Pharmacology: Alzheimer’s Disease

Alzheimer’s Disease is the most common type of
Dementia

What are the 2 pathological hallmarks of AD?
1) Neurofiblirally Tangles (intracellular lesions)
2) B-Amyloid Plaques (extracellular lesions)

Alzheim’ers disease is associated mainly in a reduction of
Cholinergic neurons in subcortical areas of the brain

Drugs we used for AD have what main function
Increase the ACETYLCHOLINE IN THE BRAIN

What does the excitotoxicity pathophysiology say has a part in AD?
Nerve cells are damaged by excessive stimulation by NTs likes glutamate > NMDA or AMPA receptors are overactivated > high calclium levels get into the neuron and activates enzymes which can damage the neuron if they are overstimulated

What are the 2 classes of drugs used to treat AD
1) Cholinesterase Inhibitors
2) NMDA receptor Antagonist

AChE inhibitor MOA
Inhibit AChE which is the enzyme that breaks down acetycholine, thus increasing the amount of acetylcholine available

Why do we use AChE inhibitors in PD?
1) PD is associated with the loss of acetylcholine neurons so we replace the ACh
2) This slows or prevents deterioration of cognitive functions

Why isn’t the AChE inhibitor Tacrine used much now?
Hepatotoxicity leading to liver failure

Donepezil MOA
Selectively inhibits AChE IN THE BRAIN AND NOT IN PERIPHERAL TISSUE (therefore less side effects)

Rivastigmine MOA
Nonselective AChE inhibitor, blocks acetylcholinesterase and butrylcholinesterase in plasma

Galantamine MOA
Selective AChE inhibitor AND nicotinic receptor agonist so it will actually bind the receptor that ACh binds to and activate it

Which drugs reduce the effectiveness of AChE inhibitors?
Anticholinergic agents

Memantine MOA
NMDA antagonist (thought to block excitotoxicity of glutamate & NMDA receptors)

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-aka Dementia: a syndrome with progressive deterioration in intellectual functioning secondary to structural or functional changes. – Alzheimer’s disease is the most common type of dementia -Alzheimer’s disease is an irreversible form of senile dementia caused by nerve cell deterioration. …

-aka Dementia: a syndrome with progressive deterioration in intellectual functioning secondary to structural or functional changes. – Alzheimer’s disease is the most common type of dementia -Alzheimer’s disease is an irreversible form of senile dementia caused by nerve cell deterioration. …

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