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
Rasagiline (Azilect)
1. How is it different from Selegiline?
- More potent than Selegiline but all other properties are the same
Adverse effects of all MAO-B’s
5
- Insomnia
- Jitteriness
- Dyskinesias
- Orthostatic hypotension
- May enhance levadopa adverse effects
MAO-B Inhibitors
Use caution with what diseases?
7
Contraindications? 3
- Impaired liver function
- CV disease
- Cerebral vascular disease
- Seizure disorder
- Hyperthyroidism
- Diabetes
- Psychiatric disorders
Concurrent use with
- TCA’s,
- SSRI’s
- Demerol
When should we prescribe Selegiline?
5mg with breakfast and 5 mg with lunch
Should not take later in day due to insomnia
How should we prescribe Rasagiline?
2
- 1mg QD when used alone
2. 0.5mg QD when used with Sinemet
The two reasons we use MOAB inhibitors?
2
- Often 1st line in patients with mild disease to slow progression and delay need for levadopa
Has neuroprotection - Used as adjunctive therapy to decrease “wearing off”.
Bromocriptine (Parlodel) and Pergolide (Permax)
What should we remeber about this?
DONT USE THESE
Older agents
Ergo derivatives- fungus was a problem because it likes to eat heart valves
Pramipexole (Mirapex) and Ropirinole (Requip)
- MOA?
- What is it effective at doing?
- What may it delay?
- Who could this be first line in?
- Stimulate dopamine receptors in the substantia nigra
(wake em up so they can take up more dopamine) - Effective in delaying motor complications during the first 1-2 years of treatment
- May delay the need for levadopa/carbidopa
- Moderate symptoms in younger patient may be treated with dopamine agonists as first line.
Dopamine Agonists
Adverse affects?
7
- Drowsiness and sleepiness
- Nausea and constipation
- Headache
- Orthostatic hypotension
- Nasal congestion
- Nightmares, hallucinations, psychosis
- dyskinesias
Dopamine Agonists
Contraindications?
4
- Patients with psychotic illness
- Patients with recent MI
- Patients with PUD
- Ergo derived best avoided in patients with PVD
Apomorphine (Apokyn)
- used to treat what symptoms?
- Administered how?
- Why is it not prescribed often?
- What do you after to give it with?
- To treat acute episodes of “hypermobility” or “freezing”
- Given SQ
- Very expensive
- Cause profound nausea, must be given with antiemetic
- –No Zofran or Kytril can be used with this drug, must use another antiemetic- block dopamine
Apokyn (Apomorphine)
Adverse effects?
5
- Nausea and vomiting
- Yawning
- Dyskinesias
- Sedation
- Dizziness
COMT inhibitors:
Entacapone (Comtan), Tolcapone (Tasmar)
MOA? 2
- selectively inhibit the enzyme COMT- metabolizes levadopa to a unwanted degradation product
- Increases concentration of existing dopamine in the brain by inhibiting its breakdown.
Diminishes peripheral metabolism.
COMT inhibitors: Entacapone (Comtan), Tolcapone (Tasmar) 1. What does it improve? 2. What does it reduce the need for? 3. Who is it only indicated in? 4. What do we need to decrease?
- Improve motor fluctuations related to wearing-off and improve on time.
- Reduce need for levadopa/carbidopa
- Only indicated in patients taking levadopa/carbidopa
- Often need to decrease levadopa/carbidopa
COMT Inhibitors
Adverse affects?
6
- Involuntary muscle movements
- Mental confusion and hallucinations
- Cramps, nausea and diarrhea
- Insomnia
- Headache
- Urine discoloration
try for the first few weeks then take it off. Pts notice these SE immediately and they are very common
Amantadine
- Useful when?
- What side effects does it help? 2
- Used as what kind of therapy?
- Useful for early mild symptoms
- Benefits may be short-lived but does favorably influence
-akinesia,
-rigidity.
Not really effective with tremor.
Used as adjunct therapy
Amantadine
adverse affects? 5
Caution with who?
- Sedation
- Vivid dreams
- Dry mouth
- Depression
- Hallucinations
Caution with renal dysfunction
Anticholinergic
Acetylcholine-blocking Drugs:
Trihexyphenidyl (Artane),Benztropine (Cogentin)
1. Used primarily for what?
2. Also helps with what?
3. No effect on what?
4. If patient does not respond to one drug what should we do?
- Used primarily for tremor
- Helps with rigidity
- No effect on akinesias
- If patient does not respond to one drug, a trail with another is warranted
Anticholinergic
Acetylcholine-blocking Drugs:
Trihexyphenidyl (Artane),Benztropine (Cogentin)
MOA?
blocks inhibition. less likely to block the good things that dopamine is trying to do
Acetylcholine-blocking Drugs
Adverse affects CNS? 5
Adverse affects systemic? 8
- Drowsiness
- Mental slowness
- Restlessness
- Confusion
- Hallucination
- Dry mouth
- Blurred vision
- Mydriasis
- Urinary retention
- N/V
- Constipation
- Palpitations, arrhythmias
- IOP
Acetylcholine-blocking Drugs
Contraindications?
3
- BPH
- Obstructive GI disease
- Angle closure glaucoma
