Chapter 57: Drug Therapy for Attention Deficit Hyperactivity Disorder and Narcolepsy

What are the major characterizations of attention deficit hyperactivity disorder (ADHD)?

• Persistent hyperactivity

• Short attention span

• Difficulty completing assigned tasks

• Restlessness

• Impulsiveness

What is the most common psychiatric/neurobehavioral disorder in children?

ADHD

Describe the etiology of ADHD

ADHD may be an inherited disorder and with subtle dysfunction in the frontal lobe and functionally related subcritical structures playing a major role in clinical manifestations. Dopamine and norepinephrine transport dysfunction in the brain has also been implicated.

At what ages is ADHD usually diagnosed?

3-7 years old

Describe how children with ADHD may act in social settings

Children with ADHD may find it harder to get along with others and may find difficulty in situations requiring controlled behavior.

Which gender is more susceptible to ADHD?

Males

In addition to ADHD, what other disorders may children with ADHD may also have that hinders academic and emotional development?

Learning Disabilties

Describe ADHD in adolescents and adults

~50% of children diagnosed with ADHD will still have ADHD by the time they are adolescents and/or adults. In adolescents/adults with ADHD, hyperactivity is usually not apparent, however, impulsiveness, inattention, and difficulties in structured environments are usually prominent. Diagnosis of ADHD in adults has increased in recent years.

Indications for usage of drug therapy in those with ADHD

• Moderate to severe symptoms

• Symptoms persist for several months

• Symptoms interfere with special, academic, and/or behavioral functioning

What are the goals of treatment of ADHD?

• Symptom control (Based on individual S/S)

• Facilitation of learning

• Promotion of social development

In addition to drug therapy, what else should treatment of ADHD include?

Counseling and Psychotherapy

How should activity timing with relation to pediatric ADHD be approached?

Many children with ADHD will greatly benefit from short, intense periods of physical activity.

What are the major characteristics of Narcolepsy?

• Excessive sleepiness

• Sleep attacks at inappropriate times

Clinical Manifestations of Narcolepsy

• Disturbed nocturnal sleep

• Abnormal daytime sleep pattern

• Cataplexy

• Hypnagogic hallucinations

• Sleep paralysis

What factors are involved in the development of narcolepsy?

• Genetics (Genetic variation and congenital)

• Environmental (Infections)

Hypnagogic Hallucinations are a clinical manifestation of narcolepsy. What are they?

Vivid, many times frightening, dreamlike experiences that occurs while dozing, falling, asleep, or awakening.

Describe Cataplexy

Episodic, sudden loss of muscle tone in response to strong emotion.

What are the two major forms of narcolepsy?

• Type 1

• Type 2

Describe Type 1 Narcolepsy

Narcolepsy with cataplexy. This type is associated with significant loss of neurons and orexin neuropeptides.

Describe Orexin Neuropeptides

Orexin-A (Hypcretin-1) and Orexin-B (Hypocretin-2) are neuropeptides made by the hypothalamus. They have excitatory effects when released during wakefulness and increases other brain activity involved in wakefulness.

Loss of orexin signaling has been implicated as a cause of Type 1 Narcolepsy. Why?

Loss of excitatory Orexin-A and Orexin-B enables for REM sleep-related phenomena to intrude into wakefulness. This is caused by death of orexin-producing neurons. The cause of this neuronal death is unknown but may be autoimmune in nature.

What is HLA-DBQ1?

A gene belonging to a family of genes called the human leukocyte antigen (HLA) complex. This gene is involved producing a protein that plays a role in how the immune system reacts to foreign proteins. A variation of this gene had been linked to those with Type 1 narcolepsy.

Describe Type 2 Narcolepsy

Narcolepsy without cataplexy. This type of narcolepsy has an unknown etiology.

Other than medications, what else can a patient with narcolepsy benefit from?

• Avoidance of shift work

• Short naps

Goal of Narcolepsy Treatment

• Prevention of sleep deprivation

• Regular sleep and waking times

*Treatment based on individual S/S

What drug classes are given for the treatment of ADHD and Narcolepsy?

1. Amphetamines

2. Amphetamine-Related CNS Stimulants

3. Selective Norepinephrine Reuptake Inhibitors

4. Sympatholytics

5. CNS Depressants

6. Xanthines

Amphetamine Prototype

Dextroamphetamine (Dexedrine)

*These medication are Schedule II Drugs

Dextroamphetamine (Dexedrine) Action

Triggers increase of norepinephrine, dopamine (Higher doses), and possibly serotonin in the brain.

Describe how stimulants in general aid those with ADHD and/or Narcolepsy

Facilitation of the initiation and transmission of nerve impulses that excites other cells.

How can Stimulants benefit a patient with ADHD?

Improvement in academic performance, behavior, and interpersonal relationships.

How can Stimulants benefit a patient with narcolepsy?

Improvement in the performance of daily activities.

Amphetamine-Related CNS Stimulants Prototype

Methylphenidate (Ritalin)

*These medications are Schedule II Drugs and are widely sold on the street

Methylphenidate (Ritalin) Action

Mild cortical stimulant and acts on CNS-like amphetamines.

Describe Modafinil

An Amphetamine-Related CNS Stimulant used to help with the fatigue associated with ADHD activity.

Selective Norepinephrine Reuptake Inhibitor Prototype

Atomoxetine (Strattera)

Atomoxetine (Strattera) Action

Inhibits reuptake of norepinephrine in nerve synapses

Sympatholytic Prototype

Guanfacine (Intuniv)

Guanfacine (Intuniv) Action

Selective agonist of postsynaptic Alpha2A-Adrenoreceptors in the prefrontal cortex. The result is believed to be improvement in delay-related firing of prefrontal cortex neurons affecting working memory and behavioral inhibition. Decreased sympathetic nerve impulse leading to reduced sympathetic outflow and decreased vasomotor tone and HR is also triggered.

Guanfacine (Intuniv) Uses

• Used when atomoxetine is ineffective or triggers adverse side effects

CNS Depressant Prototype

Sodium Oxybate (Xyrem)

Sodium Oxybate (Xyrem) Action

Depression of the CNS.

Xanthine Prototype

Caffeine

What is the most commonly consumed CNS stimulant in the world?

Caffeine (Usually from dietary sources)

Caffeine effects in low to moderate amounts

• Increased alertness

• Wakefulness

• Increased capacity to work

Caffeine effects in large amounts

• CNS

  • Anxiety

  • Agitation/Irritability

  • Hyperactivity

  • Insomnia

  • Nervousness

  • Restlessness

• G.I.

  • Diarrhea

  • Nausea

  • Vomiting

• CV

  • PVC

  • Tachycardia

• Musculoskeletal

  • Tremors

Caffeine effects in toxic amounts

Delirium and Seizures