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Methylphenidate and Attention DeficitHyperactivity Disorder

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Title: Methylphenidate and Attention DeficitHyperactivity Disorder


1
Methylphenidate andAttention Deficit/Hyperactivi
ty Disorder
  • by Lisa Taylor
  • Drugs and Behavior
  • Dr. Paul Young

2
Amphetamine-like drugs
  • Classified as stimulants and have been used to
    treat AD/HD in children and adolescence since
    1936 (Julien, 1998, 145).
  • Treatment started with the use of amphetamine and
    dextroamphetamine (Julien, 1998, 145).
  • Used to elevate mood, induce euphoria, increase
    alertness, reduce fatigue, decrease appetite,
    improve task performance and relieve boredom
    (Julien, 1998, 119).

3
Attention Deficit Hyperactivity Disorder
  • ADHD is the most common psychological disorder of
    childhood, estimated to affect 3 to 9 of
    school-age children.
  • ADHD is characterized by problems with attention,
    learning, impulse control, and hyperactivity.
  • 1.29 million children with ADHD are being treated
    with stimulant medication.
  • (Julien, 1998, 144).

4
AD/HD continued
  • 40-60 of affected individuals with AD/HD have
    persisting symptoms beyond childhood into
    adulthood.
  • Comorbidity with conduct disorder, oppositional
    defiant disorder, learning disorders, anxiety
    disorders and mood disorders exists within 2/3 of
    elementary school-age children with ADHD
  • (Julien, 1998, 144).

5
ADHD and school peformance
  • High risk relative to normal population with
    respect to scholastic and social failure in
    school settings (DuPaul Eckert, 1997, 5).
  • Methylphenidate results in immediate improvements
    on various academic type tasks (reading
    performance, classroom seatwork, academic
    performance and tasks) (Carlson Bunner, 1993,
    184).

6
Methylphenidate (Ritalin)
  • Ritalin has been used since 1954 to treat ADHD
    and has historically has had a high safety
    record.
  • Distribution of methylphenidate in the United
    States increased dramatically from 1990-95
    (Morrow, Morrow Haislip, 1998, 1121).
  • The U.S produces 90 of the worlds Ritalin
    (Diller, et al., 1997, 730).
  • Ritalin is prescribed for children at least age 5
    into adulthood (Borgstadt, et al., 1998, 125).

7
Predisposition to AD/HD
  • When the parents have experienced affective
    disorders, their children are at a higher risk of
    suffering from ADHD.
  • Youth coming from families that suffer familial
    dysfunction or are disorganized are at high risk
    for ADHD.
  • There is a possible genetic component
  • (Julien, 1998, 145).

8
Genetically predisposed?
  • A research team from Duke University found that
    hyperactivity symptoms were caused by too little
    serotonin in addition to high concentrations of
    dopamine.
  • The research team has gathered information from a
    genetically modified mouse
  • dopamine transporter gene eliminated -- high
    concentrations of extracellular dopamine
    concentrations -- good response to Ritalin
  • (Berger, 1999, 212).

9
Other etiology
  • Frontal lobe theory
  • children with ADHD have dysfunctional or
    disproportionate sizes in their frontal lobe
  • Parietal lobe theory
  • differences in right parietal lobe in children is
    a possible secondary cause
  • (Aman, Pennington Roberts Jr., 1998, 956).

10
Genetic contributions twin studies
  • monozygotic twins and dizygotic twins were
    studied in which one of the twins had ADHD
  • In these case of identical twins , 55- 92 of
    the time, when one twin had ADHD, the other would
    develop the condition
  • (Barkely, 1998, 66).

11
Pharmacology and AD/HD
  • Stimulant drugs improve behavior and learning
    ability in 60-80 of children correctly
    diagnosed.
  • The primary psychopharmacological agents are the
    CNS stimulants.
  • The prototype drugs are dextroamphetamine,
    methylphenidate and pemoline (Julien, 1998, 145).
  • Methylphenidate is considered to be the drug of
    choice (Volkow et al, 1998, 1325).

12
Pharmacokinetics of Ritalin
  • Oral administration
  • adverse effects of chewing methylphenidate(Pleak,
    1995, 811).
  • Rapid onset
  • Short duration administered at breakfast and
    lunchtime
  • not administered in evening to permit the blood
    level to drop, allowing for normal sleep.
  • Short half-life can be troublesome for some
    children (Julien, 1998, 147).

13
Drug effects
  • Because Ritalin resembles the amphetamines and
    cocaine there is great potential for reinforcing
    effects and abuse.
  • The rate of clearance from the brain is extremely
    slow and can be considered a limiting factor in
    promoting its frequent self-administration.
  • (Julien, 1998, 147).

14
Pharmacodynamics of Ritalin
  • Therapeutic effects of methylphenidate are due to
    its ability to increase the synaptic
    concentration of dopamine
  • This increase is performed by blocking dopamine
    transporters
  • Levels of dopamine transporter blockade achieved
    at therapeutic doses in treatment are not known
  • (Volkow, et al., 1998, 1325).

15
Side effects
  • Stimulant effects include weight loss,
    increased somatic complaints, and parent/teacher
    reports of reduced inattentiveness,
    aggressiveness and oppositionality. (Smithee et
    al., 1998, 233).
  • Insomnia, decreased appetite, stomachaches, and
    headaches are the most commonly reported by
    children on stimulants (Efron, Jarman Barker,
    1998, 662).

16
Other effects
  • Dizziness
  • anxiousness
  • irritability
  • proneness to crying
  • (Efron, Jarman Barker, 1997, 662).

17
Growth hormone effects? Why?
  • Decreased appetite leads to low weight gain
    causing slow growth
  • Alterations in dopaminergic pathways have a role
    in the pathogenesis of ADHD
  • Association between growth failure and ADHD may
    have an endocrine cause
  • Methylphenidate may have direct effects on
    cartilage metabolism.
  • (Rao, et al., 1998, 497).

18
Co-morbidity
  • High comorbidity between learning disabilities
    and ADHD
  • social perception problems and poor social skills
    result
  • family relationship problems
  • trouble interacting with teachers
  • fewer friends
  • low self-esteem
  • (Bolen, et al., 1998, 125).

19
An alternative to Ritalin
  • Methylphenidate labeled with a radioactive
    tracer, carbon 11, small amounts injected into 2
    volunteers.
  • Using PET scans they found that the form of MPH
    known as the d-threo enhancer targets the basal
    ganglia, the part of the brain involved in
    therapeutic effect
  • l-threo enantiome delivers itself
    non-specifically throughout entire brain

20
d-threo/l-threo entantiomes contd
  • a proposal was made at the American Medical
    Society for using the d-threo enantiomer alone
  • l-threo is less effective and may be the
    contributor of side effects
  • d-threo appears to block dopamine uptake better
    than the l-threo form
  • (Wu, 1998, 213).
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