Pharm. - Movement Disorders

Front 1

ALS symptoms:

Back 1

-progressive muscular weakness
-muscle atrophy
-spasticity
-respiratory compromise
-decreased bladder control (overactive)

Front 2

ALS results from

Back 2

the degeneration of spinal, bulbar and cortical neurons

Front 3

two types of treatments for ALS

Back 3

1. GAGAb agonists
2. muscarinic receptor antagonists

Front 4

name a GABAb agonist

Back 4

Baclofen

Front 5

GABAb Mech. of Action

Back 5

controls the release of excitatory neurotransmitters (predominantly glutamate), so has an inhibitory effect

Front 6

name 5 muscarinic antagonists

Back 6

1. dicyclomine
2. flavoxate
3. oxybutynin
4.oxyphencyclimine
5. trihexylphenidyl

Front 7

Huntington's Disease symptoms

Back 7

-incoordination
-cognitive decline
-severe psychosis

Front 8

cause of Huntington's

Back 8

genetic (autosomal dominant disorder)

Front 9

average age of onset Huntington's

Back 9

35-40

Front 10

treatment of Huntington's

Back 10

Baclofen (the GABAb agonist)

Front 11

Parkinsons prominent symptoms:

Back 11

-rigidity
-tremors (fine motor 1st)
-bradykinesia
-altered gait
-excessive salivation
-facial mvmt/tongut mvmt

Front 12

Parkinsons onset usually over the age of

Back 12

40

Front 13

cause of Parkinsons

Back 13

etiology or cause is not precisely known

Front 14

Parkinsons thought to involve what neurotransmitter?

Back 14

Dopamine

Front 15

Dopamine has an inhibitory effect on

Back 15

cholinergic outflow (AcH)

Front 16

Decreased dopamine allows the actions of AcH to predominate in what areas of the brain?

Back 16

-extrapyramidal system
-basal ganglia

Front 17

projections from the substantia nigra end up where?

Back 17

-caudate
-putamen

Front 18

With Parkinsons, what happens to these projections from the substantia nigra?

Back 18

they die off

Front 19

in general, treatment for Parkinsons has the goal of:

Back 19

compensating for the loss of endogenous DA

Front 20

6 ways that we can treat Parkinsons (and increase effects of DA)

Back 20

1. direct DA replacement
2. DA releasers (presynaptic)
3. DA agonists (postsynaptic)
4. COMT inhibitors
5. MAOb inhibitors
6. Anticholinergics

Front 21

3 meds involved in direct replacement of DA

Back 21

1. levodopa
2. carbidopa
3. carbidopa/levodopa combo = SIMEMET

Front 22

why can't we just give dopamine directly?

Back 22

it doesn't cross the BBB

Front 23

M of A Levodopa

Back 23

it is the precursor to dopamine that crosses the BBB

Front 24

2 problems with giving Levodopa

Back 24

1. 90% is destroyed in the gut
2. it is broken down by dopadecarboxylase in the periphery, so it is changed into DA which can't cross the BBB

Front 25

M of A Carbidopa

Back 25

inhibits dopadecarboxylase (=no more breakdown of LDopa)

Front 26

M of A Sinemet

Back 26

a combination of levodopa and carbidopa. Given together, a greater amt of DA leaves the gut, isn't broken down and reaches the brain.

Front 27

What is the problem with Parkinsons disease progression?

Back 27

the presynapses die off, so any drug that acts with/at the presynapse will not be as effective.

Front 28

meds usually used as last resort when Parkinsons has progressed and there aren't many presynapses left?

Back 28

(meds that are NOT presynapse dependent)
1.anticholinesterases
2. postsynaptic receptor agonists

Front 29

name a DA releaser (presynaptic)

Back 29

1. amantadine

Front 30

amantadine M of A

Back 30

releases stored pools of DA

Front 31

is amantadine effective in end stages of Parkinsons?

Back 31

no.
Usually given as an adjunct.

Front 32

name 4 agonists at postsynaptic Da receptors

Back 32

1. bromocriptine
2. pergolide
3. pramipexole
4. ropinirole

Front 33

which of the postsynaptic DA agonists work at both D1 and D2 receptors?

Back 33

1. bromocriptine
2. pergolide

Front 34

which of the postsynaptic DA agonists work at only D2 receptors?

Back 34

3. pramipexole
4. ropinirole
(the "oles")

Front 35

COMT inhibitor M of A

Back 35

inhibits COMT which is responsible for DA degradation (postsynaptic)

Front 36

name 2 COMT inhibitors

Back 36

the "capones"
1. entacapone
2. tolcapone

Front 37

problem with the COMT inhibitors

Back 37

black box warning: hepatotoxicity (no longer given!)

Front 38

MAOb Inhibitors M of A

Back 38

inhibit MAOb which also metabolizes DA (presynaptic)

Front 39

where is MAOb located?

Back 39

in the Brain

Front 40

name an MAOb inhibitor

Back 40

1. selegiline

Front 41

when is selegiline normally used?

Back 41

1. early on, or
2. when sinemet stops working effectively

Front 42

name 2 anticholinergics used to tx Parkinsons

Back 42

1. trihexlphenidyl
2. benztropine

Front 43

what is trihexlphenidyl specifically used for? (2 reasons)

Back 43

1. early,mild parkinsons
2. adjunct w/ dopaminergic drugs

Front 44

3 drugs used as adjunctive therapy but not alone in parkinsons

Back 44

1. diphenhydramine
2. ethopropazine
3. procyclidine

Front 45

diphenhydramine M ofA in parkinsons dz treatment

Back 45

aside from blocking histamine, also blocks reuptake of DA

Front 46

ethopropazine M of A

Back 46

anticholinergic properties

Front 47

procyclidine M of A

Back 47

atropine like activity

Front 48

procyclidine is particularly useful for

Back 48

1. excess salivation
2. muscle rigidity

Front 49

general SE profile for antiparkinsons drugs

Back 49

-nausea/vomiting
-anorexia
-ataxia
-orthostatic hypotension
-tachycardia
-neuroleptic malignant syndrome
-endocrine symptoms

Front 50

n/v SE caused by DA activation of what brain center?

Back 50

Chemoreceptor Trigger Zone

Front 51

tachycardia SE is caused by

Back 51

DA's effect on the heart

Front 52

Neuroleptic malignant syndrome is caused by

Back 52

abrupt withdrawal of levodopa (decreased DA levels, like with the antipsychotics)

Front 53

4 problems associated with long term tx with antiparkinsons

Back 53

1. dyskinesias
2. end-of-dose failure
3. on-off phenomenon
4. secondary levodopa failure

Front 54

end of dose failure =

Back 54

shortening of effectiveness of each dose

Front 55

on off phenomenon =

Back 55

large day to day fluctuations in symptomatic control

Front 56

in secondary levodopa failure, effectiveness drops off after _________

Back 56

2-5 yrs

Front 57

2 types of drug interactions w/ antiparkinsons

Back 57

1. MAOIs
2. Vitamin B6

Front 58

how does antiparkinsons affect the endocrine system?

Back 58

decreases prolactin (opposite of antipsychotics)

Front 59

Why do antiparkinsons interact with MAOIs?

Back 59

With MAOIs or ANY DRUG THAT AFFECTS DOPAMINE NEUROTRANSMISSION, you run the risk of:
-hypertensive episodes
-stroke
(too much DA)

Front 60

why do antiparkinsons interact with high levels of B6?

Back 60

-increases GI dopadecarboxylase activity (resulting in decreased DA levels, a counteractive effect)

Front 61

last resort procedure after drugs:

Back 61

Deep Brain Stimulators