Tratamiento del Alzheimer y similares

1. TRATAMIENTO DE LOS
TRASTORNOS
DEGENERATIVOS DEL SNC
CRISTIAN OSWALDO MUÑOZ POLO
R2 NEUROLOGÍA ADULTOS

2. TRASTORNOS NEURODEGENERATIVOS
• Parkinson
• Huntington
• Alzheimer
• ELA
• *Alivio de síntomas
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

3. CARACTERÍSTICAS COMUNES
• Proteinopatías
• Alfa sinucleina
• A beta y tau asociada a
microtúbulos
• TDP-43
• Huntingtina
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

4. VULNERABILIDAD SELECTIVA
• Parkinson  sustancia negra
• Alzheimer  hipocampo y neocorteza
• Huntington  neoestriado
• ALS  Neuronas motoras
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

5. GENÉTICA Y AMBIENTE
• Cada uno puede ser de naturaleza familiar
• Factores de riesgo genéticos
• P. ej. Fenotipo Apo E
• Factores ambientales
• Agentes infecciosos
• Toxinas ambientales
• Daño cerebral adquirido
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

6. ENFOQUE PARA LA TERAPIA
• Neuroquímicas
• Neuroprotectoras
• Objetivo neurotoxicidad
• Antagonistas de glutamato (memantina y riluzol)
• Envejecimiento
• Pérdida del metabolismo oxidativo
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

7. PARKINSON
• 4 características fundamentales
• Idiopática +
• Sin tratamiento progresa en 5-10 años
• Neuronas dopaminérgicas (+)
• Trastornos no motores
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

8. FISIOPATOLOGÍA
• Síntesis de dopamina
• TH Tirosina hidrolasa
• AADC L aminoácido aromatico
descarboxilasa
• VMAT 2: Trasportador de
monoaminas vesiculares 2
• OCT: Transportador de cationes
orgánicos
• ALDH: Aldehido deshidrogenasa
• HVA: Ácido homovanilico

9. Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

10. Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

11. TRATAMIENTO
• Levodopa
• Maximo 0.5-2 horas
• Vida media 1-3 hr
• Inhibidores de la AADC
periférica (carbidopa,
beserazida)
• Carbidopa/levodopa
25/100 mg
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

12. • Fenómeno de desgaste
• Discinesias
• Trastornos en el control de impulsos
• Alucinaciones y confusión
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

13. PRESERVACIÓN FARMACOLÓGICA DE LEVODOPA Y DA
ESTRIATAL
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

14. AGONISTAS DEL RECEPTOR DE DOPAMINA
• Duración más larga
• Ropinirol y pramipexol
• Rigotina (transdérmico)
• Alivio de síntomas clínicos
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

15. AGONISTAS DEL RECEPTOR DE DOPAMINA
• Apomorfina
• Subcutanea
• Receptores D4
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

16. INHIBIDORES DE COMT
• Tolcapona
• entacapona
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

17. INHIBIDORES SELECTIVOS DE MAO-B
• Combinación segura con levodopa
• Selegilina
• Rasagilina
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

18. AGOSNISTAS DEL RECEPTOR MUSCARINICO
• Trihexfenidilo, mesilato de benzotropina, hidrocloruro de
difenhidramina
• La base biológica no se entiende completamente
• Terapia inicial en parkinson leve
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

19. AMANTADINA
• Antiviral
• Actividad antiparkinsoniana
• Propiedades anticolinérgicas y bloqueo de receptores de glutamato
• Dosis: 100 mg dos veces al día
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

20. ALZHEIMER
• Etapa preclínica
• Etapa de deterioro
cognitivo leve (perdida
de la memoria episódica)
• Etapa de demencia
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

21. DIAGNÓSTICO
• Clínico
• Marcadores
• RMN estructural y PET
• Florbetapir, flutemetanol y florbetaben
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

22. GENÉTICA
• Mutación en tres genes
• A beta
• PSEN 1
• PSEN 2
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

23. FISIOPATOLOGÍA
• Placas amiloides
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

24. NEURQUÍMICA
• Deficiencia de ACH
• Degeneración de neuronas colinérgicas subcorticales
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

25. TRATAMIENTO
• Tratamiento de los síntomas cognitivos
• Memantina
• Antagonistas reversibles de colinesterasas
• Tratamiento de los síntomas conductuales
• Citalopram
• Antipsicóticos atípicos
• Benzodiacepinas
• Haloperidol

26. Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

27. ENFERMEDAD DE HUNTINGTON
• Descoordinación motora y
deterioro cognitivo
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

28. FISIOPATOLOGIA
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

29. GENÉTICA
• Autosómico dominante
• Edad entre 35-45 años
• Brazo corto cromosoma 4
• Repetición trinucleotida polimórfica (CAG)
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

30. TRATAMIENTO
• Tratamiento sintomático
• Ninguno ralentiza la progresión
• Tetrabenazina y reserpina (inhibidores de VMAT 2)
• Antidepresivos
• Antipsicóticos atípicos
• Benzodiacepinas
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

31. ESCLEROSIS LATERAL AMIOTRÓFICA
• Neuronas motoras asta ventral y neuronas corticales
• Debilidad rápidamente progresiva
• Cambios conductuales
• Disfunción cognitiva
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

32. ETIOLOGÍA
• 10% casos familiares
• Expansión de la repetición de hexanucleotidos en C9ORF72
• 90% casos esporádicos
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

33. TRATAMIENTOS
• Riluzol
• PO
• Metabolismo hepático
• Vida media 12 horas
• Inhibición de liberación de glutamato
• Bloquea receptores NMDA
• 50 mg dos veces al día
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

34. EDARAVONA
• FDA 2017
• Eliminación de radicales libres
• IV
• Ciclos de 14 días
• Excreción urinaria
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

35. TERAPIA SINTOMÁTICA : ESPASTICIDAD
• Baclofeno
• Agonista del receptor GABA b
• 5-10 mg al día dosis inicial
• Tizanidina
• Agonista de receptores adrenérgicos alfa 2
• 2-4 mg en HS
Goodman & Gilman’s. The Pharmacological Basis of Therapeutics by Brunton, Laurence L., Hilal-Dandan, Randa and Knollmann, Björn C., editors. Copyright ©
2018 by McGraw-Hill

36. GRACIAS