Drugs for Parkinson's

Question 1

A progressive disorder of movement that occurs most commonly in the elderly

Answer 1

Parkinson’s Disease

Question 2

The result of loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) in the basal ganglia

Answer 2

Parkinson’s Disease (PD)

Question 3

In PD dopamine is progressively lost, the effect of acetylcholine is relatively

Answer 3

Increased

Question 4

Parkinson’s Disease is diagnosed at an advanced stage of approximately

Answer 4

80% cell loss

Question 5

In PD there is a late appearance of symptoms - probably because of adaptive increase in dopamine receptors until the effect

Answer 5

“Max out”

Question 6

MPTP is metabolized to the free radical, MPP+, which produces oxidative stress resulting in

Answer 6

Cell Death

Question 7

Lead to the hypothesis that metabolism of dopamine could lead to the same effect via production of free radicals

Answer 7

MPTP Toxicity

Question 8

The goal of treatment in PD is to facilitate

Answer 8

Dopaminergic Neurotransmission

Question 9

The single most effective agent in treatment of PD

Answer 9

Levodopa (L-Dopa)

Question 10

Is normally synthesized from L-tyrosine

Answer 10

L-Dopa

Question 11

L-dopa is largely inert and unlike dopamine, it can cross the

Answer 11

Blood-brain barrier

Question 12

The rate and extend of Levodopa absorption is dependent upon the rate of gastric emptying and

Answer 12

pH of gastric juice

Question 13

Absorbed rapidly from small intestine by active transport system

-Competitive with aromatic amino acids

Answer 13

L-Dopa

Question 14

High protein meal will delay absorption and reduce peak plasma concentration of

Answer 14

L-Dopa

Question 15

The peak plasma concentration of L-Dopa is reached 1-2 hours after oral dose and the plasma half-life is

Answer 15

1-3 hours

Question 16

An L-aromatic amino acid decarboxylase inhibitor

Answer 16

Carbidopa

Question 17

Increases the fraction of levodopa that remains unmetabolized and available to enter the CNS

-Does not itself penetrate the blood-brain barrier

Answer 17

Carbidopa

Question 18

Allows reduced dosage of levodopa which reduces peripheral side effects

Answer 18

Carbidopa

Question 19

A Carbidopa + Levodopa combo drug with a 1:4 and 1:10 ratio of carbidopa : levodopa

Answer 19

Sinemet

Question 20

If Levodopa is given without peripheral decarboxylase inhibitor (carbidopa) then 80% of patients experience

Answer 20

Anorexia, Nausea, and Vomiting

Question 21

Combination with carbidopa reduces GI effects to occurrence in

Answer 21

20% of patients

Question 22

Can also cause arrhythmias and postural hypertension

Answer 22

L-Dopa

Question 23

Markedly accentuates levodopa actions and may precipitate a life-threatening hypertensive crisis

Answer 23

Administration with nonspecific MAO inhibitors

Question 24

Enhances extracerebral metabolism of levodopa

Answer 24

Pyridoxine (B6)

Question 25

Accenuate peripheral effects of L-dopa and can cause hypertensive crisis

Answer 25

MAO-A inhibitors

Question 26

L-dopa is contraindicated in

Answer 26

Psycotic patients and patients with angle-closure glaucoma and active peptic ulcer

Question 27

What percentage of patients will experience response fluctuations after 5 years of L-dopa therapy?

Answer 27

50%

Question 28

What percentage of patients will experience response fluctuations after 15 years of L-dopa therapy?

Answer 28

70%

Question 29

Long term use of L-dopa can result in an increase in the side effects of

Answer 29

Dyskinesias and psychiatric disturbances

Question 30

In early PD, the duration of the beneficial effects of levodopa exceeds the plasma lifetime of the drug, because the nigrostriatal dopamine system retains some capacity to

Answer 30

Store and Release Dopamine

Question 31

After the long-term use of levodopa therapy this "buffering“ capacity is lost, and the patient's motor state may fluctuate dramatically with each dose of levodopa. This is called the

Answer 31

Wearing Off Phenomenon

Question 32

Each dose of levodopa effectively improves mobility for 1-2 hours, but symptoms return rapidly at the end of the

Answer 32

Dosing Interval

Question 33

Patients fluctuate rapidly between having no apparent effects of medication (“off”) and having effects of medication (“on”)

Answer 33

The unpredictable O/Off phenomenon

Question 34

Off-periods of marked akinesia alternate over the course of a few hours with on-periods of improved mobility, but often of marked

Answer 34

Dyskinesia

Question 35

For severe off-periods if not responding to other measures, we can use

Answer 35

Apomorphine

Question 36

What are the two COMT inhibitors used to treat PD?

Answer 36

Tolcapone and entacapone

Question 37

Has central and peripheral effects

Answer 37

Tolcapone

Question 38

Has peripheral effects only

Answer 38

Entacapone

Question 39

Adjunct to levodopa/carbidopa allowing reduction of levodopa dose

Answer 39

COMT inhibitors

Question 40

Prolongs plasma half-life of levodopa and increases availability of levodopa to brain

Answer 40

Inhibition of COMT

Question 41

Approved for patients with late PD who have developed response fluctuations

Answer 41

COMT inhibitors

Question 42

Concurrent use with a non-specific MAO inhibitor could severely limit metabolism of levodopa and is contraindicated

Answer 42

COMT inhibitors

Question 43

Can cause an increase in aminotransferase and transaminase activity which results in hepatotoxicity

Answer 43

Tolcapone

Question 44

Is not associated with hepatotoxicity

Answer 44

Entacapone

Question 45

Are secondary pharmacologic therapies of PD

Answer 45

Dopamine agonists like pramipexole, ropinrole, bromocriptine, and pergolide

Question 46

Agonists selectively affecting certain (but not all) dopamine receptors may have more limited adverse effects than

Answer 46

Levodopa

Question 47

A D2 agonist that is an ergot derivative

Answer 47

Bromocriptine

Question 48

A non-ergot derivative D2 agonist

Answer 48

Ropinirole

Question 49

A non-ergot derivative D3 agonist

Answer 49

Pramipexole

Question 50

Could be used as monotherapy in patients with mild disease - Well absorbed orally - Plasma hlf life of 3-7 hours

Answer 50

Bromocriptine

Question 51

Has similar affects to levodopa but more severe hallucinations than with levodopa alone

Answer 51

Bromocriptine

Question 52

Metabolized by CYP1A2, so drugs that are metabolized by the liver may significantly reduce clearance

Answer 52

Ropinirole

Question 53

Excreted largely unchanged in urine

Answer 53

Pramipexole

Question 54

Has the RARE side effect of uncontrollable tendency to fall asleep at inappropriate times; requires discontinuation of medication

Answer 54

Ropinirole and pramipexole

Question 55

Administered as a once-daily transdermal patch allowing continuous absorption leading to less serum fluctuation as compared to oral administration several times a day

Answer 55

Rotigotine

Question 56

In addition to producing adverse side effects seen with other DA receptor agonists, application site reactions (erythema [redness] and pruritis [itching]) were reported in 37% of patients in clinical studies

Answer 56

Rotigotine

Question 57

Available as a subcutaneous injection to treat “off” episodes in patients with advanced PD -Mostly interacts with D2 receptors

Answer 57

Apomorphine

Question 58

Rapidly taken up in the brain leading to clinical benefit that begins within 10 min of injection

Answer 58

Apomorphine

Question 59

Causes emesis (vomiting/nausea) and requires pretreatment with antiemetic trimethobenzamide 3 days before initial treatment and continued for at least 2 months of therapy, if not indefinitely

Answer 59

Apomorphine

Question 60

Contraindicated with antiemetics of the 5HT3 receptor class. Causes severe hypotension and loss of consciousness

Answer 60

Apomorphine

Question 61

Metabolizes dopamine selectively

Answer 61

MAO-B

Question 62

Metabolizes norepinephrine, serotonin, and dopamine; also found in liver and GI tract

Answer 62

MAO-A

Question 63

Irreversible MAO-B inhibitor => B selective at 10 mg/day or less (at higher doses also inhibits MAO-A)

Answer 63

Selegiline

Question 64

Retards breakdown of dopamine in striatum without inhibiting peripheral metabolism of catecholamines

Answer 64

Selegiline

Question 65

Should not be taken together with analgesic meperidine - stupor, rigidity, agitation, and hyperthermia (mechanism is unknown), tramadol, methadone, cyclobenzaprine, St. John’s wort

Answer 65

Selegiline

Question 66

More selective MAO-B inhibitor than selegiline -Does not produce amphetamine metabolites

Answer 66

Rasagiline

Question 67

Retards breakdown of dopamine in striatum without inhibiting peripheral metabolism of catecholamines

Answer 67

Rasagiline

Question 68

Studies suggest that rasagiline and selegiline might have a

Answer 68

Neuroprotective effect

Question 69

Provide neuroprotection by reducing the oxidation of dopamine

Answer 69

Selegiline and Rasagiline

Question 70

Mechanism is unclear but may cause: - Increase in dopamine release - Blocking of dopamine reuptake - Increase in dopamine synthesis

Answer 70

Amantidine (antiviral)

Question 71

May favorably influence bradykinesia, rigidity, and tremor -It also has antidyskinetic properties

Answer 71

Amantidine

Question 72

Amantidine overdose may cause acute toxic

Answer 72

Psycosis