Antiparkinsons Flashcards
What is the epidemiology of Parkinson’s Disease (PD)?
- SG 0.3% for population aged >50yrs
- young-onset PD: age 21-40, affects 5-10% of PD
- juvenile-onset PD: <20yo, higher freq of genetically inherited PD amongst this grp
What is the pathophysiology of PD?
- “impaired garbage disposal system”
- impaired clearing of abnormal/damaged intracellular proteins by ubiquitin-proteasomal system
- Failure to clear toxic proteins -> accumulation of aggresomes –> apoptosis
- Lewy bodies = aggresome, containing alpha-synuclein and ubiquitin (bad, abnormally aggregated)
IMPT what is the main pathophysiology of PD?
- degeneration of dopaminergic neurons w Lewy body inclusions in substantia nigra
(other sites: locus ceruleus, cortical association areas, hypothalamic neurons, sympathetic ganglia parasympathetic neurons, olfactory bulb) - substantia nigra has dopaminergic projections to basal ganglia (impt in controlling movement)
- basal ganglia faciliates and modulates motor movements initiated by motor cortex.
Is there any diagnosis of PD?
- no reliable diagnostic marker for PD
- diagnosis and diagnosis criteria based on: presence of clinical features, and the exclusion of alternative diagnoses
- PD is the MAIN cause of parkinsonism; however, 10-25% of pts w parkinsonian syndromes don’t have PD
- common differential diagnoses are the atypical parkinsonian disorders
IMPT What are the 3 cardinal features of PD?
- rest tremors
- rigidity
- bradykinesia
What are some non-motor manifestations of PD?
- autonomic, neuropsychiatric, olfactory, and sensory
- common in PD; 88% of pts have at least one nonmotor smx and 11% w 5 nonmotor smx
- more prominent in later stages of PD
- Relatively resistant to, and may be worsened by dopaminergic agents
- Cause significant disability
- Often neglected in PD management
How is the course of disease?
- progressive disorder
- rate of disability progression is most marked in the early years of the disease.
- significant disability 10-15 yrs after onset
- at later stages, PD pts become increasingly dependent in their activities of daily living
- Motor fluctuation, dyskinesia, and non-motor smx (e.g. falls, postural instability, postural hypotension, confusion, dementia, suboptimal nutrition, speech and sleep disorders) are common at later stages
When is medication is started for PD pts?
- individualised
- early symptomatic disease without complications may not even need oral med if coping well
- if taking, go slow, start low
IMPT What is levodopa?
- gold standard
- dopamine precursor, “2-in-1” preparation with PERIPHERAL decarboxylase inhibitors
- combi
~ madopar: levodopa + benserazide
~ sinemet: levodopa + carbidopa - available as regular form or long acting form (HBS
or CR) (HBS = Hydrodynamically Balanced System; hbs Madopar)
What is the MOA of levodopa?
Levodopa is converted to dopamine via the action of DOPA decarboxylase.
This occurs both in the peripheral circulation and in the central nervous system after levodopa has crossed the blood brain barrier.
L-dopa needed as precursor in syn for dopamine
L-dopa needed in the brain so that dopamine can be syn with the enzyme dopa-decarboxylase
If l-dopa converted to dopamine in the peripheral, cannot cross BBB into brain
The peripheral decarboxylase inhibitors: Prevent L-dopa to convert to dopamine before entering BBB –> L-dopa can enter BBB and then converted to Dopamine –> thus lower dose of levodopa to get the same effect
Give more precursor to remaining neurons –> convert easier and produce inc of dopamine
IMPT what are the side effects of levodopa?
- short-term: N/V, postural hypotension
- long-term: motor fluctuations and DYSKINESIA (10%/yr)
IMPT Is it okay to give levodopa? risk of dyskinesia?
although levodopa is the most efficacious drug for the symptomatic management of both early and late PD, the dose of levodopa should be kept to a MINIMUM necessary to achieve GOOD MOTOR FUNCTION
IMPT what is an example of an Anticholinergic?
Trihexyphenidyl (Artane) 2-15mg/day
IMPT what are the advantages of trihexyphenidyl?
- may be effective in controlling tremor
- peripherally acting agents may be useful in treating sialorrhea (excessive secretion of saliva)
IMPT what are the side effects of trihexyphenidyl?
Dry mouth, sedation, constipation, urinary retention, delirium, confusion, hallucinations
(esp in elderly)
