Adhd

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ADHD common dx in?

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peds pt's,4--12% of peds pt's, can be seen in adults too.

Boys 3 times as likely to be dx than girls

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Criteria for treating ADHD

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American Academy of Pediatrics guidelines for diagnosing and treating ADHD

DSM IV

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Diagnosis must include evaluation in two settings

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Objective measures-
Conner scale
Vanderbuilt scales

Parents fill out one scale and school fills out other and a comparison is made to ID components of ADHD

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In addition to the objective measures Determine if other factors present

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Learning disabilities
Oppositional defiant disorder
Anxiety disorders
Mood disorders

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Other medications used to treat ADHD

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Tricyclic antidepressants (desipramine, imipramine)

Bupropion (Wellbutrin®)

Both of these treat HTN
Clonidine
Guanfancine

Non-pharmacological tx: Dietary supplementation
-Essential Fatty Acids
-Vitamins/Minerals
-Limit sugar intake & carbs intake

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1st class Methylphenidate Short Acting

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(Ritalin®, Methylin®)-
Duration 3-5hrs

Dosing Schedule 5-20mg BID to TID

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Methylphenidate Intermediate-acting

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(Ritalin SR®, Metadate ER®, Methylin ER®)-
Duration 3-8hrs
Dosing Schedule20-40mg QD, or 40mg in am and 20mg in early pm

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Methylphenidate Long-acting

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(Concerta®, Metadate CD®, Ritalin LA®, Daytrana®-transdermal patch)
Duration 8-12hrs
Dosing Schedule 18-72mg QD

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Dexmethylphenidate (subclass of methylphenidate) Focalin®, Focalin XR®
Mechanism of Action

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More pharmacologically active enantiomer in comparison to methylphenidate

CNS stimulant that blocks the reuptake of dopamine and norepinephrine in nerve terminals

May indirectly affect action of serotonin

First peak 1 hour, second peak ~5 hrs later-XR formulation (unique to XR formulation)

Capsule can be opened and contents sprinkled on food (granulations)

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Dextroamphetamine 2nd class short acting

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Short Acting (Dexedrine®)
Duration 4-6 hrs
Dosing Schedule 5-15mg BID or 5-10mg TID

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Dextroamphetamine 2nd class Intermediate-acting

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(Adderall®)
Duration 6-8 hrs
Dosing Schedule 5-30mg QD or 5-15mg BID

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Dextroamphetamine 2nd class Long-acting

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(Adderall XR®)
Duration 8-12 hrs
Dosing Schedule 5-30mg q am

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Lisdexamfetamine subclass of Dextroamphetamine 2nd class

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Vyvanse®
Prodrug of dexamfetamine

Drug attached to lysine, inactive until GI enzymes detach lysine from drug creating the active formulation

Long Half life up to 13 hours, 6—8 hours in children (shorter in kids) and 10—12 hours in adults

Can be dissolved in liquid

Lower potential for abuse due to prodrug formulation

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Lisdexamfetamine Vyvanse subclass of Dextroamphetamine 2nd class Mechanism of action

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Mild CNS stimulant (Schedule II controlled substances- can't be RX by NP unless DR approves)

Thought to prevent the reuptake of dopamine, serotonin, and norepinephrine in the presynaptic nerve endings allowing them to stay creating their effects

This action stimulates the cerebral cortex, brain stem and provides stimulation to become more attentive

Clinical use
ADHD
Narcolepsy

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Vyvanse Pharmacokinetics

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Rapidly absorbed after oral administration

Onset, peak and duration vary depending on formulation

Metabolized in liver

Widely distributed throughout the body, including the CNS cross brain-blood barrier

Excreted by kidneys

High potential for tolerance limited therapeutic effect after a while so you will need ot increase dose or pt can take a med holiday

Choose based on schedule of person

Short-acting dosed BID
Long-acting dosed QD

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Stimulants Adverse effects (TX is by trial and error, some may work well in 1 pt and not in others)

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CNS: insomnia*, restlessness*, irritability*, euphoria, headache, dizziness, tremor*, motor tics

GI: anorexia-decreased appetitie often present*, abdominal discomfort, weight loss*

CV: tachycardia*, palpitations*, arrhythmias, blood pressure changes* so make sure to evaluate CV status

Potential for growth suppression*, temporary decrease in linear growth and weight gain
May have wt loss so look at growth chart ad diet so increase protein and fats to prevent wt loss

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Drug interactions

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MAO inhibitors-hypertensive reaction if given together

Other serotonergic agents
Increased risk for serotonin syndrome

Lithium-effects of either drug may be altered

TCA-increased cardiovascular effects

May alter metabolism of some anticonvulsant meds increasing their levels (phenytoin, primidone, phenobarbital)

Can counteract antihypertensives bc of activity on NE

May alter insulin levels slightly (just monitor levels, not a reason to not use)

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Contraindications

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Contraindicated during pregnancy and lactation

Structural cardiac abnormalities, aortic stenosis, CAD, cardiac arrhythmias

Hyperthyroidism

Glaucoma

Motor tics
Tourette’s syndrome
Severe anxiety, agitation, psychosis (bc with these it can exacerbate sx's and can cause psychotic events in psychotic pt's)

MAO inhibitor use within 14 days can cause hypertensive crisis

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Precautions

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Caution with hypertension

Anxiety, bipolar disorder bc severe anxiety or psychosis is contraindicated

Caution with seizure disorder
-May reduce seizure threshold

Caution with history of alcohol/drug abuse bc stimulants can be abused as well

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Precautions

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Feb 2006 black box warning-use in children with cardiac abnormalities-increased incidence of sudden death & also possibilities of aggressive behavior.

AHA recommendations:
Full H&P including PMHx, Fam Hx before starting stimulant medications (hx of sudden death in family)

Can include EKG

Risk factors of sudden death or findings on PE-refer to cardiologist before placing on stimulants

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Other tx options- nonstimulant agents

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Straterra and guanfancine

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Atomoxetine (Strattera®)

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Approved Dec 2002
Not controlled substance

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Atomoxetine (Strattera®)
Mechanism of Action

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Selective norepinephrine reuptake inhibitor (SNRI)-non-stimulant medication

Selectively inhibits the neuronal reuptake of norepinephrine (NE)

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Atomoxetine (Strattera®)
Pharmacokinetics

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Only one formulation, not an ER med...

Administered orally, readily absorbed from GI tract

Substrate for CYP2D6- may have more drug interventions

Excreted in urine

May take up 2-8 weeks to see therapeutic effects- limitation, stimulants usually exert effects quickly and this is not quick

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Atomoxetine (Strattera®)
Clinical Uses

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Only 1 use: Treatment of ADD in children >6 years old, adolescents and adults

Black Box Warning
May increase risk of suicidal thinking in children and adolescents
similar to ATD

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Atomoxetine (Strattera®)
Adverse effects

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GI: nausea, vomiting, anorexia (similar to stimulants)*, decreased appetite*, dyspepsia

CNS: fatigue, dizziness, insomnia (adults)*, headaches, mydriasis

CV: palpitations*, chest pain, hypertension(bc of activity on NE)*

GU: decreased libido*, impotence (both in adults)(similar to ATD)*, urinary retention, dysmenorrhe

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Atomoxetine (Strattera®)
Drug interactions

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Avoid alcohol use

Use with MAOIs can cause serious reactions-seizures, confusion, severe hypertension

Caution with sympathomimetics may increase HR and BP

Strong inhibitors of CYP2D6 will icrease drug plasma levels (some SSRI’s, venlafaxine, cimetidine) different than in stimulant meds

CV effects of beta agonists potentiated with concurrent use (increased HR and BP)
bc of NE

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Atomoxetine (Strattera®)
Contraindications and precautions

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Contraindicated with MAOI use due to hypertensive crisis possibility

Contraindicated in those with closed angle glaucoma (may worsen sx's)

Caution in those with bipolar disorder (may cause manic episode)

Caution in those with liver disease (dose adjustment if liver D/O present)

Caution in those with BPH, bladder obstruction (worsens urinary retention may occur)

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Atomoxetine (Strattera®)
Contraindications and precautions

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Caution with cardiac arrhythmias (bc of effect on NE), cerebrovascular disease, CAD, HTN, stroke, tachycardia, ventricular arrhythmias, ventricular tachycardia and other conditions that increases risk due to elevated blood pressure or pulse rate.

Pregnancy category C(not commonly used)

Must be weaned off when discontinuing due to effects on NE similar to EFFEXOR this way

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Intuniv® (Guanfancine)

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Guanfancine in long acting formulation (hypertensive agent)

Stimulation of central alpha 2 adrenergic receptors agonist similar to clonidine but longer effect

Improves prefrontal cortical function through post-synaptic alpha-2-receptor agonist effects in the prefrontal cortex

Clinical uses FDA approved only for :
ADHD

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Intuniv® (Guanfancine)

Pharmacokinetics

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Long acting formulation

70% protein bound

Metabolized by CYP3A4

Renally eliminated

Half life 13-14 hours in children

Not used in children <6 yrs old

Starting dose 1mg/day, titrate dose weekly by 1mg, max dose 4mg daily
titration rate weekly so they must return weekly until they are at a dose they can tolerate and therapeutic effects are seen

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Intuniv® (Guanfancine)

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CNS depression*, excessive sedation (biggest problem)* and drowsiness*, fatigue*, weakness*
GI: dry mouth*, constipation(similar to clonidine and short acting guanfancine)*, abdominal pain, decrease appetite
CV-chest pain, bradycardia*, hypotension*
Abrupt discontinuation: anxiety, nervousness, diaphoresis, rebound hypertension less common in comparison to short acting central acting alapha 2 agonist

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Intuniv® (Guanfancine)
Drug Interactions

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CNS depressants worsen

Antihypertensives further hypotension and bradycardia can occur

Inhibitors/inducers of CYP3A4 alters plasma level of med

TCAs and guanfancine-increased blood pressure

MAOIs-hypertensive crisis

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Intuniv® (Guanfancine)
Contraindications and Precautions

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Caution with hx of hypotension, AV block, bradycardia, CAD, MI (can worsen bc it can cause these)

Caution with renal impairment (dosing adjustment if it is there)

Caution with hx of depression, syncope ca worsen

Pregnancy category B