Treatment of Parkinson's Flashcards
types of abnormal movements
tremor chorea athetosis dystonia tics
tremor
rhythmic oscillations in joints
when at rest often assoc. w/ Parkinson’s
chorea
irregular jerkiness, esp at proximal muscles of limbs
athetosis
slow & writhing abnormal movements
dystonia
sustained (abnormal posture)
tics
sudden, coordinated abnormal movements
What are the effects of less DA in Parkinson’s disease?
less DA from Pars Compacta leads to more GLU from sub thalamic nucleus
About Parkinson’s disease
(What is it?) tell me about the disease
(movement disorder)
- Tremors
- Rigidity
- Bradykinesia (slow movements) or akinesia (can’t initiate movement)
- Posture Instability
What does Parkinson’s disease cause?
- degeneration of DA secreting neurons (sub migration PC)
- Imbalance b/w DA & ACh
- from toxin? (MPTP also knocks out same cells)
- Maybe from MAO-B producing a toxin
What initiates the progression of Parkinson’s disease?
- DA (from sub migration) activate receptors that inhibit GABA output (inhibit an inhibitory pathway)
- ACh activates the same area that GABA inhibits. May be a imbalance b/w DA & ACh that’s important
What is MPTP?
Methyl phenyl tetra hydropyridine
- a prodrug to the neurotoxin MPP+, which causes permanent symptoms of Parkinson’s disease
- destroys dopaminergic neurons in the substantia migration in the brain
MPTP hypothesis
manufacturing MPPP turned into MPTP, which allowed a patient to respond well to the Parkinson’s treatment.
he then died due to MPPP being a bad batch!
MPPP
Methyl phenyl proprionoxypiperidine
(DEA has labeled it as schedule I drug in the U.S.)
- heroine like drug (meperidine-like)
- quite addicting
- gives euphoria & peaceful sense
Drugs that may induce PD
Serenace (haloperidol) Stemetil (prochlorperazine) Maxolon (metoclopramide) Neulactil (pericyazine) Risperidal (risperidone)
DA/ACh imbalance in Parkinson’s
dopamine deletion blocks auto inhibition of ACh through muscarinic autoreceptors which lead to excessive ACh release
(higher levels of ACh cause dyskinesia)
drugs used
Levodopa (MOST DRUG USED FOR THIS DISEASE)
- dopamine won’t cross BBB
- L-Dopa crosses BBB then gets converted to DA by dopa decarboxylase
- “usually” reverses all effects of Parkinson’s
* * but some do NOT respond
- “usually” reverses all effects of Parkinson’s
- Up to 98% is converted to DA in periphery
- causes GI distress & arrythmia
- given with a peripheral dopa decarboxylase inhibitor
Tyrosine/dopamine
enzymes in body convert tyrosine into dopamine
hense., tyrosine plays a critical role for the production of dopamine
Side effects of Levodopa w/ Carbidopa
- Nausea/ vomiting
- CV
- Diskinesias
- Depression & Anxiety
- Loss of Efficacy
- End-of-Dose Phenomenon
Nausea/ vomiting
(less frequent w/ decarboxylase inhibitor)
CV
(arrhythmia & postural hypotension)
Diskinesias
(in about 80% of patients)
(include dystopias, myoclonus, tics, tremors)
(usually after 3 months to 10 years on L-Dopa)
Depression & Anxiety
(w/ elderly & w/ decarboxylase inhibitors)
Loss of Efficacy
(due to tolerance)
due to progression of disease
End-of-loss Phenomenon
(due to plasma concentrations)
use sustained release or change timing of drug administration
Drug holidays
removing patient from L-Dopa for days/weeks so that can respond to the drug again
they may now need less of the drug for response
NOT EFFECTIVE IN ALL CASES
Dopamine Agonists
- Bromocryptine/ Pergolide (older, not used) OR
Paramipexole (D3) OR Ropinirole (D2) - Used w/ L-Dopa for synergistic effect or for early treatment in patients that don’t tolerate L-Dopa well
Side effects of Dopamine Agonists
GI–> Nausea/ vomiting
CV–> Postural hypotension
CNS–> Confusion, hallucinations
Rasagiline & Selegiline
(MAO-B inhibitor)
- Used w/ levodopa
Entacapone & Tolcapone
(COMT inhibitors)
Benztropine
(antimuscarinic)
- Balance ACh effects that’s strong in Parkinson’s
(used w/ L-Dopa)
(can reduce tremor & rigidity)
Amantidine
(anti-viral w/ unknown mechanism)
- used w/ L-Dopa or anti-cholinergics
(helps reduce symptoms w/ mild side effects)
Treatment
May start w/ selegiline or amantidine, then L-Dopa
Newest Treatments
Mirapex (pramipexole), Requip (ropinirole)
Tasmar (tolcapone), Comtan (entacapone)
Mirapex (pramipexole), Requip (ropinirole)
- Non-ergot DA agonists (type 2 autoreceptors)
- Less DA release > less MAO free radicals > less Parkinson’s - like damage
- Side effects:
orthostatic hypotension, hallucinations, diskinesias, dry mouth
Tasmar (tolcapone), Comtan (entacapone)
COMT inhibitors
- Side effects:
liver damage, sleep disturbances, hallucinations, dizziness/hypotension
