Pharmacology 2 Parkinson's Disease

Front 1

What are the signs of Parkinson disease (PD)

Back 1

Bradykinesia; Muscular Rigidity; Tremors; Gait abnormalities; Postural istability

Front 2

What neurotransmitter pathway is affected in PD

Back 2

Dopaminergic pathway (inhibitory neurons) in the substanstia nigra and corpus striatum (neurotransmitter ratio shifts toward decreased DA and increased Ach)

Front 3

What does increased levels of DA in the tuberoinfundibular tract lead to

Back 3

Decreased prolactin levels

Front 4

What does increased levels of DA in the CTZ lead to

Back 4

Increased emesis

Front 5

What does increased levels of DA in the mesolimbic-mesocortical tracts lead to

Back 5

Increased psychomotor activity; Psychosis; Schizophrenia; Increased reinforcement

Front 6

Which DA receptor subtype is implicated in PD

Back 6

D2 receptor subtype (inhibitory receptor subtype that decreases cAMP levels in the corpus striatum)

Front 7

Given the abnormal DA/Ach shift in the striatum, give two pharmacologic strategies in the treatment of PD

Back 7

Medications that will increase DA levels; Medications that will decrease Ach levels

Front 8

Do anti-Parkinson’s medications affect pathology, symptoms, or both

Back 8

Symptoms

Front 9

Name two antimuscarinic medications that are used in the treatment of PD

Back 9

Benztropine; Trihexyphenidyl

Front 10

Is benztropine more or less lipid soluble than atropine

Back 10

More lipid soluble (therefore, greater CNS penetration)

Front 11

Which characteristic of PD is not affected by anticholinergics

Back 11

Bradykinesia

Front 12

Is benztropine useful in the treatment of tardive dyskinesis

Back 12

No (may actually exacerbate tardive dyskinesia)

Front 13

What are the adverse effects of benztropine and trihexyphenidyl

Back 13

Xerostomia; Blurred vision; Constipation; Urination retention; Sedation; Mydriasis

Front 14

How does amantadine work in the treatment of PD

Back 14

May inhibit reuptake of DA into presynaptic neurons; May increase DA release from presynaptic fibers

Front 15

Amantadine is used to treat what condition other than PD

Back 15

Influenza A

Front 16

What is the name of the dermatologic adverse effect caused by amantadine

Back 16

Livedo reticularis

Front 17

What is livedo reticularis

Back 17

A network-patterned discoloration of the skin caused by dilation of capillaries and venules

Front 18

Which characteristic of PD is not affected by amantadine

Back 18

Tremors

Front 19

Which selective MAOD inhibitor is commonly used as first-line treatment for PD

Back 19

Selegiline

Front 20

What is the mechanism of action of selegiline

Back 20

Inhibition of DA metabolism in presynaptic neurons located in the CNS via inhibition of MAOB

Front 21

What are the two active metabolites of selegiline

Back 21

Amphetamine; Methamphetamine

Front 22

What are the main adverse effects of selegiline

Back 22

Cardiovascular stimulation (hypertension, tachycardia, palpitations; arrythmias; angina)

Front 23

Name two ergot derivatives that act as DA agonists in the nigrostriatal system

Back 23

Bromocriptine; Pergolide

Front 24

Bromocriptine is used to treat what conditions other than PD

Back 24

Prolactin-secreting adenomas; NMS; Acromegaly; Postpartum lactation

Front 25

What are the adverse effects of bromocriptine

Back 25

Headache; Dizziness; Nausea; Orthostatic hypotension; Dyskinesia; Hallucinations; Confusion; Psychosis

Front 26

Name two nonergot DA agonists

Back 26

Pramipexole; Ropinirole

Front 27

What are the adverse effects of the nonergot DA agonists

Back 27

Sedations; Syncope; Nausea; Vomiting; Hallucinations; Dyskinesia

Front 28

What is the mechanism of action of tolcapone and entacapone

Back 28

Inhibition of peripheral COMT thereby increasing CNS uptake of L-Dopa

Front 29

What reaction does COMT catalyze

Back 29

Conversion of L-Dopa to 3-O-methyldopa (partial DA agonist) in peripheral tissues

Front 30

What are the adverse effects of COMT inhibitors

Back 30

Orthostatic hypotension; Headache; Fatigue; Nausea; Diarrhea; Anorexia; Dyskinesia; Muscle cramps; Brown-orange urine discoloration; Hallucinations; Diaphoresis

Front 31

Which of the COMT inhibitors is hepatotoxic

Back 31

Tolcapone

Front 32

Are COMT inhibitors used as first-line therapy, adjunctive therapy, or both in the treatment of PD

Back 32

Adjunctive therapy ( in combination with carbidopa/ levodopa)

Front 33

Are the nonergot DA agonists used as first-line therapy, adjunctive therapy, or both in the treatment of PD

Back 33

Both

Front 34

What is the precursor of DA

Back 34

Levodopa (L-Dopa)

Front 35

What enzyme converts L-Dopa to DA

Back 35

Dopa-decarboxylase (DDC)

Front 36

What is another name for DDC

Back 36

Aromatic amino acid decarboxylase

Front 37

Does DA cross the BBB

Back 37

No

Front 38

Does levodopa cross the BBB

Back 38

Yes (converted to DA by dopaminergic neurons in the substantia nigra)

Front 39

Is levodopa effective in treating PD when all of the dopaminergic neurons in the substanstia nigra have been destroyed

Back 39

No (dopaminergic neurons in the substanstia nigra are required to convert levodopa to DA)

Front 40

What is the mechanism of action of carbidopa

Back 40

Inhibition of peripheral DDC thereby increasing the amount of levodopa that is available to cross the BBB into the CNS (this allows for lower doses of levodopa needed thereby decreasing levodopa adverse effects)

Front 41

Does carbidopa cross the BBB

Back 41

No (only inhibits peripheral DDC)

Front 42

How does levodopa work in the treatment of PD

Back 42

Decreases symptoms of PD, such as rigidity, bradykinesia, and tremors

Front 43

What is the “on-off” phenomenon

Back 43

Levodopa has such a short half-life (1 to 2 hours) that plasma concentrations may decline rapidly causing the patient to experience rigidity, bradykinesia, and tremors

Front 44

Which amino acids compete with levodopa for GI absorption

Back 44

Isoleucine: Leucine

Front 45

What are the adverse effects of levodopa

Back 45

Anorexia; Nausea; Vomiting; Tachycardia; Hypotension; Discoloration of saliva and urine; Mydriasis; Hallucinations; Dyskinesia; Increased intraocular pressure; Cardiac arrhythmias

Front 46

Why should vitamin B6 (pyridoxine) not be used in combination with levodopa

Back 46

Pyridoxine enhances peripheral metabolism of levodopa thereby rendering the medication ineffective

Front 47

What is drug-induced parkinsonism

Back 47

Parkinsonian symptoms can be caused by potent antipsychotic agents such as haloperidol because they block dopamine receptors

Front 48

What is the treatment for drug-induced parkisonism

Back 48

There are three treatment options:
Lower the drug levels
Change the drug to a less potent one
Use an anticholinergic agent

Front 49

Define Huntington's disease

Back 49

A genetic disorder due to a single defect on chromosome 4

Front 50

What are the symptoms of Huntington's disease

Back 50

Individuals who have this disease display dementia and/or chorea

Front 51

What is the pathophysiology of Huntington's disease

Back 51

This disease is thought to occur because of excessive dopaminergic activity and diminished GABA functions in the basal ganglia (caudate and putamen)

Front 52

What is the treatment for Huntington's disease

Back 52

Dopamine blockers such as haloperidol (Haldol) or tetrabenazine are used to treat this disorder

Front 53

What is Tourette's syndrome

Back 53

A disease characterized by abnormal tics and facial movements

Front 54

What is the treatment for Tourette's syndrome

Back 54

Clonidine (Catapres). Haloperidol has also been used

Front 55

Define Wilson's disease

Back 55

Wilson's disease is a genetic disorder of copper metabolism. Excess copper is deposited in the liver, brain, and other tissues

Front 56

What is the treatment for Wilson's disease

Back 56

A copper chelating agent known as penicillamine (Depen)