Licht: CNS Cognitive Enhancers

Question 1

What are the potential uses of cognitive enhancers?

Answer 1

1. ADHD
2. Alzheimers
3. Smart drug

Question 2

What are the key characteristics of ADHD?

Answer 2

1. Co-existance of: attentional problems and hyperacativity, each behavior occurs infrequently alone
2. Symptoms usually start before 7 years of age

Question 3

How should ADHD be diagnosed?

Answer 3

At least 6 attention symptoms or 6 hyperactivity/impulsivity symptoms w/ some sympotoms presenting before age 7

Symptoms:

1. Must be present for at least 6 months
2. Seen in 2 or more settings
3. not caused by another problem

Symptoms must be severe enough to cause prolbems at home, school and in relationships w/ peers

Question 4

What are psychostimulants?

Answer 4

First line treatments for ADHD

Methylphenidate and Amphetamines

80-90% effective in children

Question 5

What is Amoxetine?

Does it have abuse potential?

Answer 5

Highly selective NE reuptake inhibitor.

It selectively elevates DA in the prefrontal cortex NOT the NA or the striatum.

(NA mediates euphoric properties of psychostimulants–so it allows you to control behavior w/out the euphoria)

Only first line ADHD medication with NO abuse potential.

Can have adverse effects on working memory.

Question 6

What are two amphetamines used to treat ADHD?

Answer 6

1. Dexedrine- immediate release
2. Dexedrine Spansules and Adderal- sustained release

Question 7

What are two mehylphenidates used to treat ADHD?

Answer 7

1. Ritalin- immediate release
2. Concerta and Metadate- sustained release

Question 8

Why are sustained release drugs great?

Answer 8

Only need to be administed in the AM!

That way schools don’t need to worry about drug administration.

Question 9

Why are STIMULANTS effect in treating disorders characterized by HYPERACTIVITY?

Answer 9

Areas of the prefrontal and limbic cortex (involved with focusing, maintaining attention and prioritizing behaviors) are ACTIVATED by psychostimulants at LOW therapeutic doses.

They essentially TURN OFF external cues and TURN ON some inhibitory areas of the brain.

**areas of the brain involved iwth motor activity/arousal get activated at HIGHER doses, worsening behavior.

Question 10

What are the main pathways of NE in the brain? What does the pathway do?

Answer 10

LC to the prefontal cotex and limbic cortex

Focus, attention, energy, fatigue, interest and working memory

Question 11

What is the DA pathway in the brain and what does it do?

Answer 11

Tegmentum –> prefrontal and limbic cortex

Cognitive functions, focusing attention, prioritizing behavior and modulating behavior

Motor activity and impulsivity

Euphoria

Question 12

What causes ADHD?

Answer 12

Deficiency in NE/DA activity–>

Hyperactivity

Impulsivity

Inattention

Question 13

How do you reduce the symptoms of ADHD?

Answer 13

Raise the levels of DA and NE

Question 14

Which drugs enhance DA release and block reuptake? Which drugs enhance NE release

Answer 14

**DA: **Methylphenidate and Amphetamine

NE: Amphetamine

Question 15

What are the MACROSCOPIC findings in pts with Alzheimers?

Answer 15

Destruction of cholinergic neurons in several areas of brain–>

Nucleus basilus - earliest sight of damage

Cortical Atrophy- signal no longer comes to certain areas of brain

Question 16

What are the microscopic changes in pts with Alzheimers Disease?

Answer 16

1. Neurofibrilary Tangles

• Structurally incompetent tau protein surrounds neuron’s microtublues and interfere with the cell’s ability to transport essential chemicals from teh cell body to the axon terminal. This congested “conveyor” leads to cel ddeath.

2. B- amyloid polypeptides are overproduced

• Accumulate in synapse of NBM neurons and interferes iwth normal cholinergic neurotrasnmission–> first signs of memory loss.
• Over time damage becomes more wide spread (areas of brain innervated by NBM–hippocampus and amygdala die off)

Question 17

What drugs are used to treat AD? What are their adverse effects?

Answer 17

Cholinesteras inehibitors delay the progression of the disease. Cognitive Deterioration is delayed by one year in approximately 20% of patients.

Achesterases raise ACh throughout brain–> nausea, anorexia, vomitting and diarrhea. This limits the maximal dose that can be used clinically.

Question 18

What does Galanatamine do?

Answer 18

Inhibits AChE

Stimulates nicotinic cholinergic neuorns to release more stored ACh

Caution: can increase risk of stomach ulcers, not good to take with anti-depressants.

Question 19

What does Rivastigmine (Exelon) do?

Answer 19

Inhibits BOTH AChE and Bu CHE

Administed twice daily

Can cause gastrointestinal problems and muscle weakness

Question 20

What does Tacrine (Cognex) do?

Answer 20

Short half life–needs to be given multiple times per day--> poor compliance

Many drug interactions (especialy with NSAIDS)

May cause liver damage.

Used as a second line therapy.

Question 21

What is Memantine (namenda)?

Answer 21

Used for patients with moderate to severe AD.

Question 22

Why is Memantine?

Answer 22

It works thorugh GLUTAMATE instead of ACh!

It’s an antagonist at the NMDA glutamate receptor.

Found to help pt in later stages of disease who no longer respond to ACh inhibitors.

**AE: dizziniess, HA, constipation and confusion

Question 23

What are Nootropics?

Answer 23

Smart drugs, memory enhancers, cognitie enhancers

Question 24

What are eugeroics?

What are examples of eugeroics?

Answer 24

Wakefulness enahncers

Modafinil (popular in performance-enhancing use by uni students) and Armodafinil

Question 25

What is the mechanism of action of Modafinil and Armodafinil?

Answer 25

Increase levels of NE And DA

Also elevates hypothalamic histamine levels

Question 26

Eurogenics are FDA approved for:

Answer 26

1. Narcolepsy
2. Shift work sleep disorder
3. Excessive daytime sleepiness associated with obstructive sleep apnea