Central Nervous System _____ and _____ cord Integrates _____ information and generates ______ output Billions of _______ and surrounding _____ cells _______ are responsible for the flow of information ___________- chemicals relay, amplify, and modulate signals Excitatory or Inhbitory

brain, spinal sensory, motor neurons, glial Neurons NeurotransmittersAttach Sounds

Voltage vs. Ligand Gated Channels Voltage - ____ mediated Primarily located on the initial segment of the axon as well as axon itsself (___ action potential) Ligand - ______ mediated Ligand (inotropic) receptor - _____ opens Metabotropic receptor - engages _-protein to produce ______ messanger (_____-gated) Calcium-___synaptic-____ channel function Potassium-___synaptic-____ opening of channel

ion fast neurotransmitter directly G, second, voltage pre, inhibit post, slow Voltage such as Na, Ca, K Ligand more neurotransmitter based

Acetylcholine (Ach) - Neurotransmitter responsible for _____ contraction (n____ receptors) and ________ component of the autonomic nervous system (_______ receptors) Central Nervous System Assists in: l____, m_____, neuro_____, c______ Peripheral Nervous System _____ relaxation, skeletal and _____ contraction

- muscle (nicotinic), parasympathetic (muscarinic) learning, memory, neuroplasticity, concentration Cardiac, muscle

Goals of Therapy Improve _ _ _ Improve or slow the loss of ____/_____ Maintain and maximize independent ______ Minimize _ _ of drug therapy

QOL memory/cognition function AE NO CURE =(

Cholinesterase Inhibitors May _____ deterioration of ______ function Preserves m_____, l_____, a______ Does not effect:

slow, cognitive memory, learning, attention underlying degenerative process

Neurology Pt 1 Alzheimers and Parkinson's Flashcards by Felita Salim

Central Nervous System

_____ and _____ cord
Integrates _____ information and generates ______ output
Billions of _______ and surrounding _____ cells
_______ are responsible for the flow of information
___________- chemicals relay, amplify, and modulate signals
- Excitatory or Inhbitory

brain, spinal
sensory, motor
neurons, glial
Neurons
NeurotransmittersAttach Sounds

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Neuron

Building block of the CNS
- Process/transmit information
Classified based on f_____, l_____, and n______ released
Form dendritic trees - receive from other neurons and transmit to cell body =
Cell body =
Carries signal from cell body eventually to synapse =
Junction of neurons where NT are released to interact with receptors or other neurons
- ultimately stimulates channels that allow _____ and ______ allowing for necessary communication/processes

function, location, neurotransmitter
Dendrites
Soma
Axons
Synapse
- opening, closing

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Voltage vs. Ligand Gated Channels

Voltage - ____ mediated
- Primarily located on the initial segment of the axon as well as axon itsself (___ action potential)
Ligand - ______ mediated
- Ligand (inotropic) receptor - _____ opens
- Metabotropic receptor - engages _-protein to produce ______ messanger (_____-gated)
  - Calcium-___synaptic-____ channel function
  - Potassium-___synaptic-____ opening of channel

ion
- fast
neurotransmitter
- directly
- G, second, voltage
  - pre, inhibit
  - post, slow

Voltage such as Na, Ca, K*
Ligand more neurotransmitter based*

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Where do CNS drugs primarily work?

1) Supplementing the NT*
ex) deficiency in norepi, give norepi*

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Neurotransmitters and Receptors

Serotonin is responsible for a myriad of things*
Notice there are so many different receptors*
ex) dopamine has like 4 receptors

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Neurotransmitters and Receptors cont.

Gaba-primary inhibitory transmitter*
Glutamate-primary excitatory transmitter*

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Neurotransmitters and Receptors cont.

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Alzheimer’s Disease

Characterized by?

Acetylcholine Deficiency

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Acetylcholine (Ach)

Neurotransmitter responsible for _____ contraction (n____ receptors) and ________ component of the autonomic nervous system (_______ receptors)
Central Nervous System
- Assists in: l____, m_____, neuro_____, c______
Peripheral Nervous System
- _____ relaxation, skeletal and _____ contraction

muscle (nicotinic), parasympathetic (muscarinic)
learning, memory, neuroplasticity, concentration
Cardiac, muscle

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What is Alzheimers?

Accounts for __-__% of dementia

A progressive degenerative disease ultimately resulting in cerebral atrophy

50-75%

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Primary risk factors for Alzheimers

Age and Family Hx

Cerebral trauma, Vascular disease

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Signs and Symptoms of Alzheimers

Difficulty performing ____ t____
Difficulty r_____ and w______
Loss of _______
D_____, D______, A_______

basic tasks
reading, writing
memory
Delusions, Depression, Agitation

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Three histopathological hallmarks can impair neurotransmitter function of ________ leading to _____ deficits

1. 3.

Beta-amyloid-rich senile plaques (lots of ongoing research)
Neuritic plaques and neurofibrillary tangles
Neuronal degeneration

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Pharmacological Considerations

Cholinergic pathways are damaged -> ____ of Ach transmission
Overstimulation of _____ receptor by ______ -> neuronal damage
Inhibition of ________ receptors -> impairs cognition

loss
NMDA, glutamate

- nicotinic

Perhaps inhibiting glutamate will prevent further progression of disease

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Goals of Therapy

Improve _ _ _
Improve or slow the loss of ____/_____
Maintain and maximize independent ______
Minimize _ _ of drug therapy

QOL
memory/cognition
function
AE

NO CURE =(

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Medications Used in the Tx of Alzheimer’s

2 classes, 5 agents

Cholinesterase Inhibitors
- Donepezil (Aricept)
- Rivastigmine (Exelon)
- Galantamine (Razadyne)
NMDA receptor Antagonist
- Memantine (Namenda)
Combination
- Donepezil + Memantine (Namzaric)

Not many tx options unfortunately*
Aricept and Memantine most common*
Onset: takes about 2-4 wks for these drugs to kick in*

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Cholinesterase Inhibitors

MOA

Selectively inhibits cholinesterase (enzyme that hydrolyzes (inactivates) Ach) in the CNS

Increases Ach concentrations in the cerebral cortex

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Cholinesterase Inhibitors

Indication

For mild to moderate disease

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Cholinesterase Inhibitors

Agents

Routes

Donepezil (Aricept) - oral, ODT

Rivastigmine (Exelon) - oral, transdermal patch

Galantamine (Razadyne) - oral

Oral disintegrating tablet since alot of older adults have trouble swallowing

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Cholinesterase Inhibitors

May _____ deterioration of ______ function
- Preserves m_____, l_____, a______
Does not effect:

Study These Flashcards

slow, cognitive
- memory, learning, attention
underlying degenerative process

Cholinesterase Inhibitors Adverse Effects

Donezepil:
Galantamine:
Rivastagmine:
ALL (3) - (_____ titrate dose)
____cardia, d_____, s______
Urinary ______
Hyper______, sw_______

Study These Flashcards

Cholinesterase Inhibitors

Drug Interactions

Study These Flashcards

Anticholinergic drugs (drugs that block cholinergic receptors)

Donepezil is a minor substrate of CYP3A4

Anticholinergic = blocks acetylcholine receptors*
Know that its a minor substrate, will not question on enzymes*

Cholinesterase Inhibitor Adverse Effects

Study These Flashcards

Diarrhea
Urination
Miosis
Bronchospasm
Emesis
Lacrimation
Salivation

Cholinergic Crisis Signs and Symptoms

What is it?

Study These Flashcards

To much Ach from inactivity of AchE enzyme that usually breaks it down

Salivation
Lacrimation
Urination
Defecation
Gastric upset
Emesis

**Memantine (Namenda)** MOA

NMDA (glutamate receptor) antagonist - Attenuates (reduces) excitotoxic effects of glutamate (neuroprotective) * Glutamate is very excitatory but very neurotoxic as well*

**Memantine** Drug Interactions

No CYP 450 drug interactions

**Memantine** Indication

Moderate to severe Alzheimer's disease - often used in combination with cholinesterase inhibitor

**Memantine (Namenda)** Adverse Effects

* Constipation * HA, confusion, dizziness, hallucinations * HTN

**Memantine (Namenda)** Route

Oral - Available as combination with donepezil (Namzaric) which is also given PO

Parkinson's Disease What's the issue?

Lack of Dopamine *Goal: Increase Dopamine*

Background * Degenerative disease of the _____ \_\_\_\_\_\_, resulting in gradual decline in \_\_\_\_\_, \_\_\_\_\_\_, and _____ functioning * Severe loss (~80%) of dopaminergic neurons of the substantia nigra * Presence of _____ \_\_\_\_\_ (intracellular inclusions) * Creates **\_\_\_\_\_\_\_** of acetylcholine and dopamine * __ treatment = progresses to an ______ state (5-10 yrs) * Mortality due to ______ (aspiration pneumonia, clotting disorders, etc)

* basal ganglia, motor, autonomic, cognitive * Lewy bodies * **imbalance** * No, akinetic * imobility * Occurs when you have about 80% loss of dopaminergic neurons*** * Due to Lewy Bodies that block transmission of neuro signals* * Homeostasis of acetylcholine and dopamine messed up* * IMMOBILITY\*-**All the effects usually secondary to immobility*

Dopamine (DA) * Catecholamine, synthesized in dopaminergic neurons from tyrosine * DA receptors ( __ total, grouped into D\_ and D\_) * D1 - _____ synthesis of cyclic AMP **(\_\_\_\_\_)** * D2 - _____ synthesis of cyclic AMP, suppresses CA currents, activate K currents **(\_\_\_\_\_)** * ****Neostriatum of the basal ganglia regulates flow of information from the _____ cortex to the motor neurons of the _____ cord

* 5, D1, D2 * stimulate, **excitatory** * inhibit, **inhibitory** * cerebral, spinal *5 diff dopamine receptors - 2 types*

Pathophysiology - *\_\_\_ receptors impacted* * - _____ \_\_\_\_\_ -*\> protein degradation -\> terminal degredation

- *D2* * -* Lewy Bodies

Pharmacologic Targets \_\_\_\_\_ and _______ function depend on the coordinated ____ of _____ and \_\_\_\_\_\_ How to treat? 1) _____ Dopamine 2) _____ Acetylcholine

Motor, Cognitive, interaction, Dopamine, Acetylcholine 1) Increase 2) Decrease

Presentation * ________ Symptoms * ________ (slow/lack of movements) * Muscular _______ (e.g. cogwheel) * ______ tremor (e.g pill rolling) * ______ instability * ____ (e.g shoulder shrugs) * Dys\_\_\_\_\_\_ * Loss of \_\_\_\_\_ * A\_\_\_\_\_\_\_

* Extrapyramidal * Bradykinesia * Muscular Rigidity * Resting tremor * Postural instability * Tics * Dystonia *voice changes* * Loss of Smell * Anxiety

Risk Factors | (3)

1. Age * Natural loss of DA neurons of the corpus striatum (70-80% loss) * Terminal of DA neuron degenerates * Lewy bodies form in the soma of DA neuron which results in protein degradation amongst others 1. Environmental exposures *(amphetamine and cocaine use)* 2. Hereditary * Chromosomal mutations

Goals of Therapy * Improve ____ and _ \_ \_ * Prevent long term \_\_\_\_\_\_, minimize _____ disability * Slow disease \_\_\_\_\_\_\_ * Maximize ___ therapy and minimize _ \_

* symptoms, QOL * complications, functional * progression * drug, AE

Medications Used in the Treatment of Parkinson's Disease ## Footnote (7)

1. Dopaminergic agents (think replacement) 2. Decarboxylase Inhibitor 3. Caetchol O methyl transferase (COMT) inhibitors 4. MAO-B Inhibitors 5. Dopamine receptor agonists *(NOT ON EXAM)* 6. Acetylcoline receptor agonists 7. Adenosine A2A receptor antagonist *(NOT ON EXAM)*

1) Dopaminergic agents ## Footnote (2)

* **Levodopa (L-DOPA)** * Amantadine (Symmetrel)

2) Decarboxylase Inhibitors ## Footnote (1)

**Carbidopa** * always used with levodopa (Sinemet) * NOT ACTIVE ALONE

3) COMT Inhibitors ## Footnote (3)

**Entacapone (Comtan)** **Tolcapone (Tasmar** **Opicapone (Ongentys)**

4) MAO-B Inhibitors ## Footnote (3)

**Safinamide (Xadago)** **Selegline (Eldepryl)** **Rasagline (Azilect)**

6) Acetylcholine Receptor Antagonists ## Footnote (2)

**Benztropine (Cogentin)** **Trihexyphenidyl (Artane)**

* *Dopamine in the periphery =* * *Goal is to get levodopa to the?* * *2 enzymes that break down down in the periphery (2)*

* *Does nothing and wreaks havoc* * *Brain* * *COMT, Decarboxylase*

**Levodopa** ## Footnote * What is it? * Metabolized by what in the peripheral tissue? * If given as a monotherapy, what happens? * Always give it with?

* Biosynthetic precursor of dopamine * Increases concentration of dopamine in the brain * **Decarboxylase** and **Catechol-O-methyl transferase (COMT)** * Less than 1% reaches the brain (always need decarboxylase inhibitor and often also needs COMT-inhibitor) * **ALWAYS** give in combo with **carbidopa** ## Footnote * What dopamine itself causes - GI upset* * Too much dopamine = depression, delirium, paranoia, hallucinations -\> makes sense bc in schizophrenia they have too much dopamine*

**Levodopa** AE (4)

* N/V (Antacid 30-60min before may help) * Orthostatic hypotension, Sedation * Depression, Delirium, Paranoia, Delusions, Hallucinations (CNS effects associated with long-term use) * Motor fluctuations (end of dose wearing off: peak-pose dyskinesa) *Breakthrough dyskinesia*

Levodopa * Always combined with \_\_\_\_\_ * Examples of combined formulations

* Carbidopa * Sinemet, Sinemet CR, Parcopa ODT * Rytary (new formulation that has advanced control release to reduce motor fluctuations, less frequently dosed, can be opened and sprinkled unlike sinemet (not interchangeable with), expensive/should not be first line)

**Carbidopa** MOA

Decarboxylase Inhibitor * Inhibits conversion of levodopa to dopamine in peripheral tissues (thereby decreasing GI and CV effects) * Increases amount of levodopa in the brain

**Carbidopa** ## Footnote * Always give in combination with ______ (\_\_\_\_\_) * Titrate dose ____ up to __ mg of carbidopa daily * Reduce incidence of peripheral conversion = reduced _ \_ * Wearing off Phenomenon, what is it?

* Levodopa (Sinemet) * Slowly, 75 * **Loss of efficacy** over time (proven effective for 2-5 yrs) OR **Fluctuation in response** to meds occurs over time and may need higher doses ## Footnote *Story time: Carbidopa is that friend you bring to the grocery when you are super hungry to stop you from grabbing too much food and not getting to your destination\> always have carbidopa by your side bc it inhibits dopamine breakdown in periphery*

Neurology Pt 1 Alzheimers and Parkinson's Flashcards

(49 cards)