lecture 13: drugs for ADHD and narcolepsy

reuptake inhibitors of DA and NE

MOA of amphetamines/methylphenidate

○ Amphetamines displaced stored catecholamines from vesicles

○ Methylphenidates block NET enhanced reuptake and enhance NE signaling

what is the main difference between amphetamine and methylphenidate

atomoxetine

treatment of ADHD with a past medical history of drug abuse, use

weight loss, growth retardation

side effects of stimulants for ADHD in childlren

alpha 2 receptor agonists: clonidine, guanfacine

2nd lline treatment for ADHD in children to prevent growth retardation

HTN, CV effects, insomnia

most common side effects of amphetamines

-modafinil

-sodium oxybate

1st line agents for narcolepsy

Dopamine reuptake inhibitor

MOA of modafinil

GABA-B modulator

MOA of sodium oxybate

Stimulants

•Amphetamine-Dextroamphetamine mixed salts

•Methylphenidate

name the first line therapies for ADHD

Non-stimulants

atomosetine, guanfacine, clonidine

2nd line therapies for ADHD

amphetamines, methylphenidates

MOA: increases central DA and NE activity

amphetamines

Enter synapse using NET transporter and displace stored catecholamines from vesicles, causing reverse transport into synapse via NET

methylphenidates

Block NET-mediated NE reuptake and enhance NE signaling

-interfere with dopamine reuptake by blocking DAT

methylphenidate

MOA: Mild CNS stimulant

•***It blocks the reuptake of NE and DA into presynaptic neurons****

Methylphenidate (Ritalin)

considered first line stimulant in nyounger age groups

-better tolerability

amphetamines

MOA: Inhibit NE and DA reuptake; induce NE and DA release from vesicular storage sites into synapses → ↑↑ NE and DA

amphetamines

1st lline stimulant in adults

-Urinary alkalinizing agents (↑pH) → increase nonionized drug → ↓ excretion

-Acidification of the urine (↓pH) → increase ionized drug → ↑ excretion

describe how pH contributes to stimulant excretion

tics, priapism, dysphoria, psychosis

rare side effect of stimulants

Use w/in 14 days of MAOIs** (phenelzine, selegilin)― **risk of hypertensive crisis

contraindication of stimulants for ADHD

-decrease excretion--> increase toxicity

agents that alkalinize the urine __________ excretion of stimulants

atomoxetine

MOA : •Selective NE reuptake inhibitor (NRI)

oInhibits presynaptic reuptake of NE to increase NE in adrenergic synapse

atomoxetine

•**Not a controlled substance

•GI ADRs ↓(take with food or split daily dose)

•***Low risk of dependence or abuse

•No tapering required upon discontinuation

•Doesn't impact growth**

•Not recommended in pregnancy – limited data

guanfacine and clonidine

Role in therapy: Monotherapy or adjunctive treatment to stimulants (6-17 yo**)

centrally acting alpha 2A adrenergic receptor agonist

MOA of guanfacine and clonidine

-guanfacine: longer half life, once daily dosing

-clonidine: shorter half life, twice daily dosing

what is the difference in dosing guanfacine and clonidine

XR (extended release)

only _____ formulations of clonidine and guanfacine are FDA approved to treat ADHD

atomoxetine, guanfacine, and bupropion

2nd line treatments for ADHD for those whoa re unresponsive or are unable to tolerate stimulants

-excessive day time somnonlence/intrusive drowsiness

-cataplexy

-hallucinations

-sleep paralysis

what is the tetrad of narcolepsy?

narcolepsy

caused by loss of normal function of hypocretin (orexin) system

•Modafinil/Armodafinil

•Sodium oxybate

main treatments for the excessive daytime somnnolence symptoms of narcolepsy

modafinil and armodafinil

•Wakefulness-promoting agents**

•Non-amphetamine CNS stimulants (less potential for abuse**)

•Inhibition of DA reuptake (weak*) → stimulate hypocretin (orexin)-containing neurons in prefrontal cortex and hypothalamus

•Increase levels of DA in the nucleus accumbens

MOA of modafinil and armodafinil

modafinil

Modafinil induces cytochrome P450 enzymes (CYP3A4), which increases estrogen metabolism, reducing the effectiveness of birth control pills

decreases the efficacy of oral combined contraceptive pills and antiseizure meds

sodium oxybate

MOA: CNS depressant that acts on GABA-B receptors, promoting deep sleep and reducing cataplexy (GABA-B modulator**)

atomoxetine

antidepressants

off lalbel use of TCAs, SNRIs, SSRIs

-seleggiline

classes of drugs for cataplexy

insomnia and anxiety

most common side effect of modafinil

alcohol

______ should be avoided when taking sodium oxybate

modafinil

has a lower risk that amphetamines in excacerbating anxiety

Armodafinil is the longer-acting R-enantiomer of modafinil

how is armondafil differ from modafinil?

opioids

take _____ with cation while on oxybate