ADHD Pahtophysiology Flashcards

1
Q

ADHD Defined

A

Inattention (distractibility from sustained tasks)
Hyperactivity (excessive physical restlessness and activity)
AND/OR
Impuslsivity (impaired impulse control)

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2
Q

ADHD Cause

A

Exact cause is unknown but it involves hypoactivity of key dopaminergic and/or adrenergic pathways in the basal ganglia and frontal cortex

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3
Q

Combined Type ADHD

A

If both inattention and hyperactivity/impusivity criterion are met for 6 months

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4
Q

Predominatly Inattentive Type ADHD

A

if inattention criterion is met but hyperactivity/impulsivity criterion is not met for the past 6 months

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5
Q

Predominantly Hyperactive-Impulsive ADHD

A

If hyperactivity/impulsivity criterion is met but inattention criterion is not met for the past six months

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6
Q

Comorbidities seen in untreated ADHD

A

MDD or anxiety disorder (25%)
Oppositional Defiant Disorders (60%)
Substance abuse, academic failure, work/family problems and emotional distress

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7
Q

**Genes in ADHD

A

Dopamine (MAJOR)
Serotonin
NE (alpha 2A)

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8
Q

**Environmental Causes of ADHD

A

Smoking
Lead exposure
Alcohol
Viral infections
Food and food additive (less than 5% of cases)
Lack of essential fatty acids or thyroid hormones

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9
Q

Age of Onset for ADHD

A

Around 6 or 7
Symptoms of inattention become noticeable
Synapses begin to be eliminated here and continue through early adolescence

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10
Q

What symptoms increase with age?

A

Inattention

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11
Q

What symptoms decrease with age?

A

Impulsivity and hyperactivity (you learn what is and isn’t okay)

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12
Q

Hypotheses of ADHD Malfunction

A

Response inhibitoin of executive brain function is deficient in the PFC
Dysregulation of arousal (treatments modulate DA and NE to improve executive function and regulate arousal)

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13
Q

PFC in Humans

A

It makes us human
It exerts executive control over decision making and behavior
It helps anticipate reward, punishment, for empathy and complex emotions

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14
Q

Dorsal Anterior Cingulate Cortex =

A

SELECTIVE ATTENTION

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15
Q

Dorsolateral PFC =

A

SUSTAINED ATTENTION, PROBLEM SOLVING AND EXECUTIVE FUNCTION

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16
Q

PFC =

A

HYPERACTIVE SYMPTOMS

17
Q

Orbitofrontal Cortex =

A

IMPULSIVE SYMPTOMS

18
Q

Deficient Arousal

A

State of hypoarousal during the day may experience inattentiveness, cognitive dysfunction and sleepiness with impulsivity all caused by HYPOACTIVITY in the OFC

19
Q

Enhancing Arousal in PFC

A

Increase teh drive of the arousal netwrok by enhancing arousal NT DA and NE

20
Q

Excessive Arousal

A

All due to PFC being out of tune
Associated with phasic firing of DA and NE neurons
Stress activates NE and DA circuits leading to phasic firing!!

21
Q

Stimulant MOA

A

Slow-dose stimulants amplify tonic NE and DA signals (Block NET in PFC and DAT in NA)

22
Q

Methyphenidate MOA and dose

A

Daytrana patch, concerta, ritalin
Blocks NET adn DAT
Low dose given slowly

23
Q

Ampehtamine MOA

A

Adderall, adderall XR, vyvanse

Competitive inhibitor and psuedosubstrate for NET and DAT

24
Q

Stimulant Effects

A

Improvement depends on how fast, how much and how long
Want: slow onset, robust drug levels and long duration
Don’t Want: pulsatile stimulants bc they cause rapid increase in NE and DA leading to euphoria and abuse

25
Q

Stimulants QD

A

Provide 8-12 hours of control

Methylphenidate (concerta and daytrana patch)

26
Q

Stimulant side effects

A

Rare: height deficit
Reduced appetite and weight loss
Insomnia and headache

27
Q

Non-Adrenergic Agents MOA

A

PFC lacks high concentrations of DAT so DA uses NET sometimes
Inhibiting NET increases both DA and NE in the PFC (not much happens in NA so no abuse potential)

28
Q

Atomoxetine Brand, MOA, time to work

A

Strattera
Selective NE Reuptake Inhibitor
Takes 2-4 weeks to start working
Initially worsens the situation but then will normalize firing

29
Q

Atomoxetine (Strattera) SE

A
Nausea
Anorexia
Fatigue
Sedation
Insomnia
Suicidal thoughts
30
Q

Alpha 2 Adrenergic Receptors

A

High presence in PFC but not NA

Adjuncts to reduce disruptive behavior and aggression and to improve sleep

31
Q

Clonidine MOA & SE

A

Alpha 2 Non-Selective Receptor Agonists

Binds also to imidazoline receptors causes sedation and hypotensive effects

32
Q

Guafacine brand, MOA

A

Intuniv
Selective Alpha 2A Receptor Agonists
Reduced side effect profile