Therapy of Alzheimer

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Therapy of Alzheimers Disease

• Department of Pharmacology
• Zhang Yan-mei

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• Alzheimers disease is a specific process
  that results in dementia, and is unrelated to the
  dementias associated with stroke, brain trauma,
  and alcohol.
• It is the commonest cause of dementia,
  accounting for 70 of all cases of dementia in
  the community.
• The female male ratio is 31

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1. Degenerative disease closely related with age.
2. Progressive
3. Deterioration in cognitive function and impaired
   memory.

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Pathogenesis

1. Shrinkage of the brain substance (hippocampus and
   basal forebrain)
2. Loss of neuronal tissue (relative selective loss
   of cholinergic neurons).
3. Neuritic plaques deposition of ß-amyloid
   protein.
4. Neruofibrillary tangles (Tau).

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Therapeutic target

• Restoration of cholinergic function
• Cholinesterase inhibitors (Tacrine)
• Muscarinic agonists
• 2 . Nerve growth factor (implanting cells
  engineered to secrete NGF are under
  investigation)
• Other approaches inhibitors of APP NSAIDs
  inhibition of
  excitotoxicity, putative vasodilators, et al.

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TacrineMechanism of action

• Prevents the breakdown of acetylcholine and
  enhances endogenous cholinogenic activity.
• Promotes the release of Ach.
• Acts as a partial agonist at muscarinic
  receptors.
• Inhibits MAO.

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Pharmacokinetics

• It is lipid-soluble, and can penetrates the BBB
  and accumulates in the brain

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Indications

• Mild to moderate dementia in Alzheimers disease

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Adverse effects

• ALT was elevated in nearly 25 of patients
  within 4-12 weeks of first dose and return to
  normal 6 weeks after discontinuation.
• Nausea, vomiting, diarrhoea, anorexia, and
  agitation