Parkinson's and Alzheimers Flashcards by Alex Steinmann

what are the 4 major clinical features of parkinson’s disease

bradykinesia
muscular rigidity
resting tremor
impairment of postural balance, gait

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what class is Selegiline (Deprenyl®) in

MAO-B inhibitor
- inhibit MAO-B in CNS
- reduces striatal metabolism of DA
- does not affect peripheral metabolism of DA by MOA-A

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what class is Rasagiline (Azilect®) in

MAO-B inhibitor

inhibit MAO-B in CNS
function: reduces striatal metabolism of DA
does not affect peripheral metabolism of DA by MOA-A

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what class is Tolcapone (Tasmar®) in

COMT inhibitor

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what class is Entacapone (Comtan®) in

COMT inhibitor

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List the Dopamine receptor agonists

Bromocriptine (Parlodel®)
Pramipexole (Mirapex®)
Ropinirole (Requip®)
Apomorphine (Apokyn®)

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what class is Amantadine (Symmetrel®) in

dopamine releasers

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what class is Benztropine (Cogentin®) in

anticholinergic

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what class is Trihexyphenidyl (Artane®) in

anticholinergic

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List the L-Dopa drugs used in parkinson’s disease

Levodopa (Dopar®; Larodopa®)
Carbidopa (Lodosyn®)
Carbidopa/levodopa (Sinemet®)

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List the drugs to tx alzheimers dz

Donepezil (Aricept®)
Rivastigmine (Exelon®)
Galantamine (Reminyl®)
Memantine (Namenda®

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What causes parkinson’s dz

characterized by the degeneration of dopamine (DA) neurons projecting from the substantia nigra (SN) to the corpus striatum (nigrostriatal pathway).
- symptoms = 70- 80% decrease in striatal dopamine neurons

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What happens to DA/ACh balance in parkinson’s ? what is the overall effect

Degeneration of DA neurons in the SN leads to an imbalance between DA and acetylcholine (ACh), such that the ACh pathways are now dominant.
- DA pathways normally inhibit GABA output from the striatum, whereas acetylcholine stimulates it.
- Loss of DA thus leads to overactivity of inhibitory GABA neurons

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what is responsible for metabolism of dopamine

MAO-B
COMT

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MOA of L-Dopa (Levodopa; dopar; larodopa)

increase dopamine levels
“replacement” therapy
L-dopa crosses BBB and is converted into DA in the neuron

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peripheral effects of L-Dopa (Levodopa; dopar; larodopa)

severe nausea and vomiting

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clinical uses of L-Dopa

improves PD for 3-4 years
effectiveness will go down over time
does not affect progression, DA neurons continue to degenerate
not effective in drug induced parkinsonism

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why does L-Dopa need to be administered in high doses

only 1-3% gets into the CNS
- short half life: taken 3-4 x /day

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MOA of Carbidopa

dopa decarboxylase inhibitor that does not cross the blood brain barrier
- Therefore, it inhibits the synthesis of DA from l-dopa in the periphery, but does not affect DA synthesis in the brain

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effect of combining L-Dopa with Carbidopa (sinemet)

decreases dose of L-Dopa needed
decreases peripheral effects -> nausea

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side effects of L-Dopa with Carbidopa (sinemet)

Nausea/emesis (still present)
- don’t take antiemetics that block DA D2 (prochlorperazine)
dyskinesias
psychosis is possible -> tx with atypical antipsychotics

What is the on-off phenomenon

only occurs in patients who have been treated with l-dopa; may result from brain adaptation
“off” = akinesia- due to falling drug levels
“on” = improved mobility accompanied by dyskinesia

tx of on-off phenomenon

increase frequency of L-dopa doses
adjust diet
apomorphine (D2 agonist) used as “rescue”
- temporary relief

MOA of MAO-B inhibits in tx of parkinsons

inhibit dopamine metabolism
- inhibit MAO-B in CNS
- reduces striatal metabolism of DA

MAO-A are responsible for metabolism of dopamine where

in peripheral system

adverse effects of MAO-BI

* insomnia

drug interactions with MAO-BI

* **severe hypertension** if combined with other MAOIs * Do NOT combine with Meperidine * if combined with TCAs or SSRI -\> **serotonin syndrome**

MOA of COMT inhibitors in tx of parkinsons

* inhibit DA and L-dopa metabolism

MOA of Tolcapone

* inhibits COMT in CNS and periphery * not used often- associated with hepatic failure

MOA of Entacapone

* inhibits COMT in periphery only * increases pool of l-dopa for transport into brain

unique side effects of COMT inhibitors

* orange color in urine

MOA of DA receptor agonists in tx of parkinsons

* stimulate DA receptors * primarily DA D2 * act **directly on receptors** so continue to be effective as the disease progresses * used in combination with L-dopa during "on-off" periods

Bromocroptine is an Ergot derivative and thus associated with what side effect

* Erythromelalgia * itchy and burning feet

What are the dopamine receptor agonists of choice for tx of parkinsons. What are they used for?

* Ropinirole * Pramipexole \*monotherapy in mild PD; soothing response to L-dopa in late PD

DOC restless leg syndrome

Ropinirole

MOA of Ropinirole

* pure DA D2 agonist

use of apomorphine

* temprorary relief "rescue" of off periods in patients on L-dopa therapy * typically injected

side effects of apomorphine

* nausea * pt should take antiemetic prior to introduction

List the side effects of dopamine agonists

* N/V * posutral hypotension, cardiac arrhythmias * mental distrubances (inc dopa -\> inc risk of psychosis)

MOA of Amantadine in tx of parkinsons

* antiviral used for influenza that increase Dopamine neurotransmission * used to tx eraly or mild cases of PD

side effects of Amantadine

* livedo reticularis: reddish/blue spotting of skin * toxic psychosis and convulsions with overdose

MOA of Benzotropine and Trihexyphenidyl in tx of parkinsons

* **anticholinergics**: restores DA/ACh balance in striatum * improves **rigidity, tremor** * little effect of bradykinesia

list the risk factors for alzheimers

* age * genetics: small risk * gender: female * lack of education * head injury

autopsy of alzheimer brain shows

* neuritic plaques: **B amyloids** * neurofibrillary tangles: **tau proteins** * toxic effect on acetylcholine

Degeneration of what leads to alzhiemers

* **degeneration of cholinergic neurons (Ach)** * from the nucleus basalis of Meynert which project to the cerebral cortex and hippocampus * involved in memory and cognition

MAO of Donepezil

* cholinesterase inhibitor * inhibit metabolism of ACh, increase amount of ACh in the nerve terminal

MOA of Rivastigmine

* cholinesterase inhibitor * inhibit metabolism of ACh, increase amount of ACh in the nerve terminal

MOA of Galantamine

* cholinesterase inhibitor * inhibit metabolism of ACh, increase amount of ACh in the nerve terminal

cholinesterase inhibitors (AChE inhibitors) are metabolized by

CYP450

side effects of cholinesterase inhibitors

* peripheral effects of cholinergic side effects * N/V * diarrha * stomach cramps

use of AChE inhbitors in the tx of alzheimers

* taken once/day * increase brain activity and improves cognitive symptoms * may slow progression of dz

MOA of Memantine

* **NMDA receptor antagonist** (channel blocker) * blocks pathological activation of NMDA receptors * **reduces** excitotoxic effect of **glutamate** * slow degeneration