Alzheimer's and Parkinson's Drugs

When should you discontinue an Acetylcholinesterase Inhibitor?

If no improvement is seen in 6-8 weeks of treatment

What is the MOA of Acetylcholinesterase Inhibitors?

Inhibits AChE which increases acetylcholine at the synapses

What are the acetylcholinesterase inhibitors?

Donepezil, Rivastigmine, Galantamine

Which acetylcholinesterase inhibitor selectively inhibits central AChE?

Donepezil

Which acetylcholinesterase inhibitor has the longest half life?

Donepezil

Which acetylcholinesterase inhibitor is indicated for severe alzheimer's disease?

Donepezil

Which acetylcholinesterase inhibitor inhibits both AChE and BChE activity?

Rivastigmine

Which acetylcholinesterase inhibitor is available in patch form?

Rivastigmine

What is the MOA of Galantamine?

Allosterically modulates nicotinic receptors

How can you attempt to ease side effects of Galantamine?

Advise patients to take at bedtime

What are some class side effects of acetylcholinesterase inhibitors?

N/V/D, cholinergic effects

What is the MOA of Memantine (Namenda)?

Non-competitive NMDA receptor antagonist which causes a reduction in CNS glutamate

How should Namenda be administered to patients to achieve maximum efficacy?

In combination with acetylcholinesterase inhibitors (aka Namzaric)

What are the anti-amyloid agents?

Donanemab, Lecanemab, Aducanumab

What is the MOA of anti-amyloid agents?

Binds B-amyloid to increase the clearance

What are BBW side effects of anti-amyloid agents?

-Brain swelling

-Small brain bleeding

What are the downsides of anti-amyloid agents?

-Concerning side effects

-Results are not that impressive

Which class of Alzheimer's drugs required periodic MRIs?

Anti-amyloid agents

What is levodopa?

Metabolic precursor of dopamine that is able to cross the BBB

What is the MOA of Carbidopa?

Dopa-decarboxylase inhibitor that reduces the amount of levodopa that is broken down in the peripheral system

Why must levodopa and carbidopa be administered together?

Carbidopa enhances the amount of levodopa that crosses into the BBB

What is a major side effect of levodopa/carbidopa?

Peak-dose choreiform dyskinesias

What are peak-dose choreiform dyskinesias?

Involuntary choreiform movements involving the neck, trunk and lower extremities

How can you mitigate peak-dose choreiform dyskinesias?

Lower the dose of levodopa/carbidopa

What are the COMT inhibitors?

-Tolcapone

-Entacapone

-Stalevo

What is COMT?

The enzyme responsible for the biotransformation of levodopa (into 3-OMD)

What is the MOA of COMT inhibitors?

Block the conversion of levodopa into 3-OMD to allow it to cross into the BBB

Which COMT inhibitor is the preferred agent?

Entacapone

What is a BBW of Tolcapone?

Acute fulminant liver failure

How should COMT inhibitors be used in parkinson's patients?

In combination with levodopa/carbidopa

What are the dopamine agonists?

-Pramipexole

-Ropinirole

-Bromocriptine

-Apomorphine

-Rotigotine

What is the MOA of dopamine agonists?

Stimulates post-synaptic dopamine receptors in the corpus striatum

What is a common side effect seen with dopamine agonists?

Sudden excessive daytime somnolence

Who are the preferred patients for dopamine agonists?

<65 YO, younger patients that are likely to develop motor complications

What is apomorphine's role in therapy?

Used as an injectable rescue agent for hypomobility

What should you avoid when taking dopamine agonists?

5-HT3 antagonists (Zofran)

What is a side effect of apomorphine?

Severe hypotension

What are the monoamine oxidase inhibitors (MAOIs)?

-Selegiline

-Rasagiline

What is the MOA of Selegiline?

Selective irreversible inhibitors of MAO-B which prevents the breakdown of dopamine

What is the MOA of Rasagiline?

Potent selective irreversible inhibitors of MAO-B which prevents the breakdown of dopamine

What does Rasagiline specifically treat in Parkinson's?

Early symptoms

What should be avoided in MAOI administration?

Combination administration of both form of MOI inhibitors and levodopa as it can cause a hypertensive crisis

What is contraindicated in the use of MAOIs?

Opioid analgesias

What are MAOIs role in therapy?

They are adjunctive agents

A Parkinson patient recently starts carbidopa/levodopa and develops involuntary choreiform movements. What is this?

Peak dose dyskinesias

How do you mitigated peak dose dyskinesias?

Lower dosage and give more frequently throughout the day