ic16 parkinsons disease phx management Flashcards
what is mainstay tx for PD and what is it useful/ not useful for
LEVODOPA
(dopamine does not cross BBB, only L-DOPA)
management of bradykinesia and rigidity
less effective for speech, postural reflex, gait disturbances
PK levodopa (absorption)
absorbed in proximal small intestine
crosses BBB by an active saturable carrier system for large neutral amino acids
[COUNSELLING POINT] + what lowers the absorption of levodopa
decreased absorption
with high fat or high protein meals
take drug on an empty stomach
BA of levodopa (and combination products)
33% mono
75% with benserazide and carbidopa
PK of DCI?
dopa decarboxylase inhibitors
DO NOT readily cross BBB
adverse effects of levodopa
N/V, postural hypotension
CNS: drowsiness, sudden sleep onset, hallucinations, psychosis
dyskinesia (3-5 years of initiation)
motor complications of levodopa
associated with disease progression DESPITE optimal dosing therapy of levodopa.
on-off phenomenon
wearing off phenomenon
- effect wanes off before end of dosing interval = shortened ON time = parkinsonism symptoms appear
dykinesia of levodopa?
involuntary, uncontrollable,
twitching
dystonia
“choreatic dyskinesia”
despite peak dose (cmax) of levodopa
management of motor complications of levodopa
1) adjust levodopa dose = increase dose.
2) change dosing frequency = increase dosing frequency
3) explore dosage forms
4) adjunctive agents: dopamine agonists, MAO-B, COMTi.
different dosage forms for levodopa and how to dose adjust from IR formulation
SUSTAINED RELEASE
- release over 4-6 hours
IR -> CR: increase dose by 25-50%
CR -> IR: decrease dose
use of SR dosage forms
useful for decreased stiffness on waking.
ie when symptoms reappear in the moring or during the night when the dose wane off
drug interactions with levodopa
1) pyridoxine/vitamin b6 (high dose/high potency vit b complex)
- cofactor for dopa decarboxylase
2) iron, protein (food, protein powder)
- affect absorption = space out administration
3) dopamine antagonists
- metoclopramide, prochlorperazine
- FGA
- risperidone?
what antiemetic of choice in PD?
DOMPERIDONE
- peripherally acting
class and examples of dopamine agonists
ergot derivatives
- bromocrtptine
- pergolide
- cabergoline
non-ergot derivatives
- pramipexole
- ropinirole
- rotigotine (transdermal)
- apomorphine (SQ)
moa of dopamine agonist
act on D2 receptors in the basal ganglia
PK of dopamine agonists
ergot derived: lower F due to extensive first-pass metabolism
t1/2 and DOA longer than levodopa
PK of ropinirole (M)
liver metabolism mainly - caution in hepatic impairment
PK of pramipexole (M)
excreted largely unchanged in urine
can be used in hepatic impairment?
caution w/ renal impairments
side effect of dopamine agonists
1) DOPAMINERGIC
peripheral:
N/V, orthostatic hypotension, leg oedema
central:
hallucinations (usually visual > auditory)
somnolence, day time sleepiness
compulsive behaviours: gambling, shopping, eating, hypersexuality
2) NON-DOPAMINERGIC (lower risk w non-ergot)
- fibrosis = pulmonary, pericardiac, retro-peritoneal (possible to partially reverse after withdrawal)
- valvular heart disease
when should dopamine agonists be used
used in young onset PD patients to maximise tx and delay onset of levodopa induced motor complications
* can also be used to manage the motor complications
monotherapy in young onset
adjunct to levodopa in moderate to severe PD
what are the MAOi (and the dosing)
selegiline, rasagiline
irreversible MAO-B inhibitors
selegiline 5mg OM to BD
metabolised to amphetamines = no effect on MAO-B
rasagiline 0.5-2mg OD
drug interactions with MAO-B I
SNRI, SSRI, TCA
pethidine, tramadol (opioids)
linezolid
DMP
dopamine
sympathomimetic: pseudoephedrine, phenylephrine
another MAOI
counselling for MAOI
AVOID tyramine rich foods eg aged cheese, craft beer, fermented food…
place in therapy of MAO in PD
monotherapy in early stages
can also be used as adjunct in late stages
most commonly used in early stages of young onset PD
place in therapy of COMT i
only used as adjunct to levodopa,
otherwise not effective
entacapone moa
selective reversible inhibitor of COMT
how to take Entacapone
take at the same time as levodopa
drug interactions with entacapone
iron, calcium
non-selective MAO and MAO-A selective inhibitors
cathecolamine drugs
warfarin = may enhance anticoagulation effect
cathecolamine drugs: dobutamine, dopamine, epinephrine, & isoproterenol
SE of entacapone
diarrhoea
urinary discolouration (ORANGE)
WITH LEVODOPA
possible dyskinesia on initiation (lower levodopa dose)
possible potentiation of dopaminergic effects = orthostatic hypotension, N/V
caution entacapone
HEPATIC IMPAIRMENT
but no need to monitor LTs
place in therapy of anticholinergics? examples of drugs
used primarily to control tremors
benztropine and trihexyphenidyl
NMDA antagonists example, used and MOA
AMANTADINE
inhibits NMDA mediated excitotoxicity due to glutamate = dyskinesia (levodopa induced)
possibly used to manage dyskinesia with increased levodopa dosing/ advanced PD where dyskinesia is random
MOA of amantadine
dopamine agonist
NMDA receptor agonist
increased released of stored dopamine
inhibit presynaptic uptake of catecholamines (ML)
NMDA antaognist
anticholinergic
upregulation of D2 receptors (WPS)
adr of amantadine
livedo reticularis
n/v, insomnia, confusion, hallucination
place in therapy of amantadine
used as an adjunctive agent AND
to manage levodopa induced dyskinesia
