Ação

35Pró-droga

Neurotransmissores

FUNCIONAIS

Reduções significativas de ativação nas regiões frontaisConectividade atípica da rede funcional na rede padrão

Excesso de ativações e subativações 12em regiões do cérebro

ESTRUTURAIS7,8Desenvolvimento cortical

7,9,10Redução no volume de várias regiões do cérebroAnomalias estruturais na conexão dentro de redes

11que regulam a atenção e a emoção

ELÉTRICAS

Necessidade de mais pesquisas para comprovar EEG para uso como um biomarcador no diagnótico do TDAH

Padrões de EEG individuais associados com TDAH estão sob investigação para avaliar a utilidade em

13,14,15personalizar protocolos de neurofeedback

QUÍMICOS

Maturação posterior de determinadas 20vias neurais dopaminérgicas

Desequilíbrio nos níveis de dopamina 16-19e noradrenalina

S istema simpático

Prazer e iniciativa

Ação

Vigilância

Ansiedade eirritabilidade

Função Cognitiva

Motivação

Sexoapetite

agressão

Sistemaparassimpático

Controle do impulso

Sono

IMPACTOSTDAH e o CÉREBRO

Responsável pela elaboração dopensamento, planejamento,

programação de necessidades individuais e emoção.

TEMPORAL

FRONTAL

PARIENTALTambém está relacionado com a

lógica matemática.Responsável pela sensação de dor,

gustação, tato, temperatura e pressão. Estimulação de certas regiões deste

lobo em pacientes conscientes, produzem sensações gustativas.

Está relacionado com o processamento da memoria e emoção e também com o sentido

de audição.

OCCIPITALResponsável pelo processamento

da informação visual.

1PRÉ-FRONTALEstá relacionado ao controle das funções

executivas – responsáveis pelo planejamento, tomada de decisão,

controle inibitório, atenção e memória de trabalho. Prejuízos nas funções

relacionadas ao cortex pré-frontal conduzem a uma maior impulsividade, agressividade e inadequação social.

* Adaptado de de Almeida, RM; Cabral, JC; Narvaes, R. . "Behavioural,

hormonal and neurobiological mechanisms of aggressive behaviour in human and nonhuman primates".