parkinsons Flashcards
cardinal symptoms
tremor, rigidity, bradykinesia
non-cardinal symptom
postural instability
pathophysio
Impaired clearing of abnormal INTRACELLULAR PROTEINS by ubiquitin-proteasomal system →
Leads to accumulation of aggressomes, known as Lewy bodies →
Degeneration of dopaminergic neurons with Lewy body inclusions in the substantia nigra →
Dysfunction of nigrostriatal pathway causing movement disorder
direct pathway of loss of dopaminergic input
Hypoactivation of excitatory D1 receptors → weakens striatal inhibition of GPi (globus pallidus internal) → hypokinesia
Indirect pathway of loss of dopaminergic input
Hypoactivation of excitatory D2 receptors → weakens striatal inhibition of GPe (globus pallidus external)→ hypokinesia
medications associated with drug induced parkinsonism
antipsychs (haloperidol, CPZ)
alpha methyl dopa
metocloperamide
tetrabenazine
dopamine agonists moa
Mimics action of dopamine by acting on D2 receptors in basal ganglia
dopamine agonists space out with
iron, protein
dopamine agonists avoid
dopamine antagonists (antipsych, metoclopramide)
examples of ergot derivatives
bromocriptine, cabergoline
examples of non ergot derivatives
ropinirole (IR/SR), pramipexole (IR/SR), rotigotine
levodopa benefits
bradykinesia, rigidity.
less effective for speech and gait disturbances
levodopa food interactions
high fat or protein meals. space 2h
side effects of levodopa
Dyskinesias
Dystonia
NV (domperidone)
Orthostatic hypoT
Drowsiness
Hallucinations / Psychosis
dopaminergic side effects of dopamine agonists
NV
Orthostatic hypoT
Led oedema
Compulsive behaviours
Hallucinations
Somnolence
non-dopaminergic side effects (mostly ergot) of dopamine agonists
Fibrosis
Valvular heart disease
ropinirole / pramipexole: renal or liver
Ropinirole: liver metabolism
Pramipexole: renal clearance
maobi moa and examples
Irreversible MAOb inhibitors, inhibiting dopamine breakdown
selegiline
rasagiline
which has hepatic metabolism to ampetamines, which is stimulating, hence must not be taken at night
selegiline
maobi or comti preferred for early stage PD
maob-i
foods to avoid with maobi
tyramine, soy sauce, aged cheese, fermented food, beer
se of maobi
gi: heartburn, loss of appetite
CNS: Anxiety, palpitations, insomnia, nightmares, visual hallucinations
comti moa
Selective, reversible catechol-o-methyltransferase (COMT) inhibitor, preventing COMT conversion of L-DOPA into inactive form.
comti administration requirement
Requires concurrent levodopa
comti drugs to avoid
iron/calcium, concurrent non-selective maobi, warfarin, catecholamine drugs
comti side effects
dyskinesias upon initiation, potentiation of dopaminergic effects, diarrhoea, urine discolouration (orange)
comti benefits
decreases ‘off’ time
levodopa food interactions
high fat or protein meals. space 2h
issues with levodopa
‘on off phenomenon’: unpredictable and unrelated to dosing’
‘wearing off’: shortened on time
peak dose dyskinesias
amantadine moa
nmda antagonist and antichol, increases sensitivity of d2 receptors
amantadine place in therapy
adjunctive and monotherapy (ad)
se of nmda
Stimulating
Nausea
Light-headed
Insomnia
Confusion
Hallucinations
Livedo reticularis
dopamine agonist what to counsel pts/caregivers on
compulsive behaviours
livedo reticularis is caused by?
amantadine
which drug class interacts with warfarin
com ti
example of com ti
entacapone
