Cognitive Enhancers

Question 1

Main drugs used to enhance cognitive performance

Answer 1

caffeine, amphetamines, methylphenidate, modafinil

often in absence of medical advice

Question 2

improve mental performance in fatigued subjects (simple, tedious tasks)
increase ability to focus and maintain self control. In addition to reducing fatigue,

Answer 2

amphetamines

Question 3

reduces fatigue and has a positive effect on long-term memory consolidation

Answer 3

methylphenidate

Question 4

improves attention in rested individuals, while improving wakefulness, memory and executive functions in sleep-deprived individuals

Answer 4

modafinil

Question 5

ADHD etiology

Answer 5

thought to be disorder or NE and DA pathways in frontal cortex and basal ganglia

Question 6

DA and NE roles

Answer 6

mesocortical DA - cognitive functions, also hyperactivity

prefrontal NE - focus and attention

Question 7

main tx thought for ADHD

Answer 7

deficient NE and/or DA activity - so raise levels of DA and NE

Question 8

why are cns stimulants effective in treating ADHD

Answer 8

Areas of the prefrontal and limbic cortex involved with focusing and maintaining attention and prioritizing behaviors are activated by psychostimulants at low (therapeutic) doses (vs euphoria etc at high doses)
ADHD patients respond differently to stimulants - tolerance develops at slower pace than in non-ADHD pts

Question 9

atomoxetine (strattera) mechanism

Answer 9

Highly selective NE reuptake inhibitor, also elevated DA levels in prefrontal cortex
BUT not in nucleus accumbens or striatum (euphoric)
NOT a controlled substance
less effective in reducing ADHD sxs than stimulants

Question 10

AE straterra

Answer 10

n/v, weight loss
sleep problems
liver damage

Question 11

Main pathological features alzheimers

Answer 11

amyloid plaques
neurofibrillary tangles
loss of neurons (particularly cholinergic neurons of the basal forebrain)

Question 12

amyloid plaques AD

Answer 12

aggregates of the Aβ fragment of amyloid precursor protein (APP), a normal neuronal membrane protein, produced by the action of β- and γ-secretases

Question 13

Inhibitors of β- and γ-secretase

Answer 13

effective in reducing Aβ formation, but appear to make cognition impairment worse

Question 14

Kinase inhibitors aimed at preventing Tau phosphorylation

Answer 14

The large number of phosphorylation sites and different kinases make this a difficult approach

Question 15

Immunization against AβB

Answer 15

initial trials in humans had to be terminated because of neuroinflammatory complications

Question 16

Monoclonal Aβ antibodies

Answer 16

little/no benefit, make things worsE?

Question 17

NSAIDs

Answer 17

epidemiological studies suggested that some NSAIDs reduce the likelihood of developing AD
clinical trials with various NSAIDs have so far failed to show evidence of consistent benefit

Question 18

main class for AD

Answer 18

cholinesterase inhibitors

Question 19

first drug approved for treating AD

Answer 19

tacrine

Question 20

mechanism cholinesterase inhibitors AD

Answer 20

enhancement of cholinergic transmission

Question 21

Donepezil, rivastigmine, galantamine

Answer 21

same basis, also limited efficacy, less toxicity than tacrine

Question 22

Side effects cholinesterase inhibitors

Answer 22

Side effects can be limiting
gastrointestinal symptoms (nausea, diarrhea, cramps)
altered sleep with unpleasant or vivid dreams
bradycardia (usually benign)
muscle cramps

Question 23

memantine

Answer 23

weak antagonist at NMDA receptors (AD)
works in moderate or severe AD
not neuroprotective

Question 24

memantine mech

Answer 24

Possible mechanism
Selective inhibition of excessive, pathological NMDA receptor activation
Preserves more physiological NMDA receptor activation

Question 25

AE memantine

Answer 25

Headache
Dizziness
Drowsiness
Constipation
Shortness of breath
Hypertension
Many other less common problems