principles of drug action exam 3 adhd Flashcards
what is adhd
ADHD is a neurodevelopmental disorder characterized by developmentally inappropriate levels in various combinations across home, school, work and social settings
Inattention
Hyperactivity Impulsivity
most commonly diagnosed behavioral disorder of childhood.
Children must have at least six symptoms from either (or both) the inattention group of criteria and the hyperactivity and impulsivity criteria, while older adolescents and adults (over age 17 years) must present with five
how many symptoms must children and adults have to show signs od adhd
ADHD is the most commonly diagnosed behavioral disorder of childhood.
affects about 3 - 7% of school aged children
In 40–60% of all cases ADHD persists into adolescence and adulthood
(Faraone, Biederman, & Mick, 2006)
Children must have at least six symptoms from either (or both) the inattention group of criteria and the hyperactivity and impulsivity criteria, while older adolescents and adults (over age 17 years) must present with five
Some Symptoms for Inattention:
Failure to sustain attention
Failure to pay close attention to tasks
Difficulty organizing tasks
Doesn’t pay attention to instructions/details
Some symptoms for Hyperactivity
Fidgeting, squirming
Talks excessively
Can’t stay seated if required
how does adhd arise
decreased mesocortical DA and NE
stimulation in the PFC and cortex
Stimulants working through dopaminergic and/or NE pathways increase inhibitory tone on frontal cortical and subcortical structures underlying impulsivity and motor activity
drugs used for adhd first line stimulants
First line drugs include stimulants:
Methylphenidate (Ritalin, Equasym, Equasym XL, Concerta XL)
Ampheatamines (Adderall)
Second line drugs include regulators of
DA/NE:
May be used if stimulants are ineffective or there is concern for abuse potential by patient or family
Atomoxetine (Strattera) Antidepressants (TCAs, Wellbutrin) Clonidine
Guanfacine
Amphetamines are
non-catecholamine, sympathomimetic amines
promote release of catecholamines (primarily dopamine and norepinephrine) from their storage sites in the presynaptic nerve terminals.
Block the reuptake of catecholamines by competitive inhibition
Compete with MAO and reduce breakdown of endogenous biological amines
Amphetamine is exchanged for DA at the vesicle increasing DA in cytosol which is then exchanged with amphetamine to interact with postsynaptic receptors.
(DEXTRO)AMPHETAMINE
Adderall, Adderall XR
pharmacology
1) competes for reuptake;
2) causes the release of norepinepherine from neurons, and dopamine and serotonin at higher doses;
3) inhibits MAO
Mixture of amphetamine salts
Recemic amphetamine aspartate Racemic amphetamine sulfate Dextroamphetamine saccharide Dextroamphetamine sulfate
S isomer is several fold more potent in CNS effects than R isomer
ADDERALL (DEXTROAMPHETAMINE)
Duration
black box warning
dosage recommendations
Duration of action: 4-6 hours
Black Box warnings:
Schedule II controlled substance-addictive potential
Cardiovascular events and death
Dosing recommendations:
Not approved for children under 3
Adderall XR not approved for children under 6
XR- capsules approximately 8-12 hours duration of dosing
Less abuse potential than immediate delivery
Convenience
BUT-Risk of overdose in small children with XR formulations; use only IR forms
DEXTROAMPHETAMINE
Adverse Drug Reactions-
Most common side effects are psychomotor agitation, insomnia, loss of appetite, and nausea
Effect on sleep can be reduced by making sure no drug is given after 12 pm.
Cardiovascular – Palpitations, tachycardia, increased blood pressure, increased heart rate
CNS – Dizziness, euphoria, tremor, precipitation of tics, Tourette’s syndrome, and rarely, psychosis
GI – Anorexia and weight loss, diarrhea, constipation.
Growth inhibition, but usually not lasting but should be monitored
DEXTROAMPHETAMINE-PK
duration of action
half life
metabolism
time to peak
excretion
- *Duration of action:** Tablet: 4 to 6 hours
- *Absorption:** Well-absorbed. Adderall XR: Food does not
affect absorption, but prolongs Tmax by 2 to 3 hours.
Half-life elimination:
Children 6 to 12 years: d-amphetamine: 9 hours; l- amphetamine: 11 hours
Adolescents 13 to 17 years: d-amphetamine: 11 hours; l- amphetamine: 13 to 14 hours
Adults: d-amphetamine: 10 hours; l-amphetamine: 13 hours
Metabolism: Hepatic oxidation via cytochrome P4502D6 to 4-hydroxyamphetamine (active) norephedrine (active), and alpha-hydroxy-amphetamine with both active metabolites subsequently oxidized to 4-hydroxy-norephedrine
Time to peak: Adderall: 3 hours; Adderall XR: 7 hours
Excretion: Urine (highly dependent on urinary pH with acidic urine with more unchanged)
DEXTROAMPHETAMINE drug interaction
Adrenergic blockers, or alpha-blockers, such as the blood pressure drugs doxazosin, prazosin and terazosin may not be as effective. Adderall can increase the potency of tricyclic antidepressants and lead to cardiovascular side effects. Antacids increase absorption of Adderall and should be avoided.
LISDEXAMFETAMINE (VYVANSE) prodrug
Prodrug that is converted to the active component dextroamphetamine
Metabolized to lysine and dexamphetamine noncatecholamine, sympathomimetic amine
METHYLPHENIDATE
pharmacology
half life
schedule drug
formulations
Ritalin, Ritalin SR, Ritalin LA, Concerta, Metadate ER, Metadate CD, Focalin, Daytrana
Pharmacology: mild CNS stimulant related to amphetamine; blocks reuptake of DA and NE, BUT not as effective at release or MAO inhibition
Half-Life – 3-4 hours; 6-8 hours for sustained release
Schedule II controlled substance
Formulations
Tablet, capsule, or liquid
Short acting- 1 dose per day then up to 2 per day
Long acting- 1 dose per day
