Lecture 11 ADHD Flashcards
What kind of disorder is ADHD?
It is a cognitive neurodevelopmental disorder
What is the criteria for ADHD
A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development.
Name the subtypes of ADHD
inattentive, hyperactive-impulsive or combined
What is the prevalence of ADHD?
5% in children (2:1 prevalence in males)
2.5% in adults (1.6:1 in males)
What often co-occurs with ADHD?
Conduct disorder, antisocial personality disorder, borderline personality disorder, bipolar disorder, depression, anxiety disorders, and substance use disorders
What appears to cause the symptoms of ADHD?
Abnormal functioning of various regions of the prefrontal cortex
Dorsal anterior cingulate cortex is important for what?
Selective attention
What are the selective attention deficits in ADHD?
Little attention to detail careless mistakes does not listen loses things distracted forgetful
What does the stroop test evaluate?
Selective attention
DLPFC is important for what?
Sustained attention
trouble following through and finishing tasks
difficulty with organization
avoids sustained mental efforts
The premotor cortex is important for what?
Hyperactivity
fidgeting
gets out of seat frequently
frequent running/climbing
always on the go
The orbitofrontal cortex is important for what?
Impulsivity
Talks excessively
blurts out
interrupts
What is the low arousal theory?
ADHD patients suffer from low arousal of the PFC and seek activity for self stimulation
What are possible factors for ADHD?
Genetics (75% of cases)
Environmental factors
Dietary factors
Childhood neglect, abuse or poor educational opportunities
What are some of the environmental factors for ADHD?
alcohol, nicotine or pesticide during pregnancy results in higher risk of ADHD
How may genetics influence ADHD?
Possibly related to mutations in genes encoding proteins related to monoamine transmission
What are the dietary factors for ADHD?
ADHD has been associated with food colorings and preservatives
Why does ADHD frequently occur in children?
May be due to abnormal neuron/synapse elimination during development of the brain.
What is the hypothesized neural basis of ADHD?
Low levels of NE and DA in the PFC lead to reduced stimulation of DA and NE receptors especially alpha2A and D1 receptors.
What is the general approach in pharmacological treatment of ADHD?
Increase PFC activity to more optimal levels, without “overloading” other systems to produce addiction, psychosis or motor issues.
Name 2 NDRIs and how they work
Methylphenidate and dexmethylphenidate
Block DAT and NET resulting in increased stimulus of DA and NE receptors in the frontal cortex
What composes adderall?
25% mixture of amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate and dextroamphetamine sulfate
How does adderall work?
Amphetamine is a substrate for VMAT and reverse DAT and NET. These amphetamines promote DA/NE release resulting in increased stimulation of DA and NE receptors in the frontal cortex
What is lisdexamphetamine and how is it different from other amphetamines?
Vyvanse is dextroamphetamine conjugated to the amino acid lysine.
Vyvanse itself is inactive but acts as a prodrug to form dextroamphetamine upon cleavage of the from the molecule.
What is beneficial about using a prodrug like vyvanse?
It is longer lasting and less easily abused version of dexamphetamine
Name the 4 selective NE reuptake inhibitors (NRIs) and how they work.
atomextine
reboxtetine
desvenlafaxine
duloxetine
Primarily block NET, they also increase DA levels in the PFC since NETs in this region have high affinity for dopamine
Name two selective alpha2A agonists
Guanfacine and clonidine
these are potentially ideal for patients whose symptoms seem to be mediated by NE deficits only.
What is a draw back of the alpha2A agonist clonidine?
It is not selective and also activates alpha 2b and alpha 2c NE receptors as well as imidazoline receptors which increase side effects such as hypotension, sedation
