23. Drugs Used In Neurological Disorders Flashcards
(36 cards)
What is meant by idiopathic Parkinson’s disease (IPD)?
- cause is unknown
- also known as ‘parkinsons’
- most common type of Parkinsonism
- neurodegenerative disorder
What are the clinical features of Parkinsonism?
Mnemonic: TRAP (patients trapped in their poorly mobile body)
1) Tremor: pill rolling, resting tremor. Abolished by movement. Usually unilateral (later can be bilateral)
2) Rigidity: cog-wheel rigidity (other form is lead pipe)
3) Akinesia/bradykinesia: slowing down and loss of spontaneous automatic movements. Hypomimia, micrographia, hypophonia, drooling
4: Postural instability: impaired balance so patients fall over easily.
Describe the non motor manifestations of parkinsons
- mood changes: depression,anxiety
- pain
- frequency of micturition
- sleep disorders: REM sleep disorder, violent + vidid dreams
- sweating
What is the prognosis of PD?
- drugs can help but the degeneration of the brain will continue
- dyskinesia
- falls (shouldn’t fall in early parkinsons)
- hallucinations
- swallowing difficulty
- somnolence
Name some other causes of Parkinsonism (i.e. differentials for IPD)
Mnemonic: VODKA
V: Vascular events e.g. stroke, MI
O: orthostatic hypotension and atonic bladder (look for multi system organ failure)
D: dementia and vertical gaze paralysis (consider supranuclear palsy)
K: Kayser-Fleisher ring (consider Wilson’s disease)
A: apraxia gait (communicating hydrocephalus)
What are the parkinsons plus disorders?
- Respond poorly to the standard treatments for Parkinson disease
- Often have a poor prognosis with faster rate of progression and death
5 Separate syndromes:
1. Multiple system atrophy (MSA)
2. Progressive supranuclear palsy (PSP)
3. Parkinsonism-dementia-amyotrophic lateral sclerosis complex
4. Corticobasal ganglionic degeneration (CBD)
5. Dementia with Lewy bodies (DLB)
Clinical Features: - Early onset of dementia
- Early onset of postural instability
- Early onset of hallucinations or psychosis
- Early autonomic symptoms: postural hypotension and urinary incontinence
- Ocular signs
What is a DAT scan?
- labelled tracer looking at pre synaptic uptake of dopamine
- if dopaminergic neurones disappear dont see as much
This is not a test for Parkinson’s however. Though it is abnormal in parkinsons
Describe the pathology of IPD?
- neurodegeneration
- reduced dopamine
- Lewy bodies (synucleinopathy)
- loss of pigment
Normally, dopamine has an inhibitory effect on ACh. What happens if you lose dopamine?
- more ACh activity
- ACh will then stimulate GABA which is inhibitory
- this causes slowness of movement
How is dopamine synthesised?
- synthesised from L-Tyrosine
- then L-DOPA
- then dopamine
- then noradrenaline
- then adrenaline
The enzyme that converts L-DOPA to dopamine is DOPA decarboxylase
How is dopamine degraded?
- dopamine is eventually degraded to homovanillic acid
The major enzymes involved are: - Monoamine oxidase and aldehyde dehydrogenase
*Catechol-O-methyl transferase
The 2 intermediates are:
3-methoxytyramine
3,4 dihydrophenol acetic acid
Name the drug classes which can be used in IPD?
- Levodopa (L-Dopa)
- Dopamine receptor agonists
- MAO type B inhibitors
- COMT inhibitors
- Anticholinergics
How does L-dopa work?
- taken up by dopaminergic neurones into the substantia nigra
- converted into dopamine
- this is why if there’s no dopaminergic neurones left then it wont be able to work
- so as disease progresses the treatment doesn’t work as well
What food should be avoided when taking L-Dopa?
- protein rich e.g. steaks
- because it can be antagonised by amino acids
- in competition with vitamin B6
Discuss the pharmacokinetics of L-Dopa focussing on half life and bioavailability
- taken orally
- short half life 2hrs
- 90% inactivated in intestinal wall
- 9% that has been absorbed is converted to D2 in peripheral tissues
- so less than 1% enters the CNS
Need strategies to preserve it
What do we give L-DOPA in combination with? Give 2 examples
A peripheral DOPA decarboxylase inhibitor
Co-careldopa- Sinemet
Co-beneldopa - Madopar
This allows us to reduce the dose, so less side effects and increased L-DOPA reaching the brain
What are the side effects of L-DOPA?
- nausea and vomiting (can give domperidone)
- hypotension
- tachycardia
- hallucinations/delusions and paranoia
What are the long term motor complications of giving the drug L-DOPA?
- on/off, wearing off
- freezing
- dystopia
- dyskinesia
What are the potential interactions of L-DOPA with other drugs?
- Pyridoxine (vitamin B6) increases the peripheral breakdown of L-DOPA
- MAOIs: risk of hypertensive crisis
Many antipsychotics block dopamine receptors resulting in Parkinsonism as a side effect so check their other drugs.
Name some dopamine receptor agonist (both ergot and non ergot)
Ergot: bromocriptine, cabergoline
Non-ergot: Ropinirole
Patch: rotigotine - good for those that can’t take it orally
In patients with severe motor fluctuations can give apomorphine as rescue medication.
What are the advantages of dopamine receptor agonists?
- direct acting and don’t require dopaminergic neurones to be in place
- less motor complications
- possible neuroprotection
What are the disadvantages of dopamine receptor agonists?
- less efficacy then L-dopa
- impulse control disorders: hyper sexuality, gambling, compulsive shopping
- more psychiatric side effects e.g. hallucinations, confusion
- nausea, hypotension
How do MAOI work?
- normally monoamine oxidase metabolises dopamine
- if you inhibit it you will enhance dopamine
- can be used alone or to prolong action of L-DOPA
Give 2 examples of MAOI’s?
- selegiline
- rasagiline
