Download L5 ADHD

Attentional deficit
Hyperactivity Syndrome
Frequency/prevalence
4 – 6 % of school children
more boys than girls
About 75 % are affected in adulthood
Symptoms
Attention deficit: distractable, problems to
concentrate, to finish a task
Hyperactivity: inability to remain seated
talking too much
Impuslivity:
interrupts other spakers
can‘t wait for anything
antisocial behaviour
No insight into their own disease-state
Cause
There is a strong genetic component
Speculative:
Polymorphism of the D4 gene ???
of the DA-transporter Gene ???
Environmental factors alone can not explain
the disease
Psychostimulants in ADHD
Amphetamines:
Amphetamine (Adderall®))
Methamphetamine (Adderall ®)
Methylphenidate (Ritalin ®)
Non Amphetamines: Pemoline (Cylert ®)
Atomoxetine (Strattera®)
Modafinil
Under Ivestigation:
ABT-418 (N-ACH-R-Ago)
S-Citalopram (Escitalopram®, Lexapro®)
Histamine H3 receptor antagonists (Komater et al. 2
Amphetamines:
1-Methylphenidate: Ritalin ®, Medikinet®, Equasym®,
Concerta ® Methadate ®
2-D-Amphetamine
Dexamphetamine
Tx for those who do not respond to Ritalin
3-Adderall ®
is an amphetamine coctail
Behavioural pharmacology of amphetamine
Self-administered
Dopamine-dependent, mediated by the brain reward
system
Dose dependent increase in:
-All behaviours resulting in fragmentation of behaviour
swichtching – finally stereotypy
Dopamin-dependent, mediated by striatum and
N.accumbens
Methylphenidate
• is a derivative of piperidine and is
structurally related to
dextroamphetamine, an older drug still
used to treat AD/HD
Atomoxetine (Strattera®)
• Approved in USA and UK for ADHD in
children,
• adolescents and adults.
• In Germany: March 2005
• No psychostimulant drug
• Contraindication: MAO inhibitors
• Metabolism:
• P450 pathway
Atomoxetine: Mechanism of action
• Selective noradrenaline reuptake inhibitor
SNARI
• Some selectivity for the prefrontal cortex
• Reboxetine
Atomoxetine effects in humans
1-Mood brightening, but no psychostimulant-like high.
2-Neuropharmacology
a-Enhancement of noradrenaline tone
b-Facilitates neuronal differentiation during developent
c-Facilitates neuronal plasticity
d-protects against various neurotoxins.
3-Behavioural pharmacology
Alerting effects
Histamine H3-antagonists in ADHD
The H3 receptor is a presynaptic auto- and
Heteroreceptor.
It inhibits histamine an Catecholamine release
H3-antagonists enhance catecholamine release
Nicotine-R agonists in ADHD
Nicotinic ACH-Receptors are located
Presynaptically as heteroreceptors on
Catecholaminergic terminals
Nicotine-R-agonists enhance catecholamine
release
ADHD in adulthood
Untreated ADHD persists in about 66% to
Adulthood and results in:
adverse/inappropriate/antisocial behaviour
addiction.
Misuse of ADHD drugs as enhancers
For combating sleep
For enhacement of motivation for work
For mood brightening
For cognition enhancement (learning,
memory, communication)