RXRS 418 - Alertness and Attention

How does ADHD present differently in different types of people?

• How may this impact treatments?

• more common in males compares to females (2:1 in children)

• female present with more inattentive features

• many children outgrow ADHD, but adult ADHD is also common

  • drug therapy for both children and adults is the same

What are the risk factors of ADHD?

• low birth weight, fetal alcohol or cigarette exposure, perinatal stress

• neurotoxin exposure, infections

• genetics

What is the diagnostic criteria for ADHD?

• persistent inattention and/or hyperactivity-impulsivity that interferes with functioning/development

  • 6 or more symptoms for at least 6 months

• symptoms are present prior to age 12

• present in two or more settings (e.g., home, school, or work)

What are the top treatments used for children younger than 19 in the US?

1. methylphenidate (Concerta)

2. atomoxetine (Strattera)

3. amphetamine/dextroamphetamine (Adderall)

Why are psychomotor stimulants the main treatment for ADHD?

because they are drugs that produce behavioral activation → leads to increased arousal, alertness, and motor activity

What are the acute effects of stimulants?

• encreases in ability to focus, sociability, libido, and mood elevation

• euphoria, increased vigor, decreased need for sleep, and ergogenic effects (increased power output)

• neurocognitive enhancing effects in healthy individuals

What is the difference between amphetamines and methamphetamines?

• methemphetamine is the methylated derivative of amphetamine

• methyl group increases drug’s ability to cross BBB

What is the MOA of amphetamines?

• mimic norepinephrine, the primary mediator of the sympathetic nervous system

• increase the availability of norepinephrine in the synapse in three different ways:

  • promote neurotransmitter release

  • block neurotransmitter reuptake

  • block neurotransmitter metabolism

What is the difference between the L and D isomers of amphetamines?

• What are examples of each type?

• D-amphetamine is more psychoactive

  • adderall (contains D and L salts in a 3:1 ratio) is used to treat ADHD and narcolepsy

• L-isomer is still the active ingredient in nasal decongestant inhalers

  • example: Vicks Vapor Inhaler

What are the physiological effects of amphetamines?

• anything that is sympathetic (due to release of norepinephrine and epinephrine)

  • increased BP, HR, bronchial dilation, pupillary dilation

  • decreased glandular secretions

• mnemonic: can’t see can’t pee, can’t shit can’t spit

What is cocaine?

• a schedule II drug that is derived from coca plant Erythroxylon coca

• coca chewing originated in Peru to sustain performance of laborers in Peruvian silver mines

• travel medicine to prevent altitude sickness

What was Coca Cola originally marketed as, and what did it contain?

• originally marketed as brain tonic/intellectual beverage, but actually contained cocaine

• cocaine was eventually removed in 1903

What is the MOA of cocaine?

• reputable inhibition of norepinephrine, serotonin, and dopamine

Do stimulants inhibit growth?

• evidence is INCONCLUSIVE

• may be related to poor nutrition, lack of appetite, and inhibitory effects of increased DA on growth hormones

What are modafinil and armodafinil used for?

• treatment for narcolepsy

• available as a racemic mixture (modafinil) and as the r-enantiomer (armodafinil)

What is the MOA of modafinil and armodafinil?

• weak inhibitor of dopamine (DA) and norepinephrine (NE) reuptake transporters

• requires dopamine transporter and intact alpha-1 adrenergic receptors for activity

• activates neurons in the locus coeruleus

• activates orexin-releasing neurons in the lateral hypothalamus

What are clinical pearls related to modafinil and armodafinil?

• no sleep rebound

• low abuse potential

• ADRs

  • headache

  • nausea

  • dizziness

  • insomnia

What is the MOA of methylxanthines?

• non-selective inhibition of phosphodiesterase

• increase in cyclic adenosine monophosphate and cyclic guanosine monophosphate

• adenosine receptor antagonist

What are the different doses of caffeine, and what are their effects?

• 100–200 mg

  • decrease in fatigue

  • increased mental status

  • alertness

• 1.5 g

  • anxiety

  • tremors

• 10 g

  • cardiac arrhythmias

What are the adverse effects of methylxanthines?

• cardiovascular effects

  • positive inotropic

  • positive chronotropic

• diuretic effects

  • increases excretion of sodium, chloride, and potassium

• gastric

  • stimulate secretion of gastric acid

Polygonum multi florum

• Parts used

• Indication

• MOA

• Special notes

• parts used: white foti, red foti

• indication: energy improvement

• MOA: increase circulation, nourish the blood, liver, and kidneys

• special notes:

  • active ingredients: anthraquinones, lecithin, tannins, and tetrahydroxystilbene glucoside

  • do not use in pregnancy and lactation

  • also helps skin, hair health, and energy levels

  • possible effects on alzheimer's and parkinson's, need more data

Spearmint

• Indication

• MOA

• Special notes

• indication: cognitive support, attention improvement

• moa: modestly improves attention ONLY (but not other measures of cognitive function)

• special notes:

  • active ingredient: rosmarinic acid → might modestly improve memory quality in older adults with cognitive decline

Omega 3

• Indication

• MOA

• indication: not well established for ADHD

• moa: epa/dha have been studied for mood disorders

S-Adenosyl-L-Methoionine (SAME)

• MOA

• Special notes

• MOA: involved in methylation and/or phosphorylation processes that affect membrane fluidity

• special notes: take on empty stomach

Pycnogenol

• MOA

• MOA: influence the release of catecholamines

What are other notable mentions of supplements from other lectures?

• eleuthero root

• rhodiola rosea

ToF: chewing spearmint-flavored gum during memory testing does not improve memory or attention compared to chewing unflavored gum

true

ToF: exercise is not a potential treatment for ADHD

false; exercise can have positive effects on ADHD symptoms