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Alzheimer’s disease Dr. Manodeep Chakraborty. Cognition enhancer: These are a heterogenous group of drugs used in Dementia & other cerebral disorders (Alzheimer’s disease)
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Alzheimer’s disease Dr. ManodeepChakraborty
Cognition enhancer: • These are a heterogenous group of drugs used in Dementia & other cerebral disorders (Alzheimer’s disease) • Dementia: acquired global impairment of intellect, memory, personality. Memory, capacity to solve problems of day to day living, performance of learned motor skills, social skills and control of emotions are affected. • Alzheimer’s disease: a progressive neurodegenerative disorder which affects older individuals and is the most common cause of dementia. • atrophy of cortical, subcortical areas, • β-amyloid deposition, • neurofibrillary tangles, • cholinergic deficiency. • Neurofibrillary tangles (NFTs) are aggregates of hyperphosphorylated microtubule-associated protein known as tau, causing it to aggregate, or group, in an insoluble form. tau proteins are most commonly known as a primary marker of Alzheimer's disease.
The indications of cognition enhancers include: • 1. Senile dementia of Alzheimer type (DAT) and multi infarct dementia (MID). • 2. 'Common symptoms' of the elderly: dizziness and memory disturbances. • 3. Mental retardation in children, learning defects, attention deficit disorder. • 4. Transient ischemic attacks (TIAs), cerebrovascular accidents - stroke. • 5. Organic psychosyndromes and sequelae of head injury, ECT, brain surgery
The mechanism by which they are believed to act are: 1. lncreasing global/regional cerebral blood flow (CBF) 2. Direct support of neuronal metabolism 3. Enhancement of neurotransmission 4. lmprovement of discrete cerebral functions, e.g. memory.
CLASSIFICATION OF DRUGS: a. Cholinergic activators: Tacrine, Rivastigmine, Donepezil, Galantamine b. Glutamate (NMDA) antagonist: Memantine c. Miscellaneous cerebroactive drugs: Piracetam, Pyritinol, Dihydroergotoxine, Piribedil, Ginkgo biloba
Cholinergic activators: • Since brain Ach levels are markedly reduced and cholinergic • neurotransmission is the major sufferer in AD, various approaches to augment brain ACh have been tried. • Anticholinesteraselike physostigmine produce symptom improvement, but many peripheral side effects are seen. • Tacrine, Rivastigmine, Donepezil, Galantamine • Rivastigmineinhibits both AChE and BuChE (butrylcholineesterase inhibitor), more selective for AChE. • High lipid soluble, enter brain easily. • mild peripheral effect • b. Glutamate (NMDA) antagonist: Memantine • NMDA receptor antagonist. • Moderate to severe AD-slows functional decline • in mild disease benefit is unclear • Side effects:Constipation, tiredness, headache, drowsiness.
c. Miscellaneous cerebroactive drugs: • Piracetam, Pyritinol, Dihydroergotoxine, Piribedil, Ginkgo biloba • Piracetam: cyclic GABA derivative but no GABA like activity • Improve ATP/ADP ratio, ↑synaptic transmission, have antithrombotic effect • ↑learning, memory, ↑interhemisphere information transfer, increased tonic cortical control on subcortical areas • Reduce blood viscosity • Dihydroergotoxine: semi-synthetic ergot alkaloid having adrenergic blocking property, • ↑cerebral flow • ↑ release of Ach, ↑DA & 5-HT in some areas