23. Drug Treatment Of Neurodegenerative Disorders

Front 1

Which four mechanisms can underlie neurodegenerative diseases?

Back 1

- Protein misfolding

- Excitotoxicity

- Oxidative stress

- Mitochondrial dysfunction

Front 2

What is the pharmacological basis of Alzheimer treatment?

Back 2

Alzheimer is characterised by loss of cholinergic neurons. Increasing cholinergic transmission in the CNS treats the symptoms.

Front 3

Name the drugs which are used in the treatment of Alzheimer

Back 3

Cholinesterase inhibitors:

Donepezil, rivastigmine, galantamine

NMDA antagonist:

Memantine

Front 4

What is the mechanism of action of memantine?

Back 4

Memantine is an NMDA glutamate receptor antagonist. It decreases glutamate excitotoxicity.

Front 5

What is the pharmacological basis of Parkinson treatment?

Back 5

Parkinson disease is characterised by loss of dopaminergic neurons in the basal ganglia, particularly in the substantia nigra. This causes disinhibition of cholinergic neurons in the striatum.

The treatment of Parkinson disease mostly involves increasing dopaminergic activity in the CNS.

Front 6

What is the first line treatment of Parkinson disease?

Back 6

Levodopa + carbidopa

Front 7

Why do we not treat Parkinson disease with dopamine?

Back 7

Because dopamine doesn't cross the blood brain barrier

Front 8

What should levodopa always be combined with?

Back 8

A DOPA carboxylase inhibitor like carbidopa.

Front 9

What is the problem with long-term treatment with levodopa?

Back 9

Levodopa loses its efficacy after 3 - 5 years.

Front 10

Which drugs are used in the treatment of Parkinson disease?

Back 10

- DOPA activity increasers (levodopa, carbidopa)

- Dopamine agonists (bromocriptine)

- MAO-B inhibitors (selegiline)

- COMT inhibitors (entecapone)

- Safinamide

- NMDA antagonists (Amantadine)

- Anticholinergics (Benztropine, biperiden)

Front 11

What is the mechanism of action of COMT and MAO-B inhibitors?

Back 11

COMT and MAO-B inhibitors inhibit enzymes that break down dopamine.

Front 12

What are typical side effects of anti-Parkinson drugs?

Back 12

Due to peripheral dopamine:

Nausea, orthostatic hypotension.

Due to central dopamine:

Depression, dyskinesia, confusion, psychosis

Front 13

What is the "on", "off" phenomenon?

Back 13

Patients taking levodopa experiences "on" periods, where the symptoms are relieved by levodopa, and "off" periods, where the symptoms return.

Front 14

Which drugs are indicated in Huntington disease?

Back 14

Antipsychotics (haloperidol, clozapine)

NMDA antagonists (amantadine)

Tetrabenazine

Baclofen

Front 15

What is the mechanism of action of baclofen?

Back 15

Baclofen is a GABA-B agonist.

Front 16

What is the mechanism of action of antipsychotics?

Back 16

Antipsychotics are dopamine D2 antagonists.

Front 17

Which drugs can be effective in the treatment of stroke?

Back 17

Alteplase, aspirin

Front 18

What is the mechanism of action of alteplase?

Back 18

Alteplase is a recombinant tissue plasminogen activator, meaning that activates plasminogen. By converting plasminogen into plasmin, it breaks up any clots that would impair circulation.

Front 19

What is the treatment of Wilson disease?

Back 19

Drugs that chelate copper, like penicillamine

Front 20

What is the mechanism of action of tetrabenazine?

Back 20

Tetrabenazine is a VMAT inhibitor. VMAT is the protein that transports dopamine into transport vesicles. By inhibiting this protein transport vesicles will contain less dopamine, so dopaminergic transmission in the CNS decreases.