Drug Therapy Of Parkinson's Dz

Front 1

the goals of pharmacological therapy of Parkinson's disease are?

Back 1

-increased dopaminergic activity
-decrease excess cholinergic activity

Front 2

name three drugs which maximize the effects of residual endogenous dopamine and which increase availability of dopamine from dopamine agonists

Back 2

-selegiline
-amantadine
-tolcapone

Front 3

MOA of selegine

Back 3

-inhibits DA metabolism

Front 4

MOA of amantadine

Back 4

-increases DA release and inhibits reuptake

Front 5

MOA of tolcapone

Back 5

-inhibits of catehol-o-methyl transferase

Front 6

what are three dopamine agonists that are levodopa "sparing" therapies

Back 6

-bromocriptine (Parlodel)
-pramipexole (Mirapex)
-ropinirole (Requip)

Front 7

levodopa/carbidopa (Sinemet)

Back 7

dopamine agonist

Front 8

benzotopine (Cogentin)

Back 8

-tx for anticholinergic actions of Parkinson's
-major benefit is reduction of resting tremor

Front 9

the current therapies for Parkinson's disease include?

Back 9

-drugs which maximize the effects of residual endogenous dopamine and increase availability from dopamine agonists
-dopamine agonists
-benzotropine (Cogentin)

Front 10

neurologists favor initiation of tx ________ in an attempt to __________

Back 10

1. at or soon after diagnosis
2. change the time course of the dz by preventing or delaying loss of function with earlier intervention

Front 11

MOA of levodopa/carbidopa (Sinemet)

Back 11

-levodopa is an amino acid which crosses BBB and is converted to dopamine in the brain
-carbidopa inhibits the peripheral enzyme dopadecarboxylase
-carbidopa does not cross BBB (keeps levodopa from being changed to DA before it crosses BBB)

Front 12

what are the problems with chronic therapy on levodopa/carbidopa (Sinemet)
(occur in about 40% of pts after 4-6 yrs of therapy)

Back 12

-motor fluctuations
-periods of worsening symptom control ("wearing off")
-peak dose dyskinesias

Front 13

levodopa/carbidopa (sinemet) dosage forms and instructions

Back 13

-immediate release tablets (take on empty stomach)
-extended release tablets (take with food)

Front 14

if the "wearing off" effect occurs, the _____form may be of more benefit by providing __________

Back 14

1. extended release levodopa/carbidopa (Sinemet)
2. a more continual release of drug

Front 15

ER form of levodopa/carbidopa (Sinemet) may help to lessen the incidence of _________

Back 15

-peak dose dyskenesias

Front 16

dosage of levodopa/carbidopa (Sinemet)

Back 16

- most pts have best results with the lowest effective levodopa dose combined with a total daily dose of 75-100mg of carbidopa

Front 17

ADR of levodopa/carbidopa (Sinemet)

Back 17

-peak dose dyskinesias
-central effects (agitation, hallucinations, delirium)
-motor fluctuations between mobile and immobile states ("on-off" effect)

Front 18

peak dose dyskinesias are more likely to occur with ____ than with _________, suggesting __________

Back 18

1. levodopa (agonist at D1 and D2 receptors)
2. dopamine agonists (D2 receptor agonists only)
3. D1 receptor involvement

Front 19

_______ and ________block dopamine receptors in the brain and inhibit levodopa activity

Back 19

1. neuroleptics
2. metoclopramide

Front 20

levodopa/carbidopa (Sinemet) interact with monoamine oxidase inhibitors to cause ______-

Back 20

hypertensive crisis

Front 21

contraindications to levodopa/carbidopa (Sinemet)

Back 21

-hx of malignant melanoma (DA is a precursor of melanin)
-narrow angle glaucoma

Front 22

most clinicians begin tx with levodopa/carbidopa (Sinemet) when?

Back 22

-when pt reports worsening of functionality

Front 23

levodopa should be started at the point in the dz course when __________

Back 23

the individual pt is definitely bothered and physically impaired

Front 24

what are the effects of long-term use of levodopa on DA receptors?

Back 24

-makes them less sensitive to the presence of DA and beneficial drug effects are diminished ("wearing off") particularly near the end of a dosing interval

Front 25

The "on-off" effect is a sudden response fluctuation from _________ to __________. These fluctuations may last ________in frequency and increase intensity as the dz progresses.

Back 25

-mobility to the Parkinsonian state
-minutes to hours

Front 26

to counter the "on-off" effect, may need to add _____ or ______ to decrease levodopa dose required

Back 26

1. dopamine agonist
2. selegiline

Front 27

MOA of amantadine

Back 27

-inhibits DA reuptake by presynaptic neurons
-increased presynaptic DA release

Front 28

the most effective use for amantadine is for _______________

Back 28

levodopa-induced dyskinesias

Front 29

ADR of amantadine

Back 29

clinically significant anticholinergic effects

Front 30

indications for amantadine

Back 30

-monotherapy only in early or mild dz; may be used up to 12 mo before starting levodopa
-adjunct to levodopa in treating rigidity and bradykinesia and in advanced dz for pts with motor fluctuations and dyskinesias

Front 31

response of DA agonist stimulation of:
1. D1 rec
2. D2 rec

Back 31

1. stimulation may result in dyskinesias
2. stimulation improves dyskinesias and rigidity, but can also cause CNS effects (confusion, hallucinations)

Front 32

direct-acting DA agonists are best avoided in ___________

Back 32

>/= 70yr old pts

Front 33

amantadine is approved as _____________in the latter stages of Parkinson's dz to help reduce________

Back 33

1. adjunctive use with levodopa
2. motor fluctuations ("on-off" effect) that accompany chronic levodopa therapy

Front 34

pts on levodopa/carbidopa and a dopamine agonist require ___________

Back 34

less levodopa in both early and late dz stages

Front 35

early tx with DA agonists reduces the risk of developing _____________

Back 35

motor complications (dyskinesias) associated with levodopa

Front 36

therapy can be begun with DA agonists and add levodopa only when _____________

Back 36

the DA agonist no longer provides adequate control of motor symptoms

Front 37

MOA of bromocriptine

Back 37

-directly stimulates D1(excitatory) and D2(inhibitory) receptors in the corpus striatum

Front 38

when bromocriptine is used with levodopa, it decreases the ________and enhances the response to __________

Back 38

1. incidence of "on-off" effect
2. levodopa (so that dose may be decreased)

Front 39

ADR of bromocriptine

Back 39

-mental changes
-dyskinesias
-orthostatic hypotension
-GI distress (N/V)::potent emetrogenic (take with food)

Front 40

what are two non-ergot DA agonists?

Back 40

-pramipexole
-ropinirole

Front 41

indications for non-ergot DA agonists

Back 41

-monotherapy for idiopathic Parkinson's in early dz with no prior levodopa exposure
-adjunct therapy with levodopa in advanced dz

Front 42

when non-ergot DA agonists are added to levodopa , ________is decreased , _________is improved, and ______is permitted

Back 42

1. "on-off" time
2. motor function
3. reduction in levodopa dosage

Front 43

dopamine agonists primarily affect _________receptors and are less likely to cause _________than levodopa (nonselective for D1 and D2 rec)

Back 43

1. D2
2. dyskinesias

Front 44

ADR for non-ergot DA agonists (premipexole and ropinirole)

Back 44

-somnolence: "sleep attacks"
-dyskinesias may be worsened if used in conjunction with levodopa
-orthostatic hypotension

Front 45

major uses of antimuscarinics in Parkinson's dz?

Back 45

-reduce resting tremor; current role as monotherapy is limited to cases where slow tremor is the major clinical symptom

Front 46

benzotropine

Back 46

anticholinergic/antimuscarinic agent used in PD

Front 47

benztropine contraindications

Back 47

-narrow-angle glaucoma
-prostatic hypertrophy
-GI obstruction

Front 48

withdrawal of benztropine may cause___________

Back 48

-an immediate worsening of symptoms

Front 49

selegiline

Back 49

selective monoamine oxidase inhibitor

Front 50

MOA of selegine

Back 50

-acts in brain to prevent the metabolism of endogenous residual dopamine by selectively and irreversibly blocking monoamine oxidase type B
-dopamine catabolism by MAO results in formation of toxic metabolites that may cause degeneration of DA rec.

Front 51

selegine does not mormally cause hypertensive crisis in the presence of _____ or other _____, unless used in very high doses where _____is lost

Back 51

1. tyramine-containing foods
2. catecholamines
3. MAO selectivity

Front 52

selegine can extend the therapeutic effects of _______, increase duration of ______, and allow reduction of _______

Back 52

1. levodopa
2. levodopa action
3. levodopa dosage

Front 53

selegine may be most effective in ___________stage of the dz since it may ___________

Back 53

1. early stages
2. delay the requirement for levodopa

Front 54

______________is the first approved drug in the class of drugs which are inhibitors of catechol-o-methyl transferase (COMT)

Back 54

Tolcapone

Front 55

with use of tolcapone the average bioavailability of levodopa is __________

Back 55

increased 3- to 4-fold

Front 56

use of tolcapone significantly reduced ______ by 25% and allowed ________ and ________ for levodopa/carbidopa

Back 56

1. "on" time
2. decreased dosage
3. decreased dosing frequency

Front 57

boxed warning for tolcapone

Back 57

-potentially fatal acute fulminant hepatic failure