Stimulants and Attention Deficit Hyperactivity Disorder (ADHD) Flashcards
The reticular activating system (RAS)
Very complex, contains dopamine, adrenergic, serotonergic, and cholinergic neurons. Regulates arousal, sleep-wake transitions and synchronization of EEG.
genetic factors of ADHD
PTPRF, FOXP1/2, MEF2C, SORCS3, DUSP6
Clinical presentation of ADHD
Symptoms at ages 5 - 9 y.o. (generally before 12 for diagnosis)
Six or more symptoms must be present
Significant impairment in two or more settings (e.g., home vs. school)
Symptoms documented by parent, teacher, and clinician
Interferes with functioning and development
implicated systems in ADHD
Dopamine transporter, COMT, cholinergic receptors, cholesterol metabolism, CNS development, glutamate receptors.
ADHD symptoms
Inattention examples: difficulty organizing tasks/activities, does not seem to listen, easily distracted, loses things for activities
Hyperactivity examples: fidgets or squirms
Impulsivity examples: leaves seat, runs/climbs excessively (e.g., in the mouse model), interrupts
possible circuity mechanism: medial prefrontal cortex (mPFC) control might not be fully functional
Pharmacological treatments
Stimulants (methylphenidate and amphetamine formulations)
Non-stimulants (noradrenaline reuptake inhibitors and a2-adrenergic agonists)
Clinical guidelines recommend stimulants as the first-choice- medication for ADHD
Non genetic ADHD causes
perinatal smoking lead, FASD and low birth weight
Methylxanthines
(stimulant) indirect-acting sympathomimetics: stimulant compounds mimic the effect of endogenous agonists of the sympathetic nervous system
caffeine
a methylxanthine that is broken down into paraxanthine theobromine and theophylinne
Pharmacology of Methylxanthines
Antagonize Adenosine Receptors
Inhibit Phosphodiesterases: Increase cAMP (potentiate Gs-linked receptors)
Increase activity of ryanodine receptors, increasing intracellular Ca2+
Methylxanthines and adenosine receptors (A1)
A1 – Gi/o-linked, pre and post synaptic; inhibitory modulation of many neurotransmitters
Located in cerebral cortex, hippocampus, cerebellum, thalamus, brain stem, and spinal cord.
CNS Activation: sedation,anxiolysis, anticonvulsant activity
Peripheral Activation : decreased heart rate
Methylxanthines and adenosine receptors (A2A)
A2A – Gs-linked, pre and post synaptic;
Located in cerebral vasculature and striatum: vasodilation
Heterodimerize with A1 and D2 dopamine receptors
Methylxanthines and adenosine receptors (A2B)
Gs-linked, mostly on glial cells function unknown
Methylxanthines and adenosine receptors (A3)
Gq-linked, hippocampus and thalamus
(only activated in states of excessive catabolism; e.g., seizures,
hypoglycemia, stroke; not antagonized by methylxanthines)
action of methylxanthines
Mild cortical arousal
increased alertness
Decreased fatigue
Nervousness/insomnia
Ionotropic/ chronotropic effects
Vasoconstriction (cerebral vessels)
Smooth muscle relaxation
Diuretic actions
reward pathways
prefrontal cortex, nucleus accumbens and ventral tegmental area
Indirect-acting sympathomimetics
cocaine alkaloid, inhibit 9blockade only) monoamine transporters (NE, 5HT, DA) used as local anesthetic
amphetamine
Amphetamines
Non-selective activation of monoamines (exception MDMA which is more selective for 5-HT; research use: may increase sociability, “psychedelic revival”)
Wakefullness, alertness, increased ability to concentrate
Highly rewarding = abuse potential
High doses can elicit psychotic behaviors
Abuse: Increase with increased prescribing
amphetamine drugs
Dextroamphetamine (Dexedrine),
Lisdexamfetamine (Vyvanse)
(Amphetamine vs Methamphetamine)
Methylphenidate (Ritalin, d,l-methylphenidate HCl) Dexmethylphenidate
(Focalin, d-methylphenidate)
(Adderall) mixture of salts long acting
(Mydayis) Mixture of amphetamine salts
Adderall
Mixture of salts: long-acting agent dextroamphetamine saccharate, amphetamine
aspartate amphetamine sulfate, and dextroamphetamine sulfate
Non Stimulants for ADHD
Atomoxetine (Stratterera), norepinephrine transporter NET (reuptake) inhibitor (for adult)
TCAs
Bupropion (Wellbutrin)
Clonidine (Catapres)/ Guanfacinen (Tenex)
Modafinil (Provigil)-approved for narcolepsy not ADHD
Alternative Therapies Approaches for ADHD
Elimination of artificial food additives,
colors, and/or preservatives
EEG biofeedback
Essential fatty acid supplementation
Yoga/massage
Green outdoor spaces
Narcolepsy
Excessive daytime sleepiness
Cataplexy/Weakening of muscles
Poor quality of sleep
Sleep paralysis
Hypnogogic hallucinations
Treatment for Narcolepsy
Solriamfetol (Sunosi)-NET and DAT:Treatment of Obstructive sleep apnea and Narcolepsy Excessive Sleepiness (TONES)
Modafinil (Provigil)
Antidepressants
Xyrem (GHB) - Sodium oxybate, which is the sodium salt of gamma-hydroxybutyrate (GHB)
Pitolisant (Wakix) - histamine 3 (H3) receptor antagonist/inverse agonist (presynaptic)
