Neuropharmacology Flashcards
Describe the pathophysiology of Parkinson’s
- Loss of Dopaminergic neurones in Substantia Nigra
- Results in reduced inhibition in Neostriatum
- Allows increased ACh production
List 5 drug classes used to treat the motor symptoms of Parkinson’s
- L-Dopa (Levodopa)
- Dopamine receptor agonists
- MAO-B Inhibitors
- COMT Inhibitors
- Anticholinergics
Describe the effectiveness of L-Dopa
L-Dopa can cross the BBB in contrast to Dopamine
- Taken up by dopminergic cells in Substantia Nigra, then converted to Dopamine
- As disease progresses there are fewer cells left to do this, so reduced effectiveness
Why is L-Dopa given with DOPA Decarboxylase Inhibitors?
Prevents conversion of L-Dopa to Dopamine in peripheral tissues therefore;
- Reduced dose required
- Reduced side effects
What’s the importance of the fact that L-Dopa is absorbed via Active Transport
Competes with Amino Acids, so caution with high protein meals eaten within an hour of medication
List 2 preparations of L-Dopa and their contents, including the Peripheral DOPA Decarboxylase inhibitor
Sinemet/ Co-careldopa;
- Levodopa + Carbidopa
Madopar/ Co-beneldopa;
- Levodopa + Benserazide
List ADRs of L-DOPA
- Nausea + Vomiting
- Hypotension
- Psychosis (hallucinations, delusions)
- Tachycardia
List 3 DDIs of L-Dopa
- Vitamin B6 increases peripheral breakdown of L-DOPA
- Antipsychotics (D2 antagonists)
- Risk of Hypertensive Crisis with Monoamine Oxidase Inhibitors/ MAOIs (not MAO-B Inhibitors at normal dose)
Why are Ergot derived Dopamine receptor agonists now avoided in favour of Non-Ergot derived agonists?
They had retroperitoneal fibrotic side effects
(Ergot derived: Bromocryptine, Pergolide, Cabergoline)
(Non-ergot derived: Ropinerole, Pramipexole)
Suggest 2 advantages and 3 disadvantages of using Dopamine agonists over L-Dopa?
Advantages;
- Direct acting
- Less motor complications
Disadvantages;
- Less efficacy
- More psychiatric side effects
- Can develop impulse control disorders (Gambling, hypersexuality, compulsive shopping)
List 5 ADRs of Dopamine Agonists
- Sedation
- Hallucinations
- Nausea
- Confusion
- Hypotension
What class of drug are Selegiline, Rasagaline and Safinamide?
How do these work?
- Monoamine Oxidase B/ MAO-B Inhibitors
- Inhibit MAO-B, which metabolises Dopamine
What class of drugs are Opicapone and Entacapone?
Do these have any therapeutic effect on their own?
How do they work?
- COMT Inhibitors
- No, they reduce the peripheral breakdown of L-DOPA
Procyclidine and Orphenadrine are Anticholinergics used in Parkinson’s.
List advantages and disadvantages of using Anticholinergics for this
Advantages;
- Treat tremor
- Not acting via Dopamine systems
Disadvantages;
- No effect on Bradykinesia
- ADRs: Confusion, Drowsiness, Usual anticholinergic ones
How does Amantidine work? (Used in improving Dyskinesia)
- NMDA receptor inhibition
- Dopamine receptor agonism
