ADHD Patho Med Chem Study Guide

- increase Presynaptic DA and NE release

- inhibit DAT, NET, SERT

Amphetamines MOA

- Adderall

- Vyvanse

- Dexedrine

- Evekeo

Amphetamines drugs

S-amphetamine (dextro) is 3-4x more potent than R-form

Amphetamines potency

Lisdexamfetamine (Vyvanse): converted in liver

Amphetamines prodrugs

β-Phenethylamines; branching at α-position reduces MAO

Amphetamines chemistry

High, with euphoric "rush" feeling

Amphetamines abuse potential

- priapism

- hallucinations (DA)

- dependence risk

Amphetamines AEs

- Inhibit DAT and NET

- some increase DA/NE release

- possible MAOi

Methylphenidates MOA

- Ritalin

- Concerta

- Focalin

- Azstarys

Methylphenidates drugs

Dexmethylphenidate is more potent than racemic version

Methylphenidates potency

Serdexmethylphenidate (Azstarys): gut conversion

Methylphenidates prodrugs

Methylphenidate racemic or dextrorotatory enantiomers

Methylphenidates chemistry

Also high, especially patch formulations

Methylphenidates abuse potential

Skin discoloration with patch form (e.g., Daytrana)

Methylphenidates AEs

First-line for ADHD

Stimulants use

Increase DA and NE signaling (release or reuptake inhibition)

Stimulants MOA

- headache

- insomnia

- weight loss

- stomach ache

- irritability

- priapism

- hallucinations

- skin discoloration (methylphenidate patch)

- Risk of abuse, misuse, and dependence

Stimulants AEs

- Alpha-2 Adrenergic Receptor Agonists

- NET Inhibitors

Non-Stimulants

- Guanfacine (Intuniv)

- Clonidine

Alpha-2 Adrenergic Receptor Agonists drugs

Likely act on α2-AR in prefrontal cortex (not fully understood)

Alpha-2 Adrenergic Receptor Agonists MOA

- Sedation

- dizziness

- constipation

- headache

- less sedation with guanfacine

Alpha-2 Adrenergic Receptor Agonists AEs

- Atomoxetine (Strattera)

- Viloxazine (Qelbree)

NET Inhibitors drugs

- Inhibit NE transporter (NET)

- increase NE (and possibly DA)

NET Inhibitors MOA

- increase HR/BP

- aggression

- insomnia

- dry mouth

- growth retardation

NET Inhibitors Atomoxetine AEs

- increase HR/BP

- insomnia/lethargy

- nausea, headache

NET Inhibitors Viloxazine AEs

Abuse, misuse, addiction

Stimulants (all) BBW

Suicidal thoughts and behaviors

Atomoxetine (Strattera) BBW

Suicidal thoughts and behaviors

Viloxazine (Qelbree) BBW

They mimic sympathetic nervous system activity.

Stimulants are sympathomimetic agents

- increase NE = increase sympathetic tone (fight or flight)

- increase BP and HR

- Vasoconstriction → decrease blood flow to skin/GI

- increase Blood sugar, increase breathing rate

Sympathetic Effects MOA

Risk of hyperthermia, seizures, arrhythmias, heart failure

stimulants high doses

- Contraindicated

- risk of hypertensive crisis due to excessive catecholamine levels

MAOIs and stimulants DDI

increase Risk of CV effects (e.g., decongestants like pseudoephedrine)

other sympathomimetics and stimulants DDI

- CYP2D6 substrate

- CYP2C19 substrate

- potential interaction with inhibitors

Atomoxetine

- CYP2D6 metabolism

- similar interaction potential

Methamphetamine

Reduced efficacy due to stimulant-induced vasoconstriction

Antihypertensives and stimulants DDI

- May counteract stimulant effects

- can lead to unpredictable CNS toxicity when combined

CNS depressants and stimulants DDI