Pharmacology - Drug Tx of Parkinson's (Exam 3)

Question 1

Tremor at rest, postural instability, dysphagia, drooling, bradykinesia, may progress to akinesia

Answer 1

Dyskinesias

Question 1

Chronic, idiopathic neurodegeneration of extrapyramidal system causing loss of control of movement

Answer 1

Parkinson’s Disease

Question 2

Dementia, depression, impaired memory

Answer 2

Psychological disturbances of PD

Question 3

Parkinson’s like symptoms:

Drug side effects
Component of other disorders (Shy-Drager syndrome)
Less responsive to drug therapy used for PD

Answer 3

Parkinsonism

Question 4

Idiopathic loss of nigrostriatal dopaminergic neurons

Answer 4

Parkinson’s Disease

Question 5

Drug therapy increases _________ in striatum

Answer 5

dopamine

Question 6

Levels of what neurotransmitter are reduced in PD?

Answer 6

Striatal dopamine

Question 7

What are potential side effects, complications, and interactions of PD?

Answer 7

Facial movements
Hypotension
Nausea
Opioid interactions
Catecholamine interactions

Question 8

Describe the neuropathophysiology of PD (4 things)

Answer 8

1. Loss of cell bodies in substantia nigra
2. Genetic risk factors
3. Antipsychotic drugs/environmental agents can cause parkinson-like syndrome
4. MPTP (dopamine neurotoxin) causes parkinson-like syndrome

Question 9

What is involved in the extrapyramidal system? (4 things)

Answer 9

1. Nigrostriatal dopaminergic pathway
2. Striatal cholinergic neurons
3. GABAergic neurons
4. Balance between dopaminergic and cholinergic activity (controls voluntary movement)

Question 10

Inhibitory neurons innervating striatum

Answer 10

Nigrostriatal dopaminergic pathway

Question 11

What is the goal of drug therapy for PD?

Answer 11

Raise dopamine levels

Question 12

What is the goal of drug therapy for parkinsonism?

Answer 12

Lower ACh levels

Question 13

Disease where there is a defect in GABAergic neurons

Answer 13

Huntington’s Disease

Question 14

Genetic disease caused by triplet nucleotide repeat

Answer 14

Huntington’s Disease

Question 15

Mechanism of Levodopa (L-dopa)

Answer 15

Converted to dopamine in striatum

Question 16

T/F dopamine crosses the blood brain barrier

Answer 16

FALSE

Question 17

T/F DOPA crosses the blood brain barrier

Answer 17

True

Question 18

Which enzyme converts Tyrosine to Dihydroxyphenylalanine (DOPA)?

Answer 18

Tyrosine hydroxylase

Question 19

Which enzyme converts Dihydroxyphenylalanine (DOPA) to dopamine?

Answer 19

Aromatic L-amino acid decarboxylase

Question 20

What are the symptoms of peripheral toxicity of Levodopa?

Answer 20

GI: nausea, vomiting
Heart: postural hypotension, arrhythmia

Question 21

What are the symptoms of CNS toxicity of Levodopa?

Answer 21

Neurological: dyskinesias (abnormal mouth movements, tongue thrusting, chewing motions)

Behavioral: insomnia, anxiety, delirium, depression

Question 22

Sympathomimetic drug (B agonist) + Levodopa

Answer 22

Cardiac stimulation

Question 23

Pyridoxine (vitamin B6) + Levodopa

Answer 23

Decreased efficacy of Levodopa

Question 24

Antipsychotic drugs + Levodopa

Answer 24

Decreased efficacy of Levodopa

Question 25

Monoamine oxidase inhibitors (MAOIs) + Levodopa

Answer 25

Hypertensive crisis

Question 26

What are the 2 fluctuations in therapeutic response of Levodopa?

Answer 26

1. "Wearing off" phenomenon 2. "On-off" phenomenon

Question 27

What are the components of the "wearing off" phenomenon of Levodopa?

Answer 27

Related to timing Nigrostriatal tract degeneration

Question 28

What are the components of the "on-off" phenomenon of Levodopa?

Answer 28

Alterations in drug availability NOT related to timing

Question 29

What is Sinemet a mix of?

Answer 29

Levodopa + Carbidopa

Question 30

Advantages of Carbidopa

Answer 30

1. Increased half-life of Levodopa 2. Decreased peripheral side effects 3. Diminished CNS (dopamine) fluctuations

Question 31

Disadvantages of Carbidopa

Answer 31

Increased CNS side effects

Question 32

T/F Carbidopa does NOT cross the blood brain barrier

Answer 32

True

Question 33

What is the mechanism of Carbidopa?

Answer 33

Inhibits dopa-decarboxylase

Question 34

What is the mechanism of Amantadine?

Answer 34

Increases synaptic dopamine concentration

Question 35

What is Amantadine frequently administered with?

Answer 35

Levodopa

Question 36

T/F Amantadine is less efficacious and less toxic than Levodopa

Answer 36

True

Question 37

Which drugs are the dopamine receptor agonists (also called ergot alkaloids)?

Answer 37

Bromocriptine Pergolide

Question 38

What are the symptoms of toxicity of Bromocriptine and Pergolide?

Answer 38

Arrhythmia Nausea Dyskinesias Delusions Hallucinations Hypotension

Question 39

What are Bromocriptine and Pergolide used for?

Answer 39

Additive therapeutic effects with Levodopa

Question 40

Which drug has been associated with valvular heart disease and is therefore no longer available?

Answer 40

Pergolide

Question 41

What drugs are the synthetic dopamine agonists? What receptors are they involved with?

Answer 41

Pramipexole (D3 agonist) Ropinirole (D2 agonist)

Question 42

T/F Pramipexole and Ropinirole are used alone in the early stages of PD

Answer 42

True

Question 43

What effects do Pramipexole and Ropinirole have?

Answer 43

Effects similar to older agonists

Question 44

What is Ropinirole metabolized by?

Answer 44

CYP1A2

Question 45

What can inhibit CYP1A2 and cause decreased metabolism/increased blood concentration of Ropinirole?

Answer 45

Ciprofloxacin

Question 46

What is the rare side effect of Pramipexole and Ropinirole?

Answer 46

Compulsive gambling

Question 47

What is the mechanism of Apomorphine?

Answer 47

Dopamine agonist

Question 48

What is Apomorphine used for?

Answer 48

Rescue of akinesia in "off" periods

Question 49

How is Apomorphine administered?

Answer 49

Injected subcutaneously (fast action)

Question 50

What are the side effects of Apomorphine?

Answer 50

Nausea

Question 51

What can you use as a pretreatment to prevent nausea associated with Apomorphine?

Answer 51

Trimethobenzamide

Question 52

What drugs are monoamine oxidase B inhibitors?

Answer 52

Selegiline Rasagiline

Question 53

What does Selegiline decrease?

Answer 53

"On-off" fluctuations

Question 54

What does Selegiline prolong?

Answer 54

The usefulness of Levodopa

Question 55

What is a side effect of high doses of Selegiline when given with Levodopa?

Answer 55

Dyskinesias

Question 56

T/F Rasagiline is a less potent MAO-B inhibitor

Answer 56

FALSE, it is more potent

Question 57

T/F Rasagiline is NOT metabolized to amphetamine/methamphetamine

Answer 57

True

Question 58

What drugs are the Catechol-O-Methyltransferase (COMT) inhibitors?

Answer 58

Tolcapone Entacapone

Question 59

What is the mechanism of Tolcapone and Entacapone?

Answer 59

Inhibit metabolism of Levodopa to 3-O-methyldopa

Question 60

What do Tolcapone and Entacapone enhance?

Answer 60

Uptake of Levodopa

Question 61

Tolcapone has action in the __________ and the __________

Answer 61

periphery; CNS

Question 62

Entacapone has action in the __________ only

Answer 62

periphery

Question 63

Selegiline has action in the __________ only

Answer 63

CNS

Question 64

Which MAO receptor is in the periphery?

Answer 64

MAO-A

Question 65

Which MAO receptor is in the brain?

Answer 65

MAO-B

Question 66

What drugs are the anticholinergic drugs? What do they treat?

Answer 66

Benztropine Trihexyphenidyl They treat Parkinsonism

Question 67

What is the mechanism of Benztropine and Trihexyphenidyl?

Answer 67

Block muscarinic receptors to restore balance of neurotransmitters

Question 68

Benztropine and Trihexyphenidyl have ________ efficacy compared to Levodopa

Answer 68

less

Question 69

What are the symptoms of toxicity for Benztropine and Trihexyphenidyl?

Answer 69

Peripheral atropine-like effects CNS toxicity (delirium, confusion)

Question 70

PD is a _________ disease

Answer 70

progressive

Question 71

T/F Levodopa does not lose its effectiveness

Answer 71

FALSE

Question 72

What are the drug interactions for drugs used to treat PD?

Answer 72

MAO inhibitors Catecholamines Anti-muscarinics

Question 73

What are the important side effects of drugs used to treat PD? (3 things)

Answer 73

1. Oral dyskinesias (causes dental problems: inflammation, tooth movement, difficulty wearing dentures) 2. Orthostatic hypotension 3. Sensitive to epinephrine induced arrhythmias

Question 74

What are some important things to consider for patients with PD?

Answer 74

1. Drug induced xerostomia 2. Nausea/vomiting effects on enamel 3. Difficulty brushing/flossing 4. Dysphagia 5. Difficulty comprehending/remembering - be sure to write down instructions