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Therapeutics - Parkinson's Disease
Parkinson's Disease: Pathophysiology, Drugs, Side effects.
26
Pharmacology
Undergraduate 4
10/06/2010

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Cards

Term
Describe the pathophysiology of Parkinson's Disease.
Definition
  1. Destruction of dopaminergic neurons in substantia nigra pars compacta
  2. Depletion of dopamine stores and degeneration nigrostriatal pathway
  3. Imbalance of Ach and D in corpus striatum
  4. Impairment of extrapyramidal tracts responsible for body movements
  5. Tremors, Rigidity, bradykinesia
Term
What are lewy bodies?
Definition
Spherical intracytoplasmic aggregates in the remaining neurons of substantia nigra pars compacta
Term
What part(s) of the brain can lewy bodies be found during preclinical phase of Parkinson's disease?
Definition

medulla oblongata

locus ceruleus

raphe nuclei

olfactory bulb

Term
During the progression of Parkinson's disease, lewy bodies may ascend from the medulla oblongata, locus ceruleus, raphe nuclei and olfactory bulb to what?
Definition
Midbrain (substantia nigra pars compacta)
Term

In advanced cases of Parkinson's Disease, where can Lewy bodies be found?

 

What can this cause?

Definition

Cortex;

 

behavioural and cognitive changes

Term
What is 'cog wheeling'?
Definition

jerky, stiff, variable rigidity affecting upper arms

painful stiffness when walking

Term
What is 'freezing'?
Definition
feeling of total muscle rigidity and inability to walk at initiation of movement
Term
Other than tremor, rigidity, and bradykinesia, what other symptoms may be observed in Parkinson's patients?
Definition

Postural instability

Constipation

Sweating

Pain

Speech/facial expression

Poor sleep

Fatigue

Anxiety

Depression

Term

How is Parkinson's Disease diagnosed?

 

Progression monitored?

Definition

Neurologic assessment

Neuroimaging - MRI, PET (Positron Emision Tomography) -     needs to be validated

Diagnose confirmed by response to therapy

Progression monitored by using assessment scale (Unified Parkinson's Disease Rating Scale)

 

Term
Apart from carbidopa and benserazide, which drugs decrease the metabolism of levadopa?
Definition

entacapone (COMT inhibitor)

 

selegiline (MAO-B inhibitor)

Term
Name 6 dopamine agonists; 3 ergot, 3 non-ergot.
Definition

Ergot: Bromocriptine, Cabergoline, Pergolide

 

Non ergot: Pramipexole, Ropinirole, Apomorphine

Term

Which drugs may be used to treat 'wearing-off' symptoms of levadopa?

 

 

Definition

Selegiline

 

COMT inhibitors- entacapone, tolcapone

 

 

Term
What is the usual daily dose of levadopa?
Definition
800-1000mg
Term
What are counselling points associated with levadopa?
Definition

Take on empty stomach, though if feeling GI discomfort, take with food.

 

 

Term
Which complications are associated with long-term therapy of Levadopa?
Definition

movement fluctuations

 

dyskinesia

Term
What are the side effects of dopamine agonists?
Definition

nausea

orthostatic hypertension

lower extremity oedema

Term
What are the side effects of Levadopa?
Definition

GI: nausea, vomiting (treat with domperidone), constipation, dry mouth, peptic ulcers

 

CVS: orthostatic hypotension, syncope (fainting), dizziness, fatigue. Treat hypotension with more carbidopa; addition of fludrocortisone with salt; midodrine; or use of elastic stockings.

 

CNS: sedation, psychosis - reduce or stop amantadine, MAOIs and Anticholinergics stopped. Give clozapine or quetiapine

 

Motor: Fluctuations - end of dose wearing off, and also dykinesias: involuntary movements

 

Term
What drug may be used as a 'rescue therapy' for "off" episode inspite of optimal dose?
Definition
Apomorphine
Term
Nocturnal symptoms of parkinson's are relieved by what?
Definition

Clonzepam, or

 

small doses of carbidopa/levadopa

Term
How is entacapone and tolcapone categorised? MOA?
Definition
COMT inhibitor
Term
What is the normal dose for tolcapone?
Definition
100-200mg
Term
What surgery may be done in treating Parkinson's disease?
Definition
Chronic high frequency deep brain stimulation.
Term
What are the side effects of anticholinergics?
Definition

Dry mouth

blurred vision

dry eyes

constipation

urinary retention

tachycardia

memory loss

Term
What anticholinergic drugs are used in the treatment of Parkinson's disease?
Definition

benztropine

trihexyphenidyl

biperiden

Term
What are the side effects of amantadine?
Definition

confusion

hyperexcitability

insomnia

dizziness

orthostatic hypotension

livedo reticularis (vascular cutaneous reaction with redish purple fish net mottling on extremeties)

 

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