Parkinson Disease Drugs Flashcards
What are the 3 ways a nuerotrasmitter is removed from the synaptic cleft?
- reuptake
- enzymatic degradation
- diffusion
What types of drugs cannot cross the blood brain barrier?
protein bound and highly ionized
What types of drugs can cross the blood brain barrier?
- lipid soluble
- drugs that use transport systems
Monoamine neurotransmitters of the CNS include?
- dopamine
- epi
- NE
- serotonin
Opioid peptides of the CNS include?
- dynorphins
- endorphins
- enkephalins
What is the term for a decreased response that occurs with prolonged drug use?
tolerance
What are the cardinal symptoms of Parkinson Disease?
- resting tremor
- rigidity
- postural instability
- bradykinesia
What is the cause of the motor symptoms in parkinsons disease?
loss of dopamine releasing neurons in the substantia nigra resulting in excessive stimulation of acetylcholine
What is dyskinesia?
disorder of movement
What is the term for slowed body movements?
bradykinesia
What is the term for complete loss of movement?
akinesia
In persons with PD, what two neurotransmitters are out of balance?
- dopamine
- acetylcholine
What is dopamine’s MOA?
GABA inhibition
What two classes of drugs are used to treat PD?
- anticholinergic agents
- dopaminergic agents
What are the 4 mechanisms of action for the dopaminergic drugs?
- direct dopamine receptor activation
- monoamine oxidase B inhibitors
- increase release of dopamine
- prevent dopamine reuptake
What is levodopa’s MOA?
- direct dopamine receptor agonist
- enters into dopaminergic neuron in the striatum of the brain, where it is converted to dopamine
What is the drug of choice for the initial treatment of mild PD symptoms?
MOA-B inhibitor
Rasagiline is what type of drug?
MOA-B inhibitor
Selegiline is what type of drug?
MOA-B inhibitor
What does monoamine oxidase-B do?
breaks down dopamine
What is the drug of choice for the initial treatment of severe PD symptoms?
Levodopa/carbidopa or dopamine agonist
What is the only drug recommended for levodopa induced diskinesias?
amantadine
What is Entacapones MOA?
inhibits breakdown of levodopa by COMT
Long-term use of these drugs are associated with “off times” or loss of symptom relief and drug-induced diskinesia
levodopa and dopamine agonists
Pramipexole is what type of drug?
nonergot dopamine agonist
Ropinirole is what type of drug?
nonergot dopamine agonist
Rotigotine is what type of drug?
nonergot dopamine agonist
Bromocriptine is what type of drug?
ergot dopamine agonist
What is Amantadine MOA?
promotes release of dopamine and may block reuptake
How long does it take for full PD symptom relieve with levodopa use?
months
Gradual loss of symptom relief or “wearing off” with levodopa is due to what?
subtherapeutic plasma levels
How to minimize wearing off with levodopa?
- shorten dosing interval
- add drug that prolongs half-life (entacapone)
- add direct acting dopamine agonist
Abrupt loss of symptom relief or “on-off” phenomenon with levodopa is due to what?
thought to reflect disease progression and not tolerance to the drug
Drugs that can help reduce on-off phenomenon with levodopa?
- entacapone
- rasagiline
GI considerations for levodopa use?
- food delays absorption by delaying gastric emptying
- high protein foods reduce therapeutic effects
How is levodopa metabolized?
- decarboxylase enzymes convert levodopa to dopamine in the periphery and brain
True or False: Dopamine can not cross the BBB?
true
Pyridoxone enhances the effects of which enzyme?
decarboxylase
What are the adverse effects of levodopa?
- N/V
- Dyskinesias
- postural hypotension
- arrhythmias
- psychosis
- CNS effects
- dark sweat or urine
What psychosis symptoms present with levodopa?
- hallucinations
- vivid dreams/nightmares
- paranoid
How to reduce the pyschosis AE of levodopa?
reduce dose
Treatment of levodopa induced psychosis?
clozapine and quetiapine
CNS side effects of levodopa?
- anxiety
- agitation
- memory loss
- cognitive impairment
Hypertensive crisis can occur with concurrent use of levodopa with?
MAOi
Which drug type are the first choice of treatment for mild to moderate PD?
dopamine agonist
Apomorphine is what type of drug?
nonergot dopamine agonist
cabergoline is what type of drug?
ergot dopamine agonist
Drugs for Parkinson Disease?
- levodopa
- carbidopa
- pramipexole
- entacapone
- selegiline
- amantadine
- benztropine
Pramipexole is used to treat what?
- PD
- mod-severe restless leg syndrome
- highly selective for dopamine 2 and D3 receptors
Ropirinole is used to treat what?
- PD
- restless leg syndrome
Rotigotine is used to treat what?
- PD
- mod-severe restless leg syndrome
What is apomorphine used to treat?
- hypomobility during off episodes in advance PD
- NOT for routine treatment of PD
- given by injection
What type of drug is entacapone and tolcapone?
Catechol-O-Methyltransferase Inhibitors (COMTi)
What is entacapone used to treat?
PD by inhibiting the metabolism of levodopa
Entacapone adverse effects?
- vomitting
- yellow-orange urine
Talcapone adverse effects?
- liver failure
- yellow-orange urine
Selegiline is what type of drug?
- selective, irreversible MAO-B inhibitor
- prevents destruction of dopamine
What is Selegiline used to treat?
PD
What can occur when you combine selegiline with an SSRI (prozac)?
fatal serotonin syndrome
SSRI’s should be withdrawn how long before giving selegiline?
at least 5 weeks
Rasagiline is what type of drug?
- selective, irreversible MAO-B inhibitor
- prevents destruction of dopamine
Why does selegiline cause insomnia?
it is metabolized into l-amphetamine and l-methamphetamine
What foods should be avoided when taking selegiline and rasagiline?
tyramine rich foods, cause hypertensive crisis
Amantadine MOA?
- inhibition of dopamine uptake
- stimulation of dopamine release
- anticholinergic
- NMDA antagonist
- glutamate receptor blocker
What is tested for in a BMP?
a. Bicarb
b. BUN
c. Creatinine
d. Calcium
e. Chloride
f. Glucose
g. Potassium
h. Sodium
What is tested for in a CMP?
a. Albumin
b. Alkaline phosphatase (ALP)
c. ALT
d. AST
e. Bicarb
f. Bilirubin
g. BUN
h. Creatinine
i. Calcium
j. Chloride
k. Glucose
l. Potassium
m. Sodium
n. Total protein
