Drugs In Neuropathology Flashcards
L-dopa pharmacokinetics
Oral
Compete with amino acids for transporter uptake, so don’t take with high protein meals
T1/2 2 hrs, so take tablets regularly
9% converted to dopamine in peripheral tissue, so give with a dopa decarboxylase inhibitor
<1% effective
L- dopa uses
Used in Parkinson’s
Crosses the BBB
Is then converted to dopamine
L dopa pros
Effective
Few side effects
L dopa cons
Needs enzyme inactivation
Get wearing off, on/off, dyskinesia, dystonia, freezing
L dopa ADRs
Nausea/anorexia
Hypotension
Tachycardia
Psychosis
L dopa DDIs
Antipsychotics - have parkinsonian side effects
MAOIs- risk hypertensive crisis
Pyridoxine (vit B6) increases peripheral breakdown
Dopamine receptor agonists uses
De novo or add on therapy in Parkinson’s
Bromocryptine
Pergolide
Cabergoline
Ergot derived dopamine receptor agonists
Rarely used due to side effect profile
Ropinerole
Pramipexole
Non Ergot derived dopamine receptor agonists
Rotigotine
Dopamine receptor agonist that can be given by patch
Apomorphine
Dopamine receptor agonist that can be given subcutaneously, but only for patients with severe motor fluctuations
Dopamine receptor agonist pros
Possible neuroprotection
Less motor complications
Direct action
Dopamine receptor agonist cons
Less efficacy than L-dopa
Impulse control disorders
Expensive
More psychiatric side effects
Dopamine receptor agonist ADRs
Sedation Nausea Confusion Hypotension Hallucination
Monoamine oxidase B inhibitors uses
Prevents dopamine metabolism Increases dopamine Can be used alone or to prolong L dopa action Smooths out motor response May be neuroprotective
Selegine
Rasagiline
Monoamine oxidase B inhibitors
Catechol-o-methyl transferase inhibitors uses
Prolong motor response to L dopa by preventing peripheral breakdown
No therapeutic effect alone
Tolcapone
Catechol-o-methyl transferase inhibitor
Can cross BBB but main effects are peripheral
Entacapone
Catechol-o-methyl transferase inhibitor
Doesn’t cross BBB
Anticholinergic uses in Parkinson’s
ACh can antagonise dopamine
Minor role in treatment
Reduces tremor
No effect on bradykinesia
Trihexyphenidyl
Orphenadrine
Procyclidine
Anticholinergics used in Parkinson’s
Anticholinergics in Parkinson’s ADRs
Usual anticholinergic profile
Confusion, drowsiness
Amantidine
Used in Parkinson’s
Mechanism uncertain
Poorly effective
Few side effects
Surgery in Parkinson’s
Lesion -thalamus for tremor, GPi for dyskinesia
DBS - subthalamic nucleus
Acetylcholinesterase inhibitor uses
Myasthenia gravis
Neostigmine
Acetylcholinesterase inhibitor
Oral or IV
Pyridostigmine
Acetylcholinesterase inhibitor
T1/2 4-6 hours
Oral
Acetylcholinesterase inhibitor ADRs
Lacrimation Salivation Emesis Sweating Urinary incontinence Diarrhoea Over treatment causes cholinergic crisis
