Parkinson's Disease

Question 0

What are the cardial signs of Parkinson’s disease?

Answer 0

Resting tremor (a slow rhythmic tremor in hands or extremities that subsides during movement), rigidity (often with cogwheeling), bradykinesia (slowness of movement), gait disturbances and postural instability

Question 1

What is a progressive neurological disorder characterized by the progressive loss of dopaminergic neurons within the substantia nigra of the midbrain?

Answer 1

Parkinson’s

Question 2

What is the mean age of onset for Parkinson’s disease?

Answer 2

55 years (incidence increases dramatically with age)

Question 3

Is Parkinson’s considered to be a genetic or sporadic disorder?

Answer 3

Sporadic (95% forms of unknown etiology)

Question 4

It has been hypothesized that sporadic Parkinson’s disease is due to what?

Answer 4

Exposure to environmental toxins in genetically susceptible individuals

Question 5

Familial (inherited) forms of Parkinson’s disease is due to what?

Answer 5

AD or AR mutations in various genes, many of which are involved in proteosome functions

Question 6

Pharmacological treatment of Parkinson’s disease is effective during what stage of the disease?

Answer 6

Early stages

Question 7

Is there a cure for Parkinson’s disease?

Answer 7

No

Question 8

What are the pathological hallmarks of Parkinson’s disease?

Answer 8

Loss of nigral dopaminergic neurons within the midbrain and cytoplasmic inclusions termed “Lewy Bodies”

Question 9

The cytoplasmic inclusions “Lewy Bodies” in Parkinson’s disease contain what proteins?

Answer 9

Alpha-synuclein and ubiquitin (role unknown)

Question 10

Is Parkinson’s a hypo or hyperkinetic disorder?

Answer 10

Hypokinetic

Question 11

Parkinson’s disease is often contrasted to what hyperkinetic disorder that also affects basal ganglia function?

Answer 11

Huntington’s disease

Question 12

What disease is exclusively a hereditary AD neurodegenerative disease characterized by the progressive degeneration of striatal GABAergic neurons?

Answer 12

Huntington’s

Question 13

What disease is caused by an expanded Trinucleotide CAG repeat in the gene encoding the Huntington protein (unknown function) which causes neuronal inclusions that are comprised of aggregates of mutated Huntington protein?

Answer 13

Huntington’s

Question 14

How does dopamine regulate basal ganglia function?

Answer 14

Suppresses indirect pathway (D2 receptor function)

Enhances direct pathway (D1 receptor function)

Question 15

Over reactivity of the subthalamic nucleus and impaired motor function due to enhanced tonic inhibition of the thalamocortical neurons describes what?

Answer 15

Reduced inhibition of the indirect pathway

Question 16

What pathway direct or indirect functions to facilitate movement in a healthy individual?

Answer 16

Direct

Question 17

What is the net result of dopamine loss?

Answer 17

Tipping of the balance toward indirect pathway activity leading to impaired ability to initiate and terminate voluntary movements.

Question 18

What Parkinson’s drug is a metabolic intermediary in the synthesis of Catecholamines?

Answer 18

Levodopa

Question 19

What enzyme converts levodopa to dopamine in the CNS and the periphery?

Answer 19

AADC aka DDC (dopamine decarboxylase)

Question 20

What percentage of levodopa is decarboxylated by DDC peripherally?

Answer 20

95%

Question 21

Levodopa is administered with what other drug in order to reach therapeutic levels in the CNS?

Answer 21

Carbidopa

Question 22

The trade name drug for the combination of levodopa and carbidopa is what?

Answer 22

Sinemet

Question 23

What allows levodopa to cross the blood brain barrier?

Answer 23

Large Neutral Amino Acid transporter ( LNAA)

Question 24

What takes up levodopa as it crosses the BBB?

Answer 24

Dopaminergic nerve terminals within the striatum

Question 25

Involuntary movements (dyskinesias and dystonias) and psychiatric disturbances are side effects of long term use of what Parkinson's drug?

Answer 25

Levodopa

Question 26

What percentage of patients will suffer from some combination of insomnia, unpleasant dreams, anxiety, depression, mania, paranoia, or hallucinations?

Answer 26

15%

Question 27

Psychiatric side effects of levodopa are usually related to what?

Answer 27

Dose

Question 28

The administration of levodopa can produce what kind of clinically significant cardial effects by the conversion of peripheral dopamine to norepinephrine?

Answer 28

Sympathomimetic

Question 29

The cardiac side effects of levodopa administration can be controlled with what drug?

Answer 29

Propranolol

Question 30

What side effect of levodopa is common early in treatment?

Answer 30

Orthostatic hypotension

Question 31

What gastrointestinal side effects to levodopa are observed early in treatment and are thought to be due to stimulation of dopamine receptors in the emetic centers of the brain such as the area postrema where the BBB is not intact?

Answer 31

Nausea, vomiting, anorexia

Question 32

Concurrent use of levodopa with what other type of drug can lead to hypertensive crisis?

Answer 32

Non-selective monoamine oxidase inhibitors (phenylzine)

Question 33

What type of drugs can decrease the effectiveness of levodopa by a direct antagonistic action on dopamine receptors? ( treatment with dopamine receptor antagonists can lead to drug induced Parkinsonian symptoms)

Answer 33

Antipsychotic medications (haloperidol)

Question 34

What can decrease levodopa's effectiveness by competing for the amino acid transport systems in the gut and brain?

Answer 34

Dietary amino acids (large doses)

Question 35

Patients develop tolerance to cardiovascular and gastrointestinal side effects of levodopa usage however patients never develop tolerance to what other side effects?

Answer 35

Psychiatric and involuntary movement side effects

Question 36

What Parkinson's drug markedly reduces the symptoms of bradykinesia and rigidity and requires extreme precaution when administering to patients with a history of cardiac or psychiatric disease?

Answer 36

Levodopa

Question 37

What drug is a peripheral decarboxylase inhibitor (inhibits L-aromatic acid decarboxylase), in the ionized form and doesn't cross the BBB, must be given with levodopa allowing a greater portion of levodopa to reach the CNS?

Answer 37

Carbidopa

Question 38

What are the advantages of using sinemet instead of levodopa therapy alone?

Answer 38

- 1/4 dose of levodopa is needed compared to treatment without levodopa - levodopa/carbidopa combo nearly abolishes CV and GI side effects - effective therapeutic dose is achieved sooner

Question 39

Sinemet will not abolish what type of side effects?

Answer 39

CNS side effects (involuntary movements and psychiatric disturbances)

Question 40

Levodopa/carbidopa is administered in what ratios?

Answer 40

10:1 and 4:1 (levodopa:carbidopa)

Question 41

What are 2 examples of dopamine agonists?

Answer 41

Pramipexole and ropinerole

Question 42

What 2 dopamine agonists bind selectively to dopamine D2 receptors, are potent dopamine D3 receptor agonists, and are used as adjuncts to sinemet by reducing "off" times and improving motor function and by permitting a decrease in sinemet dosage?

Answer 42

Pramipexole and ropinerole

Question 43

What are some side effects of dopamine receptor agonists?

Answer 43

Orthostatic hypotension, nausia, hallucinations, somnelence and dyskinesia

Question 44

What is an antiviral drug that is used in Parkinson's for the effect of release of dopamine from the functionally intact dopaminergic terminals of Parkinson's patients?

Answer 44

Amantadine

Question 45

When is amantadine treatment most effective?

Answer 45

When administered with levodopa in patients who cannot attain a full therapeutic response with levodopa alone

Question 46

What are the 2 isozyme forms of monoamine oxidases?

Answer 46

MAOa and MAOb

Question 47

What monoamine oxidase metabolizes dopamine to a greater extent than serotonin and norepinephrine?

Answer 47

MAOb

Question 48

What monoamine oxidase metabolizes serotonin and norepinephrine?

Answer 48

MAOa

Question 49

What Parkinson's drug is a relatively selective MAOb inhibitor and is used to conserve dopamine levels in the brain without causing a marked elevation in norepinephrine and serotonin levels?

Answer 49

Selegiline

Question 50

What Parkinson's drug has been shown to block or reduce the destruction of substantia nigral neurons by the neurotoxin MPTP in laboratory animals, postpones the need for treatment with levodopa 6-9 months, reduces the required dose needed for levodopa, increases the duration of levodopa effect while minimizing the side effects and has reduced incidence of psychiatric side effects compared to dopamine agonists?

Answer 50

Selegiline

Question 51

What are 2 examples of reversible COMT inhibitors that are used as adjuncts to l-dopa therapy, decrease the clearance rate of l-dopa making more l-dopa available to the brain and prolonging the duration of action of l-dopa 20-30%?

Answer 51

Tolcapone and entacopone

Question 52

What percentage of l-dopa is O-methylated by COMT?

Answer 52

10%

Question 53

Where can COMT be found in the body?

Answer 53

Periphery ( liver and kidney) and CNS

Question 54

What COMT inhibitor used in Parkinson's inhibits COMT peripherally and does not cross the BBB?

Answer 54

Entacopone

Question 55

What COMT inhibitor used in Parkinson's inhibits COMT both peripherally and centrally?

Answer 55

Tolcapone

Question 56

Increased dyskinesias (which can be managed by decreasing the dose of l-dopa), nausea, mild somnelence, and rarely orthostatic hypertension are side effects of what drugs?

Answer 56

COMT inhibitors ( Entacopone, tolcapone)

Question 57

What muscarinic cholinergic antagonist help restore the DA/ACh balance by blunting the muscarinic cholinergic influence and has side effects similar to atropine in the blockade of the PNS?

Answer 57

Benztropine

Question 58

Anticholinergics (benztropine) are useful in what situations?

Answer 58

- early in treatment when symptoms are minimal | - as an adjunct to l-dopa (sinemet) to enhance levodopa's effectiveness

Question 59

In contrast to l-dopa Muscarinic cholinergic antagonist reduce tremor more effectively than they reduce what other two symptoms?

Answer 59

Rigidity and bradykinesia

Question 60

Levodopa is only maximally effective for what duration of time?

Answer 60

3-6 years

Question 61

What is the "wearing off" effect?

Answer 61

Nigrastriatal dopinergic neurons undergoing progressive degeneration, patients experience a shorter duration of drug action requiring a higher frequency of dosing and elevation of dose

Question 62

What percentage of Parkinson's patients experience an on-off phase characterized by symptomatic relief being unpredictable following a given dose of sinemet?

Answer 62

50%

Question 63

Debilitating rigidity and immobility is characterized as what phase?

Answer 63

Off phase

Question 64

Debilitating dyskinesia or painful dystonia is characterized by what phase?

Answer 64

On phase

Question 65

If levodopa is discontinued how many days should it take to be tapered off?

Answer 65

3-4 days

Question 66

A state of fever, rigidity, and confusion resembling a neuroleptic malignant syndrome in addition to causing Classic Parkinson's symptoms is characteristic of what?

Answer 66

Sudden discontinuation of levodopa

Question 67

What percentage of patients respond favorable to taking selegiline upon diagnoses of Parkinson's and then taking the lowest effective dose of sinemet?

Answer 67

75%

Question 68

When low doses of sinemet are no longer effective, instead of increasing the dose of sinemet the addition of what drug has the effect of lowering the overall incidence of both "wearing off" effects and dyskinesias?

Answer 68

Dopamine receptor agonists (ropinirole)

Question 69

What type of drugs are used sparingly as an adjunct only when tremors are a prevalent symptom?

Answer 69

Muscarinic cholinergic antagonists