Cognitive enhancers

Question 1

Developmental disorder characterized by co-existence of attention problems and hyperactivity

Answer 1

ADHD

Question 2

Two NE pathways:

Roles?

Answer 2

Locus cereleus –> prefrontal cortex

LC –> limbic cortex

Sustain and focus attention

mediates energy, motivation, and interest

working memory

Question 3

Three DA pathways:

Roles?

Answer 3

Mesocortical: Tegmentum –> prefrontal cortex, limbic cortex
-cognitive function

Nigrostriatal: substantia nigra –> striatum
-motor hyperactivity, impulsivity

Mesolimbic: ventral tegmentum –> nucleus accumbens
-Euphoria

Question 4

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

Answer 4

RAISING levels of DA and NE

**allows inhibition of hyperactivity, impulsivity, inattention

Question 5

Two drugs for ADHD treatment in children:

Answer 5

Methylphenidate
-(Ritalin-immediate release, Concerta and Metadate-sustained release)

Amphetamines
-(Dexedrine-immediate release, Dexedrine Spansules and Adderall XR-sustained released

Question 6

Highly selective NE reuptake inhibitor that also elevates DA levels in prefrontal cortex but NOT nucleus accumbens or striatum (no euphoric effect)

only first-line ADHD med with no abuse potential and only drug FDA approved to treat adult ADHD

Answer 6

Atomoxetine (Strattera)

Question 7

Ach in prefrontal cortex released ONLY by activation of which two receptors (and NTs)?

Answer 7

D1-dopamine

a1-NE

**another effect of atomoxetine on improvement of attention and memory

Question 8

• Brain center where many cholinergic (ACh) neuron cell bodies originate
• Site of earliest damage to the brain in AD

Answer 8

Nucleus Basalis of Meynert

Question 9

Four key cholinergic pathways originating in NBM:

Answer 9

1. to neocortex
2. to prefrontal cortex
3. to amygdala
4. to hippocampus

Question 10

Two characteristics of the micropathology of ALZ:

Answer 10

Neurofibrillary tangles (tau protein build up inside neurons blocks axonal transport)

B-amyloid polypeptides overproduced to form plaques (intERneuronal problems, especially cholinergic neurotransmission for memory)

Question 11

Three step progression of Alzheimer:

Answer 11

1. first memory sx, initial damage to NBM
2. (~3 yrs) cell damage and loss spreads to areas receiving NBM innervation
   - patient loses functional independence
3. (3-6 years) neocortex heavily involved, death typically within 3 years

Question 12

Only way to delay progression of AD…doesn’t work very good

Answer 12

raise Ach levels throughout brain with AchE inhibitors

**lots of adverse effects (more Ach in other parts of the body too

Question 13

Adverse effects of anti-AchE drugs:

Answer 13

nausea, anorexia, vomiting, diarrhea

Question 14

Used to treat AD

Inhibits AchE and BuChE

BID

more GI probs and muscle weaknesss than other cholinesterase inhibitors

Answer 14

Rivastigmine (Exelon)

Question 15

Second line therapy AD drug

short half life, needs to be given multiple times/day (poor compliance)

many drug interactions (esp NSAIDs)

hepatotoxic?

Answer 15

Tacrine (Cognex)

Question 16

AD med

Inhibits AchE

Stimulate nicotinic cholinergic neurons to release more stored Ach

increased risk of stomach ulcers (careful with NSAIDs!)

Answer 16

Galantamine (Razadyne)

**also interacts with antidepressants and drugs with anticholinergic side fx (may interfere with elimination)

Question 17

Med for more severe AD

Antagonist of NMDA subtype of GLU receptor

May help pts in later stage AD maintain additional independence

side fx: dizziness, headache, constipation, confusion

Answer 17

Memantine (Namenda)

Question 18

“Wakeful enhancers”

lower abuse potential

increase NE and DA

elevate hypothalamic histamine levels

Answer 18

Modafinil (Provigil)

Armodafinil (Nuvigil)