Antiparkinsons' Flashcards
The main pathophysiology of Antiparkinsons
- Substantia nigra has dopaminergic projections to basal ganglia (striatum, to control thalamus), which is important to control movement
- Degeneration of dopaminergic neurons with Lewy Body inclusions in Substantia Nigra cause it to be unable to send dopaminergic signals to the striatum to control movements
The 3 cardinal features of PD (IMPORTANT!!)
- Rest Tremors
- Rigidity
- Bradykinesia (slowness of movement)
What are some non-motor manifestations of PD and when are they the most prominent? Can they be treated with dopaminergic agents?
Autonomic, neuropsychiatric, olfactory, sensory
- More prominent in later stages of PD and are resistant to dopaminergic agents
Main principle of drugs usage in PD
Go slow, start low
Treatment of PD has to be individualised according to what factors?
- Age
- Stage of disease
- Level of Activity
- Associated Psychological factors
- Associated medical conditions
- Other patient factors
When PD is diagnosed in a patient, but patient does not shows signs and symptoms, should treatment be started?
No. Oral meds not required if patient is coping well, even with mild symptoms
Some non-pharmaco therapy for PD
- Physiotherapy and exercise regime (e.g. stretching, balance, posture)
- Healthy and balacned diet
- Social support
- Knowledge on PD
Classes of oral medications for PD
- Anticholinergics
- MAO-B/COM-T inhibitors
- Dopamine agonists
- Levodopa
- Levodopa is gold standard for PD
Mechanism of Levodopa in PD
Dopamine precursor (analogue of L-dopa). Converted to dopamine in the neurons = more dopamine = more control of movements
Levodopa (dopamine precursors) usually comes as “2-in-1” preparation with peripheral decarboxylase inhibitors. Why is this so?
- Levodopa can be converted in peripheral to dopamine
- Levodopa can cross BBB, but Dopamine cannot
- Inhibitors minimise levodopa’s conversion in peripheral, allow more to cross BBB
- Hence lower dose of levodopa required for same effect
Main concern of long-term usage of Levodopa
Cumulative increased risk of motor fluctuations and dyskinesia (10%/yr). Chronic and irreversible, even if levodopa is withdrawn
Ways to minimise risk of dyskinesia from using Levodopa?
- Use other meds adjunct with levodopa, allowing lower doses of levodopa to be used. Other meds can be used as monotherapy too
- Use minimum effective dose
An example of anticholingergics used in PD
Trihexyphenidyl
Two advantages of Anticholinergics in PD?
- May be effective in controlling tremor
2. Peripherally acting agents useful in treating sialorrhea
Roles of anticholinergics in PD
- Symptomatic monotherapy OR
2. Adjunct to levodopa to treat tremors and stiffness
An example of MAO-B inhibitor used in PD
Selegiline
Mechanism of action of MAO-B inhibitors. State its disease modifying effect
- Inhibits MAO-B = decreased dopamine breakdown
- May have disease modifying effect –> Delay nigral brain cell degeneration
Side effects of MAO-B inhibitors?
Many sympathetic CNS related side effects (think noradrenaline)
Roles of MAO-B inhibitors in PD
- Symptomatic monotherapy, may be used in early stages of Parkinson’s disease
Two examples of COMT inhibitors used in PD
- Entacapone
2. Tolcapone
MoA of COMT inhibitors
Blocks COMT (Catechol-O-methyltransferase) and prevents it from converting levodopa into an inactive form, thus increasing the amount of levodopa available to enter the brain
Role of COMT inhibitors in PD
- Used with levodopa to increase duration of each dose of levodopa
- Help treats “wearing off” response
note: NO effect if only itself is used
One SE of Tolcapone
Liver dysfunction
General SE of COMT inhibitors
- Dyskinesia
- Nausea, diarrhea
- Urinary disclouration
- Visual hallucinations
- Daytime drowsiness, sleep disturbances
Examples of Dopamine agonists used in PD
- Bromocriptine
- Pergolide
- Piribedil
- Ropinirole
- Pramipexole
Role of Dopamine agonists in treating PD?
- Adjunct (to levodopa)
- Symptomatic Monotherapy
- Initial therapy in younger PD patients
One benefit of dopamine agonist
Prevent or delay onset of motor complications
Between dopamine agonist and levodopa, which is more effective in managing PD?
Levodopa. Hence Levodopa is still the gold standard
Notable SE of ropinirole and pramipexole
Somnolence
Notable SE of Pergolide
Restrictive valvular heart disease
On top of SE that are similar to levodopa, what other SE does dopamine agonist have?
- Fibrosis
2. Pedal Edema
MoA of Amantadine
- Enhance release of stored dopamine
- Dopamine receptor agonist
- Inhibit presynaptic uptake of catecholamine
- NMDA receptor antagonist
Benefit of Amantadine
Reduce dyskinesia in patients with motor fluctuations (Antidyskinetic effect)
Role of Amantadine in PD
- Adjunct to levodopa (can reduce risk of dyskinesia SE)
2. Monotherapy
Can Amantadine be used in PD patients with seizures and psychiatric syndromes? Why or why not?
No. It can worsen seizure disorders and psychiatric symptoms, in Schizo or PD
SEs of Amantadine
- Cognitive impairment (inability to concentrate)
- Hallucination
- Insomnia
- Nightmares
- Livedo reticularis (venule swelling due to thromboses, hence reticulated discoloration of limbs)
