Anti-Parkinson Drugs Flashcards
What is Parkinson’s disease?
- Parkinson’s is a neurodegenerative disorder characterized by abnormalities in movement and gait.
- Dopaminergic neurons degenerate, leading to a decrease in the amount dopamine in the brain.
Epidemiology of Parkinson’s disease
- Incidence and prevalence of Parkinson’s Disease increase with age.
- Average age of onset early to mid-60s.
- Young-onset PD (21-40 y/o): rare
- Juvenile-onset PD (starts before 20 y/o): higher frequency of genetically inherited PD
Pathophysiology of Parkinson’s disease
- IPD is not a single disease, it is sporadic, familial.
- Impaired clearing of abnormal/damaged intracellular proteins by ubiquitin – proteasomal system.
- Failure to clear toxic proteins leads to accumulation of aggresomes (Lewy bodies), which will eventually overwhelm the cell and lead to apoptosis.
- Degeneration of dopaminergic neurons with Lewy body inclusions in substantia nigra.
- Since substantia nigra has dopaminergic projections to basal ganglia, which facilitates and modulates motor movements initiated by the motor cortex, a decrease in dopaminergic neurons helping to serve the basal ganglia will result in the loss of control of movement.
Diagnosis of Parkinson’s Disease
- No reliable diagnostic marker for PD
- Diagnosis and diagnostic criteria are based on
» The presence of clinical features,
» The exclusion of alternative diagnoses - While PD is the main cause of parkinsonism, not all patients with parkinsonian syndromes have PD
3 cardinal clinical features of Parkinsonism
- Rest tremors
- Rigidity
- Bradykinesia
Non-motor, clinical manifestations of PD
- Autonomic, neuropsychiatric, olfactory, and sensory
- Common in PD, more prominent in its later stages
- Relatively resistant to, and may be worsened by dopaminergic agents
- Causes significant disability
- Often neglected in PD management
Course of PD
- Progressive disorder
- Rate of disability progression is most marked in the early years of the disease.
- Significant disability 10-15 years after onset
- Motor fluctuation, dyskinesias and non-motor symptoms are common at later stages.
Course of treatment of early symptomatic PD without complications
- May not even need oral medications if coping well
- Most importantly,
» Physiotherapy and exercise regime (stretching, maintain balance and posture)
» Healthy and balanced diet
» Knowledge on disease
» Social support
MOA of levodopa
- Dopamine precursor, “2-in-1” preparation with peripheral decarboxylase inhibitors.
- Levodopa + benserazide: madopar
- Levodopa + carbidopa: Sinemet
- Available as regular or long acting form
Side effects of levodopa
- Short term: nausea, vomiting, postural hypotension
- Long term: motor fluctuations and dyskinesia
Levodopa dosage regimen
Dose of levodopa should be kept to the minimum necessary to achieve good motor function.
MOA of anticholinergics (Trihexyphenidyl (Artane) 2-15mg/day)
Inhibitors at cholinergic receptors
Therapeutic effects of anticholinergics (Trihexyphenidyl (Artane) 2-15mg/day)
- May be effective in controlling tremor
- Peripherally acting agents may be useful in treating sialorrhoea
Side effects of anticholinergics (Trihexyphenidyl (Artane) 2-15mg/day)
(Especially in elderly):
-Dry mouth, sedation, constipation, urinary retention, delirium, confusion, hallucinations
Dosage regimen of anticholinergics (Trihexyphenidyl (Artane) 2-15mg/day)
- Anticholinergic agents may be used as symptomatic monotherapy or as adjunct to levodopa to treat tremors and stiffness in Parkinson’s disease.
