Alzheimer's Disease Flashcards

1
Q

Define Alzheimer’s disease.

A

A degenerative disorder that attacks the brain’s nerve cells resulting in loss of memory, thinking and language skills, and behavioral changes.

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1
Q

What areas of the brain does Alzheimer’s disease affect?

A

Alzheimer’s disease affects most areas of the brain.

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2
Q

Alzheimer’s disease is the most common cause of dementia.
What is dementia?

A

A group of brain disorders that cause the loss of intellectual and social skills.

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3
Q

Dementia of the Alzheimer’s type has three distinguishing features.
Mention them.

A
  1. Accumulation of senile plaques (β-amyloid accumulations).
  2. Formation of numerous neurofibrillary tangles.
    Explanation: In Alzheimer’s disease, abnormal chemical changes cause tau to detach from microtubules and stick to other tau molecules, forming threads that eventually join to form tangles inside neurons. These tangles block the neuron’s transport system, which harms the synaptic communication between neurons.
  3. Loss of cortical neurons, particularly cholinergic neurons.
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4
Q

Do the pharmacologic agents available to manage Alzheimer’s disease cure it?

A

No. Pharmacologic interventions for Alzheimer’s disease are only palliative and provide modest short-term benefit.

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5
Q

What is the strategy of treatment of Alzheimer’s disease?

A

Current therapies are aimed at:

  1. Improving cholinergic neurotransmission in the CNS.
  2. Preventing the excitotoxic actions resulting from the overstimulation of NMDA-glutamate receptors in selected brain areas.
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6
Q

What is acetylcholinesterase?

A

An enzyme that metabolites acetylcholine. It exists centrally and peripherally.

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7
Q

What are acetylcholinesterase inhibitors (AChE)?

A

Drugs that inhibit acetylcholinesterase enzyme thereby improving the cholinergic neurotransmission within the brain cortex, at least in the functioning surviving cholinergic neurons.
They are used primarily to treat mild to moderate Alzheimer’s disease.

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8
Q

What are the four reversible AChE inhibitors that are approved for the treatment of mild to moderate Alzheimer’s disease?

A

Donepezil.
Galantamine.
Rivastigmine.
Tacrine.

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9
Q

Which AChE inhibitors are non-competitive?

A

Donepezil.
Rivastigmine.
Tacrine.

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10
Q

Which AChE inhibitors are competitive?

A

Galantamine.

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11
Q

Galantamine, in addition to being an AChE inhibitor, has an additional mechanism of action.
What is this additional mechanism?

A

In addition to inhibiting acetylcholinesterase, galantamine also increases cholinergic neurotransmission by stimulating nicotinic receptors in the CNS.

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12
Q

What are the drug-drug interactions of acetylcholinesterase inhibitors?

A

All of these drugs are substrates for cytochrome P450 and have a strong potential of drug-drug interactions.

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13
Q

Which anti-Alzheimer’s disease drug has the safest drug-drug interaction profile?

A

Rivastigmine. This drug is hydrolyzed by acetylcholinesterase enzyme in the liver to a carbamylated metabolite and therefore has no interactions with drugs that alter the activity of cytochrome P450-dependent enzymes (like acetylcholinesterase inhibitors).

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14
Q

What are the adverse effects of acetylcholinesterase inhibitors?

A

Nausea.
Diarrhea.
Vomiting.
Anorexia.
Bradycardia.
Muscle cramps.

Tacrine is associated with hepatotoxicity.

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15
Q

What is the most commonly used NMDA-receptor antagonist?

A

Memantine.

16
Q

Why is overstimulation of glutamate receptors, particularly of the NMDA type, results in excitotoxic effects on neurons?

A

The overstimulation of glutamate receptors, particularly of the NMDA type, triggers apoptotic programmed cell death processes. Also, excess intracellular Ca+2 can activate a number of processes that damage the neurons.

17
Q

How does memantine work?

A

Memantine acts by physically blocking the NMDA receptor-associated ion channel, but at therapeutic doses, only a fraction of these channels are actually blocked.

So, memantine ultimately limits Ca+2 influx, decreasing intracellular ca+2.

18
Q

Why has memantine replaced phencyclidine?

A

Phencyclidine blocks all NMDA receptor-associated ion channels, whereas memantine is selective for hyperactive channels (due to it being voltage-dependent), minimizing NMDA receptor excitation without inhibiting natural NMDA receptor processes.

19
Q

How are NMDA receptor antagonists used?

A

They have been shown to slow the rate of memory loss, but there is no evidence that they prevent the degeneration of neurons or that they are more effective than acetylcholinesterase inhibitors, so they are used in combination with acetylcholinesterase inhibitors.

20
Q

What are the side effects of NMDA receptor antagonists?

A

Although they are well tolerated, they are known to cause:
Confusion.
Agitation.
Restlessness.
These symptoms are indistinguishable from the symptoms of Alzheimer’s disease.