Neurological Disorders Flashcards
What are the clinical features of Parkinsonism?
Tremor
Rigidity
Bradykinesia
Postural instability
- due to low dopamine and disturbance of other neurotransmitters.
Name some of the non motor manifestations of Parkinson’s?
- mood change
- pain
- cognitive change
- urinary symptoms
- sleep disorder
- sweating
- swallowing issues
What might be required for the diagnosis of IPD?
Clinical features, response to treatment, functional neuro imaging and structural neuro imaging being normal.
Exclude other causes of Parkinsonism: Drug induced Vascular Progressive supranuclear palsy Multiple systems atrophy Corticobasal degeneration
What is the pathology of IPD?
Neurodegeneration
Lewy bodies - synucleinopathy
Loss of pigment - >50% loss =symptoms, increased turnover and upregulate receptors
Reduced dopamine
What is the amino acid involved in the dopamine synthesis?
Tyrosine
What enzyme converts L-DOPA to Dopamine?
DOPA decarboxylase
Which two enzymes degenerate dopamine?
Monoamine oxidase
Catecholamine-o-methyl transferase
Why is levodopa prescribed instead of dopamine?
L-Dopa crosses the blood brain barrier via active transport, whereas dopamine cannot cross.
It can then be taken up by dopaminergic cells in the substantia nigra before being converted to dopamine.
What are the potential problems with levodopa?
Absorbed by active transport, in competition with amino acid.
90% inactivated in intestinal wall by MAO and DOPA decarboxylase.
9% converted to dopamine in peripheral tissues and so less than 1% enters CNS.
Short half life 2 hrs, short dose interval and fluctuations in levels and symptoms.
why L-DOPA not advised to be taken with large protein meals?
Both are absorbed by active transport and therefore there is competition between L-DOPA and amino acid uptake.
L-DOPA is given in formulations because?
Given with a peripheral DOPA decarboxylase inhibitor, therefore up to 10% L-DOPA crosses the BBB.
What tablet formulations can L-DOPA come in?
Standard dosage Controlled release preparations Dispersible madopar (not soblube)
What are some of the side effects of L-DOPA?
Nausea/anorexia
Hypotension
Psychosis
Tachycardia
What are some of the issues with L-DOPA?
Requires enzyme conversion and dopaminergic neurones
Involuntary movements
Motor complications
What are the potential interaction problems with L-DOPA?
Pyridoxine (vit B6) increases peripheral breakdown of L-DOPA.
MAOIs risk hypertensive crisis
Many antipsychotic drugs block dopamine receptors and cause Parkinsonism.
What drugs may be given to patients with IPD?
Levodopa Dopamine receptor agonists MAOI type B inhibitors COMT inhibitors Anticholinergics Amantidine
Why might dopamine receptor agonists be prescribed and what are the advantages?
De novo therapy or add on.
Direct acting, less dyskinesia/ motor complications, possible neuroprotection.
What are the disadvantages of dopamine receptor agonists?
- less efficacy than L-DOPA
- expensive
- more psychiatric side effects
- impulse control disorders
What is impulse control disorders (or dopamine dysregulation syndrome)?
- pathological gambling
- hypersexuality
- compulsive shopping
- desire to increase dosage
- punding
What are some dopamine receptor agonist side effects?
Sedation Hallucinations Confusion Nausea Hypotension
What are MAOB inhibitors and why might they be used?
Enhance dopamine, by preventing the breakdown by monoamine oxidase.
Includes selegiline and rasagaline.
Can be used alone, prolong action of L-DOPA. Smooth out motor response and may be neuroprotective.
How do COMT inhibitors work and why must they be given as a combination?
They reduce peripheral breakdown of L-DOPA to 3,o-methyldopa which competes with L-DOPA for active transport across BBB.
Therefore have a sparing effect and prolongs motor response to L-DOPA.
Alone they have no therapeutic effect.
What three drugs form stalevo?
COMT inhibitor
L-DOPA
Peripheral dopa decarboxylase inhibitor
Why might anticholinergics be prescribed to IPD patients?
ACh may have an antagonistic effect to dopamine.
Therefore treat tremor and not acting via dopamine system.
Includes trihexyphenidydyl, orphenadrine and procyclidine
