Neurodegenerative Flashcards
Parkinson’s Disease is a neurodegenerative disorder of the extrapyramidal system associated with neurotransmission of the balance of ____ and ____ in the striatum
dopamine and acetylcholine (ACh)
Pramipexole (Mirapex)
Mechanism of action
Dopamine agonist
Levodopa/carbidopa (Dopar) (Sinemet)
Mechanism of action
Dopamine precursor
Entacapone (Comtan)
Mechanism of action
Blocks COMT (enzyme that breaks down L-Dopa)
What is the most effective drug for Parkinson’s and what is the biggest downside of it?
Levodopa is most effective, but long-term use carries a higher risk for disabling dyskinesias
What is levodopa given in combination with?
Carbidopa
What is an important food-drug interaction for Levodopa?
Neutral amino acids compete with levodopa for intestinal absorption and for transport across the blood-brain barrier. High protein foods will reduce therapeutic effects
What does carbidopa reduce the incidence of?
-Adverse cardiac effects
-Nausea/vomiting
Levodopa
Adverse effects
-Orthostatic hypotension
-Dyskinesias
-Psychosis
-Nausea/vomiting
-Sudden “off phenomenon”
What helps with the “off phenomenon” in with Levodopa?
Can be reduced with dopamine agonists, COMT inhibitors
Levodopa/carbidopa drug interactions
First generation antipsychotics
What does carbidopa do?
Increases available levodopa in the CNS and allows for 75% decrease in levodopa dosage, therefore it reduces cardiovascular and GI adverse effects
How long does it take for Parkinson’s drugs to take effect?
Up to a month
Pramipexole (Mirapex)
Adverse effects
-Nausea
-Dizziness
-Daytime somnolence
-Rare instances of “sleep attacks”
What is the pathophysiology of Alzheimer’s?
Degeneration of neurons
-Early in the hippocampus
-Later in the cerebral cortex
Reduced cholinergic transmission
-Levels of ACh 90% below normal
What are risk factors for AD?
-Age
-Family history
-Female
-Head injury
-Low educational level
-Production of apoE4
-Estrogen/progestin therapy
-Tobacco use
-Sedentary lifestyle
How is AD diagnosed?
-One episodic memory impairment
-One AD biomarker (MRI, PET scan)
What is the goal of drug therapy in AD?
Drugs make the neurons that are still functional work a little better for a period of time
How well do AD drugs work?
Drugs yield improvement that is statistically significant but clinically marginal
______ inhibitors may delay or slow progression of the AD but will not stop it
Cholinesterase
Cholinesterase inhibitors
Drug interactions
Drugs that block cholinergic receptors reduce the response to cholinesterase inhibitors - antihistamines, TCAs, conventional antipsychotics
Cholinesterase inhibitors
Donepezil (Aricept) and Rivastigmine (Exelon)
Patch prescribed for AD
Rivastigmine
AD drugs - Cholinesterase inhibitors - Donepezil and Rivastigmine
Adverse effects
Bradycardia (uncommon)
Orthostatic hypotension (uncommon)
GI
Dizziness
Headaches
Memantine (Namenda)
Mechanism of action
NMDA receptor antagonist
Memantine (Namenda)
Indication
Moderate to severe AD
Drugs for neuropsychiatric symptoms in AD
atypical antipsychotics - Risperidone (Risperdal) and olanzapine (Zyprexa)
