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PHM701 UB Pharmacy > ADHD > Flashcards

ADHD Flashcards

1
Q

Patho/Physical Signs of ADHD

A

Decreased brain volume in prefrontal cortex, caudate nucleus, anterior cingulate gyrus, and cerebellum

As symptoms remit → increased cortical thickening and greater brain volume in regions controlling attention and behavior

-Reduced activity in prefrontal and anterior cingulate cortex - reversed with stimulants
-Lack of connectivity between the prefrontal cortex and precuneus
causes lapses in attention and impulse control
-Decreased activation of the ventral striatum when anticipating reward
-Default mode network over-activity - methylphenidate suppresses
-Active attention: network is suppressed

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2
Q

Symptoms of ADHD

A

Inattention (trouble focusing, etc.)
Hyperactivity (excessive motor activity)
Impulsivity (Desire for immediate rewards or inability to delay gratification)

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3
Q

Diagnosis of ADHD (DSM 5 Criteria)

A

Onset of symptoms must be before 12 years of age
Significant impairment must be seen in > 2 settings (i.e. home, work, school); and symptoms must be documented
Symptoms not aligned with other psychiatric disorder and evidence of impedance in work, school, etc.

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4
Q

Diagnosis (DSM5 Criteria) for Inattention/Hyperactivity (Impulsivity) in ADHD

A

6 or more of the following symptoms must be present for at least 6 months that are inconsistent with developmental level and that negatively impacts directly on social and academic/occupational activities
-Mixed / Predominant Inattention Presentation / Predominant Hyperactive or Impulsive Presentation
For older adolescents and adults (>17 years) at least 5 symptoms are required

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5
Q

Amphetamine vs Methylphenidate Potency

A

Amphetamines > Methylphenidate ; Amphetamines are MORE POTENT
Therefore
Changing methyl. to amphet.? Lower Dose
Changing amphet to methyl? Higher Dose

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6
Q

Stimulants IR vs. ER Advantages

A

Immediate release formulations:
- Dose BID-TID (short half life)
- Drug onset: 15-30 minutes
- Duration: 2-6 hours
Advantages: Lower cost, less insomnia, fewer growth related ADE

Long-acting/extended release formulations:
- QDay
- 8-12 hours symptom control
Advantages: Adherence

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7
Q

Stimulants Adverse Effects

A

Psychiatric: psychosis/mania, aggression/violent behavior, severe anxiety/anxiety attacks
- dose reduction or cessation of stimulant and supportive treatment

Cardiac
-Increased HR by ~5 BPM, increased BP by ~2-7 mmHg
-20% increased risk for ED visits

Growth
- ~1 cm/yr decrease over 1-3 yrs (kind of negligible)
- ~3 kg weight deficit in 1st year (1.2 kg in 2nd year) - ~6.6 lbs weight loss because appetite suppression. Plateaus while on drug
- Drug free trial every year

High fat meals can delay onset of stimulants

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8
Q

Stimulants Dosing

A

Low/slow, no weight based dosing

Effects are rapid, can titrate doses every 3-7 days

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9
Q

Stimulants - Drug Interactions

A

Additive adverse effects when used in combination with other psychostimulants (caffeine, modafanil, nicotine, etc.)
MAOIs should not be used within 14 days of stimulants
MPH can increase TCA concentrations
Antacids, PPIs, and H2RAs can increase absorption of MPH IR formulations and reduce the delayed-release formulations
Antacids decrease excretion of AMP, PPIs can increase rate of absorption of AMP
Acidic agents (i.e. fruit juices) can lower absorption of AMP
CYP2D6 inhibitors can increase mixed AMP salt exposure
Concomitant use with alcohol can result in stimulant dumping

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10
Q

Stimulants Adverse Effects and Management

A

Reduced appetite/weight loss = High calorie meals when stimulant effect low (breakfast/bedtime) ; Cyproheptadine at bedtime
Stomachache = Take on full stomach ; Lower dose
Insomnia = Give dose earlier in the day; Lower the last dose of the day/give earlier ; Add sedating medication at bedtime (guanfacine, clonidine, melatonin, or cyproheptadine)
Headache = Divide dose, give with food, or give an analgesic
Rebound symptoms = Long-acting stimulant trial ; Atomoxetine, antidepressant
Irritability/jitteriness = Assess for comorbid condition ; Reduce dose ; Consider mood stabilizer or atypical antipsychotic

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11
Q

Uncommon Adverse Effects with Stimulants

A

Consider dose reduction/consider medication change:
Dysphoria/Euphoria (re-evaluate diagnosis)
Zombie-like state
Tics or abnormal movement
HTN or pulse fluctuations

Hallucinations - Discontinue stimulant, Reassess diagnosis, Mood stabilizer and/or antipsychotic may be needed (possibly schizophrenia or other psychiatric disease)

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12
Q

MPH IR

A

Ritalin ; Methylin
5-20mg TID usually
MDD 60mg

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13
Q

MPH ER

A

Metadate ER ; Quillivant XR
Usual Dosing 20-40 mg QAM
MDD 60 mg
Shorter duration of effect for ER: 3-8 hours
30% IR/70% ER

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14
Q

MPH ER Chew

A

Quillichew
Usual dose 20-30mg QAM
10-12 hour duration of action
30% IR/70% ER
Tablets scored and able to be halved

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15
Q

MPH CD

A

Metadate CD
Biphasic; Has 2 peaks (1.5h and 4.5h)
6-8h duration of effect
Usually 20-40mg QAM
MDD 60mg
30% IR & 70% ER beads
Can open and put on applesauce

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16
Q

MPH LA

A

Ritalin LA
Biphasic; 2 peaks at 2h and 7h
6-8h duration of effect
Usually 20-60mg QAM
MDD 60mg
50% IR & 50% ER beads
• Can open and put on applesauce
• Best for more severe morning symptoms compared to CD/MLR

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17
Q

MPH XR Suspension

A

Quillivant XR
Usual dose 20 mg QAM (doses >60 mg not studied)
• Requires VIGOROUS shaking for at least 10 seconds
• Reconstituted by Rph – good for 4 months

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18
Q

MPH OROS

A

Unique product that releases at different parts of the GI tract. Less peaks and troughs. More difficult to abuse
10-12h duration of effect
Usual dose 20-60 mg QAM
MDD 60 mg
• Swallow WHOLE, do not crush/chew

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19
Q

MPH MLR

A

Aptensio XR
Duration of effect 12h
Usual dose 10mg QD
• Better for rebound afternoon symptoms due to larger ER ratio

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20
Q

MPH MLR-02

A

Adhansia XR
13 hour duration of effect
Usual dose 25mg QD

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21
Q

MPH XR-ODT

A

Cotempla XR-ODT
12h duration of effect
Usual dose 17.3mg QD
Increase dose weekly in increments of 8.6-17.3mg
MDD 51.8mg
Do not push tablet through foil; peel foil back
Dissolve on tongue, no liquid needed

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22
Q

MPH Transdermal Patch

A

Daytrana
11-12h duration of effect
Usual dose 10-30mg
Apply 2h before affect needed
FDA Approved 6-17yo, not FDA approved >17yo
Can only apply to HIP
Max wear time is 9 hours
Effects last ~1h after removal, up to 3h
>50% of methylphenidate remains in patch - abuse/misuse potential when discarding
Application Site Rxns: Erythema / contact sensitization, Chemical, Leukoderma/Hypopigmentation
BBW: Skin reaction: Chemical leukoderma and/or severe allergic contact sensitization
Tics occur more often with patches

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23
Q

Dexmethylphenidate (Dex-MPH) IR

A

Duration of effect 3-6h
Usual dose 5-10 mg BID
MDD 20mg
• No greater benefit over MPH
• ½ dose of MPH because higher potency when adding dex

24
Q

Dexmethylphenidate (Dex-MPH) XR

A

Duration of effect 9-12h
Usual dosage 5-20mg QAM
MDD 20mg
50% IR & 50% ER beads
• Peak serum 1.5 &6.5 hrs after taken
• Afternoon symptom control not as good as OROS

25
Q

Dexmethylphenidate / Serdexmethylphenidate

A

2h onset of effect
10-12 hour duration of effect
Usual dosage 52.3mg for ser-dex and 10.4mg for dex-MPH
• Serdexmethylphenidate pro-drug of dexmethylphenidate
• Risk suicidal ideation

26
Q

MPH PM

A

Jornay PM
Multiple Layer Beads - Unique Product
Onset of Effect >/10 hours
Duration of Effect 24-36h
Usual dosage 25-100mg QD
• No more than 5% of total drug absorbed in first 10 hours
• Administer between 6:30-9:30 PM
Sprinkle-able
Not recommended to convert mg to mg from other methylphenidate products

27
Q

MPH PK and Dosing

A

Pharmacokinetics
-Selectively inhibits presynaptic reuptake of DA & NE → increased neurotransmitter activity
in the CNS
-DA&raquo_space; NE
-Time to peak concentrations can be delayed by high fat meals

Dosing
-Titrate weekly until clinical response observed
-IR products dosed at least BID
Preferred for patients <16 kg
-Afternoon IR dose should not be given <6 hours before bedtime

28
Q

Preferred stimulant in children/adolescents

A

Methylphenidate! Even though it doesn’t have the FDA approval

29
Q

MPH Pearls

A

• Ramp effect: behavioral effects are proportional to the rate of methylphenidate absorption into CNS
• Use in caution in patients with glaucoma, tics, psychosis, and concurrent monoamine oxidase inhibitor (MAOI) use
• Safe/effective in patients with epilepsy
• Priapism reported in pediatrics and adults after prolonged exposure, dose increases, or drug withdrawal

30
Q

Mixed AMP - IR salts

A

Adderrall
5-8h duration of effect
Usual dosage 5-20 mg BID
MDD 40 mg
FDA approved in children 3 yo and older

31
Q

Amphetamine Sulfate IR

A

Evekeo
4-6h duration of effect
Usual dosage 5-40 mg Qday to BID (start@2.5 mg in 3-5 y/o)
FDA approved in children 3 yo and older

32
Q

Amphetamine Sulfate ODT

A

Evekeo ODT
4-6h duration of effect
Usual dosage 10-40mg QD

33
Q

Mixed AMP-XR salts

A

Adderall XR
Duration of effect 10 hours
Usual dosage 5-30 mg QAM
MDD 30 mg
• 50% IR & 50% ER
• May be opened and sprinkled on applesauce

34
Q

Amphetamine sulfate XR solution

A

Dayanavel XR
Duration of effect 8-10h
Usual dosage 2.5-5 mg Qday
MDD 20 mg
• Dose conversion NOT 1:1 – must retitrate
Side effects: epistaxis (nose bleed), upper abdominal pain, allergic rhinitis

35
Q

Amphetamine sulfate XR-ODT

A

Adzenys XR-ODT
Duration of effect 10-12 hours
Usual dosage 6.3-12.5 mg QD
DO NOT CHEW - ODT must be dissolved

36
Q

Amphetamine sulfate ER suspension

A

Adzenys ER
Duration of effect 10-12h
Usual dosage 6.3-12.5 mg QD

37
Q

Amphetamine sulfate XR

A

Mydayis
Duration of Effect 16h (longest of amphetamine agents)
Usual dosage 12-50 mg QD
FDA approval ONLY for >/13 years old
MDD 50 mg adults / 25 mg adolescents
Cannot convert mg-to-mg with other amphetamines
Triple time release beads within capsule to reduce medication wearing off

38
Q

Dextroamphetamine (d-AMP) IR

A

Dexedrine, Zenzedi
Duration of effect 4-6h
Usual dosage 2.5 mg – 40 mg per day

39
Q

d-AMP-IR liquid

A

ProCentra
Duration of effect 4-6h
Usual dosage 2.5 mg – 40 mg per day

40
Q

d-AMP-ER

A

Dexedrine Spansule
Duration of effect 6-10h
Usual dosage 5-40 mg QD

41
Q

Lisdexamfetamine

A

Vyvanse
Duration of effect 8-14h
Usual dosage 10-30 mg QAM
MDD 70 mg
• Designed for less abuse potential

42
Q

Dextroamphetamine transdermal

A

Xelstrym
FDA approved for >/6 years & adults
Dosage ranges 4.5-18mg
Usual dosage 4.5 mg/9h Qday
MDD 18 mg/9H
Apply 2h before effect is needed
Can apply to Hip, upper arm, chest, upper back, flank
Max wear time of 9 hours
3h of effect after removal
<10% dextroamphetamine remains in patch
Application Site Reactions: Pain, itchiness (resolves with wear)

43
Q

Amphetamine PK

A

-Increase the release of DA and NE into the synapse from pre-synaptic nerve terminal (different from MPH which inhibits presynaptic reuptake)
-Enhance release of NE in periphery
-High doses – stimulate serotonin release and acts as serotonin agonist
-High fat meals delay time to peak concentration

44
Q

Amphetamines dosing and contraindication

A

Preferred stimulant in adults
Dosing
-Titrate weekly until clinical response
-IR formulations given at least BID
-Preferred for <5 years old
-Afternoon dose should not be given <6 hours before bedtime
Contraindications
-Not the preferred agent if patient has history of cardiovascular disease (moderate to severe HTN, arrhythmias, heart failure, recent MI)

45
Q

Preschool Aged Children (3-5yo)

A

MPH recommended first line medication
-Strongest safety/efficacy in this population, but available evidence NOT strong enough for FDA approval
AMP only medication with FDA approval because FDA approval was less stringent at time of drug development
Non-stimulants NOT recommended for treatment in ages 4-5 years
Pharmacologic treatment reserved for:
-Moderate-to-severe dysfunction, persisting for at least 9 months, manifesting at home and at school, not responding adequately to PTBM

46
Q

Atomoxetime

A

Strattera
Norepinephrine Reuptake Inhibitor
Dosed QD-BID, BID to improve tolerability in children
Onset of effect 1-2 WEEKS
Duration of effect 10-12 hours
Usual dosage range 5-20mg BID ; MDD 40mg
Potential for liver toxicity with long term use
Increased concentrations by paroxetine & fluoxetine
Behavior may worsen initially

47
Q

Viloxazine ER

A

Qelbree
Norepinephrine Reuptake Inhibitor
1 dose per day
Onset of Effect 1-2 WEEKS
Duration of effect 24h
Usual dosage range: 100 – 600 mg Qday
<17 y/o: MDD 400 mg
Adults: MDD 600 mg
Renal dose adjustment required
Lots of DDIs: Viloxazine (strong CYP1A2 inhibitor, weak CYP2D6 & CYP3A4 inhibitor):
• Antidepressants – duloxetine, fluoxetine, paroxetine, venlafaxine, TCA’s
• Antipsychotics – aripiprazole, asenapine, chlorpromazine, clozapine, olanzapine, perphenazine,
risperidone, thioridazine
• Benzodiazepines
• Buprenorphine, hydrocodone, methadone, oxycodone
(Can’t use Viloxazine in pt getting methadone from clinic)

48
Q

Norepinephrine Reuptake Inhibitor

A

Atomoxetine and Viloxazine ER
• Inhibits pre-synaptic reuptake of norepinephrine
• Safe and effective in children, teenagers and adults
• Head-to-head trials show stimulants have greater efficacy than atomoxetine
• Full benefit may not be seen for 6-8 weeks
Adverse effects:
• Upset stomach, psychiatric, and cardiovascular effects (QTc prolongation)
• Not recommended in those with structural heart defects or serious heart problems
• Greater risk fatigue, sedation, and dizziness
• Only FDA approved ADHD medication with a BBW for new-onset suicidality
Drug interactions: (agent specific not included)
• Do not use in combination with one another
• QTc prolonging medications (antipsychotics, TCA’s)

49
Q

Clonidine ER

A

Kapvay
Alpha-Adrenergic Receptor Agonists
Dosed 1-2 times a day
Onset of Effect 1-2 WEEKS
Duration of effect 10-12h
Usual dosage range: 0.1 mg QHS or BID
MDD 0.4 mg
Commonly added adjunct to stimulants
See general class card for more info

50
Q

Guanfacine ER

A

Intuniv
Alpha-Adrenergic Receptor Agonists
Dosed QD
Onset of Effect 1-2 WEEKS
Duration of effect 18 hours
Usual dosage range: 1-4 mg QD
MDD 7 mg
See class card for more info

51
Q

Alpha-Adrenergic Receptor Agonists

A

Clonidine ER and Guanfacine ER

• Increase blood flow to pre-frontal cortex (enhances working memory and executive functioning)
and inhibits norepinephrine release
• Not as effective as stimulants for monotherapy (nothing is)
Adverse effects:
• Sedation/dizziness
• Hypotension
• Constipation
• Heart block
Extended release should not be taken with a high fat meal

52
Q

Bupropion

A

50-300 mg/day
(3-6 mg/kg/day for all formulations)
Weak dopamine and norepinephrine reuptake inhibitor
Found beneficial in adolescents with ADHD and depression
Metabolized faster in prepubertal children → BID dosing optimal for dosing (even in SR formulations)
Adverse effects:
-Less appetite suppression and weight loss compared to stimulants
-Seizures - lowers seizure threshold, don’t use in pt who have seizures

53
Q

Tricyclic Antidepressants

A

Dr. Burns skipped past, doesn’t like these as an option

Imipramine: 50-150 mg/day
Desipramine: MDD 300 mg/day
Nortriptyline: MDD 300 mg/day
Up to 4 weeks to see maximum effects
Adverse effects
-Sedation/dizziness
-Constipation
-Heart block
-Weight gain
-Overdose toxicity*
-Rapid heart beat

54
Q

Lithium / Anticonvulsants

A

Lithium, valproate, carbamazepine
Effective for:
-Aggression
-Explosive behavior
-Impulsivity
-Childhood-onset bipolar disorder or combined ADHD-bipolar disorder

55
Q

Antipsychotics

A

Usually used with stimulants in patients with ADHD
We normally stay away from FGA because EPS risk
Chlorpromazine & haloperidol
-Hyperactivity
-Impulsivity
-Negative effects on learning, cognitive function, and can cause extrapyramidal side effects

Second generation: risperidone, olanzapine, quetiapine, ziprasidone, & aripiprazole
-Severe aggression (comorbid conduct or bipolar disorder)
-Risk of metabolic syndrome

56
Q

Extra Material

A

-Methylphenidate formulations less likely to have drug interactions than amphetamine salts
-Males have increased bioavailability of methylphenidate compared to females
-Monitoring all agents: Height, weight, eating, sleeping patterns – baseline and every 3 months
Atomoxetine/viloxazine/bupropion: adequate trial = 6 weeks at maximum tolerated dose
Guanfacine/clonidine: monitor blood pressure and pulse; adequate trial = 1-2 months
-EKG not mandatory, but often completed

57
Q

What types of agents can’t be used in <6yo?

A

Non-stimulants
Patches
ER formulations

PHM701 UB Pharmacy (10 decks)

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