Neuroscience Week 7: ADHD and Stimulant Drugs Flashcards
Uses of stimulants
4 main categories

ADHD was first identified in?

What structures are affected by ADHD?

What impairs PFC cognitive abilities?

ADHD pharmacology drug classes
4 listed
- Stimulants
- NE uptake inhibitior
- α2 adrenergic agonists
- antidepressants

Stimulants to treat ADHD
3 listed
- Methylphenidate
- D-amphetamine
- Modafinil
NE Uptake inhibitor to treat ADHD
Atomoxetine (Strattera)
α2 adrenergic agonists to treat ADHD
Guanfacine
Antidepressants to treat ADHD
Bupropion
Methylphenidate AKA
2 listed
- Ritalin
- Metadate
Methylphenidate MOA
- DAT Blocker
- increases extracellular DA/NE by blocking reuptake (DAT and NET)
D-Amphetamine AKA
3 listed
- Adderall
- Dextrostat
- Methamphetamine HCL
D-Amphetamine MOA
- Desoxyn: DA/NE releaser taken up into vesicles
- Increases extracellular DA by triggering transporter (DAT and NET) reversal
Modafinil AKA
Provigil
Modafinil MOA
inhibits NET and DAT (also increases 5HT and GABA levels (structurally different from amphetamine)
Atomoxetine AKA
Strattera
Atomoxetine MOA
- Selective NET blocker
- increases extracellular NE via reuptake blockade (non-stimulant)
Guanfacine MOA
Selective NE α2A receptor agonist
Bupropion MOA
unicyclic antidepressant (resembles amphetamine) elevates NE via NET
Amphetamine-like stimulants
4 listed

Stimulants like ADHD drugs are likely to?

Stimulant site of action

Question

Amphetamine-like agents CNS effects
4 listed

Amphetamine-like CNS actions

Amphetamine-like drugs side effects
6 listed
- decreased sense of fatigue
- increase in motor activity and mental alertness
- mild euphoria
- brighter spirits
- mild anorexic effect
- insomnia
Dextroamphetamine structure
is the d-isomer of amphetamine and is twice as potent a CNS stimulator on a weight basis than racemic amphetamine
Dextroamphetamine compared to other catecholamines
has a greater CNS-stimulating activity than epinephrine or other catecholamines
Dextroamphetamine clinical uses
- Narcolepsy
- ADD
- ADHD
Methylphenidate MOA
Blocks DAT and NET leading to increased DA
and NE
Methylphenidate structure and properties
- chemically similar to amphetamine
- peripheral pharmacologic actions are milder than those of the amphetamines
Methylphenidate clinical uses
- more noticeable effects on mental function than on motor activities
- narcolepsy
- ADHD
- post-stroke depression
- strong effect on measures of attention
- distractibility
- impulsivity
- social and classroom behavior
Modafinil MOA
Increases DA and NE by blocking transporters but may also increase excitatory glutaminergic transmission
Modafinil addictive potential
- lower addictive potential
- can mitigate cocaine dependence
Modafinil side effects
- Rare cases - serious/life-threatening rash, including Stevens-Johnson Syndrome (Erythema multiforme an allergic reaction)
- Toxic Epidermal Necrolysis (TEN)
- Drug rash with Eosinophilia and systemic symptoms (DRESS) have been reported in adults and children
Can mitigate cocaine dependence
Modafinil
Stimulant-like drugs Pharmacokinetics
4 listed

Question

Amphetamine (stimulant) like agents Side effects and contraindications

Amphetamine (stimulant) like agents Somatic Side effects
- Problems sleeping
- decreased appetite
- Nausea
- Weight loss
- Headache
- Growth suppression in children
- Height and weight should be monitored
- Use with caution or avoid in patients with glaucoma
Amphetamine (stimulant) like agents Neurologic Side effects
5 listed
- Hallucinations
- Psychosis
- Tics
- Tourette’s Syndrome
- Seizure
Amphetamine (stimulant) like agents Cardiovascular Side effects
- increase systolic and diastolic blood pressure or respiratory stimulation
- at higher dosages and in overdose: heart rate may increase or reflexively decrease in response to blood pressure
- Cardiac arrhythmias may occur secondary to increased sympathomimetic effects
- sudden cardiac death especially where there are structural abnormalities
Amphetamine (stimulant) like agents and MAOI
can be a risk of serotonin syndrome and avoid in patients on MAOI
Amphetamine (stimulant) like agents Cardiovascular
recommend all children with ADHD have a thorough cardiovascular assessment prior to initiation of drug therapy
Atomoxetine structure and description
a SNRI and the first-nonstimulant drug approved for attention-deficit hyperactivity disorder
Atomoxetine is strucutrally similar to?
Fluoxetine
Atomoxetine promiscuity
minimal affinity for other neurotransmitter’s transporters or receptor sites
Atomoxetine abuse potential
no potential for abuse and is not classified as a controlled substance
Atomoxetine cardiovascular concerns
- safe in adolescents and children
- Little effect on CV
Atomoxetine clinical use
considered an alternate ADHD therapy in patients where psychostimulants are not an option
Question

B.
Atomoxetine Pharmacokinetics
- rapidly absorbed from the GI tract
- Cmax 1-2 hours

Atomoxetine side effects: Children
- Nausea/Vomiting
- anorexia or a decrease in appetite
- Dizziness and growth suppression
Atomoxetine Side effects: Adults
8 listed
- Headache
- sleepiness
- dizziness
- irritability
- change in libido
- erectile and ejaculatory dysfunction
- menstrual changes
- urinary dysfunction
Atomoxetine GI Side effects
- dry mouth
- Nausea
- abdominal pain
- Vomiting
- serious liver problems (increased hepatic enzymes and bilirubin
Atomoxetine serious risks
increased risk of suicidal ideation (children and adolescents)
Atomoxetine Cardiovascular
- patients with hypertension or cardiac abnormalities should be closely observed while on Atomoxetine as it can increase blood pressure and heart rate
- Avoid in patients with narrow angle Glaucoma
Atomoxetine avoid in patients with?
Narrow angle Glaucoma
Bupropion AKA
- -Zyban
- Wellbutrin
Bupropion description
- Antidepressant drug of the aminoketone class
- NOT a tricyclic antidepressant and is unrelated to other known antidepressants
Bupropion MOA
- Inhibitor of neuronal uptake of NE
- Some activity at SE and DA reuptake
- Bupropion and its amphetamine-like active metabolites inhibit dopamine and norepinephrine transport
- The blockade of NE and 5HT reuptake at the neuronal membrane but also SERT actions are weaker for bupropion than for tricyclic antidepressants
Bupropion structurally similar to
Amphetamine
Bupropion avoid in patients with?
Taking MAOIs
Bupropion Off-label use
Neuropathic pain
Bupropion orthostatic hypotension
well tolerated in patients experiencing orthostatic hypotension with TCAs
Does not inhibit MAO
Bupropion other effects
moderate anticholinergic effects and produces a mild local anesthesia on the oral mucosa
Bupropion clinical uses
- smoking cessation
- off-label addiction to smokeless tobacco
- off-label multiple neurological/psychological uses
- off-label neuropathic pain
Bupropion Pharmokinetics

Bupropion GI Side effects
- Dry mouth
- constipation
- Nausea
- Vomiting
- Weight loss
- Weight gain
- Anorexia
Bupropion Neurologic Side effects
- headache
- insomnia
- sedation
- agitation
- Blurry vision
- Tremor
- greater potential for causing seizures (dose-dependent)
Bupropion Sympathetic Side effects
- excessive sweating
- increased heart rate
Bupropion neuropsychiatric Side effects
6 listed
- confusion
- delusions
- hallucinations
- psychotic episodes (psychosis)
- paranoia
- suicidal thoughts
Clonidine and Guanfacine MOA
Centrally acting α2 adrenoreceptor agonists
Clonidine and Guanfacine Clinical uses
- used primarily for the treatment of systemic hypertension
- ADHD
Clonidine and Guanfacine Halflife
16 hrs
Clonidine and Guanfacine maximum concentration
3 hrs
Clonidine and Guanfacine metabolism
Guanfacine is a substrate of CYP3A4/5 and exposure is affected by CYP3A4/5 inducers/inhibitors
Clonidine and Guanfacine caution
caution in patients taking Ketoconazole and other strong CYP3A4/5 inhibitors
Clonidine and Guanfacine general Side effects
- dry mouth
- sedation
- weakness
- dizziness
- constipation
- impotence
- urinary incontinence
- conjunctivitis
- paresthesia
- dermatitis
Clonidine and Guanfacine Cardiovascular side effects
- risk of rebound hypertension is low but it can occur
- hypotension
- bradycardia
- syncope
- palpitations
- substernal pain
Clonidine and Guanfacine selectivity
- Sedation and somnolence is associated with 2b and 2C activity of clonidine
- Guanfacine is more specific to 2A only
Question

What should I know?

ADHD risk of developing dementia
3X higher