Drugs for the treatment of Attention-Deficit Hyperactivity Disorder - PowerPoint PPT Presentation


Title: Drugs for the treatment of Attention-Deficit Hyperactivity Disorder


1
Drugs for the treatment of Attention-Deficit
Hyperactivity Disorder
  • Julia Drabs

2
What is ADHD?
  • Psychological disorder characterized by three
    main traits
  • Inattention
  • Hyperactivity
  • Impulsivity

3
Characteristics
  • Poor attention and concentration
  • Easily distracted
  • Shifting activities frequently
  • Day dreaming
  • Forgetfulness

4
Long Term Effects
  • Anxiety
  • Depression
  • Divorce
  • Job loss
  • Stress
  • Antisocial behavior
  • Lower educational achievement

5
Causes?
  • Relatively unknown
  • Deficiencies in
  • Seratonergic neurotransmitter systems
  • Dopaminergic neurotransmitter systems
  • Noradrenergic neurotransmitter systems

6
DRUGS!
  • Antidepressants
  • Antihypertensive agents
  • Amino acids
  • Wake promoting agents
  • Cholinergic agents
  • Norepinephrine Reuptake inhibitors
  • STIMULANTS!

7
Antidepressants
  • Bupropion
  • Effective
  • Tricyclic Antidepressants
  • Ineffective
  • Monoamine oxidase inhibitors
  • Ineffective

8
Why Bupropion?
  • Bupropion is a dopamine and norepinephrine
    reuptake inhibitor.
  • ADHD is a deficiency in the dopamine and
    norepinephrine reuptake inhibitor
  • Selective serotonin reuptake inhibitors do not
    appear to be affective in ADHD

Bupropion
Norepinephrine
Dopamine
9
Antihypertensive Agents
  • ?-adrenoceptor agonists
  • Clonidine
  • Guanfacine
  • Not very effective in treating ADHD

10
Amino Acids
  • One study
  • Ineffective

11
Wake Promoting agents
  • Drugs used to treat narcolepsy
  • Recently approved
  • 2 studies
  • 1st study, 48 responded positively
  • 2nd study, no difference from placebo

12
Cholinergic Agents
  • Nicotine shown to reduce symptoms of ADHD

13
Norepinephrine reuptake inhibitors
  • Atomoxetine
  • AKA Strattera

14
Structure
P450 Enzyme
Strattera
4-hydroxyatomoxetine
15
Discovery
  • Eli Lilly and Company
  • 2003



Norepinephrine
P450 Enzyme
Strattera 4-hydroxyatomoxetine
16
Norepinephrine Binding Site
17
Strattera Pathway


Pre synaptic site
Presynaptic site where atomoxetine is pushed
instead of dopamine




18
Side Effects
  • Abdominal Pain
  • Vomiting
  • Decreased Appetite
  • Dizziness
  • Headache
  • Irritability
  • Coughing

19
Stimulants
  • Methylphenidate
  • AKA Ritalin
  • Adderall

20
Ritalin
  • Discovered 1957, Novatris
  • Leading stimulant to treat ADHD
  • Lasts about 4 hours

21
Structure

Dextroamphetamine Ritalin
  • Ritalin was discovered as a piperidine derivative
    of dextroamphetamine.

22
Enantiomers

d-threo enantiomer l-threo enantiomer
  • Ritalin consists of a mixture of d-threo and
    l-threo enantiomers, but only the d-threo
    enantiomer is active

23
Ritalin Pathway


Pre synaptic site
Presynaptic site where atomoxetine is pushed
instead of dopamine




24
Side Effects
  • Decreased appetite
  • Insomnia
  • Headaches
  • Tics
  • Stomach aches
  • Jitteriness
  • Irritability
  • Proneness to crying (children)
  • RARE
  • Psychotic symptoms
  • Sensitivity reactions
  • Cognitive Toxicity

25
Adderall
  • Discovered in the 1960s as a treatment for
    obesity, known as Obetrol, Rexar Pharmacal
  • 1994, Richwood Pharmaceutical Company purchaced
    Rexar Pharmacal, and changed Obetrol to Adderall.

26
Structure
4 salts of equal parts (by weight)

Dextroamphetamine sulfate Dextroamphetamine
saccharate

Amphetamine sulfate Amphetamine asparate
All four salts come in a d-levo and l-levo
form, although the d-levo is the active form, and
comes in a ratio of 31
27
Mechanism
  • CNS Stimulant
  • Mode of therapeutic activity is unknown
  • Theory
  • Blocks the reuptake norepinephrine, but also
    stimulates the release of these
    neurotransmitters, increasing the amount of each
    available presynaptically.

28
Side Effects
  • Dry mouth
  • Difficulties sleeping
  • Dizziness
  • Headache
  • Loss of appetite
  • Nausea
  • Rapid heart rate
  • Weight loss

29
Compare
Drugs Stimulant? Addictive/ easily abused? Side Effects Targeted audience Time frame
Strattera No No More prominent Adults 4 hours
Ritalin Yes Yes Some Children 4 hours
Adderall Yes Yes Some Both 8 hours
30
Future
  • Longer lasting Drugs
  • Ritalin
  • Ritalin-SR
  • OROS (Concerta)
  • Metadate CD
  • Ritalin LA
  • Transdermal Ritalin
  • Adderall
  • SLI-381 (Adderall XR)
  • Cholinergic agents

31
Referances
  • A Comparison of Ritalin and Adderall Efficacy
    and Time-Course in Children with
    Attention-Deficit/Hyperactivity Disorder.
    Pediatrics, Apr99 part 1 of 2, Vol. 103 Issue 4,
    p 9805-806.
  • Adderall The New Psychostimulant. Brown
    University Psychopharmacology Update, Nov94, Vol.
    5 Issue 11, p 1-2.
  • Doffing, Melissa A., Wolraich, Mark L.
    Pharmacokinetic Considerations in the Treatment
    of Attention-Deficit Hyperactivity Disorder with
    Methylphenidate. CNS Drugs. 2004, 18(4),
    243-250.
  • FDA Clears use of Adderall for
    Attention-Deficit Disorder. Brown University
    Child and Adolescent Behavior Letter. Mar96, Vol.
    12, Issue 3.
  • Health and Medicine Week, September 6, 2004, 79.
  • Markowitz, John S., Patrick, Kennerly S.
    Pharmacology of Methylphenidate, Amphetamine
    Enantiomers and Pemoline in Attention-Deficit
    Hyperactivity Disorder. Human Psychopharmacology.
    1997, 12, 527-546.
  • McKeage, Kate, Scott, Lesley J. SLI-381
    (Adderall XR). CNS Drugs. 2003 17(9), 669-675.
  • Plosker, Greg L., Dimpson, Dene Atomoxetine A
    Review of its Use in Adults with Attention
    Deficit Hyperactivity Disorder. Drugs. 2004,
    64(2), 205-222.
  • Wilens, Timothy E. Drug Therapy for Adults with
    Attention-Deficit Hyperactivity Disorder. Drugs.
    2003, 63(22), 2395-2411.
  • http//www.rx-counter.com/
  • http//www.neurologyreviews.com/jan03/newsroundup.
    html
  • http//faculty.washington.edu/chudler/amp.html
  • http//www.cwu.edu/chem/courses/Chem564/Scott_Lau
    ra_ADHD.htm
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Title: Drugs for the treatment of Attention-Deficit Hyperactivity Disorder


1
Drugs for the treatment of Attention-Deficit
Hyperactivity Disorder
  • Julia Drabs

2
What is ADHD?
  • Psychological disorder characterized by three
    main traits
  • Inattention
  • Hyperactivity
  • Impulsivity

3
Characteristics
  • Poor attention and concentration
  • Easily distracted
  • Shifting activities frequently
  • Day dreaming
  • Forgetfulness

4
Long Term Effects
  • Anxiety
  • Depression
  • Divorce
  • Job loss
  • Stress
  • Antisocial behavior
  • Lower educational achievement

5
Causes?
  • Relatively unknown
  • Deficiencies in
  • Seratonergic neurotransmitter systems
  • Dopaminergic neurotransmitter systems
  • Noradrenergic neurotransmitter systems

6
DRUGS!
  • Antidepressants
  • Antihypertensive agents
  • Amino acids
  • Wake promoting agents
  • Cholinergic agents
  • Norepinephrine Reuptake inhibitors
  • STIMULANTS!

7
Antidepressants
  • Bupropion
  • Effective
  • Tricyclic Antidepressants
  • Ineffective
  • Monoamine oxidase inhibitors
  • Ineffective

8
Why Bupropion?
  • Bupropion is a dopamine and norepinephrine
    reuptake inhibitor.
  • ADHD is a deficiency in the dopamine and
    norepinephrine reuptake inhibitor
  • Selective serotonin reuptake inhibitors do not
    appear to be affective in ADHD

Bupropion
Norepinephrine
Dopamine
9
Antihypertensive Agents
  • ?-adrenoceptor agonists
  • Clonidine
  • Guanfacine
  • Not very effective in treating ADHD

10
Amino Acids
  • One study
  • Ineffective

11
Wake Promoting agents
  • Drugs used to treat narcolepsy
  • Recently approved
  • 2 studies
  • 1st study, 48 responded positively
  • 2nd study, no difference from placebo

12
Cholinergic Agents
  • Nicotine shown to reduce symptoms of ADHD

13
Norepinephrine reuptake inhibitors
  • Atomoxetine
  • AKA Strattera

14
Structure
P450 Enzyme
Strattera
4-hydroxyatomoxetine
15
Discovery
  • Eli Lilly and Company
  • 2003



Norepinephrine
P450 Enzyme
Strattera 4-hydroxyatomoxetine
16
Norepinephrine Binding Site
17
Strattera Pathway


Pre synaptic site
Presynaptic site where atomoxetine is pushed
instead of dopamine




18
Side Effects
  • Abdominal Pain
  • Vomiting
  • Decreased Appetite
  • Dizziness
  • Headache
  • Irritability
  • Coughing

19
Stimulants
  • Methylphenidate
  • AKA Ritalin
  • Adderall

20
Ritalin
  • Discovered 1957, Novatris
  • Leading stimulant to treat ADHD
  • Lasts about 4 hours

21
Structure

Dextroamphetamine Ritalin
  • Ritalin was discovered as a piperidine derivative
    of dextroamphetamine.

22
Enantiomers

d-threo enantiomer l-threo enantiomer
  • Ritalin consists of a mixture of d-threo and
    l-threo enantiomers, but only the d-threo
    enantiomer is active

23
Ritalin Pathway


Pre synaptic site
Presynaptic site where atomoxetine is pushed
instead of dopamine




24
Side Effects
  • Decreased appetite
  • Insomnia
  • Headaches
  • Tics
  • Stomach aches
  • Jitteriness
  • Irritability
  • Proneness to crying (children)
  • RARE
  • Psychotic symptoms
  • Sensitivity reactions
  • Cognitive Toxicity

25
Adderall
  • Discovered in the 1960s as a treatment for
    obesity, known as Obetrol, Rexar Pharmacal
  • 1994, Richwood Pharmaceutical Company purchaced
    Rexar Pharmacal, and changed Obetrol to Adderall.

26
Structure
4 salts of equal parts (by weight)

Dextroamphetamine sulfate Dextroamphetamine
saccharate

Amphetamine sulfate Amphetamine asparate
All four salts come in a d-levo and l-levo
form, although the d-levo is the active form, and
comes in a ratio of 31
27
Mechanism
  • CNS Stimulant
  • Mode of therapeutic activity is unknown
  • Theory
  • Blocks the reuptake norepinephrine, but also
    stimulates the release of these
    neurotransmitters, increasing the amount of each
    available presynaptically.

28
Side Effects
  • Dry mouth
  • Difficulties sleeping
  • Dizziness
  • Headache
  • Loss of appetite
  • Nausea
  • Rapid heart rate
  • Weight loss

29
Compare
Drugs Stimulant? Addictive/ easily abused? Side Effects Targeted audience Time frame
Strattera No No More prominent Adults 4 hours
Ritalin Yes Yes Some Children 4 hours
Adderall Yes Yes Some Both 8 hours
30
Future
  • Longer lasting Drugs
  • Ritalin
  • Ritalin-SR
  • OROS (Concerta)
  • Metadate CD
  • Ritalin LA
  • Transdermal Ritalin
  • Adderall
  • SLI-381 (Adderall XR)
  • Cholinergic agents

31
Referances
  • A Comparison of Ritalin and Adderall Efficacy
    and Time-Course in Children with
    Attention-Deficit/Hyperactivity Disorder.
    Pediatrics, Apr99 part 1 of 2, Vol. 103 Issue 4,
    p 9805-806.
  • Adderall The New Psychostimulant. Brown
    University Psychopharmacology Update, Nov94, Vol.
    5 Issue 11, p 1-2.
  • Doffing, Melissa A., Wolraich, Mark L.
    Pharmacokinetic Considerations in the Treatment
    of Attention-Deficit Hyperactivity Disorder with
    Methylphenidate. CNS Drugs. 2004, 18(4),
    243-250.
  • FDA Clears use of Adderall for
    Attention-Deficit Disorder. Brown University
    Child and Adolescent Behavior Letter. Mar96, Vol.
    12, Issue 3.
  • Health and Medicine Week, September 6, 2004, 79.
  • Markowitz, John S., Patrick, Kennerly S.
    Pharmacology of Methylphenidate, Amphetamine
    Enantiomers and Pemoline in Attention-Deficit
    Hyperactivity Disorder. Human Psychopharmacology.
    1997, 12, 527-546.
  • McKeage, Kate, Scott, Lesley J. SLI-381
    (Adderall XR). CNS Drugs. 2003 17(9), 669-675.
  • Plosker, Greg L., Dimpson, Dene Atomoxetine A
    Review of its Use in Adults with Attention
    Deficit Hyperactivity Disorder. Drugs. 2004,
    64(2), 205-222.
  • Wilens, Timothy E. Drug Therapy for Adults with
    Attention-Deficit Hyperactivity Disorder. Drugs.
    2003, 63(22), 2395-2411.
  • http//www.rx-counter.com/
  • http//www.neurologyreviews.com/jan03/newsroundup.
    html
  • http//faculty.washington.edu/chudler/amp.html
  • http//www.cwu.edu/chem/courses/Chem564/Scott_Lau
    ra_ADHD.htm
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