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 Tricyclic Antidepressants
Effective
Tricyclic Antidepressants
Ineffective
Monoamine oxidase inhibitors

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
ά-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 Strattera 4-hydroxyatomoxetine
Norepinephrine
P450 Enzyme
Strattera 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 1960’s 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 3:1

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
More prominent
Adults
4 hours
Ritalin®
Yes
Some
Children
Adderall®
Both
8 hours

30. Future Longer lasting Drugs Cholinergic agents Ritalin Adderall
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
“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),
“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,
McKeage, Kate, Scott, Lesley J.; “SLI-381 (Adderall XR®).” CNS Drugs (9),
Plosker, Greg L., Dimpson, Dene; “Atomoxetine: A Review of its Use in Adults with Attention Deficit Hyperactivity Disorder.” Drugs. 2004, 64(2),
Wilens, Timothy E.; “Drug Therapy for Adults with Attention-Deficit Hyperactivity Disorder.” Drugs. 2003, 63(22),