Drugs for Neurodegenerative Disease

Question 1

Malfunction of substantia nigra causes (hyper/hypo)kinetic

Which disease?

Answer 1

Hypokinetic

Parkinsonism

Question 2

Malfunction of striatum causes (hyper/hypo)kinetic

Which disease?

Answer 2

Hyperkinetic

Huntington’s disease

Question 3

What disease?

Involve muscle weakness and atrophy due to degeneration of motor neurons in spinal cord and cerebral cortex

Answer 3

Amyotrophic lateral sclerosis (ALS)

Question 4

Alzheimer’s disease is due to degeneration of neurons in what parts of the brain?

Answer 4

hippocampus and cerebral cortex

Question 5

Lewy bodies are characteristic of what disease?

Answer 5

Parkinson’s disease

Question 6

Which of the following is a characteristic of Parkinson's disease?
A. Hyperkinesia
B. Intentional tremor
C. Muscular flaccidity
D. Mask-like face, shuffling gait
E. Unaffected speech

Answer 6

D

A. Bradykinesia
B. Resting tremor
C. Muscular rigidity
E. Impaired speech

Question 7

D1 receptor controls ____ in the basal ganglia

Answer 7

direct pathway: accelerates movement

Question 8

D2 receptor controls ____ in the basal ganglia

Answer 8

indirect pathway: slows movement

Question 9

A reduction in dopamine acting at D1 and D2 causes

Answer 9

Inhibition of direct pathway

Activation of indirect pathway

Question 10

Name the drugs that increase DA synthesis (3)

Answer 10

L-DOPA (levodopa)
Levodopa/Carbidopa (Sinemet)
Entacapone/Levodopa/Carbidopa (Stalevo)

Question 11

Which of the following is TRUE about L-DOPA (levodopa)?
A. Poor oral availability
B. 8-10 hour half life
C. Good brain penetration
D. Metabolized peripherally by aromatic I-amino acid decarboxylase
E. Effect does not wane long term

Answer 11

D

A. Good oral availability: quick absorption from small intestine
B. Short half life: 1-2 hrs
C. Poor brain penetration (1-3%)
E. “Wearing off” effect after 3-5 years

Question 12

Which of the following is NOT a side effect of L-DOPA?
A. Nausea/vomiting, anorexia 
B. Cardiac arrhythmias
C. Visual and auditory hallucination
D. Memory impairment
E. Dyskinesia

Answer 12

D

Also orthostatic hypotension and mood changes (depression, psychosis, anxiety)

Question 13

Medication of choice for Parkinson’s

Answer 13

Sinemet (Levodopa/Carbidopa)

Question 14

Aromatic I-amino acid decarboxylase inhibitor

Answer 14

Carbidopa

Question 15

Name the drug:
o Blocks peripheral metabolism of L-DOPA → increase L-DOPA availability in brain
o Allow reduced dose of L-DOPA by 4-5x → reduce side effects of peripheral DA

Answer 15

Sinemet (Levodopa/Carbidopa)

Question 16

Inhibitor of catechol-O-methyltransferase

Answer 16

Entacapone

Question 17

Name the drugs that decrease DA catabolism (2)

Answer 17

Selegiline

Rasagiline

Question 18

Which of the following is TRUE about Selegilline?
A. Inhibits I-amino acid decarboxylase
B. IV administration
C. Liver excretion
D. Limits formation of neurotoxic free radical

Answer 18

D by decreasing production of byproduct of dopamine, hydrogen peroxide

A. Carbidopa does this. Selegilline inhibits monoamine oxidase type B
B. Oral administration
C. Renal excretion

Question 19

Used adjunctive w/ levodopa

Answer 19

Selegiline

Very little benefit when taken alone

Question 20

Is metabolized to methamphetamine and amphetamine causing insomnia

Answer 20

Selegiline

Question 21

What are the advantages of Rasagiline over Selegiline?

Answer 21

More potent

Not metabolized to amphetamine-like substance

Question 22

D2 agonist, D1 partial agonist

Answer 22

Bromocriptine

Question 23

D2, D3 agonist

Answer 23

Ropinirole

Pramipexole

Question 24

Name the dopamine receptor agonists (4)

Answer 24

Ropinirole
Pramipexole
Bromocriptine
Apomorphine

Question 25

Longer half life (6-8 hours) than L-DOPA so it reduces motor control fluctuation

Answer 25

Dopamine receptor agonists

Question 26

Emergency treatment of pts w/ advanced Parkinson's for "off periods"

Answer 26

Apomorphine

Question 27

Apomorphine administration

Answer 27

SubQ injection do NOT use IV --> would cause thrombus and PE

Question 28

Name the type of drug: Benztropine Trihexyphenidyl

Answer 28

Muscarinic antagonist

Question 29

Muscarinic antagonists (Benztropine, Trihexyphenidyl) used to alleviate what symptoms of Parkinsons?

Answer 29

Tremor and rigidity | NOT bradykinesia

Question 30

Amantadine used to alleviate what symptoms of Parkinsons?

Answer 30

Bradykinesia and rigidity | NOT tremor

Question 31

Used by patients with mild-moderate disease before using L-DOPA

Answer 31

Amantadine

Question 32

Name the drug: | Block cholinergic muscarinic receptors and glutamatergic NMDA receptors

Answer 32

Amantadine

Question 33

``` Which of the following is NOT a side effect of Amantadine? A. Hallucinations, confusion B. Nausea C. Rash of upper extremities D. Dizziness ```

Answer 33

C. Rash of LOWER extremities

Question 34

``` Which of the following is NOT an AChE inhibitor A. Donepezil B. Memantine C. Galantamine D. Rivastigmine E. Tacrine ```

Answer 34

B. Memantine is a NMDA receptor antagonist

Question 35

Which AChE inhibitor has the longest half life?

Answer 35

Donepezil (70 hrs)

Question 36

Which AChE inhibitor has the shortest half life?

Answer 36

Rivastigmine (1.5 hrs)

Question 37

AChE inhibitors used to treat

Answer 37

Alzheimer's

Question 38

Donepezil, galantamine, tacrine is metabolized by ____

Answer 38

P450 liver enzymes

Question 39

Rivastigmine metabolized by ____

Answer 39

plasma cholinesterase

Question 40

All AChE inhibitors are overall safe except for ____

Answer 40

Tacrine: hepatotoxicity

Question 41

Type of drug: | Memantine

Answer 41

NMDA receptor antagonist --> protect neurons form Ca2+ overload, neuronal death