Psychopharmacologic Therapy- Neurodegenerative Disease

Question 1

Define Parkinson’s Disease

Answer 1

movement disorder occuring mostly age >60
chronic progression
some genetic risk factors

Question 2

Parkinson’s Disease is characterized by:

Answer 2

dyskinesia
muscle rigidity
tremor at rest
cognitive impairments, depression

Question 3

Pathology of Parkinson’s Disease

Answer 3

neurodegenerative disease resulting from a loss of dopaminergic neurons in the substantia nigra of the basal ganglia
degeneration of the nitrostriatal pathway leads to depletion of the inhibitory neurotransmitter dopamine

Question 4

In PD, what is imbalanced?

Answer 4

reduced dopamine in the striatum

imbalance between Ach and Dopamine

Question 5

Goal of Antiparkinson’s drugs

Answer 5

enhance the inhibitory effect of dopamine
increases amount of dopamine
drug therapy that mimics dopamine
decrease excitatory effect of ach with the administeration of centrally acting drugs

Question 6

Parkinson’s Drug Therapy Treatments

Answer 6

treats motor symptoms
treats other adverse effects of disease (depression, autonomic disturbances, cognitive impairment, side effects of drug therapy)
deep brain stimulation

Question 7

Levodopa

Answer 7

crosses BBB and is converted to dopamine, replenishes stores in the basal ganglia

Question 8

Side Effects of Levodopa

Answer 8

N/V
cardiovascular
abnormal involuntary movements
psychatric disturbances

Question 9

Why does N/V occur with levodopa?

Answer 9

due to dopamine induced stimulation of the chemoreceptor trigger zone

Question 10

Why can you have cardiovascular s/e with levodopa?

Answer 10

alpha and beta responses evoked by higher plasma levels of dopamine result in transient flushing of skim, sinus tachycardia, PACs, PVCs and orthostatic hypotension

Question 11

Lab measurements of Levodopa

Answer 11

urinary metabolites can cause false positive tests for ketoacidosis
transient increase in BUN
increase in liver enzymes

Question 12

Levodopa Drug Interactions

Answer 12

butyrophenones and phenothiazines
antagonize effect of dopamine (avoid!)
metoclopramide 
droperidol
MAO inhibitors
anticholinergics

Question 13

Levodopa is administered with

Answer 13

peripheral decarboxylase inhibitor
as it enables levodopa to enter CNS and decreases s/e of systemic dopamine
decreases incidence of N/V and cardiac dysrhymia

Question 14

Examples of peripheral decarboxylase inhibitors

Answer 14

carbidopa (sinemet)-levodopa and cardidopa

benserazide (madopar) levodopa and benserazide

Question 15

Levodopa can also be administered with

Answer 15

catachol-O-methytransferase inhibitors (COMT)
responsible for the peripheral breakdown of Levodopa
block COMT enzyme-> augments the action of levodopa by slowing elimination time

Question 16

Examples of COMT

Answer 16

tolcapone (tasmar)

entacapone (comtan)

Question 17

Synethetic dopamine agonist

Answer 17

act directly on post synaptic dopamine receptors
no enzymatic conversion required
longer 1/2 life then levodopa

Question 18

Examples of dopamine agonist

Answer 18

bromocriptine (parlodel) ergot derivative
pramipexole (mirapex) non ergot
ropinirole (requip) non ergot
rotigotine- non ergot

Question 19

Side effects of Synthetic dopamine agonist

Answer 19

sedation, vivid dreams, hallucinations

non-ergots: less nausea and orthostatic hypotension then ergot derivatives

Question 20

Anticholinergics

Answer 20

trihexyphenidyl (artane) and benztropine (cogentin)

Question 21

trihexyphenidyl (artane) and benztropine (cogentin)

Answer 21

blunt effects of excitatory neurotransmitter ach correcting balance between dopamine and ach

Question 22

side effects of trihexyphenidyl (artane) and benztropine (cogentin)

Answer 22

confusion, hallucinations, confusion, urinary retention

Question 23

Amantadine (symmetrel)

Answer 23

symptomatic improvement of parkinsonian symptoms

enhance dopamine release into the synapse and delay re-uptake into the nerve ending

Question 24

Selegiline (eldepryl)

Answer 24

highly selective irreversible inhibitor of MAOB

used as adjunct to carbidopa-levodopa

Question 25

Nonpharmacologic Rx for parkinson's

Answer 25

deep brain stimulation controls symptoms if resistant to drug therapy and/or allows reduced doses stem cell transplantation and other therapeutic mechanisms are under investigation

Question 26

Alzheimer's Disease

Answer 26

dementia

Question 27

Alzheimer's causes problems with

Answer 27

``` memory language judgement and thinking personality perception ```

Question 28

Who gets alzheimer's disease?

Answer 28

5% at 65 years of age | >90% at 95 years of age

Question 29

Early onset

Answer 29

symptoms before age 60 | genetic factors

Question 30

Late onset

Answer 30

symptoms appear after age 60

Question 31

Pathology of alzheimer's

Answer 31

``` deficits in cholinergic signaling cholinergic neuron loss -hippocampus (memory and learning) and frontal cortex (executive function) Protein aggregates: amyloid plaques neurofibrillary tangles ```

Question 32

Alzheimer's have decreases in

Answer 32

``` choline acetyltransferase activity acetylcholine amount acetylcholinersterases choline transport nicotinic acetylcholine receptor expression ```

Question 33

Current drug treatments:

Answer 33

cholinersterase inhibitors | NMDA receptor antagonist

Question 34

Cholinesterase Inhibitors MOA

Answer 34

prevents action of acetylcholinesterase thereby increasing acetylcholine concentrations in the synapse

Question 35

Examples of Cholinesterase inhibitors

Answer 35

donepezil (aricept) rivastigmine (exelon) galantamine (razadyne)

Question 36

Cholinesterase Inhibitors

Answer 36

indicated for mild to moderate AD | oral administration 1-2x/day

Question 37

S/E of Cholinesterase Inhibitors

Answer 37

nausea, diarrhea, dizziness, headache, bronchoconstriction slight improvement in cognitive function does not halter disease

Question 38

NMDA Receptor Antagonist: Memantine (Namenda)

Answer 38

indicated for moderate to severe AD | very modest benefits

Question 39

Potential side effects of Memantine (Namenda)

Answer 39

anemia, dizziness, diarrhea, fatigue, headache, HTN, rash, sedation, urinary frequency, weight gain

Question 40

memantine is proposed to work by two diferent mechanism

Answer 40

Signal To noise hypothesis/reduced excitotoxicity blocking leaky channels to help reduce calcium induced excitotoxicity blocking leaky channels helps reduce background noise, making signals relatively stronger