Exam 4 ADHD Flashcards
When the body first receives sensory or internal milieu input, where does it go?
Brainstem Reticular Formation
Ultimately, where does all sensory input end up going? (This place mediates conscience)
Cerebral Cortex
What are two possible causes of ADHD in early life?
-Low birth weight
-Fetal alcohol syndrome
What is the main implicated system in ADHD?
Dopamine transporters
What is the main physiological goal of ADHD treatment?
Increase brain activity by causing more action potentials to fire
What classifications must someone meet to be diagnosed with ADHD?
6 or more symptoms present
(for adults 17 and older, 5 symptoms are required)
Several inattentive or hyperactive symptoms must be present prior to age 12
Significant impairment in two or more settings
*Interferes with functioning and development
What is a possible circuity mechanism of ADHD?
Medial Prefrontal Cortex (mPFC) may not be fully developed
*this brain region is important for inhibition of impulsive thoughts
*not fully formed during childhood and suppressed with alcohol
What are methylxanthines and how do they work?
Indirect-Acting Sympathomimetics
-stimulants that mimic the effect of endogenous agonists of the sympathetic nervous system (fight or flight)
*stimulate the brain and make it more active
What substance is considered a stimulant and has a similar structure to the stimulant meds?
Caffeine
What are the 3 actions of methylxanthines?
-Antagonize Adenosine Receptors
(naturally produced by brain, quiets body down and slows heart rate, block this to increase alertness)
-Inhibit Phosphodiesterases
(increase cAMP)
-Increase Activity of Ryanodine Receptors
(Increase intracellular Ca)
How does Adenosine work?
-Enhances exocytosis of glutamate so there is less, this quiets the system down
-Opens the K channels so it exits the cell, this hyperpolarizes the cell and quiets it down
want to block this
Which G protein is the adenosine receptor A1 linked to?
Gi/o
(i=inhibitory)
*Inhibits modulation of many neurotransmitters
*Causes sedation/quieting down
Activation of adenosine receptor A1 causes what?
CNS: Sedation, Anxiolysis, Anticonvulsant Activity
Peripheral: Decreased heart rate
Adenosine A2A receptors are linked to which G protein?
Gs
(s=stimulatory)
Activation of Adenosine A2A receptors leads to what?
Vasodilation
Adenosine A2B receptors are linked to which G-protein and where are they found*?
Gs-linked
*Glial cells
(unknown function)
When are Adenosine A3 receptors activated?
Excessive catabolism
(seizures, hypoglycemic stroke)
*Not antagonized by methylxanthines
What are the two main functions of methylxanthines?
Increase alertness
Decrease fatigue
How does Cocaine affect norepinephrine?
Directly blocks the norepinephrine transporter (NET)
-this blocks NE reuptake
-there is an excessive amount of NE in the extracellular space, makes person feel very energized
How do amphetamines affect norepinephrine?
-Can be up taken by norepinephrine transporters (NET)
*Bind VMAT
-This confuses the transporters and they start pumping out more dopamine and NE
-Higher levels of these extracellularly increase alertness and reduce fatigue
Amphetamines act as mimics of NE and reverse transport to outside of the cell
NO DIRECT BLOCKING
What does VMAT stand for?
Vesicular Monoamine Transporter
*note: these package NE and dopamine into transport vesicles
What is a downside of using stimulants?
Target many reward pathways, potential for abuse
What is the primary monoamine affected by stimulants?
Dopamine
*also NE
What is the pharmacology of stimulants?
Monoamine transporters
What is an example of an indirect acting sympathomimetic?
Cocaine
Cocaine inhibits monoamine transporters that transport which substances?
Norepinephrine (NE)
Serotonin (5-HT)
Dopamine (DA)
What medical use does cocaine have?
Local anesthetic
Which receptor is targeted by MDMA (molly/ecstasy)?
5-HT
*research use shows it may increase sociability, researching use in autism
“Psychedelic Revival”
What ideas are fueling the “psychedelic revival”?
-Psychedelics target 5-HT
-May increase sociability/have use in autism
-Not considered as dangerous as other hard drugs
What is the difference between amphetamines and methamphetamines?
Methamphetamines are hard drugs with an extra methyl group that allows them to more easily cross the BBB
What are the Amphetamine drugs?
-Dextroamphetamine (Dexedrine)
-Lisdexamfetamine (Vyvanse)
-Methylphenidate (Ritalin)
-Dexmethylphenidate (Focalin)
-Adderall
-Mydayis
What are amphetamines used for?
-Narcolepsy
-Anorexiant/Weight loss
-ADHD
What are the non-stimulants used for ADHD?
-Atomoxetine (NET reuptake inhibitor for adults)
-TCAs
-Bupropion
-Clonidine/Guanfacine
What is Modafinil used for?
Narcolepsy
*not ADHD
Whay are the drugs used to treat narcolepsy?
-Stimulants
-Solriamfetol
-Modafinil
-Antidepressants
-Xyrem
-Pitolisant
What are stimulants used for regarding narcolepsy?
To treat sleepiness
What is Solriamfetol used for?
Treatment of Obstructive sleep apnea and Narcolepsy Excessive Sleepiness
(TONES)
What is the MOA of Solriamfetol?
NET and DAT inhibitor
What is the MOA of Pitolisant?
Histamine 3 (H3) receptor antagonist
When does a person have a higher chance of being diagnosed with ADHD?
If a first-degree relative has it
What is the etiology of ADHD?
Multifactorial
-environmental
-genetics
-physiological
What fraction of children diagnosed with ADHD will continue to have it in adulthood?
1/3
What are two co-morbid conditions that have an increased risk in people with uncontrolled ADHD?
-Substance use
-Antisocial personality disorder
How long does it take to see the effects of stimulants?
Short period of time
How do we dose stimulants?
DO NOT DO WEIGHT BASED DOSING IN PEDIATRIC PATIENTS (variations are not weight-based)
IR preferred for patients <16kg (limited low-dose availability of long-acting stimulants)
Late afternoon symptoms may require longer-acting forms
When should stimulants be taken?
Early in the day, avoid giving dose too late
*may give an after-school dose if afternoon symptoms
When would we use two different stimulants?
NEVER
-can use two different dosage forms of the same stimulant though
Which medication is only used in age 13-17?
Mydayis
Which medication has a patch formulation?
Daytrana
Which medication is a prodrug?
Vyvanse
What is the prodrug Vyvanse converted to?
Dextroamphetamine
Which medication should be taken in the evening?
Jornay PM
(between 6:30pm and 9:30pm)
What are the adverse effects of stimulants?
-Appetite loss
-Stomachache
-Headache
-Insomnia
-Decreased growth
-Hallucinations
-Increased BP!
-Increased HR!
-Priapism (sustained erection)
-Raynaud’s
-Irritability/Jitteriness
**Hallucinations (bad)
**Sudden cardiac death (bad, not high risk)
What do we want to monitor with stimulants?
-Appetite
-Behavior
-BP
-Growth rate
-Heart rate
-Sleep
-ECG (if cardiac risk)
What is Guanfacine ER a substrate of?
3A4
Which medications need to be tapered if discontinued due to rebound hypertension?
-Guanfacine
-Clonidine
Which medication has weight-based dosing?
Atomoxetine
(only up to 70 kg then not weight-based)
What is Atomoxetine a substrate of?
2D6
What is Viloxazine a substrate of?
2D6 and UGT
What is an important fact to note about Viloxazine?
STRONG 1A2 INHIBITOR
What differentiates Viloxazine from other medications?
Capsules
(can swallow whole or put in applesauce)
What are the side effects of Atomoxetine/ Viloxazine?
Increased HR and BP
Increased suicidal thinking (boxed warning) *not an antidepressant
What are the side effects of Clonidine/Guanfacine?
Decreased HR and BP
Orthostasis
Somnolence
Dizziness
Rebound hypertension w/ abrupt discontinuation
What do we monitor with non-stimulants?
Appetite
Behavior
BP
Growth rate
HR
LFT’s****
Sleep
When would we use Bupropion for ADHD?
*Not FDA approved for ADHD
-Attractive in the elderly due to increased dopamine and not controlled
-Consider if patient cannot take stimulants
-Not as effective
What is Bupropion an inhibitor of?
2D6
What medication is contraindicated in seizure disorders and eating disorders?
Bupropion
What are the main concerns with tricyclic antidepressant use for ADHD?
-Less effective than methylphenidates
-Cardiac concerns (sudden cardiac death in children, lethal overdose)
When would we use mood stabilizers/ atypical antipsychotics for ADHD?
If comorbid bipolar disorder, conduct disorder, or intermittent explosive disorder
THESE DO NOT TREAT ADHD
What is the ADHD treatment used in preschool age kids?
First-line: Parent training in behavior management (PTBM)
Second-Line: PTBM plus medications
What is the ADHD treatment used in elementary + middle-school age kids?
First-line: FDA-approved meds + PTBM
What is the ADHD treatment used in adolescents (age 12-18)?
First-line: Meds, may offer PTBM
For preschool-age children, what is the first-line medication class used?
Methylphenidates
For middle school-age kids what is the first- and second-line medications used?
First-line: Stimulants
Second-line: Atomoxetine, Guanfacine ER, Clonidine ER
Which agents can be used as adjunct treatment in ADHD?
Only Guanfacine ER and Clonidine ER
Which agents should be used in adults with ADHD?
1st: Methylphenidate or Lisdexamfetamine (Vyvanse)
2nd: Dextroamphetamine
3rd: Atomoxetine
