Anxiety & Insomnia

What type of drugs can cross the BBB?

Lipid-soluble drugs

Immune cells of the brain; removes beta-amyloid during sleep “janitor of the brain”. Helps with neural generation and repair; supports neuro metabolism, learning, and memory

Glial cells

Defects associated with glial cells

• Depression

• Alzheimer’s

Increase the likelihood that the neuron will fire an action potential

• noradrenaline/norepi (NE)

• dopamine (DA)

Excitatory neurotransmitters

Decrease the likelihood that the neuron will fire an action potential

• Serotonin (5HT)

• Gamma-aminobutyric acid (GABA)

Inhibitory neurotransmitters

• Adrenergic → norepi

• “Fight or flight”

  • Increased HR and BP

  • Dilate the airways

SNS

• Cholinergic → ACh

• “Rest and Digest”/Feed or Breed

  • Slows HR

  • Stimulate the activity of the intestines

PNS

• Slow acting response/manage chronic stress

• Activated by perceived stress and results in the release of cortisol

• Hypothalamus release CRH which stimulates pituitary glands to release ACTH which acts on adrenal gland to release cortisol

Hypothalamic pituitary adrenal (HPA) axis

• Provides adequate nutrients for ATP synthesis during stress

• Reduces protein synthesis and increases glucose synthesis for the brain

Cortisol

• Fast acting/acute response to stress

• Activated by perceived stress and results in the release of epi/norepi → fight or flight

Sympathetic-adrenal medullary (SAM) axis

• Normal response to a stressful situation

• Can motivate a person toward constructive, problem-solving, or coping activities

• Usually lasts only 2-3 weeks

Situational anxiety

• DSM-5 - Diagnostic & Statistical Manual of Mental Disorders

• Severe or prolonged; impairs ability to function in usual ADLs

• Has different subtypes

Anxiety disorder

• Excessive or exaggerated anxiety and worry for 6 months or more

• Eliminate other possible causes such as disease/meds to diagnose

• Experience little relief when stressful situation is resolved but quickly moves on to another worry

Generalized anxiety disorder (GAD)

GAD is associated ≥ 3 of the following symptoms:

• Restlessness or being on edge

• Easily fatigued

• Difficulty concentrating

• Irritability

• Muscle tension

• Sleep disturbance

Pathophysiology of anxiety disorders

• Genetic

• Exposure to physical/emotional trauma

• Stressors

• Imbalance of neurotransmitters

  • Excess of excitatory neurotransmitters

  • Deficiency of inhibitory neurotransmitters

    • GABA

    • Serotonin

• Medical disorders (respiratory, CVD, hyperthyroidism, cancer)

• Psychiatric disorders (schizo, mood disorders)

• Substance abuse

Psychological S&S/clinical manifestations of anxiety

• Increased vigilance

• Worry, dread, and apprehension

• Feeling fearful/trapped/tense

• Nervousness

• Difficulty concentrating

• Anger/irritability

• Mood swings

Physical symptoms of anxiety

• Motor tension

  • Muscle tension

  • Fatigue

• Overactivity of the ANS

  • Dyspnea

  • Palpitations/tachycardia

  • Sweating

  • Dizziness/faintness

  • ND

• Sleep disturbance

Nonpharm interventions for anxiety

• Cognitive behavioral therapy (CBT)

  • Psychotherapy/talk

• Self-treatment/care

  • Exercise & nutrition

  • Meditation/prayer

First line pharm treatment for anxiety disorders

SSRIs/SNRIs

2nd line treatment for anxiety

Benzodiazepines

Miscellaneous drugs for anxiety disorders

• BBs → block SNS

  • Helpful for physical symptoms (tachycardia, palpitations, sweating, SOB)

  • Used in specific events (ie public speaking)

Drugs used to treat anxiety disorders

• SSRIs/SNRIs (1st line)

• Benzos (2nd line)

• Nonbenzos-nonbarbituates → buspirone

• Barbiturates → old drug/used rarely due to SE

• BBs

• Antihistamines (hydroxyzine) → sedating

Common suffix for barbiturates

-barbital

Prodrug for barbiturates

Phenobarbital

MOA of barbiturates

• Binds to and stimulates GABA receptor (sedating effect); increase length/duration GABA channel is opened

• Inhibits CNS

Barbiturates indication

• Obsolete for most uses

• Treatment for seizure disorders (status epilepticus; generalized tonic-clonic)

• May be used IV as general anesthetics

Anxiety med that can be used for general anesthesia

Barbiturates

Nursing implications for barbiturates

• High r/o infection

• NTI → high r/o OD

• Schedule II-IV (addictive); phenobarbital for seizures is schedule IV

Prodrug of benzodiazepines 

Diazepam (Valium)

Common suffix/drugs for benzos

• –lam/–pam

• Clonazepam, alprazolam, diazepam

Benzo MOA

• Binds to and stimulates GABA receptors (increases channel opening frequency) → sedating effects

• Enhances inhibitory effect of GABA

Pam and Lam riding in a Benz

Benzodiazepines

Low dose benzos =

Relieves anxiety

Increased/moderate dose benzos =

Causes sleepiness/drowsiness

Very high dose benzos =

Anesthesia

Benzo indication

• Anxiety – acute/short-term (acute anxiety attacks)

• Preprocedural/preoperative sedation

• Insomnia

• Seizures

• Alcohol withdrawal

Scheduling and implications for benzos

Schedule IV; potential for dependency

• Requires judicious monitoring

• Consider alternate drug therapy if possible due to widespread substance abuse

Benzos SE/AE

LOW AND SLOW

• CNS depressant

  • Sedation, drowsiness, confusion, memory impairment

    • Anterograde amnesia; person can’t form new memories for a period of time (helpful for surgeries)

  • Impaired manual skills/impaired coordination (ataxia)

  • Shallow breathing

• Decreased HR and BP

• Paradoxical effects in elderly

  • Increases anxiety, agitation, restlessness

Paradoxical effects of benzos on elderly

Increased anxiety, agitation, restlessness

Nursing considerations for Benzos

• Observe for AEs

  • Excessive sedation

• Hypotension (OH) → changes positions and get up slowly

• Taper slowly/do not stop abruptly

• Withdrawal symptoms

  • Tremors

  • Anxiety

  • Psychosis/delirium

  • Insomnia

  • Seizures

Hold benzo dose if

Patient appears excessively sedated/drowsy or is experiencing paradoxical effects; hold dose and notify HCP

S&S of benzo withdrawal (TAPIS)

T – Tremors

A – Anxiety

P – Psychosis/delirium

I – Insomnia

S – Stress

ABUSED (S&S of benzo OD)

A – AMS (stupor, coma)

B – Bradycardia

U – Unable to walk or coordinate movements (ataxia)

S – Slurred/garbled speech

E – Eyes → blurred/double vision

D – Decreased respirations

Antidote for benzos

Flumazenil

• Reverse CNS depression; binds to and antagonize GABA receptors so benzos can’t bind and are kicked out (reversed)

• May cause withdrawal symptoms (r/o withdrawal outweighs r/o OD)

S&S of benzo OD

• A: AMS (stupor, coma, almost unconscious)

• B: bradycardia

• U: unable to walk or coordinate movements (ataxia)

• S: slurred or garbled speech

• E: eyes - blurred/double vision 

• D: decreased respirations

Patient education for benzos

• May cause hypotension (OH) and dizziness

  • Change positions and get up slowly

• Avoid alcohol or other CNS depressants

  • E.g. narcotics, antihistamines, OTC meds (antihistamines such as Benadryl), herbs

  • Causes increased sedation

• Caution w/ activities that require alertness (driving/work)

  • Take meds at night to avoid daytime drowsiness)

• DO NOT stop ABRUPTLY (taper down)

  • Withdrawal symptoms

• Usual duration for med treatment is 2-4 weeks

  • Short-term treatment; reduce risk for dependency

When should patient take benzos if they feel drowsy?

Take at night to avoid daytime drowsiness (avoid taking before doing activities that require alertness such as driving/work)

Usual therapy duration for benzos

Used for 2-4 weeks; taper slowly and do not stop abruptly. Short duration due to risk of dependency/tolerance

Benzos C/I

• Pregnancy or breast-feeding (lactation)

• Severe respiratory disorders (impaired respiratory system)

  • COPD or sleep apnea

• Hx of alcohol/drug abuse

• Narrow angle glaucoma (relaxes muscles in pupil and increase risk for NAG)

Use benzos w/ caution for

Elderly

• On Beers list → not recommended

• Elderly are sensitive; may exhibit paradoxical effects

• Increased r/o injury and falls due to hypotension (OH), dizziness, ataxia)

How do benzos affect the elderly?

• On Beers list → not recommended

• Elderly are sensitive; may exhibit paradoxical effects

• Increased r/o injury and falls due to hypotension (OH), dizziness, ataxia)

Prodrug for nonbenzo-nonbarb

Buspirone (Buspar)

MOA of nonbenzo-nonbarb (buspirone)

Increase the action of 5HT (serotonin) receptors; does not affect GABA

Nonbenzo-nonbarb (buspirone) indication

• Anxiety – GAD

  • Elderly (does not cause significant sedation)

  • Alcoholics (not controlled substance; does not produce tolerance/dependency)

Advantages of nonbenzo-nonbarb (buspirone) 

• Less SE

• Does not cause significant sedation

• Does not produce tolerance or dependency

• Can be used for elderly/alcoholics

Disadvantages of nonbenzos-nonbarbs (buspirone)

• Delayed onset of 2-3 weeks

• Not effective for immediate relief of panic attacks

SE nonbenzos-nonbarbs (buspirone)

• Dizziness

• CNS depression

• Muscle weakness

Poor sleep = brain drain, and is associated with

• Stress

• Anxiety

• Depression

Poor sleep/insomnia causes increased r/o

Stroke, cancer, and heart disease

Importance of sleep

• Conserves energy

• Promotes neural plasticity 

  • Critical in brain development and learning

• Restores

  • REM sleep → emotional health

  • Non-REM sleep → physical health

Prolonged difficulty going to sleep or staying asleep long enough to feel rested

• Occasional sleepiness is normal

• Chronic when it persists > 1 month

Insomnia

Causes of insomnia

• Medical disorders → chronic pain, fibromyalgia, neurologic disorders

• Psychiatric disorders

• Substance abuse

• Environmental factors → light, temp, noise, uncomfortable mattress

• Stress related factors → life events, deadlines, new job

• Medications → stimulants, caffeine, etc.

Clinical manifestations of insomnia

• Fatigue and lack of energy

• Irritability

• Diminished work performance

• Decreased concentration

• Over concerned with the inability

Nonpharm interventions for anxiety

• Treatment of medical or emotional issues

• Cognitive behavioral (CBT)

• Sleep hygiene

• Drug therapy

  • Nonbenzodiazepine sedative-hypnotics

  • Melatonin

  • Antihistamines

• Stress hormone from the adrenal glands

• Sunlight stimulates secretion

• High in morning and decreases throughout the day

Cortisol

• Hormone from pineal gland released in response to darkness

• High at night and lower during day

Melatonin

Melatonin MOA

• Hormone produced by the pineal gland (endocrine gland of the brain)

• Helps regulate sleep/wake cycles (circadian rhythm)

Melatonin indication

OTC supplement used for

• Insomnia

• Jet lag (circadian rhythm disorder)

SE/AE of melatonin

• HA

• Nausea

• Sedation, dizziness

• Vivid dreams (weird dreams)

Nursing considerations for melatonin

Prolonged intake of exogenous melatonin can reset the sleep-wake cycle (make patient feel sleepy during day)

Acts on H1/H3 receptors in the brain for

• Regulation of wakefulness

• Promote problem solving, creativity, and cognition

Histamine

• Promotes sleep; causes drowsiness

• Active ingredient in OTC sleep aids

  • Unisom

  • Benadryl

  • PM medications → Tylenol PM (have this as active ingredient)

Antihistamines (H1 receptor antagonists)

Prodrug of nonbenzo sedative-hypnotics

• Eszopiclone (Lunesta), zolpidem (Ambien)

Name the nonbenzo sedative-hypnotics

• Eszopiclone (Lunesta)

• Zolpidem (Ambien)

• Zaleplon

Nonbenzo sedative-hypnotics MOA

Acts on the GABA receptor at or close to the benzodiazepine receptor

Nonbenzo sedative-hypnotic indication (EZZ)

• Insomnia

  • zolpidem, zaleplon

  • short-term 7-10 days (schedule IV)

• Eszopiclone

  • Long-term: FDA approved for long-term use; > 6 months; no more than 12 months

Zolpidem, zaleplon indication

Short-term use for insomnia; 7-10 days (schedule IV)

Eszopiclone indication

Long-term treatment of insomnia; FDA approved for long-term use; > 6 months, but use no more than 12

Nursing considerations of nonbenzo sedative-hypnotics (EZZ)

• Schedule IV controlled substance

• Caution use in the elderly (Beer’s list)

Drugs on Beer’s list (DNU for elderly)

Benzos & nonbenzo sedative-hypnotics

SE/AE nonbenzo sedative-hypnotics (anything with z)

• Dizziness, lightheadedness, ataxia

• Aggression or bizarre behavior

• Worsening depression or suicidal ideation

• Hallucinations 

• Anterograde amnesia

• BBW sleepwalking and other sleep-related activates that can result in serious

  • Accidents/falls, confusion

BBW for nonbenzo sedative-hypnotics (EZZ)

• Sleepwalking and other sleep-related activates that can result in serious

  • Accidents/falls, confusion

What is the antidote for benzo OD?

Flumazenil

APISA (benzo indications)

A – Anxiety → acute/short-term (acute anxiety attacks)

P – Preprocedural/preoperative sedation

I – Insomnia

S – Seizures

A – Alcohol withdrawal

Drugs have BBW for combined use w/ opioids (cause respiratory depression)

Benzodiazepines

Drug has a BBW for r/o seizures (be aware of if patient has past hx of epilepsy)

Flumazenil

DAWHAB (SE/SE nonbenzo sedative hypnotics; EZZ)

D – Dizziness, lightheadedness, ataxia

A – Aggression or bizarre behavior

W – Worsening depression or suicidal ideation

H – Hallucinations 

A – Anterograde amnesia

B – BBW sleepwalking and other sleep-related activates that can result in serious

• Accidents/falls, confusion