Chapter 24 - Drugs for Parkinson's Disease Flashcards
What is Parkinson’s Disease?
a neurodegenerative disorder of the extrapyramidal system associated with the disruption of neurotransmission
PD is characterized by __________ and __________
dyskinesia and akinesia
PD causes an imbalance between ___________ and _____ due to the degeneration of neurons
dopamine and ACh
Why does inadequate dopamine affect neurons?
no dopamine means ACh causes excessive stimulation of neurons that release GABA
What causes motor symptoms of PD?
overactiivity of GABA neurons
What are symptoms dyskinesias?
-tremor at rest
-rigidity
-postural instability
-bradykinesia (slowed movement)
What are non-motor symptoms of PD?
-autonomic disturbances
-depression
-psychosis
-dementia
What is the therapeutic goal of PD?
improve patient’s ability to carry out ADLs
Is there a treatment that reverses neuronal degeneration?
no
What are the two drug categories for PD?
-dopaminergic agents
-anticholinergic agents
What are the most commonly used drugs for PD?
dopaminergic agents
What do dopaminergic agents do?
promote activation of dopamine receptors
What is the prototype dopaminergic agent?
levodopa
What do anticholinergic agents do?
prevent activation of cholinergic receptors
What is the prototype anticholinergic for PD?
Benztropine
What drug is used for mild symptoms of PD?
monoamine oxidase-B (MAO-B) inhibitor like SELEGILINE or RASAGILINE
What drugs are used for more severe PD symptoms?
Levodopa combined with carbidopa or benserazide
What is a long-term risk of Levodopa?
disabling dyskinesias
“OFF” times for motor fluctuations can be reduced with…
dopamine agonists, COMT inhibitors, MAO-B inhibitors
Are there drugs that provide neuroprotection for PD?
no
___________ is only given in combination with carbidopa or benserazide
Levodopa
How does Levodopa act?
-increases dopamine synthesis in the brain to restore the balance between dopamine and ACh
What is Levodopa?
the biological precursor of dopamine
What breaks levodopa down into dopamine?
enzyme dopa-decarboxylase (DDA)
How does levodopa enter the brain?
via an active transport system
What enhances the activity of decarboxylase?
pyridoxine (Vitamin B6)
Levodopa is useful for PD for ___ years before losing efficacy after 5 years
2
How is levodopa administered?
orally
What are food restrictions of Levodopa?
-food delays absorption
What kind of foods reduce therapeutic effects of levodopa?
high-protein foods
How can you minimize the wearing off effect of levodopa?
-shorten dosing interval
-give drug that prolongs half life
-give a direct-acting dopamine agonist
What are the adverse effects of Levodopa?
-N&V
-orthostatic hypotension
-palpitations
-agitation
-anxiety
-psychosis
-dyskinesias
-vivid dreams
-nightmares
-impulsivity
-memory impairment
-darkened sweat and urine
-activates malignant melanoma (SKIN ASSESSMENTS!!)
What does Levodopa interact with?
-1st gen. antipsychotics
-MAOIs (htn crisis)
-anticholinergics
How do 1st gen antipsychotics interact with levodopa?
block DA receptors and decrease therapeutic effects
How do MAOIs interact with levodopa?
htn crisis
How do anticholinergic drugs interact with levodopa?
contribute to dyskinesias, cause enhanced response to levodopa
Do carbidopa and benserazide have therapeutic effects of their own?
no
What do carbidopa and benserazide do?
inhibit decarboxylation of levodopa in intestine (helps inhibit conversion of levodopa into DA allowing it to be available in the CNS), thus decreasing the needed dosage by 75%
Carbidopa reduces what adverse effects of levodopa?
-CV
-N&V
Dopamine agonists are _____-line drugs for PD
first
How do dopamine agonists act?
directly activate dopamine receptors
How do dopamine agonists compare to Levodopa?
-are less effective
-don’t depend on enzymatic conversion to be ACTIVE
-lower incidence of response failure
-less likely to cause dyskinesia
What are the two types of dopamine agonists?
-derivatives of ergot
-non-ergot derivatives
What kind of dopamine agonist is Pramipexole?
non-ergot
How does pramipexole act?
D2 (some D3) receptor agonist
When is pramipexole used?
-early PD
-with levodopa in advancing PD
What are the adverse effects of pramipexole used alone?
-nausea
-dizziness
-somnolence
-insomnia
-constipation
-weakness
-hallucinations
What are the adverse effects of pramipexole used in combo?
-orthostatic hypotension
-dyskinesias
-hallucinations
What are rare adverse effects of pramipexole?
-impulse control disorders (gambling, shopping, eating)
-sleep attacks
What kind of dopamine agonist is rotigotine?
non-ergot
How does rotigotine act?
D2 and D3 receptor agonist, some action on other dopamine, alpha, and serotonin receptors
When is rotigotine used?
-early in tmt
-with or without levodopa
What are side effects of rotigotine?
-N&V
-dizziness
-somnolence
-site reactions
How is rotigotine applied?
patch - do not cut to get lower dose
What is a limitation of Bromocriptine?
poorly tolerated
What kind of dopamine agonist is Bromocriptine?
ergot derivative
How does Bromocriptine act?
direct dopamine agonist (activates dopamine receptors)
How is Bromocriptine used?
-early PD
-in combo with levodopa for advance PD
What are the adverse effects of Bromocriptine?
-nausea
-confusion
-nightmares
-hallucinations
-delusions
-retroperitoneal fibrosis
-pulmonary infiltrates
-Raynaud like phenomenon
-valvular heart disease
How do COMT inhibitors act?
inhibit metabolism of levodopa in the periphery by inhibiting the COMT enzyme
What are the direct therapeutic effects of COMTIs?
none. lol.
What category is Entacapone?
COMT inhibitor
Entacapone is combined with levodopa to:
-prolong the time levodopa is available in the brain
-inhibit levodopa metabolism in the intestine and periphery
What are the adverse effects of Entacapone?
-dyskinesias
-orthostatic hypotension
-nausea
-hallucinations
-sleep disturbances
-impulse control disorders
-vomiting
-diarrhea
-constipation
-yellow-orange discolouration of urine
What kind of drug is Selegiline?
a MAO-B inhibitor
Selegiline causes…
modest improvement of motor function
Benefits of Selegiline decline dramatically in ___ to ___ months
12-24 months
When is selegiline used?
early in PD progression
High doses of selegiline can interact with ___________
tyramine
How does amantadine act?
-inhibits DA uptake and stimulates DA release
-blocks cholinergic receptors
-blocks glutamate receptors
Is amantadine a first line agent?
no
How long is the amantadine response?
starts in 2-3 days, diminishes in 3-6 months
What is amantadine used for?
dyskinesias caused by levodopa
What are the adverse effects of amantadine?
-confusion
-anxiety
-blurred vision
-urinary retention
-dry mouth
-constipation
-livedo reticularis
Livedo reticularis
a condition characterized by mottle discolouration of the skin
How do centrally acting anticholinergics act?
block muscarinic receptors in the striatum
What are come centrally acting anticholinergic drugs?
-Benztropine
-Trihexyphenidyl
-Procyclidine
How do centrally acting anticholinergic drugs compare to levodopa and dopamine agonists?
-less effective
-better tolerated
Which drugs are used for younger patients with mild symptoms?
centrally acting anticholinergic drugs
centrally acting anticholinergic drugs should be avoided in…
elderly patients
