L9- Parkinson's Disease Treatment (others)

Question 1

list the dopamine receptor agonists (indicate which type is used more and why)

Answer 1

Ergots: bromocriptine (D2 agonist)- not used b/c way more AEs

Nonergots: pramipexole, ropinirole, rotigotine (trans-dermal form)

Question 2

what are the advantages of using dopamine agonists in comparison to levodopa

Answer 2

• it does not require conversion by active dopamine neurons, so the functional capacity Nigrastriatal pathway is not a factor — works better for advanced PD
• longer half-lives, dec dose frequency

Question 3

______ is a dopamine agonist that can be given by TD administration

Answer 3

rotigotine- nonergot dopamine agonist, used once a day

Question 4

name and describe the use of Nonergot Dopamine Agonists

Answer 4

Pramipexole, Ropinirole:

• increasing use as initial Tx (instead of levodopa adjunct)
• important in younger Pts as older Pts are more vulnerable to cognitive AEs

Question 5

Dopamine Agonist AEs:

• (1) GI
• (2) CVS

Answer 5

1- anorexia, n/v, constipation, dyspepsia; bleeding from peptic ulceration

2- postural hypotension, cardiac arrhythmias, peripheral edema

Question 6

Dopamine Agonist AEs: neurological

Answer 6

• dyskinesia: abnormal movements
• mental disturbances: confusion, hallucinations, delusions
• dopamine dysregulation syndrome = impaired impulse control

Question 7

Dopamine Agonist AEs: miscellaneous by subtype

Answer 7

Ergots: HA, nasal congestion, inc arousal, pulmonary infiltrates, pleural / retroperitoneal fibrosis, erythromelalgia, painless digital vasospasm, cardiac valve fibrosis

Nonergots: uncontrollable somnolence (stop med if this occurs)

Question 8

list the Dopamine agonist contraindications

Answer 8

• psychosis
• recent MI
• PVD
• PUD

Question 9

Apomorphine:

• (1) MOA
• (2) explain how to avoid important AE
• (3) other AEs

Answer 9

1- dopamine receptor antagonist

2- pretreat with Trimethobenzamide (anti-emetic) to prevent vomiting

3- QT prolongation, dyskinesia, drowsiness, sweating, hypotension

Question 10

______ are the inhibitors of dopamine metabolism

Answer 10

• MAOIs

- COMT inhibitors

Question 11

list the useful MAOIs, explain MOA

Answer 11

**MOA: selective MAO-B inhibitors (MAO-B breakdown dopamine and tyramine) – [used as ADJUNCTs]

Selegiline: dec dopamine breakdown in brain –> enhances levodopa effects (allows for dec dose)

Rasagiline: enhances levodopa effect

Question 12

what is the main difference between Selegiline and Rasagiline

Answer 12

Both are MAO-B inhibitors

• Selegiline –> metabolized to methamphetamine / amphetamine => insomnia, confusion in elderly
• Rasagiline –> not metabolized to amphetamines

Question 13

list the COMT inhibitors and why which are chosen over the others

Answer 13

Tolcapone:

• preferred MOA b/c CNS and periphery
• not preferred b/c causes fulminating hepatic necrosis
• Entacapone:
• only periphery MOA
• *preferred b/c no AE

Question 14

what are the main useful effects of COMT inhibitors

Answer 14

• dec levodopa metabolism
• dec plasma [3-O-methyldopa]
• inc uptake levodopa
• inc dopamine in the brain

Question 15

(1) is the antiviral that has antiparkinsonian actions. (1) has a (2) MOA and is used specifically for (3) in PD.

Answer 15

1- amantidine
2- unclear MOA
3- levodopa-induced dyskinesias

Question 16

what are the general effects of Amantidine in terms of PD

Answer 16

• high doses inc release and dec reuptake of dopamine
• upregulates D2 receptors
• NMDA antagonist

Question 17

Amantidine:

• (1) common neuro AEs + (2) at high doses
• (3) common cardiac AE
• (4) less common AE that clears w/in a month of drug withdrawal

Answer 17

1- restlestness, agitation, confusion, hallucinations
2- acute toxic psychosis

3- peripheral edema (responds to diuretics), used with caution for patients with h/o HF, seizures

4- Livedo Reticularis: mottled reticulated vascular pattern that appears as a lace-like purplish discoloration of the skin

Question 18

Amantidine:

• (1) common neuro AEs + (2) at high doses
• (3) common cardiac AE
• (4) less common AE that clears w/in a month of drug withdrawal

Answer 18

1- restlestness, agitation, confusion, hallucinations
2- acute toxic psychosis

3- peripheral edema (responds to diuretics), used with caution for patients with h/o HF, seizures

4- Livedo Reticularis: mottled reticulated vascular pattern that appears as a lace-like purplish discoloration of the skin

Question 19

list the Antimuscarinics used to help treat PD + include MOA

Answer 19

(tertiary amines)

• benzotropine
• trihexylphenidyl

-inhibits excitatory cholinergic interneurons in Striatum

Question 20

what are the effects of antimuscarinics in PD

Answer 20

• adjuvant therapy
• to improve tremor and rigidity
• little effect on bradykinesia

Question 21

Antimuscarinic AEs (in PD)

Answer 21

mood changes, confusion, hallucinations
xerostomia, pupillary dilation
urinary retention

Question 22

Antimuscarinic contraindication (in PD)

Answer 22

glaucoma
BPH
pyloric stenosis