Treatment of Parkinson's Disease Flashcards
4 Characteristic features of PKD
- Slowness & poverty of movement
- Muscular rigidity
- Resting tremor
- Postural instability
3 cardinal signs of PKD
1) Tremor
2) Rigidity
3) Akinesia/ Bradykinesia
- Need 2 of the 3 cardinal signs
Initial presentation of Idiopathic PD
- asymmetric
- +ve response to Levodopa/Apomorphine
- Less rapid progression (years)
How does PKD affect basic ADLs?
- Unable to perform basic ADLs (safely)
- > Mobility, feeding self, grooming, personal hygiene, toileting, showering/bathing. continence (bowel & bladder)
- Dysphagia (-> pneumonia)
- Falls due to gate instability
Pathology of PKS
Loss of dopaminergic neurons in the substantia nigra
- age-related loss???
- envt toxin/insult
- genetics?
How to “measure” level of PKD?
Hoehn and Yahr Staging
- Assesses mobility
Non-motor symptoms
Cognitive impairment
- Dementia
Psychiatric symptoms
- Depression, psychosis
Sleep disorders
- REM sleep behaviour disorder
Autonomic dysfunction
- Constipation, GI motility, Orthostatic hypot/s, Sialorrhoea
Note: PKD pts at high risk of developing hypotension, SE of Levodopa also hypotension
Fatigue
Early/onset PD
- Slower disease progression
- < cognitive decline
- Earlier motor complications
- Dystonia (common initial presentation)
Treatment: Dopamine agonists (Preferred > Levodopa bc of longer elimination t1/2 & to delay use of Levodopa)
Goals of PKD treatnment
- Manage symptoms
- Manage function & autonomy
Note: no treatment shown to be “neuroprotective”
Non-Pharmacological Treatment of PKS
Physiotherapy
- posture, transfer, stretching, walking
Occupational therapy
- mobility aids, home, workplace safety
Speech & swallowing
Surgery
Levodopa (Use, Formulations, Adverse SE, DDI, Motor complications)
Most effective esp for bradykinesia & rigidity
- Analogue of L-dopa, precursor to be converted to dopamine
- Given with DCI to prevent it from being converted in periphery
- Decreased absorption with high fat/protein meals
Formulations:
- 1:4 (Sinemet, Madopar)
- 1:10 (Sinemet)
- -> IR & SR forms
- -> SR: Release over 4-6hrs, has lower F, need to increase dose when switching from IR to CR
- -> SR useful for stiffness on waking
Adverse Effects:
- N/V, Orthostatic hypotension, drowsiness, sudden sleep onset, hallucinations, psychosis, Dyskinesia)
Motor Complications:
i) Wearing off effects (assoc with disease progression)
- > Managed by modifying times of administration +/or modified-release preparations
ii) Dyskinesia
- Involuntary uncontrollable jerking & twitching, peak dose dyskinesia, dystonia
- > Managed by adding amantadine/ modified-release levodopa
DDI:
i) Pyridoxine
- Generally not prob but just note can decrease effect of Levodopa
- High dose Vit B6 for haematological probs or in high potency Vit B complex tabs
ii) Iron/ Protein (food, powder)
- Space out administration
iii) Antidopaminergic Drugs
- Metoclopramide/Prochlorperazine
- -> Antiemetic of choice in PD = domperidone
- 1st gen antipsychotics
- Risperidone
Dopamine Agonists (Use, Options, Adverse SE, DDI)
MOA: Acts on D2 receptors in basal ganglia, mimic action of dopamine
Types:
i) Ergot derivative:
- Lower F than non-ergot derivative, longer t1/2 & duration of action > Levodopa
- Fibrosis
- Valvular heart disease
ii) Non-Ergot derivative:
- Ropinirole: Hepatic metabolism
- Pramiprexole: Renal
- -> Both avail in IR & SR forms
Use:
- Monotherapy in younger pts
- (+) Levodopa
- Manage motor complications caused by Levodopa
- Rotigotine patch: Dysphagia, unable to swallow/tube
Adverse Effects:
- (Peripheral) N/V, Orthostatic hypot/s, leg oedema
- (Central) Hallucinations (Usually > visual), Somnolence, day-time sleepiness, compulsive behaviours
- Fibrosis, Valvular HD
Levodopa vs Dopamine Agonists
Dopamine Agonists:
< motor complications but > sleep disturbance, hallucinations, leg oedema, orthostatic hypotension
MAO-B Inhibitors (Use, Options, Adverse SE, DDI)
Options: Selegiline & Rasigiline
- Irreversible enzyme inhibitors
- Short t1/2 but long DOA
Selegiline: 5mg OM to BD - Hepatically metabolised to amphetamines - Stimulating -> Insomnia Rasagiline: 0.5mg-2mg OD - Not metabolised to amphetamines
Use:
- Monotherapy in mild PKD
- Early stages of young onset PKD
DDI:
- SSRI, SNRI, TCA (Washout periods)
- Pethidine, tramadol, linezolid, dextromethorphan, dopamine, symptaomimetics, another MAOi
FDI: Tyramine
COMT Inhibitors (Use, Options, Adverse SE, DDI)
Options: Entacapone
- Selective, reversible COMT inhibitor
Forms:
Comtan: Entacapone
Stalevo: Levodopa, carbidopa & entacapone
Use: (+) Levodopa
- Decreases “off” time, good for wearing off responses
- MUST be taken @ same time as levodopa
Adverse SE:
- Diarrhoea
- Urine discolouration (orange)
- May cause dyskinesia upon initiation (usually reversible)
- May potentiate other dopaminergic effects (Orthostatic hypot/s, N/V)
DDI:
- Iron, Ca
- Avoid concurrent nonselective MAOi
- Any catecholamine drug
- Enhance anticoagulant effect of warfarin (Monitor INR)
Caution use:
- In hepatic impairment (LFT monitoring not needed)
Anticholinergics in PKD
Options: Benztropine (longer tmax) , Trihexyphenidyl (shorter tmax)
- Site of action: CNS
Limited Use: Control tremor
Adverse SE:
- Dry mouth, constipation, urinary retention, delirium, confusion, blurred vision
NMDA Antagonists in PKD
Options: Amantadine, Memantine (no gd evidence)
- NMDA antagonist
- Anticholinergic
- Upregulate D2 receptors, increases sensitivity of D2 receptors
Use:
- (+) Levodopa
- Manage levodopa-induced dyskinesias
Adverse SE:
- Nausea, light-headedness, insomnia, confusion, hallucinations, livedo reticularis
- Renal excretion
- Can be stimulating (2nd dose in afternoon)
- Avoid concurrent use with memantine
Alternative/complementary medicines for PKD
- Co-enzyme Q10 (safe but not effective)
- Creatine (safe but not effective)
- Vit E
- Glutathione
- Riboflavin
- Lipoic acid
- Acetyl carnitine
- Curcumin
Types of Parkinsonism
1) Vascular parkinsonism
2) Drug-induced parkinsonism
Vascular Parkinsonism (Presentation, characteristics, risk factors)
- Due to vasculature in brain
- Usually bilateral, no resting tremor, stepwise in progression
- Vascular risk factors usually present
- Increasing age is a risk factor
- Mostly not caused by infarct/lesions in the basal ganglia
Drug-induced Parkinsonism
- > often in elderly
- Typically symmetrical
- Acute/subacute onset
- Reversible (depends)
- Poor response to levodopa
- > common in females
- Uncommon symptoms: Rest tremors, freezing (but common in iPD)
May unmask existing PD
Course: Variable (~3mths within exposure to the offending agent)
Treatment: Withdrawal of drug
- -> Usually leads to improvement in symptoms (80% of patients)
- Anticholinergics & amantadine may be used
Typical causes of Drug-induced Parkinsonism
- D2 receptor blockers (Typical antipsychotics, Atypical antipsychotics @ higher doses)
- Dopamine depleters (Tetrabenazine, reserpine)
- Dopamine synthesis blockers (alpha-methyldopa)
- Ca2+ channel antagonists (Flunarizine, cinnarizine)
What is Parkinson’s Hyperpyrexia Syndrome and what are its complications
Rare but srs condition caused by changes in dopaminergic treatment
- Provoked by trauma, surgery, pulmonary, GI & UTI/ may also have no apparent trigger
Severe cases:
- No response to dopaminergic rescue meds, pts become progressively more immobile & rigid
Systemic complications:
- Decreased consciousness -> Aspiration pneumonia
- Rhabdomyolysis -> ARF
- Immobility -> DVT, PE
- DIVC
How to manage Parkinson’s Hyperpyrexia Syndrome
If cause is bc of a decrease in dopaminergic meds:
- Reinstate previous treatment and increase dose of levodopa gradually
If PO cannot be used, consider:
- Rotigotine patch
- Amatadine injection (if avail)
- Dantrolene, bromocriptine
How to manage Pts admitted with Parkinsonism features w/o known PD?
- Accurate diagnosis
- Rule out differential diagnosis (drug-induced, essential tremor)
- Specialist advice recc
How to manage Pts with PKD, admitted for an unrelated problem?
- Review meds
- Screen for possibly related problems
- Arrange for specialist input
What kind of special complications are PKD patients usually admitted for?
- Aspiration pneumonia
- Dopamine agonist withdrawal
- Psychosis
- Dyskinesias
