Antiparkinson Flashcards
What part of the brain is initially effected by parkinsons/huntingtons and alzheimers disease?
Parkinsons/huntington: basal ganglia–>altered voluntary movement
AD: hippocampal & cortical neurons–> impaired memory formation and cognitive deficit
What is the pathophysiology of Parkinsons? what are the misfolded proteins?
accumulations of alpha-synucelin proteins (misfolded proteins)–>form lewy bodies–>increased production of free radicals–>interfere with neuronal function lead to atrophy/death
Degeneration of D2 neurons in substantia nigra of basal ganglia:–>increased activity of ACh in basal ganglia
- increased inhibition of VA/VL thalamus
- reduced excitatory input to cortex
- diminished execution of motor movement
- overtime will spread to other parts of brain
What are the signs and symptoms of Parkinsons
Bradykinesia
Muscular rigidity
Resting tumor (goes away with voluntary movement)
Postural instability
which drug cause dopamine replacement?
Levodopa
what drug improves bradykinesia and rigidity
Levodopa
adverse effects of taking LDOPA?
LDOPA thoses its therapeutic effect over time (3-4 yrs of therapy) and patient will be less responsive to LDOPA
- dyskinesia
- response fluctuation (randomly loss of effect, or rapid return of muscle rigidity before end of dosing interval
-GI: nausea/vomiting
postural hypotension
how should response fluctuation problem be addressed
“drug holiday” by stop taking drug in order for body to improve response to fluctuation prob
Carbidopa and its effects with LDOPA
it is an inhibitor of DOPA decarboxylase in PERIPHERY
inhibit premature breakdown of LDOPA in periphery–does not cross BBB
Helps increase amt of LDOPA delivered to brain( 10% vs 2%-LDOPA alone)!
WHat are the dopamine receptor agonists agent?
Pramipexole, ropinirole,Apomorphine(less used)
which agent is used for temporary relief as the “rescue treatment” in LDOPA induced dyskinesia
Apomorphine
which agents are used as 1st line or initial therapy for PD
Dopamine receptor agonists: pramipexole, ropinirole, Apomorphine
what are the MAO-B inhibitors? and what do they do
Selegiline, rasagiline; decrease dopamine metabolization
What can cause serotonin syndrome?
MAO-B inhibitors + SSRI/TCA
Entacapone
PERIPHERAL COMT inhibitor
Tolcapone
CENTRAL and PERIPHERAL COMT inhibitor
Which COMT inhibitor is preferred? why?
Entacapone, Tolcapone has risk for acute hepatic toxicity
what is the benefit of COMT inhibitors as adjuncts with LDOPA
helps prolong action of LDOPA diminishing peripheral metabolism
what drug increases dopamine release into CNS?
Amantadine
Amantadine characteristic and side effects
Antiviral agent w/ antiparkinoism properties. Short duration/short lived–short therapeutic effectiveness
SE: livedo reticularis
What are the anticholinergic agents for Parkinsons? what are their benfits?
Benztropine, trihexyphenidyl.
Reduce tremor and rigidity; little effect on bradykinesia
what agents will lower incidence of response fluctuation and dyskinesis that are associated with long term Levodopa use?
Pramipexole, Ropinirole, Apomorphine
D2 receptor agonists
what would you avoid Selegiline with?
SSRI; TCAs to avoid serotonin syndrome
and LDOPA @ high concentration=hypertensive crisis
what improves bradykinesia and rigidity?
LDOPA
what happens with drug interaction with pyridoxine (Vitamin B)
it enhances peripheral conversion of LDOPA–>DOPAMINE in periphery!
