1- Parkinson's & Alzheimer's Flashcards
Parkinson’s disease is characterized by a loss of what neurons?
DA neurons in the substantia nigra pars compacta (sx once 70-80% loss)
What disease is characterized by bradykinesia, muscular rigidity, resting tremor, and impairment of postural balance and gait?
Parkinson’s disease
What is the MOA for L-dopa?
Increase DA levels (replacement therapy)
One L-dopa crosses the BBB it is converted to what?
DA
What are the SE of L-dopa?
Nausea and vomiting
What is the use for L-dopa?
Improvement in PD sx (specifically bradykinesia)
Will the effectiveness of L-dopa increase or decrease over time? Why?
Decrease. L-dopa does not affect the progression of the disease and neurons continue to degenerate
Will L-dopa tx the sx in drug induced Parkinson’s?
No
How is L-dopa taken?
Orally (absorption is delayed by food), need high doses to cross BBB
What is the use of L-dopa/Carbidopa?
Decreases peripheral effects of L-dopa (Nausea)
Carbidopa will block conversion of L-dopa to DA peripherally decreasing the dose of L-dopa needed
What are the SEs of L-dopa/Carbidopa?
GI (N/V)
CV (postural hypotension, arrhythmias, HTN)
Dyskinesias (tx by reducing L-dopa dose)
Behavioral (depression anxiety, agitation, sleep problems, psychosis - tx w/ atypical antipsycholytics)
What is the On-Off Phenomenon?
Fluctuations in clinical response of PD to meds when pt is on successful L-dopa therapy.
On = improved mobility Off = akinesia (due to falling drug levels)
What drug can be used as a rescue in a Parkinson’s pt w/ “Off”?
Apomorphine
How can you prevent the On-Off phenomenon in PD pts?
Increase dose frequency and L-dopa absorption w/ diet changes
L-dopa will interact w/ what drugs?
MAO-AIs => HTN crisis
Pyridoxine => Increased peripheral metabolism, decreasing L-dopas effectiveness
What is L-dope contraindicated?
Psychosis Closed Angle glaucoma (increases IOP) CVD Active PUD (increased GI bleeding) Malignant melanoma (L-dopa = melanin precursor)
What is the MOA for MAO Inhibitors (MAOIs)?
Inhibits MAO-B in CNS => Inhibits DA metabolism
does not affect peripheral metabolism of DA by MAO-A
What is the drug class for Selegiline?
MAOI inhibitor
What is the drug class for Rasagiline?
MAOI inhibitor
What is the drug class for Safinaminde?
MAOI inhibitor
What are the SEs of MAO-BIs?
Insomnia
Severe HTN (if given w/ other MAOIs)
Increase SE of L-dopa
Serotonin syndrome
What medication should you not combine w/ MAO-BIs?
Meperidine => can lead to stupor, rigidity, agitation, hyperthermia, possible serotonin syndrome
What is the MOA of COMT inhibitors?
Inhibits BA and L-dopa metabolism
What is the MOA of Tolcapone?
Inhibits COMT in CNS and periphery (prolongs DA in CNS and prolongs pools of L-dopa for transport
What drug class is Tolcapone?
COMT inhibitor
What drug class is Entacapone?
COMT inhibitor
What is the MOA of Entacapone?
inhibits COMT in periphery only (increases pool of L-dopa for transport into the brain)
What are the SEs of COMT inhibitors?
orange color in urine, dyskinesia, confusion, nausea, hypotension, abd pain, sleep disturbances
What is the MOA for DA receptor agonists?
Stimulate DA receptors directly (primarily DA D2)
Will DA receptor agonists continue to be effective as PD progresses?
Yes because they act directly on receptors
What drug class is Bromocriptine?
DA Receptor agonist
What is a SE of Bromocriptine?
Erythromelalgia (red, painful, swollen, itchy feet)
What medication is given to a pt w/ mutation in DCC (can’t synthesize DA)?
Bromocriptine
What drug class is Ropinirole?
Dopamine receptor agonist (purely DA D2)
What drug class is Pramipexole?
Dopamine receptor agonist (newer)
What is a SE of Ropinirole and Pramipexole?
Narcolepsy
What 2 drugs are used as monotherapy for mild PD?
Ropinirole and Pramipexole
What is the DOC for restless leg syndrome?
Ropinirole
What medication is a transdermal patch used for PD and RLS?
Rotigotine (DA receptor agonist)
What is the use of Apomorphine?
Rescue for “off” periods in pts w/ optimized L-dopa therapy
How is Apomorphine administered?
Injected
What are the SEs of Apomorphine?
Nausea
*give pt trimethobenzamide (antiemetic) prior to administration
Why is Apomorphine not given w/ Odansetron (antiemetic)?
Targets 5HT => HTN and LOC
Why is Apomorphine not given w/ Prochlorperazine (antiemetic)?
Blocks DA D2 receptors
What is the MOA for Apomorphine?
DA receptor agonist
What are the SEs of DA receptor agonists?
GI: Anorexia, N/V => take w/ meals
CV: Postural hypotension, cardiac arrhythmias (D/C)
Dyskinesia (reduce dose)
Mental disturbances: confusion, hallucinations, delusions
Erythromelalgia: Bromocriptine
Prolactin: DA agonists decrease release
What is the MOA of Amantadine?
Increase DA neurotransmission
What is the use of Amantadine?
Treat early or mild cases of PD (also antiviral for influenza)
What is a SE of Amantadine?
Livedo reticularis- reddish/blue spotting of skin, restlessness, depression, confusion, hallucination, peripheral edema
What are the SE of Amantadine OD?
Toxic psychosis and convulsions
What is the drug class of Benztropine?
Anticholinergic
What is the drug class for Trihexyphenidyl?
Anticholinergic
What is the MOA of anticholinergics?
Muscarinic receptor antagonists, restores DA/Ach balance in striatum
What is the use of Anticholinergics: benzotropine and trihexyphenidyl?
Improves rigidity, tremor, little effect on bradykinesia (use as adjunct therapy in PD)
What are the SEs of Anticholinergics: benzotropine and trihexyphenidyl?
Constipation, urinary retention, blurred vision, sedation, confusion
* D/C medications slowly
Diphenhydramine has what effects?
Anticholinergic effects
What is the use of Pimavanserin?
Atypical antipsychotic for tx of psychosis and delusions/hallucinations associated w/ PD
What is the MOA of Pimavanserin?
Inverse agonist/antagonist for 5-HT receptors, does not affects DA, adrenergic, cholinergic or histamine receptors
How is Pimavanserin metabolized?
By CYP3A4
What are the SEs of Pimavanserin?
GI, prolonged QT interval
Is Pimavanserin approved for the tx of dementia associated w/ Alzheimer disease?
NO. Increases mortality
Neuroprotection (antioxidants), pallidotomy, transplant of fetal neurons or stem cells, gene therapy, and deep brain stimulation are are all alternative txs for what?
Parkinson’s Disease
The deposition of B-amyloids (inside neurons) and Tau-proteins (outside neurons) resulting in degeneration of cholinergic neurons will lead to what disease?
Alzheimer’s
What is the class and MOA of Donepazil?
Cholinesterase inhibitor, inhibits metabolism of ACh => increased amount of ACh in the nerve terminal
What is the class and MOA of Rivastigmine?
Cholinesterase inhibitor, inhibits metabolism of ACh => increased amount of ACh in the nerve terminal
What is the class and MOA of Glantamine?
Cholinesterase inhibitor, inhibits metabolism of ACh => increased amount of ACh in the nerve terminal
How are cholinesterase inhibitors metabolized?
By CYP450s
Do cholinesterase inhibitors cross the BBB?
Yes
What are the SEs of cholinesterase inhibitors?
Peripheral effects: GI (N/V/D, cramps)
What is the use of cholinesterase inhibitors?
Increase brain activity and improves cognitive function
What is the class and MOA for Memantine?
NMDA receptor antagonist (channel blocker)
Blocks pathological activation of NMDA receptors => reduces excitotoxic effect of glutamate and slows degeneration
What is the use of Memantine?
Late stages of Alzheimers disease in combo w/ AChE-Is
What are the SEs of Memantine?
Agitation, insomnia, urinary incontinence, UTI, diarrhea, competes for renal tubular secretion
What should you monitor for pts on Memantine?
Monitor dose in pt w/ renal impairment
What drug is Memantine C/I with?
Meperidine
