Movemnt Disorder Pharm Flashcards
Parkinsons treatment:
- What is the problem we are trying to treat?
- So what do we attempt to do with treatment?
- Because of this what else do we need to manage?
- Normally high concentration of dopamine in the basal ganglia is reduced in Parkinsonism.
- Pharmacological attempts to restore dopaminergic activity in the brain is the goal of treatment.
- Treatment goals also include the management of side effects of dopaminergic therapy.
Parkinson’s Treatment
Gold standard?
Levodopa/Carbidopa (Sinemet)
Classes of parkinson’s treatment?
7
- Levodopa/Carbidopa (Sinemet)
- Monoamine oxidase inhibitors
- Dopamine agonists
- Catechol-o-methyltransferase inhibitors
- Amantadine (anti viral)
- Acetylcholine-blocking agents
- N-Methyl-D-aspartate (NMDA) receptor inhibitors
What are the Monoamine oxidase inhibitors?
2
- Selegiline (Eldepyrl)- mildly symptomatic pt whos younger
2. Rasagiline (Azilect)
What are the Dopamine agonists?
4
- Ropinirole (Requip)
- Pramipexole (Mirapex)
- Pergolide (Permax)
- Bromocriptine (Parlodel)
What is the Catechol-o-methyltransferase inhibitors? 1
Entacapone (Comtan)
What is the Acetylcholine-blocking agents?
3
- Benzotrpine mesylate (Cogentin)
- Biperiden (Akineton)
- Trihexyphenidyl (Artane)
What is the N-Methyl-D-aspartate (NMDA) receptor inhibitors? 1
Apomorphine (Apokyn)
What would you give to a young pt with mild parkinsons?
Selegaline (MAOB)
What are the disadvantages of levodopa/carbidopa?
Effectiveness substantially decreases after 3rd year of treatment and may return to pretreatment levels in 6-7 years.
What does it partially or completely relieve?
3
Completely or partially relieves
- akinsesia,
- rigidity and
- tremor
Why are Levadopa/Carbidopa (Sinemet) prescribed together?
2
- levadopa is precursor to dopamine. Penetrates the brain and decarboxylated to dopamine.
- carbidopa keeps it from being metabolized in the periphery
Is levadopa/carbadopa neuroprotective?
No.
The concern that prolonged use of levodopa may directly hasten the degeneration of dopamine neurons in the substantia nigra by promoting the generation of free radicals and oxidative stress is the basis for delaying the use of levodopa in the treatment of PD
What is carbadopa?
a decarboxylase inhibitor, peripheral metabolism is reduced and plasma levels of levadopa are higher and more is available to enter the brain.
Adverse physical affects of Sinemet?
5
(most common)
- Low blood pressure
- Arrhythmia
- GI effects – more so with levadopa alone
- Hair loss
- Dyskinesias (80%)
Adverse Psychiatric/mental affects of Sinemet?
4
- Confusion
- Anxiety
- Vivid dreams
- Hallucinations
Prevention of these adverse effects of Sinemet?
2
- Try giving smaller doses more frequently
2. Reduce or stop evening dose if severe psychiatric effects occur
- What is the wearing off effect?
2. Usually how many years of treatment?
- Initially may be bradykinesia or tremor in am before next dose (motor fluctuations) and on and off effects.
- May occur within 4-6 years of treatment
Prevention of wearing off effect or on and off affect?
3
- Multiple small doses on empty stomach
- Liquid form
- Controlled release formulation
Levadopa/Carbidopa (Sinemet)
Contraindications? 4
Precautions?
2
- Concurrent use with MAOI’s
- Psychotic patients
- Angle-closure glaucoma
- Hx of melanoma (dopamine driven)
- Cardiac disease
- PUD
- Whats the on-off affect?
- How fast can these be switched on and off?
- The transition may follow such symptoms as what? 3
fluctuations become extreme, a phenomenon known as the on-off effect , which consists of unpredictable, alternating periods of dyskinesia and immobility.
- Sometimes the symptoms switch back in forth within minutes or even seconds.
- intense anxiety,
- sweating
- rapid heartbeats
Reasons for the Wearing-Off Effect: Some theories suggested for these effects are the following?
4
- The disease progresses beyond the ability of levodopa to control it.
- Some patients become tolerant to prolonged exposure to dopamine and, at the same time, the disease is progressing.
- The brain’s own dopamine neurons become incapable of storing dopamine and when the levodopa wears off, little or no natural dopamine remains.
- Levodopa itself accelerates the disease by producing oxygen free radicals, unstable particles that increase injuries to the brain and dopamine degradation.
Preventing the Wearing-Off Effect?
3
- Maintain as consistent a level of dopamine as possible.
- Unfortunately, levodopa is poorly absorbed and may remain in the stomach a long time.
- Thus, the addition of dopamine agonists, MAOB’s and COMT inhibitors to the regimen.
Selegiline (Eldepryl, Zelapar)
- MOA?
- What does it enhance?
- Neuroprotective? Why?
- BBB properties?
- Stops the breakdown of dopamine
- Enhances peak levadopa levels
- May have neuroprotective properties by reducing oxidative metabolism of dopamine
- Lipophilic and penetrates blood-brain barrier rapidly