Parkinson's Disease Flashcards
(38 cards)
What is the etiology of PD?
true etiology is unknown; but thought to be caused by:
- Genetic - early onset
- Environmental factors - exposure to pesticides (MPTP) and heavy metals (iron, manganese), rural living and drinking well water
- Substantia nigra has a region that naturally has high levels of oxidative stress because free radicals are generated from dopamine metabolism by monoamine oxidase
What are the two hallmarks pathologic features of PD?
- Severe loss of dopaminergic neurons in the substantia nigra that project to the nigrostriatal pathway
- Presence of Lewy Bodies (neuronal cytoplasmic filamentous aggregates composed of the presynaptic protein α-synuclein)
When dopamine is depleted, what neurotransmitter takes over?
ACh
What is the goal for pharmacologic tx of PD?
Goal - To provide maximum relief of symptoms and maintain independence of movement
- Neuroprotection – no drugs unequivocally proven to be neuroprotective
What are the 3 types of treatment for PD?
- Symptomatic (all PD drugs here)
- Neuroprotective - nothing on the market
- Restorative - nothing on the market
What are the major medications available for the treatment of PD motor symptoms
- Levodopa – dopamine precursor
- Dopamine agonists - Stimulate dopamine receptors
- Monoamine oxidase (MAO) B inhibitors – inhibit dopamine breakdown
- Catechol-O-methyl transferase (COMT) inhibitors
- Anticholinergic agents
- Amantadine
- start low, go slow with all of these drugs
Most effective treatment for PD symptoms; Drug of first choice for bradykinesia; MOA – immediate precursor to dopamine that is able to cross the blood brain barrier (BBB) and be metabolized to dopamine
Levodopa (L-Dopa)
- Administered in combination with a peripheral decarboxylase inhibitor = Carbidopa - stops the L-Dopa from being broken down into dopamine in the periphery (dopamine can’t cross the blood brain barrier)
MOA- Inhibits peripheral conversion of L-dopa to dopamine; Reduces peripheral side effects of dopamine (N/V and orthostatic hypotension) and results in higher CNS concentrations of dopamine; Doesn’t cross BBB; Can decrease L-DOPA dose by about 75%
Carbidopa
Why should people taking carbidopa-levodopa before a meal?
competes with amino acid transporters for absorption
- generally taken 3x per day, before meals
ADRs of this drug:
Early - Nausea/vomiting, Sedation, Postural hypotension, Discoloration urine/sweat, Vivid dreams
Late - Dyskinesia, Impulse control disorder, Sleep attacks, Confusion, Hallucination, Nightmares, Motor complications
L-Dopa
- increased amount of time spent on this drug = increase side effects, with lower effectiveness
What are the motor complications of L-Dopa?
- End of dose “ wearing off” - neuronal storage capacity is lost over time
- Delayed “on” and/or no “on” response (Lack of motor symptom effect or delay to effect; May be an extension of the wearing off phenomenon)
- Freezing
- Dyskinesias
How would you manage freezing with L-Dopa?
- Least amenable to medication alterations/ interventions
1. Increase carbidopa/levodopa dose
2. Add dopamine agonist or MAO-B inhibitor
3. Physiotherapy along with assistive walking devices
How would you manage “wearing off” with L-Dopa?
- Increasing dosing frequency and/or dose
- Initiating CR formulation
- Addition of other PD medication – Dopamine agonist, MOA-B inhibitor, COMT inhibitor
How would you manage dyskinesia with L-dopa?
- this is due to the actual drug, not the disease
1. Smaller doses carbidopa/levodopa
2. Add amantadine
How would you manage delayed “on” and/ or no “on” response with L-dopa?
- Take on empty stomach
- ODT – bypass first pass metabolism
- AVOID CR (if they’re not responding to IR, they won’t respond to CR)
MOA: stimulate postsynaptic dopamine receptors in the corpus striatum directly; Efficacy is thought to be largely through stimulation of D2 receptors
Dopamine agonists
What are the types of dopamine agonists?
- Non-ergot Dopamine Agonists:
- Pramipexole (Mirapex) - tablet
- Ropinirole (Requip) - tablet – smoking decreases Ropinirole levels in body
- Apomorphine (Apokyn) –rescue therapy, subcutaneous injection (highest ADR or nausea/ vomiting)
- Rotigotine (Neupro) - patch - Ergot Dopamine Agonists
- Bromocriptine (Parlodel) - tablet/ capsule = Least effective and carries risk for fatal pulmonary fibrosis, Rarely used
- don’t abruptly stop (withdrawal)
ADRs of this drug:
Nausea, Hallucinations/ delusions, Lower extremity edema, Sedation, Sleep attacks, Impulse control disorders or compulsive behaviors, Confusion, Lightheadedness, Postural hypotension, Vivid dreaming
Dopamine agonist
- = more seen in this drug than L-Dopa
- elderly more susceptible to this
How do you decide to give a pt dopamine agonists vs L-dopa
- Younger aged pos (60-65 yrs) start dopamine agonist first; reserving L-dopa for later in illness
- older pts more likely to experience psychosis
MOA: Irreversibly inhibit MAO-B [over MAO-A] which prolongs dopaminergic activity in the brain by blocking dopamine metabolism; Will provide modest symptomatic benefit as monotherapy;
MAO-B Inhibitors
MAO-B inhibitor; Metabolic pathways of selegiline leads to L-amphetamine and L-methamphetamine
can cause insomnia and jitterines; Lipophilic and enters the BBB rapidly; BID
Selegiline
MOA: reduces the peripheral (entacapone) and central (talcapone) methylation of levodopa; Increases the plasma half life of levodopa (50-100%); Produces more stable plasma levodopa concentrations; Prolongs the therapeutic effect of each dose of levodopa ; Increase “on” time and reduce “off” time by about 1-3 hours
COMT inhibitors
- Helps reduce breakdown of L-Dopa
- helps controls “on” time better than CR
COMT inhibitor:
Very short half life needs to administered with each levodopa dose; Considered one of the 1st line choices for managing motor fluctuations with levodopa
Entacapone
COMT inhibitor:
Inhibits both central and peripheral COMT; Strict liver enzyme monitoring in the first 6 months of therapy ; Informed content signature required ; Dosed TID
Tolcapone
- associated with fatal liver toxicity
