treatment of parkinson's disease Flashcards
Cardinal features of Parkinson’s
Tremors
Rigidity
Akinesia/Bradykinesia
Idiopathic PD initial presentations
Asymmetric
Positive response to levodopa or apomorphine
Postural instability and falls not present
Less rapid progression
Autonomic dysfunction not present
Morbidity in PD
Unable to perform basic ADLs
Dysphagia
Falls due to postural imbalance
Pathology
Significant loss of dopaminergic neurons in the substantia niagra Age-related Environmental toxins Genetics - Predisposition to toxins/insults - Genetic abnormalities
Non-movement symptoms
Cognitive impairment
Sleep disorders
Psychiatric disorders
Autonomic dysfunction
Goal of treatment
Manage symptoms
Maintain function and autonomy
Non-pharmacological treatment
PT
OT
Speech and swallowing
Surgery
Levodopa
Most effective for bradykinesia and rigidity
Causes N/V, hypotension
Levodopa PK
A: proximal part in small intestines
Increased F with benserazide/carbidopa
Decreased absorption with high fat/protein meals
DOPA decarboxylase inhibitors
Do not cross BBB
75-100mg daily for saturation of dopa decarboxylase (1:1 action)
1:4 – Sinemet, Madopar
1:10 – Sinemet
Levodopa AE
N/V Orthostatic hypotension Drowsiness, sudden sleep onset Hallucinations, psychosis Dyskinesia within 3-5y
Levodopa DI
Pyridoxine (Vit B6) - cofactor for dopa decarboxylase Iron Protein Antidopaminergic drugs - Metoclopramide, prochlorperazine - 1st gen antipsychotics - Risperidone
Dopamine agonists MOA
Act on D2 receptors in the basal ganglia
Mimic action of dopamine
Dopamine agonists PK
Longer half-life and duration of action than levodopa
Ropinirole metabolised in liver to inactive metabolites, DA in hepatic impairment
Pramipexole excreted largely unchanged in urine, DA in renal impairment
Dopaminergic agonists AE
N/V Orthostatic hypotension Hallucinations Somnolence, daytime sleepiness Compulsive behaviours Fibrosis Valvular heart disease Leg edema
MAO B Inhibitors
Selegiline and rasagiline both irreversible inhibitors
Effective as monotherapy
Selegiline metabolised to amphetamines
MAO B inhibitors dosing
Selegiline 5mg OM to BD
Rasagiline 0.5-2mg OD
MAO B inhibitors DI
SSRI, SNRI, TCA Dopamine Sympathomimetics Another MAOi Penthidine, tramadol Linezolid Dextromethorphan
COMT inhibitors
Decreases “off” time, useful in wearing off phase
Not effective without concurrent levodopa
Entacapone
Selective, reversible COMT inhibitor Must be taken at the same time as levodopa DI: - Iron, calcium - Catecholamine drugs - Enhances warfarin Diarrhoea, urine discolouration May cause dyskinesia upon initiation May potentiate other dopaminergic effects
Anticholinergics
Primarily used to control tremor
Ipatropium
Hyoscine
Tolterodine
Anticholinergics SE
Dry mouth
Sedation
Constipation
Urinary retention
NMDA Antagonists
Amantadine
Glutamate activates NMDA receptor activity which activates processes that encourage cell death
Improvement in levodopa-induced dyskinesia – used for management
NMDA Antagonist PK
Renally excreted
Can be stimulating
AE: N, light-headedness, insomnia, confusion, hallucinations, livedo reticularis
Alternative medicines
Co-enzyme Q10 Creatinine Vit E Glutathione Riboflavin Lipoic acid Acetyl carnitine Curcumin
Vascular Parkinsonism
Pathology due to vasculature in the brain
Usually bilateral
No resting tremor
Stepwise in progression
Vascular risk factors present
Increasing age is risk factor
Mostly not caused by infarct/lesions in basal ganglia
Drug-induced parkinsonism
Improvement with drug withdrawal in 80% of patients in 8w No improvement with levodopa Occurs bilaterally Women at higher risk May unmask existing PD onset ~3m
Drugs that may cause drug induced parkinsonism
1st gen antipsychotics
Antiepileptics
Metoclopramide
Parkinsons Hyperpyrexia Syndrome
Caused by changes in dopaminergic treatment Provoked by trauma and infections Loss of consciousness Rhabdomyolysis Immobility Disseminated intravascular coagulation
PHS management
Reinstate previous treatment and increase dose of levodopa gradually
Rotigotine patch
Dantrolene PO/IV
Bromocriptine
