Antiparkinson Drugs

Question 1

Parkinsonism refers to the presence of ________, ______and ________ (slowness of movement). Collectively, these 3 make up the 3 cardinal features of Parkinson’s Disease.

Answer 1

1. rest tremors
2. rigidity
3. bradykinesia

Question 2

Young-onset PD starts at age ____, affects 5-10% of PD patients

Answer 2

21-40

Question 3

Juvenile-onset PD starts before age ___ years. Higher frequency of _____ PD amongst this group

Answer 3

1. 20

2. genetically inherited

Question 4

All types of PD share a common mechanism: Impaired clearing of _______ proteins by _______ system. This can lead to the accumulation of aggresomes and apoptosis.

Answer 4

1. abnormal/damaged intracellular

2. ubiquitin-proteasomal

Question 5

Characteristic ______ (≈ aggresome), containing α-synuclein and ubiquitin are seen in PD.

Answer 5

Lewy bodies

Question 6

In PD, there is degeneration of _______ neurons with Lewy body inclusions in substantia nigra, which has _______ projections to _______ (Facilitates and modulates motor movements initiated by motor cortex).

Answer 6

1. dopaminergic
2. dopaminergic
3. basal ganglia

Question 7

There are no reliable diagnostic markers for PD. Diagnosis and diagnostic criteria are based on the _______ of clinical features, and the _______ of alternative diagnoses

Answer 7

1. presence

2. exclusion

Question 8

PD is the main cause of parkinsonism, but _____% of patients with parkinsonian syndromes do not have PD. Common differential diagnoses are the atypical parkinsonian disorders

Answer 8

10-25

Question 9

Common* non-motor manifestations for PD include autonomic, _______, ______ and _____ manifestations. They are more prominent in later stages of PD.

*as many as 88% with 1 sx, 11% with 5 sx

Answer 9

1. neuropsychiatric (similar to Alzheimer’s)
2. olfactory
3. sensory

Question 10

Non-motor manifestations of PD are relatively resistant to, and may be worsened by _____ agents. They cause significant disability and are often neglected in PD management.

Answer 10

dopaminergic

Question 11

PD is a progressive disorder and rate of disability progression is most marked in the ____ years of the disease. Significant disability can happen 10-15 years after onset.

Answer 11

early

Question 12

The key treatment principle for PD is to 1. _______ treatment and to 2. ______.

Answer 12

1. individualize

2. start low, go slow

Question 13

Patients with early symptomatic disease without complications may not even need _______ if coping well. The preferred plan includes physiotherapy and exercise, healthy balanced diet, providing knowledge on disease and social support.

Answer 13

oral medications

Question 14

The 4 main classes of oral medications used in PD are – _______ agents (eg Artane)
– _______ inhibitors (eg Selegiline)
– _______ agonists (eg Bromocriptine)
– _______ (eg Madopar)

Answer 14

1. Anticholinergic
2. MAO-B / COM-T
3. Dopamine
4. Levodopa

Question 15

The ‘Gold standard’ in PD treatment is _______ (dopamine precursor). It may come in 2-in-1 preparations with ________ inhibitors to increase dopamine conversion in brain.

Answer 15

1. Levodopa

2. peripheral decarboxylase

Question 16

Levodopa is available as regular form or long acting form (HBS or CR).
Brand names:
– Levodopa + benserazide: ______
– Levodopa + carbidopa: ______

Answer 16

1. madopar

2. sinemet

Question 17

Levodopa has serious long term side effects such as ________ and _______ (10%/yr), which persists even after lowering levodopa dose.

Answer 17

1. motor fluctuations

2. dyskinesia

Question 18

To prevent long term side effects of levodopa, we have to ______ as much as possible. (i.e. use _____ medications)

Answer 18

1. lower its dose

2. adjunct

Question 19

Trihexyphenidyl (Artane) is an anticholinergic agent with side effects such as Dry _____, sedation, ______, _____ retention, delirium, confusion, hallucinations (especially in elderly).

Answer 19

1. mouth
2. constipation
3. urinary

Question 20

Trihexyphenidyl (Artane) has 2 advantages in that it may be effective in controlling ____ and that peripherally acting agents may be useful in treating ______ .

Answer 20

1. tremor

2. sialorrhea (excessive salivation)

Question 21

Trihexyphenidyl (Artane) dose is ____mg/day. It may be used as symptomatic ________ or as an adjunct to _______ to treat tremors and stiffness in Parkinson’s disease.

Answer 21

1. 2 - 15
2. monotherapy
3. levodopa

Question 22

Selegiline (Jumex®) is a ______ that reduces breakdown of dopamine. It has mild antiparkinson activity but laboratory studies suggest that it may delay the ________ (potential disease modifying effect).

Answer 22

1. MAO-B inhibitor

2. nigral brain cell degeneration

Question 23

Side effects of Selegiline (Jumex®) include: heartburn, loss of _____, nausea, constipation, dizziness, anxiety, headache, palpitation, ______, confusion, ______, visual hallucination.

Answer 23

1. appetite
2. insomnia
3. nightmares

Question 24

Selegiline (Jumex®) is efficacious as a symptomatic ________ and may be used in ____ stages of Parkinson’s disease.

Answer 24

1. monotherapy

2. early

Question 25

Entacapone (Comtan®) and Tolcapone (Tasmar®) are _______ (COMT) inhibitors that block an enzyme that converts levodopa into an _____ form. This allows more levodopa to enter the brain.

Answer 25

1. Catechol-O-methyltransferase | 2. inactive

Question 26

Entacapone (Comtan®) and Tolcapone (Tasmar®) increases ______ of each dose of levodopa, beneficial in treating “wearing off” responses (i.e. when the duration of action for levodopa gradually reduces). But they are only effective if used with ______.

Answer 26

1. duration | 2. levodopa

Question 27

``` COMT inhibitors' side effects include: – increase abnormal movements (dyskinesias) – _____ dysfunction (Tolcapone Tasmar®) – nausea, diarrhea – _____ discoloration – visual hallucinations – daytime drowsiness, _____ disturbances ```

Answer 27

1. liver 2. urinary 3. sleep

Question 28

Dopamine agonists can be used as both adjunct or monotherapy with Antiparkinsonian effects ________ compared to levodopa. It can prevent or delay onset of ______________.

Answer 28

1. not superior | 2. motor complications

Question 29

Dopamine agonists such as ______ and _______ can cause somnolence while Pergolide can cause ______ disease as an side effect.

Answer 29

1. ropinirole 2. pramipexole 3. restrictive valvular heart

Question 30

Dopamine agonists have similar side effects as Levodopa but also include other side effects such as ______ and _______. As 'ergot' derivatives, they can cause ______ in regular users.

Answer 30

1. pedal edema 2. arrhythmia 3. fibrosis

Question 31

In younger Parkinson’s disease patients, therapy should commence first with ________ rather than ______, due to milder side effects.

Answer 31

1. dopamine agonists | 2. levodopa

Question 32

Dopamine agonists are efficacious as symptomatic ________ and may also be used as an adjunct to ________ in the treatment of Parkinson’s disease

Answer 32

1. monotherapy | 2. levodopa

Question 33

Amantadine is an antiviral agent, accidentally discovered to have mild antiparkinsonian effect (tremor, rigidity, bradykinesia, dyskinesia). It is given as ______________ to levodopa.

Answer 33

monotherapy or adjunct

Question 34

Amantadine may be considered as therapy to reduce dyskinesia in patients with Parkinson’s disease who have motor fluctuations as it has _______ effects.

Answer 34

Anti-dyskinetic

Question 35

Amantadine works via: 1. Enhance release of stored _______ 2. Inhibit presynaptic uptake of ________ 3. _____ receptor agonist 4. ______ receptor antagonist (anti-glutamate)

Answer 35

1. dopamine 2. catecholamine 3. Dopamine 4. NMDA

Question 36

The usefulness of Amantadine is limited by the need to screen pts for hx of _______ symptoms. ______ limit its use in advanced disease.

Answer 36

1. seizures/psychiatric | 2. Side effects

Question 37

The side effects of Amantadine include: ________ (inability to concentrate), hallucination, insomnia, nightmares, ________ (Venule swelling due to thromboses, mottled reticulated discoloration of limbs).

Answer 37

1. Cognitive impairment | 2. livedo reticularis

Question 38

The CNS side effects of Amantadine are likely due to ________ and ________ activity and to a lesser extent its _______ activity

Answer 38

1. dopaminergic 2. adrenergic 3. anti-cholinergic

Question 39

``` Brand names of Dopamine agonists: – Bromocriptine (______) – Pergolide (Celance®, Permax®) – _______ (Trivastal Retard®) – Ropinirole (______) – ______ (Sifrol®) ```

Answer 39

1. Parlodel® 2. Piribedil 3. Requip® 4. Pramipexole