NERVOUS SYSTEM 5

Agents for Anxiety/Insomnia • Anxiety: unpleasant feeling of dread, apprehension or tension resulting from an unexpected threat to one’s feeling of self esteem or well being; may be a symptom in many disorders • Sedative (anxiolytic): agent should reduce anxiety and exert a calming effect • Insomnia: inability to fall asleep or remain asleep • Hypnotic: produce drowsiness; induce sleep • Antihistamines: • OTC agents: diphenhydramine • Beta blockers: reduce tachycardia and other symptoms • Antidepressants • SSRI’s • TCA’s • MAOI’s • Barbiturates • Rarely used • Antipsychotics (?) • Anti-seizure agents • valproic acid (?)

Benzodiazepines Agents: Alprazolam (Xanax), lorazepam (Ativan), diazepam (Valium), oxazepam (Serax) MOA: Intensify the effect of GABA Adverse Effects: Drowsiness, sedation, lethargy, ataxia, confusion Comments: Preferred agent for insomnia caused by anxiety Many other applications: seizures, EtOH withdrawal, adjunct to anesthesia, nausea Adjust dose for liver/renal dysfunction Some agents have active metabolites Antidote: flumazenil (Romazicon)

Serotonin Receptor Agonist Agents: buspirone (Buspar) MOA: unknown mechanism of action; exhibits high affinity for serotonin receptors, moderate affinity for dopamine receptors Adverse Effects: nausea, dizziness, nervousness, headache, somnolence, tachycardia, heart failure, MI, CVA Comments: Many drug-drug interactions Slow onset of action (14 days) Adjust dose for liver or renal impairment Not a controlled substance

Hypnotics Agents: Eszopiclone (Lunesta), zaleplon (Sonata), zolpidem (Ambien) MOA: Enhance the effect of GABA Adverse Effects: Taste disturbances, vomiting, diarrhea, dizziness , headache, somnolence, visual disturbances, fatigue Comments: Rapid onset Zaleplon/zolpidem: short term use only (FDA) Several drug-drug interactions Adjust dose for liver impairment Controlled substance: schedule IV

Melatonin Receptor Agonist Agents: Ramelteon (Rozerem) MOA: Activates MT1 and MT2 receptors Adverse Effects: Nausea, dizziness, fatigue, insomnia, somnolence, depression, worsening, hallucinations, mania Comments: Several drug interactions Does not appear to produce residual effects, rebound insomnia or withdrawal syndrome with prolonged use Not a controlled substance

Psychopharmacology General summary:1. ↑ DA transmission  ↓ Parkinsonism2. ↑ Ach improvement in cognitive function3. ↓ DA transmission  ↓ psychoses4. ↑ GABA receptor

stimulation  ↓ anxiety5. ↑ NE & ↑ 5-HT  ↑ mood

Bipolar Disorder

• Previously referred to as “manic-depressive” disorder

• Bipolar I disorder: manic or mixed episode +/- depression

• Bipolar II disorder: depression episode shifting w/ hypomanic episode

• Cylcothymic disorder: fluctuations between hypomania and mild depression

• Characterized by:

• Extreme opposite mood shifts, alternating from depression to mania

• Grandiosity or inflated self-esteem

• Talkativeness; flight of ideas

• Increased goal-directed activity

• Causative Theories

• Unknown

• Genetics

• NT imbalances

• Stress

Antipsychotic Agents Agents: aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), ziprasidone (Geodon) MOA: blockade of serotonin receptors > blockade of dopamine receptors Adverse Effects: tachycardia, sedation, dizziness, headache, lightheadedness, somnolence, anxiety, hostility, insomnia, nausea, dry mouth, constipation, akathisia, extrapyramidal symptoms, neuroleptic malignant syndrome, QTc prolongation, weight gain, diabetes Comments: Effective as monotherapy or adjunct therapy

Attention Deficit – Hyperactivity Disorder (ADHD) • Characterized by a persistent pattern of inattention and/or hyperactivity • Developmentally inappropriate behaviors • Difficulty paying attention or focusing on tasks • CNS Stimulants: traditional drugs to treat ADHD in children • Classic drug: methylphenidate (Ritalin) • Stimulate areas of the CNS • Heighten awareness and increase focus • May cause paradoxical hyperactivity • Non CNS Stimulants: atomoxetine (Strattera) • Clonidine, Antidepressants (?)

Pharmacotherapy CNS Stimulants Comments Dextroamphetamine (Dexedrine) D-and L-amphetamine racemic mixture (Adderall) Methylphenidate (Ritalin) Pemoline (Cyclert) • SE = nervousness, restlessness, insomnia, irritability, euphoria, palpitations, others Non CNS Stimulant Atomoxetine (Strattera) Guanfacine XR (Intuniv) • Headache, GI complaints (N, V, pain, anorexia) • Dizziness, abdominal pain, fatigue • Less effective as monotherapy compared to CNS stimulants