Parkinsons

Question 1

Name 6 treatment options Parkinson’s and examples

Answer 1

• Dopamine precursor: levodopa and carbidopa/benserazide
• dopamine agonists: pramipexole, ropinirole
• increase release endogenous dopamine: amantadine
• inhibit COMT: tolcapone, entacapone
• inhibit mao-b: selegiline, rasagiline
• affect cholinergic system: benzhexol, benztropine

Question 2

Name 3 long term side effects of dopaminergics

Answer 2

• Motor fluctuations: with Cp drop, “wearing off phenomena”
• Freezing
• dyskinesia: dystonia, akathisia, chorea, myoclonus

Question 3

First line treatment Parkinson’s?

Answer 3

Levodopa with carbidopa or benserazide: better to improve motor disability
Dopamine agonists (ropinirole, pramipexole): better to lessen motor complications

Question 4

Name 2 drug interactions with selegiline

Answer 4

• High doses: hypertension, especially with tyramine foods
• amantidine (increase release endogenous dopamine) and centrally active antimuscarinic agents: potentiate anti-pd effects

Question 5

Name a dopamine precursor

Answer 5

Levodopa

Question 6

Name 2 dopamine agonists

Answer 6

• Pramipexole
• ropinirole
(Bromocriptine, cabergoline, pergolide, apomorphine)

Question 7

Name an anti-parkinsons drug that stimulate endogenous release dopamine

Answer 7

Amantadine

Therefore not enzyme inhibitor like others.

Question 8

Name a COMT inhibitor

Answer 8

Entacapone
(tolcapone)
For Parkinson’s

Question 9

Name a mao-b inhibitor

Answer 9

Selegiline
(Rasagiline)
Parkinson’s

Question 10

Name 2 anti. Parkinson’s drugs that affect cholinergic system

Answer 10

• Benzhexol

* benztropine

Question 11

Name indications selegiline

Answer 11

• Parkinson’s mild symptomatic relief prior to initiating methyldopa

Question 12

Drug interactions with levodopa?

Answer 12

Maoi: hypertension (especially with tyramine)

Question 13

Name 2 peripheral decarboxylase inhibitors that need to be given with levodopa to prevent metabolism before crossing BBB

Answer 13

• Carbidopa

* benserazide

Question 14

Name 4 adverse effects levodopa

Answer 14

• Nausea and vomiting ( chemoreceptor trigger zone outside BBB so improve with decarboxylase inhibitor addition)
• psychiatric: schizo like
• CV: arrhythmia, postural hypotension ( improve with decarboxylase inhibitor addition)
• dyskinesias, especially face and limbs

Question 15

Which medications reduce off time of levodopa? (2)

Answer 15

Entacapone (comt I )

Rasagiline (maob-i)

Question 16

Indication anticholinergics for Parkinson’s?

Answer 16

First line for Parkinsonism caused by antipsychotics

Question 17

Which Parkinson’s medication reduce dyskinesia?

Answer 17

Amantadine (stimulate release endogenous dopamine)

Question 18

Which neurotransmitter is pertinent in Parkinson’s

Answer 18

Dopamine (decrease)

Question 19

Moa levodopa?

Answer 19

• Dopamine precursor that can cross BBB.
• transported into brain via system L amino acid transporters
• enters nerve terminals in basal ganglia where it’s decarboxylated to form dopamine by dopa decarboxylase

Question 20

Moa pramipexole?

Answer 20

Dopaminergic (d2) agonist that mimic dopamine

Longer acting than levodopa

Question 21

Moa selegiline?

Answer 21

• Selective irreversible inhibitor of intraneuronal mao-b

* prevent breakdown dopamine

Question 22

Moa entacapone?

Answer 22

• Reversible, competitive COMT inhibitor specific for cns

* prevent levodopa break down leading to increase bioavailability at nigrostriatal nerve fibres

Question 23

Moa amantadine?

Answer 23

• Stimulate release endogenous dopamine!
• other proposed moa: dopamine agonist, monoamine reuptake inhibitor, anticholinergic, NMDA r antag
• also reported to inhibit reuptake dopamine presynaptically and have direct action on dopamine R

Question 24

Moa benzhexol?

Answer 24

• Anticholinergic or antimuscarinic
• ach inhibit dopamine response
• restore balance between dopaminergic and cholinergic pathways
• reduction tremors

Question 25

Name 2 long term effects of dopaminergics

Answer 25

* Motor fluctuations (decreased levels): wearing off phenomena ( off time), freezing * Drug induced dyskinesia (increased levels): dystonia, akathisia, chorea, myoclonus

Question 26

Which anti-parkinsons drugs offer most favourable long term motor complication profile?

Answer 26

Dopamine 2 receptor agonist: pramipexole, ropinirole

Question 27

Ropinirole adverse effects? (4)

Answer 27

* Somnolence and sleep episodes * Nausea * orthostatic hypotension, syncope * nightmares and hallucinations

Question 28

Describe metabolism selegiline and active metabolites (4)

Answer 28

* Single oral dose or transdermal * extensively metabolised in liver but also intestine via n-dealkylation, carbon hydroxylation, ring hydroxylation. * active metabolites = amphetamine and methamphetamine * long half life 39 hours

Question 29

Name 3 adverse effects selegiline

Answer 29

* Agitation and involuntary movements * confusion, insomnia, hallucinations * Nausea

Question 30

Which 2 factors predict the outcome of deep brain stimulation of subthalamic nucleus for Parkinson's?

Answer 30

* Intensity to which pt responds to levodopa rx (pre-op) serves as predictor motor improvement. Not helpful for symptoms that don't respond. * younger patients with shorter disease duration or shorter motor fluctuations

Question 31

Name 5 beneficial effects of deep brain stimulation in Parkinson's

Answer 31

* effective control fluctuating responses to levodopa * Control dyskinesia that doesn't improve with med adjustment * reduce tremor * reduce rigidity * improve slowing of movement

Question 32

Which release formulation is better for levodopa?

Answer 32

At rx initiation, no difference in rate of motor complications seen between extended and immediate release formulations

Question 33

Half life levodopa-carbidopa combination?

Answer 33

2 hours

Question 34

Ropinirole drug interaction?

Answer 34

* cyp1a2 metabolise Ropinirole | * cyp1a2 inhibitors eg. ciprofloxacin, flavoxamine, reduce clearance Ropinirole

Question 35

Which drug has both antiviral and anti Parkinson’s activity?

Answer 35

Amantidine

Question 36

What percentage levodopa enter brain unaltered?

Answer 36

1-3%