Dementia Drugs

Question 1

what condition is responsible for the largest fraction of dementia cases

Answer 1

• Alzheimer’s disease

Question 2

the movement symptoms of Huntington’s disease result largely from aberrations in the _____ pathway

what happens in this pathway

Answer 2

• nigrostriatal dopaminergic
• releases dopamine into the striatum
• modulates signaling through the direct and indirect movement pathways of the basal ganglia

Question 3

early stage Huntington disease is characterized by ______ in dopamine levels

Answer 3

• increase

Question 4

drugs used to treat Huntington Disease

Answer 4

• Tetrabenazine

- Aripiprazole

Question 5

MOA of Tetrabenazine

Answer 5

• inhibit VMAT transporter which transports dopamine into presynaptic vesicles
• reduces amount of dopamine released

Question 6

MOA of Aripiprazole

may also treat

Answer 6

• dopamine antagonist
• directly compete with dopamine for binding to dopamine receptors on the postsynaptic cell
• agitation and psychotic symptoms

Question 7

toxicities of Aripiprazole

Answer 7

• extrapyramidal symptoms
• neuroleptic malignant syndrome
• gynecomastia
• amorrhea
• sexual disfunction
• metabolic syndrome
• anti-cholinergic toxicities
• orthostatic hypotension
• sedation
• prolonged QT

Question 8

Parkinson’s disease is characterized by

Answer 8

• loss of dopaminergic neurons in nigrostriatal pathway

Question 9

the pharmacotherapy goal of Parkinson’s disease is _____ that for Huntington disease

Answer 9

• opposite

Question 10

MOA of L-DOPA (Levodopa)

what do we give it with

Answer 10

• can cross the BBB where it is then converted into dopamine
• Carbidopa

Question 11

MOA of Carbidopa

can it cross the BBB

Answer 11

• inhibitor of DDC which converts levodopa into dopamine in peripheral tissues
• increases amount of drug that reaches the brain
• cannot cross the BB so so doesn’t not interfere with conversion of levodopa to dopamine in the brain

Question 12

MOA of Entacapone

when do we add this to the treatment regimen

Answer 12

• inhibits COMT which breaks down levodopa

- after therapeutic effects of levodopa and carbidopa begin to fluctuate or wear off

Question 13

what is the wearing off phenomenon with levodopa

Answer 13

• fewer neurons available in later stages of disease to convert levodopa to dopamine

Question 14

toxicities of levodopa

Answer 14

• nausea/vomiting (chemoreceptor trigger zone)
• orthostatic hypotension (medulla)
• psychosis (mesocortical pathway)

Question 15

MOA of Tolcapone

Answer 15

• COMT inhibitor

Question 16

toxicities of Entacapone

Answer 16

• diarrhea

Question 17

toxicities of Tolcapone

Answer 17

• diarrhea

- hepatotoxicity

Question 18

levodopa interacts with which drugs

why?

Answer 18

• nonselective MAOIs
• isocarboxazid
• phenelzine
• trianylcipromine
• increase dopamine levels to a dangerous point

Question 19

MOA of bromocriptine

Answer 19

• dopamine agonist in striatum

Question 20

MOA of pramipexole

Answer 20

• dopamine agonist in striatum

Question 21

MOA of Ropinirole

Answer 21

• dopamine agonist in striatum

Question 22

toxicities of Bromocriptine

useful in treating

Answer 22

• prolactin suppression from pituitary gland
• cardiac valve fibrosis
• prolactinomas and other endocrine disorders

Question 23

toxicities of pramipexole and ropinirole

Answer 23

• sedation
• somnolence
• sleep attacks

Question 24

MOA of selegiline

Answer 24

• monoamine oxidase B inhibitor

- blocks breakdown of dopamine in neurons

Question 25

MOA of rasagiline

Answer 25

- monoamine oxidase B inhibitor | - blocks breakdown of dopamine in neurons

Question 26

MOA of amantadine

Answer 26

- helpful for treating influenza | - stimulates release of dopamine from nigrostriatal neurons

Question 27

toxicities of amantadine

Answer 27

- dizziness - insomnia - somnolence - hallucinations

Question 28

MOA of benztropine | - trihexiphenidyl

Answer 28

- direct antagonist of acetylcholine - reduces contribution from cholinergic stratal neurons - re-establish balance between acetylcholine and dopamine signaling in the striatum

Question 29

toxicities of anti-cholinergics

Answer 29

- dry mouth - tachycardia - constipation - urinary retention

Question 30

what drugs are good for treating mild PD symptoms in young patients

Answer 30

- MAOi OR - amantadine OR - anti-cholinergic (avoid in older patients)

Question 31

what drugs are good for treating moderate PD symptoms in younger patients

Answer 31

- levodopa/carbidopa OR | - DA agonist (avoid in older patient)

Question 32

what drugs are good for treating severe PD symptoms

Answer 32

- levodopa/carbidopa PLUS - DA agonist OR MAOI

Question 33

what do you use to treat dementia with lewy bodies

Answer 33

- cholinesterase inhibitors

Question 34

late in Lewy body dementia, what may occurs how do you treat

Answer 34

- parkinsonian features | - same drugs as Parkinson's

Question 35

MOA of Donepezil

Answer 35

- cholinesterase inhibitor - block normal degradation of acetylcholine at the synapse - all stages of Alzheimer's treatment

Question 36

MOA of Galantamine

Answer 36

- cholinesterase inhibitor - block normal degradation of acetylcholine at the synapse - mild-moderate symptoms of Alzheimer's

Question 37

MOA of Rivastigmine

Answer 37

- cholinesterase inhibitor - block normal degradation of acetylcholine at the synapse - mild-moderate symptoms of Alzheimer's

Question 38

toxicities of cholinesterase inhibitors

Answer 38

- pro-cholinergic - arrhythmias - insomnia - vivid dreams - bradycardia - syncope

Question 39

avoid cholinesterase inhibitors with

Answer 39

- beta blockers/Ca2+ channel blockers

Question 40

treatment of Alzheimer's disease

Answer 40

- cholinesterase inhibitors | - glutamate receptor antagonist

Question 41

MOA of memantine how does this impact AD

Answer 41

- glutamate receptor competitive antagonist - glutamate cannot reuptake due to AB plaques - excess glutamate leads to excitotoxicity and cell death