Neurological drugs Flashcards
What is the pathology of idiopathic Parkinson’s Disease (IPD)?
- Neurodegeneration
- Lewy bodies
- Loss of pigment
- Reduced
Outline the basal ganglia circuit
- Loss of dopaminergic neurones in substantia nigra results in reduced inhibition in neostriatum
- Loss of inhibition in neostriatum allows increased production of ACh (excitatory)
- Chain of abnormal signalling leads to impaired mobility
What are the features of Parkinsonism?
- Tremor (low dopamine and disturbance of other neurotransmitter levels)
- Rigidity (low dopamine and disturbance of other neurotransmitter levels)
- Bradykinesia (low dopamine)
- Postural instability
How do we make a diagnosis of IPD?
- Clinical features
- Exclude other causes of Parkinsonism
- Response to treatment
- Structural neuro imaging is normal
What are some non motor manifestations of IPD?
- Mood changes
- Hallucinations
- Cognitive change
- Sleep disorder
- Restless legs
Outline catecholamine synthesis
- Origin molecule is L-tyrosine
- Gets converted to Levodopa (L-dopa)
- L-dopa is converted to dopamine
What are the drug classes in IPD?
- Levodopa (L-dopa)
- Levodopa with COMT inhibitor
- Dopamine receptor agonists
- MAOI type B inhibitors
- Anticholinergics
Why do we not just use dopamine as an IPD drug?
- Dopamine cannot cross the blood brain barrier
- Levodopa can cross by active transport
How does L-dopa work?
- Must be taken up by dopaminergic cells in substantia nigra to be converted into dopamine
- Fewer neurones are left in pts with IPD
- Levodopa works less effectively as pt’s condition deteriorates
What are the pharmacokinetics of L-dopa?
- Taken p.o.
- Absorbed by active transport
- 90% of drug inactivated in intestinal wall
- Half life is 2 hours
- 9% of drug is converted to dopamine in peripheral tissues
What does the short half life of L- dopa mean?
- Short dose interval
- Fluctuations in blood levels and symptoms
How is levodopa formulated?
- Must be used in combination with peripheral dopa decarboxylase inhibitors
- Because we don’t want drug to be broken down peripherally
Give some examples of Levadopa drugs
- Co-careldopa e.g. Sinemet
- Co-beneldopa e.g. Madopar
Why do we give levodopa alongside peripheral dopa decarboxylase inhibitors?
- Reduce dose required
- Reduce side effects
- Increased levodopa reaching brain
What are the different formulations of Levodopa?
- Tablet formulations only
- Standard dosage - variable strengths
- Controlled release preparations
- Dispersible Madopar (not soluble)
What are the advantages of levodopa?
- Highly efficacious
- Low side effects
What are the disadvantages?
- Precursor - needs enzyme conversion
- Long term: loss of efficacy, involuntary movements, motor complications
What are the side effects of levodopa?
- Nausea/anorexia
- Hypotension (central and peripheral)
- Psychosis
- Tachycardia
What are the motor complications of levodopa?
- On/off
- Wearing off
- Dyskinesias
- Dystonia
- Freezing