Transcript 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)