Drugs in Neurological Disorders Flashcards
1
Q
Describe the presentation of parkinsons disease
A
- Tremor - rotatory motion resting tremor
- Re-emerging tremor
- Rigidity - lead pipe (rigidity throughout movement)
- Bradykinesia - inability to maintain amplitude of slow moving movements
- Postural instability - abnormal gait, reduced arm swing, turn as a block
- Test through posterior draw test
- Mood changes
- Pain
- Cognitive change
- Urinary symptoms
- Sleep disorder - REM sleep behaviour disorder (no muscle atonia so act out dreams)
- Sweating
2
Q
Describe the pathophysiology of parkinsons disease
A
- Degeneration of substantia nigra pars compacta causes deficiency of dopamine
- Direct pathway - has overall stimulatory effect on thalamus without dopamine
- Pathway stimulation will decrease in Parkinson’s - bradykinesia
- Indirect pathway - has overall inhibitory effect on thalamus without dopamine
- No stimulations from the indirect pathway - bradykinesia
- Direct pathway - has overall stimulatory effect on thalamus without dopamine
- Lewy bodies present
3
Q
Describe Parkinson’s plus syndrome including presentation
A
- Neurodegenerative disorder having the classical features of Parkinsonism but also additional features that distinguishes from idiopathic Parkinson’s disease
- Will not respond to Parkinson’s disease treatment
- Poor prognosis with faster rate of progression and death
- Multiple system atrophy - classical features in addition to autonomic nervous system dysfunction (loss of sweating, postural hypotension, impotence, dry mouth, incontinence)
- Early onset of dementia, hallucinations, psychosis, postural instability
4
Q
Describe the aims of parkinsons treatment
A
- Pharmacological treatment for PD is only symptomatic and not neuroprotective
- Thus treatment may only begin when symptoms begin, and not as prophylaxis for PD
- Only provides symptomatic relief for movement disorders, rather than non-motor features
- Surgery - carried in highly selected cases where patient is not responsive to treatment or has significant side effects with L-DOPA
- Deep brain stimulation of subthalamic nucleus to excite globus pallidus interna and thus inhibit thalamus
5
Q
List the drug classes used to treat PD
A
- Levodopa
- Dopamine receptor agonists
- MAOI type B inhibitors
- COMT inhibitors
- Anticholinergics
- Amantidine
6
Q
Explain the mechanism of levodopa
A
- L-DOPA is the precursor of dopamine production, and thus increases dopamine production
- L-DOPA is able to cross the blood-brain barrier unlike dopamine
7
Q
Explain the ADRs of levodopa treatment
A
- Psychosis - schizophrenia like effects
- Nausea, vomiting, hypotension
- Long term motor complications:
- On/off - sudden freezing to excessive movement spectrum
- Wearing off - short half life so constant dosing and monitoring needed
- Dyskinesia
- Dystonia
- Freezing (occurs when L-DOPA runs out and thus no dopamine produced)
8
Q
Describe the limitation of levodopa usage
A
- Note that levodopa only effective if dopaminergic cells in the substantia nigra are present
- As Parkinson’s progresses, degeneration of cells occurs preventing the conversion of L-DOPA to dopamine in the CNS
- Short half life of 2 hours, therefore need constant doses
9
Q
Describe the mechanism and usage of carbidopa
A
- Mechanism - acts as peripheral decarboxylase inhibitor to prevent breakdown of L-DOPA in peripheries
- Used in combination with L-DOPA
- Reduces dosage of L-DOPA required as more reaches brain
- Decreases peripheral side effects
10
Q
Compare the use of dopamine receptor agonsts to levodopa
A
- Eg. Apomorphine, bromocriptine, ropinirole
- Ergot derived dopamine receptor agonists not used anymore due to significant side effects
- Non-ergot, patch and subcutaneous used
- Direct acting (do not need dopamine neurones present to act), less dyskinesia and motor complications
- Possible neuroprotection
- However less efficacy than L-DOPA, more psychiatric side effects (dose limiting) and expensive
11
Q
List potential ADRs of dopamine receptor agonists
A
Nausea, postural hypotension, psychosis, confusion, sedation
12
Q
Describe the mechanism of monoamine oxidase B inhibitors
A
- Eg. Selegiline
- Prevents metabolism of dopamine by monoamine oxidase B within the brain
- Prolongs action of L-DOPA and may be neuroprotective
13
Q
Describe the mechanism of COMT inhibitor
A
- Eg. Entacapone
- Does not cross blood brain barrier
- Prevents breakdown of L-DOPA in peripheries, therefore prolongs clinical effects of levodopa
- Used in combination with L-DOPA and has no therapeutic effect alone
14
Q
Describe the mechanism of anticholinergics in treating PD
A
- Eg. Amantadine, procyclidine
- Antagonistic effects to dopamine
- Works best for patients with tremor
15
Q
Explain the pathophysiology of myasthenia gravis
A
- Myasthenia gravis occurs when antibodies bind to postsynaptic acetylcholine receptors and thus prevent excitation at the postsynaptic neurone
- Acetylcholine is broken down by ACh - esterase without having its effect
