Parkinson's Disease Flashcards
Clinical signs of PD (TRAP pneumonic)
- Tremor at rest
- Rigidity
- Akinesia or bradykinesia
- Postural/gait instability
Neurotransmitters involved in PD
- Dopamine*** (deficiency)
- NE
- ACh
- Glutamate
- Seratonin
“1st Line PD drugs”
- Levodopa plus carbidopa +/- entacopone
- Dopamine agonists
“2nd Line PD drugs”
- Anticholinergics
- Selective MOA B inhibitors
- NMDA antagonists
Levodopa Products
- Carbidopa/Levodopa
- Carbidopa/Levodopa/Entacapone
Levodopa MOA
Travels to BBB where it gets decarboxylated to dopamine
Carbidopa MOA
- blocks conversion of levo to dopamine before BBB
- *Minimize N/V, orthostatic hypoTN ass with levo
Entacapone
-Prolong action of levo by inhibiting O-methylation
Anticholinergics
Trihexyphenidyl and Benztropine
Anticholinergics MOA
Dopamine depletion in PD = state of cholinergic sensitivity, cholinergic drugs excite and anticholinergic drugs improve parkinsonian symptoms
Clinical indications of anticholinergics
Early: mild tremor
Later: enhance the effects of levodopa, may help with drooling but ADRs frequently limit widespread application
Anticholinergics pearl
Both can be used to treat drug-induced EPS
NMDA Antagonists
Amantadine
NMDA MOA
Increase dopamine release, decrease dopamine reuptake, stimulate dopamine receptors; interferes with excessive glutamate neurotransmission
Clinical indications of NMDA Antagonists
Early: limited data
Later: *adjunct tx, usually in pts with levodopa-induced dyskinesia)
Less effective after 1 year of use
NMDA Antag Interactions
Amantadine + anticholinergics/ETOH –> additive adverse effects on mental function
NMDA Antag ADRs
Low-dose: well tolerated
High-dose: sedation/confusion, anticholinergic ADRs, LIVEDO RETICULARIS, sudden withdrawal may cause exacerbation of parkinsonian symptoms or NMS
Adenosine A2A Rec Antag
Istradefylline
Clinical indications of Adenosine A2A Rec Antag
Adjunct to carbidopa/levodopa in adults with PD who experience “off” episodes
Adenosine A2A Rec Antag pearls
Pts who smoke over 20 ciggies/day need higher dose
Do NOT use in pts with major psychotic disorder
Most common ADR of Adenosine A2A Rec Antag
Dyskinesia
Levodopa Pearls
- Most effective drug for sx tx (akinetic sx > tremor/rigidity»_space; postural instability)
- “on” time 5-6 hrs, 5-6 doses needed/day
- new pts- take with snack
- advanced pts: take on empty stomach
Carbidopa Pearls
No activity on its own
Entacapone Pearls
- No activity on its own
- When added, levo dose needs to be decreased
- May cause orange urine
Levo dosing/admin
- ER cap–> swallow whole or sprinkle on applesauce
- ER used once IR tolerated
- No response >1000 mg/day, probs not PD
Levodopa Product Pk
- Absorption issues: high protein, iron foods
- Block metabolism: MOAI (HTN crisis)
Levodopa Product Pd
- Block levo effects–> anti-HTN meds
- Old antipsychotics/old nausea meds–> dopamine receptor blockade
Levodopa Products ADRs
- N/V, anorexia
- **Orthostatics–> common w initiation and increasing dose; no alpha-antagonists (BPH meds, cavedilol)
- CNS–> vivid dreams, hallucinations, delusion, confusion (with chronic therapy or dose escalation)**
Levodopa “special” ADRs
- “On-off” fluctuations- >5 yr therapy
- Wearing off syndrome- end of dose effect <4hr following dose
- Neurotox?
- Inhalation levo- cough, URI, sputum discoloration
Dopamine Receptor Agonists (ergot derivates)
- Bromocriptine
- **Minimal use d/t ADRs
Dopamine Receptor Agonists (non-ergot derivates)
- Ropinirole
- Pramipexole
- Rotigotine
- Apomorphine
- **must do 4 week taper
Dopamine Receptor Agonist MOA
Stimulate dopamine activity in striatum and substantia nigra
Dopamine Receptor Agonist indications (oral/transdermal)
- Alt 1st line or add on to levo
- **Pramipexole, ropinirole, rotigotine FDA approved for RLS
Dopamine Receptor Agonist Indications (SQ/SL)
- Tx of “off” episodes
- Take with trimethobenzamide** for N/V
- **Seratonin receptor antagonist (ondansetron) CI b/c hypotension with LOC
Dopamine Receptor Agonist ADRs (pramipexole, ropirinole, rotigotine)
- Nausea
- Somnolence–> falling asleep when driving
- Impulse control
MAOI-B
- Irreversible–> selegiline, rasagiline
- Reversible–> safinamide
MAOI-B MOA
-MAOI-B breaks down dopamine–> drug blocks this in striatum
MAOI-B indications
- Early dz–> initial therapy to improve sx but **moderately effective (rasagiline)
- Late sz–> **adjunctive mgmt when levo efficacy deteriorating
MAOI-B ADRs
- Nausea/HA
- Orthostatics
- Confusion (elderly)
- **HTN crisis + tyramine rich foods or levo–> very low risk at usual doses
