Antiparkinson Drugs Flashcards
Parkinsonism refers to the presence of ________, ______and ________ (slowness of movement). Collectively, these 3 make up the 3 cardinal features of Parkinson’s Disease.
- rest tremors
- rigidity
- bradykinesia
Young-onset PD starts at age ____, affects 5-10% of PD patients
21-40
Juvenile-onset PD starts before age ___ years. Higher frequency of _____ PD amongst this group
- 20
2. genetically inherited
All types of PD share a common mechanism: Impaired clearing of _______ proteins by _______ system. This can lead to the accumulation of aggresomes and apoptosis.
- abnormal/damaged intracellular
2. ubiquitin-proteasomal
Characteristic ______ (≈ aggresome), containing α-synuclein and ubiquitin are seen in PD.
Lewy bodies
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).
- dopaminergic
- dopaminergic
- basal ganglia
There are no reliable diagnostic markers for PD. Diagnosis and diagnostic criteria are based on the _______ of clinical features, and the _______ of alternative diagnoses
- presence
2. exclusion
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
10-25
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
- neuropsychiatric (similar to Alzheimer’s)
- olfactory
- sensory
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.
dopaminergic
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.
early
The key treatment principle for PD is to 1. _______ treatment and to 2. ______.
- individualize
2. start low, go slow
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.
oral medications
The 4 main classes of oral medications used in PD are – _______ agents (eg Artane)
– _______ inhibitors (eg Selegiline)
– _______ agonists (eg Bromocriptine)
– _______ (eg Madopar)
- Anticholinergic
- MAO-B / COM-T
- Dopamine
- Levodopa
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.
- Levodopa
2. peripheral decarboxylase
Levodopa is available as regular form or long acting form (HBS or CR).
Brand names:
– Levodopa + benserazide: ______
– Levodopa + carbidopa: ______
- madopar
2. sinemet
Levodopa has serious long term side effects such as ________ and _______ (10%/yr), which persists even after lowering levodopa dose.
- motor fluctuations
2. dyskinesia
To prevent long term side effects of levodopa, we have to ______ as much as possible. (i.e. use _____ medications)
- lower its dose
2. adjunct
Trihexyphenidyl (Artane) is an anticholinergic agent with side effects such as Dry _____, sedation, ______, _____ retention, delirium, confusion, hallucinations (especially in elderly).
- mouth
- constipation
- urinary
Trihexyphenidyl (Artane) has 2 advantages in that it may be effective in controlling ____ and that peripherally acting agents may be useful in treating ______ .
- tremor
2. sialorrhea (excessive salivation)
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.
- 2 - 15
- monotherapy
- levodopa
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).
- MAO-B inhibitor
2. nigral brain cell degeneration
Side effects of Selegiline (Jumex®) include: heartburn, loss of _____, nausea, constipation, dizziness, anxiety, headache, palpitation, ______, confusion, ______, visual hallucination.
- appetite
- insomnia
- nightmares
Selegiline (Jumex®) is efficacious as a symptomatic ________ and may be used in ____ stages of Parkinson’s disease.
- monotherapy
2. early
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.
- Catechol-O-methyltransferase
2. inactive
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 ______.
- duration
2. levodopa
COMT inhibitors' side effects include: – increase abnormal movements (dyskinesias) – \_\_\_\_\_ dysfunction (Tolcapone Tasmar®) – nausea, diarrhea – \_\_\_\_\_ discoloration – visual hallucinations – daytime drowsiness, \_\_\_\_\_ disturbances
- liver
- urinary
- sleep
Dopamine agonists can be used as both adjunct or monotherapy with Antiparkinsonian effects ________ compared to levodopa. It can prevent or delay onset of ______________.
- not superior
2. motor complications
Dopamine agonists such as ______ and _______ can cause somnolence while Pergolide can cause ______ disease as an side effect.
- ropinirole
- pramipexole
- restrictive valvular heart
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.
- pedal edema
- arrhythmia
- fibrosis
In younger Parkinson’s disease patients, therapy should commence first with ________ rather than ______, due to milder side effects.
- dopamine agonists
2. levodopa
Dopamine agonists are efficacious as symptomatic ________ and may also be used as an adjunct to ________ in the treatment of Parkinson’s disease
- monotherapy
2. levodopa
Amantadine is an antiviral agent, accidentally discovered to have mild antiparkinsonian effect (tremor, rigidity, bradykinesia, dyskinesia). It is given as ______________ to levodopa.
monotherapy or adjunct
Amantadine may be considered as therapy to reduce dyskinesia in patients with Parkinson’s disease who have motor fluctuations as it has _______ effects.
Anti-dyskinetic
Amantadine works via:
- Enhance release of stored _______
- Inhibit presynaptic uptake of ________
- _____ receptor agonist
- ______ receptor antagonist (anti-glutamate)
- dopamine
- catecholamine
- Dopamine
- NMDA
The usefulness of Amantadine is limited by the need to screen pts for hx of _______ symptoms. ______ limit its use in advanced disease.
- seizures/psychiatric
2. Side effects
The side effects of Amantadine include: ________ (inability to concentrate), hallucination, insomnia, nightmares, ________ (Venule swelling due to thromboses, mottled reticulated discoloration of limbs).
- Cognitive impairment
2. livedo reticularis
The CNS side effects of Amantadine are likely due to ________ and ________ activity and to a lesser extent its _______ activity
- dopaminergic
- adrenergic
- anti-cholinergic
Brand names of Dopamine agonists: – Bromocriptine (\_\_\_\_\_\_) – Pergolide (Celance®, Permax®) – \_\_\_\_\_\_\_ (Trivastal Retard®) – Ropinirole (\_\_\_\_\_\_) – \_\_\_\_\_\_ (Sifrol®)
- Parlodel®
- Piribedil
- Requip®
- Pramipexole
