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Flashcards in Cognitive Enhancers Deck (38)
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What are the three areas of ADHD indicators?

inattentive symptoms

hyperactivity symptoms

impulsivity symptoms


When do ADHD symptoms present? What percent of children? Adolescence? Adults?

usually before age 7

3-5% of children globally

of those, 60-80% persist into adolescence and 30-40% persist into adulthood


What are the american academy of pediatrics guidelines for an ADHD diagnosis/

at least 6 attention symptoms or 6 hyperactivity symptoms (with some before age 7)

symptoms must be present for at least 6 months

must be seen in at least 2 settings

not caused by another problem

symptoms have to be severe enough to cause difficulties in many settings, not just school


What two NTs are disrupted in ADHD?

NE and DA


Specifically, what pathway is involved with NE in ADHD?

from the locus soeruleus to the frontal and limbic cortices

it affects sustained and focused attention, mediates, energy and fatigue, working memory


What 3 pathways are involved with DA in ADHD?

1. susbantia nigra - striatum (motor hyperactivity)

2. tegmentum - frontal and limbic cortex (cognitive functions)

3. VTA - nucleus accumbens (euphoria)


What is the mode of action for all drugs used to treat ADHD?

to raise the levels of DA and NE


What are two classes of psychostimulants used in ADHD?

Amphetamines and Methylphenidate


What are the immediate-release and sustained-release forms of amphetamines used for ADHD>

immediate release = dexedrine

sustained = dexedrine spansules and adderrall XR


What ar ethe immediate release and sustained release version of methylphenidate used for ADHD?

immediate: Ritalin

Sustained: Concerta and Metadate CD


Why are the sustained released versions so helpful

they only need to be administered in the morning - never at school, so it removes the burden on schools to manage drug administrations


What do all the amphetamines and methylphenidates do? What added mechanism does d.l-amphetamine have?

they all enhance DA release and block reuptake

d,l-amphetamine also enhances NE release


Why are STIMULANTS effective for ADHD? You would think it'd be the opposite.

areas of the PFC and limbic cortex involved in focusing and maintaining attention and prioritizing behaviors are ACTIVATED at low (therapeutic) doses



What areas of the brain are stimulated at toxic doses?

areas involved in motor activity and arousal - euphoria


How do patients with ADHD respond to stimulants differently than non-ADHD patients?

stimulants have a calming effect on them

tolerance develops at a slower place


What group of people are at risk for "reverse tolerance" with stimulants, where they becomes psychotic with chronic use of the drug even without dose escalation?

people who have abused amphetamines like cocaine


What is the mechanism of atomoxetine?

it's a highly selective NE reuptake inhibitor

also elevates DA levels in the PFC (but not nucleus accumbens or the striatum)


Why is atomoxetine (strattera) the only first line ADHD drug with no abuse potential?

remember that it doesn't elevate DA levels in the nucleus addumbens, so you don't get the mesolimbic euphoric properties


How do cholinergic neurons impact ADHD?

there are cholinergic neurons in the cortical and subcortical regions of the brain that are implicated in vigilance, attention and workin gmemory


Tzavara was observed to increase ACh release from rat frontal cortex only under what conditions to improve attention and working memory?

alpha1 receptors had to be activated by NE and D1 receptors had to be activated by DA

so Tzavara given in combo with atomoxetine or methylphenidate improved attention and memory


What NT is largely affect in the neuropathology of AD?



How do tau proteins eventually lead to cell death in AD?

the tau tangles tend to surround neuron's microtubules

this interferes with the cell's ability to transport essential chemicals form the cell body to the axon terminal


How do the beta-amyloid plaques interfere with cognition?

in the nucleus basalis, they accumulate in the synapse and interfere with normal ACh transmission



What is the general time course of AD proression?

1. memory problems start with neuronal loss in the NBM

2. within about 3 years, cell damage to areas receiving ACh from the NBM causes loss of functional independence - early disenoasis of AD cna be made

3. 3-6 years after that, the neocortex becomes heavily involved in the disease process

4. usually die over the following 3 years


What drugs can you give to hopefully delay AD progression?

cholinesterase inhibitors

(delays cognitive deterioration by about one year in 20% of patients)


What are the side effects of the anticholinesterases and why?

nausea, anorexai, vomiting and diarrhea

they raise ACh levels thorughout the brain - not just in the areas where ACh is low


What are some examples of anticholinesterases used in AD?

Donepezil = aricept

galanatamine = razadyne

rivastigmine = exelon

tacrine = cognex

memantine = namenda


What cholinesterases does rivastigmine block?

both AChE and BuChE

(this means it causes more gastrointestinal problems and muscle weakness than the others)


Why is tacrine (cognex) a second line treatemtn for AD?

It has a short half life and needs to be given multiple times per day, so compliance is poor

there are also lots of drug interactions- esp with NSAIDs

may cause liver damage


What does Galantamine (Razadyne) do>

1. inhibits AChE

2. stimulates nicotinic cholinergic neurons to release more stored ACh


What drugs should Galantamine NOT be taken with?

antidepressants: paroxetine, amitriptyline, fluoxetine, and fluvoxamine

and other drugs with anticholinergic side effects

they can interfere with the elimination of galantamine


Why should people on cholinesterase inhibitors only use NSAIDs with great caution?

cholinesterase inhibitos increase the risk of stomach ulcers


Who is memantine (namenda) particularly useful for?

patients with moderate to severe AD

it can help patients in latera stages of the disease to maintain additiona independence


What is the mechanism of Memantine (Namenda)?

it is an antagonist at the NMDA receptor


What are nootropics?

memory enhancers, "smart drugs"


What are Eugeroics?

they are "wakefulness enhancers" like modafinil and armodafinil (provigil and nuvigil)


Is ginko biloba good for AD?

it may have a modest benefit for AD patients, but serious side effects have been found - bleeding, seizures, coma!