Drug therapy of Parkinson's

Question 1

Describe the clinical signs of Parkinson’s

Answer 1

Bradykinesia, muscle rigidity, resting tremor, impaired balance, in some cases also dementia

Question 2

What is the main deficit in Parkinson’s disease?

Answer 2

Decrease in DA in basal ganglia- dopaminergic neurons are dying

Question 3

Describe four major treatment strategies to treat Parkinson’s disease

Answer 3

1. Increase DA levels by stimulating DA biosynthesis
2. Increase DA levels by inhibiting DA metabolism
3. Directly stimulate DA receptors with DA agonists
4. Block CNS acetylcholine receptors with muscarinic antagonists

Question 4

What is the role of levodopa in treating PD?

Answer 4

Precursor to DA, increase DA in CNS

Question 5

What is the role of carbidopa in treating PD?

Answer 5

Carbidopa blocks peripheral metabolism of L-DOPA → more gets to brain → can reduce dosage of L-DOPA by 75
Carbidopa does not get into CNS so blocks metabolism of L-dopa only peripherally

Question 6

List adverse reactions of levodopa-carbidopa

Answer 6

CNS: dyskinesias, head bobbing, gnawing, tics, grimaces, ballismus, rhythmic foot or hand movements, bruxism, tongue movements; anxiety, nightmares, euphoria, insomnia, anorexia, nervousness, memory loss, psychosis
CV: orthostatic hypotension, arrhythmias; infrequent and usually disappear in a few months
GI: NV early in treatment, diminishes over time

Question 7

List absolute contraindications for treatment with levodopa-carbidopa

Answer 7

Melanoma
Glaucoma
Abrupt DC

Question 8

List precautions for treatment wiht levodopa-carbidopa

Answer 8

CV dz, MI, arrhythmia

MAOIs

Question 9

Levodopa-carbidopa can be formulated with ____ which is a selective reversible inhibitor of COMT

Answer 9

Entacapone

Question 10

Describe the mechanism of acction of entacapone

Answer 10

Selective and reversible inhibitor of COMT (which metaboloizes both L-dopa and dopamine; block COMT= increase amount of DA)

Question 11

Describe the mechanism of action of selegiline

Answer 11

MAOI used ot decrease dopamine metabolism in PD (also used off label as an antidepressant)

Noncompetitive, irreversible antagonist of MAO-B

Question 12

Describe the adverse reactions seen with treatment with selegiline

Answer 12

Adjunctive therapy with levodopa or levodopa-carbidopa can potentiate adverse reactions to levodopa
CNS: anxiety, confusion, insomnia, mania
CV: orthostatic hypotension, arrhythmias
GI: pain, NVD
Edema in legs and feet

Question 13

List precautions for treatment wiht selegiline

Answer 13

Dementia, psychosis, tardive dyskinesia, tremor, peptic ulcers, sympathomimetic drugs, other MAOIs

Question 14

Describe the mechanism of action of pramipexole

Answer 14

Synthetic D2 and D3 full agonist with no significant effect on other receptors

Question 15

List adverse reactions to treatment with pramipexole

Answer 15

CNS: dizziness, drowsiness, insomnia, asthenia, hallucinations, sleep attacks
GI: NV, constipation
CV: orthostatic hypotension

Question 16

List precautions for treatment wiht pramipexole

Answer 16

Cautioned driving or operating machinery
Dosages adjustment for low CrCL
Psychosis
Cardiovascular disease

Question 17

Describe the mechanism of action of ropinirole

Answer 17

D2 and D3 full agonist, used alone or withe levodopa-carbidopa
used for PD and RLS

Question 18

List adverse reactions to treatment wiht ropinirole

Answer 18

CNS: dizziness, drowsiness, insomnia, asthenia, neuralgia, hallucinations, sleep attacks
GI: NV
CV: syncope, edema, orthostatic hypotension

Question 19

List precautions for treatment with ropinirole

Answer 19

Cautioned driving or operating machinery
Psychosis
Cardiovascular disease

Question 20

List the mechanism of action of bromocriptine

Answer 20

Ergot derived DA agonist, D2 full agonist and D1 partial agonist

Question 21

List adverse reactions associated wiht bromocriptine

Answer 21

CNS: headache, dizziness, drowsiness, fatigue, confusion, hallucinations, agitation
GI: NV, cramps
CV: syncope, orthostatic hypotension, Raynaud’s symptoms, erythromelalgia

Question 22

List precautions for treatment with bromocriptine

Answer 22

Cautioned driving or operating machinery
Psychosis
Cardiovascular disease

Question 23

List three muscarinic receptor antagonists used for the treatment of Parkinson’s disease

Answer 23

Trihexyphenidyl
Benztropine
Diphenhydramine

Question 24

Describe the mechanism of action of amantadine

Answer 24

Antiviral drug (originally for influenza A) used as second line tx for PD
Mechanism may involve inhibition of DA uptake, increased DA release, cholinergic blockade, and glutamatergic blockade

Question 25

List adverse reactions of amantadine

Answer 25

Dizziness, insomnia, naxiety, depression, drowsiness, agitation, nausea, xerostomia, diarrhea, constipation, orthostasis, edemq

Question 26

List precautions for amantadine

Answer 26

Adjust dose based on CrCL

Question 27

Apomorphine

Answer 27

DA receptor agonist: D4 > D2, D3, D5 > D1

Derivative of morphine devoid of typical opioid effects; used for acute SC TX during “off” periods, not for routine TX

Question 28

Tolcapone

Answer 28

COMT inhibitor used only wiht levodopa

Question 29

Rasagiline

Answer 29

Irreversible MAO-B inhibitor

10x more potent than selegiline and well tolerated

Question 30

Carbergoline

Answer 30

D2 agonist, 7X more selective than bromocriptine vs. D1 receptors
used alone or with levodopa; used to treat hyperprolactinemia