Cognitive Enhancers Flashcards
What are common misdiagnosis of ADHD?
Learning disabilities or mood problems
Difficult children who are just diagnosised are treated
What is ADHD?
A development disorder
What are the brain pathways of NE and DA?
Norepinephrine:
- Locus Coeruleus –> prefrontal cortex (thinking)
- LC –> limbic system (emotions)
Dopamine:
- Tegmentum –> prefrontal cortex
- Tegmentum –> limbic system
What are the two pathways for maintaining and focusing attention?
Prefrontal (NE)
Mesocortical (DA)
What happens if you have an altered pathway of NE and DA?
Primary and many secondary symptoms of ADHD
What are treatments of ADHD?
Psycostimulants - methylphenidate, amphetamines
Atomoxetine
How are amphetamines released?
Immediate - Dexedrine
Sustained - Dexedrine spansules, adderall XR
How is methylphenidate released?
Immediate - Ritalin
Sustained - concerta and metadate CD
What psycostim also enhances NE release?
d,l - amphetamine
Why do stimulants calm the patient?
Because in ADHD patients the inhibitory pathways are not working
A stimulant at low doses stimulates only the inhibitory pathway
Why does alcohol work the way it does?
It is a depressant but it takes out the inhibitory pathways
What is reverse tolerance?
Become sensitive enough they can lower the dose
Can become psychotic with chronic use
What is Atomixetine?
Highly selective NE reuptake inhibitor
Also elevates DA in prefrontal cortex but NOT in the nucleus accumbens or the striatum (euphoria)
No abuse potential, not really controlled
Only approved drug to treat adult ADHD
What are some side effects of Atomixetine?
- Difficulties in working memory
- Cholinergic neurons also effected
What is the prevalence of Alzheimer disease?
60-90 years of age
1%-40%
What are symptoms of AD from?
Destructions of several areas
- Nucleus basalis of Meynert (NBM)
- brain center where many Cholinergic neuron cell bodies originate
- earliest site of damage
What are the two microscopic pathologies?
Neurofibrillary tangles
Beta-Amyloid plagues
What are neurofibrillary tangles?
Structurally incompetent tau protein
Surrounds microtubules and stops movement
Interferes with transport
What are beta amyloid peptides?
NBM
Overproduced and accumulate in the synapse
Interferes with normal Cholinergic transmission
- memory loss
Damage goes further and then to neocortex
What is the treatment of AD?
Cannot cure
Cholinesterases inhibitors slow down but only 1yr in 20% of patient
Leads to adverse affects because you are raising ACh everywhere instead of just the places where degeneration has occurred
What is Rivastigmine (Exelon)?
Inhibits both AChE and BuChE
Twice daily
More GI problems and muscle weakness than others
What is Tactine (Cognex)?
AChE inhibitor
Short half life –> needs multiple intake –> poor compliance
Many drug interactions (NSAIDs)
May cause liver damag
Second-line treatment
What is Galantamine (Razadyne)?
Inhibits AChE
Stim nicotinic Cholinergic neurons to release more ACh
Watch out for other drugs (especially NSAIDs)
What is Memantine (Namenda)?
Moderate to severe AD
Antagonist at NMDA subtype of glutamate receptor
Better in late stages
What two drugs have no real evidence in AD?
Estrogen
Selegiline
Vitamin E
What is Ginko Biloba?
Modest benefit for AD
Serious side effects
What are Nootropics?
“Smart drugs”
Wakeful enhances”
Modafinil and Armodafinil
Increased release of NE and DA
Elevates levels of hypothalamic histamine
Lower abuse potential
What are Nootpics (Eureroics) approved for?
Treatment of:
Narcolepsy
Shift work sleep disorder
Excessive day time sleepiness associated with obstructive sleep apnea
