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Pharmacology for Nurses: Drugs for Anxiety and Insomnia

Types of Anxiety Disorders

  • Situational anxiety
  • Generalized anxiety disorder (GAD)
  • Panic disorder
  • Phobias
  • Social anxiety disorder
  • Obsessive-compulsive disorder (OCD)
  • Post-traumatic stress disorders (PTSD)

Brain Regions and Anxiety

  • Limbic System
    • Located in the middle of the brain.
    • Responsible for emotional responses, learning, and memory.
    • Sends signals to the hypothalamus.
  • Hypothalamus
    • Responsible for unconscious responses.
    • Connects with the reticular formation.
  • Reticular Formation
    • A network of neurons along the brainstem.
    • Stimulation leads to heightened awareness and arousal.
    • Inhibition leads to drowsiness and sleep.
  • Reticular Activating System (RAS)
    • Projects from the brainstem to the thalamus.
    • Responsible for sleeping and wakefulness.
    • Sends signals from the hypothalamus to higher brain centers.
    • Involved in feelings of anxiety, fear, restlessness, and interrupted sleep.

Nonpharmacologic Therapies for Anxiety

  • Cognitive behavioral therapy
  • Counseling
  • Biofeedback techniques
  • Meditation

Anxiolytics

  • Drugs that relieve anxiety.
  • Effective for anxiety that significantly affects daily activities.

Medications for Anxiety and Sleep Disorders

  • CNS depressants are used to treat anxiety and sleep disorders.
  • Four classes:
    • Antidepressants
    • Benzodiazepines
    • Nonbenzodiazepine anxiolytics
    • Barbiturates
  • CNS depression is a continuum: relaxation → sedation → sleep → anesthesia.

Sedatives and Hypnotics

  • CNS depressants are sometimes called:
    • Sedatives (relaxing effect)
    • Hypnotics (induce sleep)
    • Sedative-hypnotics (calming at lower doses, sleep at higher doses)
  • Most CNS depressants can cause physical and psychological dependence.

Patient Monitoring and Education

  • Obtain vital signs and medical/drug history.
  • Discuss lifestyle and dietary habits.
  • Determine what precipitated the anxiety.

Assessing Need for Antianxiety or Insomnia Drugs

  • Assess symptom intensity and duration.
  • Identify precipitating factors and coping mechanisms.
  • Assess for sleep disorder.

Obtaining Drug History

  • Check for hypersensitivity, alcohol/CNS depressant use, and drug abuse/dependence.

Cautious Use Considerations

  • Elderly patients
  • Patients with suicidal potential
  • Patients with impaired renal or liver function

Insomnia

  • Sleeping and waking synchronized to bodily functions.
  • Associated with anxiety.
    • Short-term (behavioral): attributed to stress.
    • Stimulants (food/beverages) may disturb sleep.
  • Long-term: often caused by depression, manic disorders, or chronic pain.
  • Nonpharmacologic means should be tried before drug therapy.
  • Rebound insomnia: caused by discontinuation of long-used sedative drug.
  • Older patients: more likely to experience medication-related sleep problems.

Electroencephalogram (EEG)

  • Tool for diagnosing sleep disorders, seizure activity, depression, and dementia.
  • Identifies two types of sleep:
    • Nonrapid eye movement (NREM)
    • Rapid eye movement (REM)

Normal Sleep Patterns

  • NREM and REM occur every 90 minutes.
  • NREM sleep has three stages.
  • REM sleep follows NREM sleep; dreaming occurs during REM sleep.

EEG Details

  • REM sleep: brain wave pattern similar to when a person is drowsy but awake.
  • Deprivation of stage III REM sleep: can lead to depression, apathy, and fatigue.
  • Lack of REM sleep: causes sleep debt, leading to patient becoming frightened, irritable, paranoid, and emotionally disturbed.

Stages of Sleep

  • NREM Stage 1:
    • Onset of sleep, drowsiness for 5-10 minutes.
    • Patient can be easily awakened.
  • NREM Stage 2:
    • Light sleep.
    • Heart rate slows, body temperature drops.
  • NREM Stage 3:
    • Deepest stage of sleep.
    • Harder to wake the patient; disorientation for a brief time.
  • REM Sleep:
    • Eye movement and loss of muscle tone.
    • Eye movement occurs in bursts.
    • Dreaming takes place.
    • The mind is very active, resembles a normal waking state.

Antidepressants

  • Treat major depression and anxiety conditions.
  • Primary medications for panic and anxiety.
    • Tricyclic antidepressants (TCAs)
    • Monoamine oxidase inhibitors (MAOIs)
    • Selective serotonin reuptake inhibitors (SSRIs)
    • Atypical antidepressants (do not fit other categories)
  • Adverse reactions can make antidepressants unusable for some patients.

Prototype Drug: Escitalopram (Lexapro)

  • Therapeutic Class: Antidepressant; anxiolytic
  • Pharmacologic Class: Selective serotonin reuptake inhibitor (SSRI)
  • Mechanism of Action: Increases availability of serotonin at specific postsynaptic receptor sites within the CNS.
  • Primary Use: Generalized anxiety and depression.
  • Adverse Effects: Dizziness, nausea, insomnia, somnolence, confusion, seizures.

Escitalopram (Lexapro) Details

  • Selective inhibition of serotonin reuptake results in antidepressant activity without sympathomimetic or anticholinergic symptoms.
  • Off-label uses include the treatment of panic disorders.

Escitalopram (Lexapro) - Pharmacokinetics

  • Onset: With once-daily dosing, steady-state plasma concentrations can be reached within 1 week.
  • Peak: 5 hours
  • Duration: Variable

Escitalopram (Lexapro) - Adverse Effects

  • Serious reactions include dizziness, nausea, insomnia, somnolence, confusion, and seizures if taken in overdose.

Escitalopram (Lexapro) - Black Box Warning

  • Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
  • Not approved for pediatric patients less than 12 years of age.

Escitalopram (Lexapro) - Contraindications

  • Should not be used in breastfeeding patients or within 14 days of MAOI therapy.

Escitalopram (Lexapro) - Interactions

  • Drug-Drug:
    • MAOIs should be avoided due to serotonin syndrome (autonomic hyperactivity, hyperthermia, rigidity, diaphoresis, neuroleptic malignant syndrome).
    • Combination with MAOIs could result in hypertensive crisis, hyperthermia, and autonomic instability.
    • Escitalopram will increase plasma levels of metoprolol and cimetidine.
    • Concurrent use of alcohol and other CNS depressants may enhance CNS depressant effects; patients should avoid alcohol.
  • Lab Tests: Unknown
  • Herbal/Food:
    • Use caution with herbal supplements such as St. John’s wort, which may cause serotonin syndrome and increase escitalopram effects.
  • Treatment of Overdose:
    • No specific treatment; treat symptoms, including dizziness, confusion, nausea, vomiting, tremor, sweating, tachycardia, and seizures.

Antidepressant Class Information

SNRIs

  • Safer than other classes.
  • Less common sympathomimetic effects (increased heart rate and hypertension).
  • Fewer anticholinergic effects.
  • Can cause weight gain and sexual dysfunction.

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

  • Many possible side effects:
    • Abnormal dreams, sweating
    • Constipation, dry mouth, loss of appetite, weight loss
    • Tremor, abnormal vision, headaches, nausea
    • Vomiting, dizziness, and loss of sexual desire

TCAs

  • Not for use in patients with heart attack, heart block, or arrhythmia.
  • Potential side effects: dry mouth, blurred vision, urine retention, and hypertension.
  • Avoid concurrent use with alcohol or other CNS depressants.

MAOIs

  • Avoid foods containing tyramine.
  • Potentiate the effects of insulin and other diabetic drugs.
  • Common adverse effects include orthostatic hypotension, headache, and diarrhea.

Benzodiazepines

Prototype Drug: Lorazepam (Ativan)

  • Therapeutic Class: Sedative-hypnotic; anxiolytic; anesthetic adjunct
  • Pharmacologic Class: Benzodiazepine; GABAA-receptor agonist
  • Mechanism of Action: Potentiates the effects of GABA in the thalamic, hypothalamic, and limbic levels of the CNS.

Lorazepam (Ativan) Details

  • One of the most potent benzodiazepines.
  • Extended half-life of 10-20 hours allows for once- or twice-a-day oral dosing.
  • Used as an anxiolytic, preanesthetic medication, and for the management of status epilepticus.
  • Unlabeled uses include the treatment of chemotherapy-induced nausea and vomiting.

Lorazepam (Ativan) - Administration Alerts

  • When administering intravenously (IV), monitor respirations every 5-15 minutes.
  • Have airway and resuscitative equipment accessible.
  • Pregnancy category D.

Lorazepam (Ativan) - Pharmacokinetics

  • Onset: 1-5 min IV; 15-30 min IM; 30 min PO
  • Peak: 90 min IM; 2 h PO
  • Duration: Variable

Lorazepam (Ativan) - Adverse Effects

  • Most common: drowsiness and sedation (may decrease with time).
  • Higher doses or IV route: amnesia, weakness, disorientation, ataxia, sleep disturbance, blood pressure changes, blurred vision, double vision, nausea, and vomiting.

Lorazepam (Ativan) - Contraindications

  • Acute narrow-angle glaucoma, closed-angle glaucoma, misuse/excessive drug use, liver disease, impaired brain function, or thoughts of suicide.

Lorazepam (Ativan) - Interactions

  • Drug-Drug:
    • Concurrent use of CNS depressants (including alcohol) potentiates sedative effects and increases the risk of respiratory depression and death.
    • May decrease the antiparkinsonism effects of levodopa and increase phenytoin levels.
  • Lab Tests: Unknown
  • Herbal/Food:
    • Use cautiously with herbal supplements (e.g., kava, valerian, chamomile, hops may have an additive effect).
    • Stimulant herbs (e.g., gotu kola and ma huang) may reduce effectiveness.
  • Treatment of Overdose:
    • Flumazenil (Romazicon), a benzodiazepine receptor antagonist, can be administered to reverse CNS depressant effects.

Benzodiazepines Uses

  • Some treat short-term insomnia; others treat various anxiety disorders.
  • Most are given orally.
  • Drugs of choice for short-term treatment of insomnia caused by anxiety (greater margin of safety).

Mechanism

  • Intensify effects of GABA
  • Examples: Xanax, Librium, Tranxene

Other important indications include

  • Seizure disorders
  • Alcohol withdrawal
  • Central muscle relaxation
  • Induction agents in anesthesia

Prototype Drug: diazepam (Valium) Details

  • Mechanism of Action: binds with GABA receptor-chloride channel molecules, intensifying effects of GABA; inhibits brain impulses from passing through limbic and reticular activating systems.

Diazepam (Valium) Uses

  • Primary Use: as sedative and hypnotic
  • Adverse Effects: tolerance, respiratory depression, psychological and physical dependence

Diazepam (Valium) Additional Information

  • Powerful CNS depressants prescribed for sedative, hypnotic, and antiseizure effects.
  • Rarely prescribed for treating anxiety or insomnia due to potential for severe adverse side effects.
  • High risk for dependence.
  • Low doses reduce anxiety; moderate doses promote sleep.

Barbiturates

Intensify effect of GABA in brain

  • Examples: Nembutal, Seconal

Nonbenzodiazepine, Nonbarbiturate CNS Depressants

  • Chemically unrelated to either benzodiazepines or barbiturates.
  • Used mainly for treatment of social anxiety symptoms.

Prototype: zolpidem (Ambien)

  • Mechanism of Action: binds to GABA receptors
  • Primary Use: as hypnotic
  • Adverse Effects: mild nausea, dizziness, diarrhea, daytime drowsiness, amnesia, sleepwalking, eating while asleep
  • Preserves sleep stage III; offers minor effects of REM sleep
  • Other nonbarbiturate CNS depressant: BuSpar

Prototype Drug Zolpidem (Ambien, Edluar, Intermezzo)

  • Therapeutic Class: Sedative–hypnotic
  • Pharmacologic Class: Nonbenzodiazepine GABAA receptor agonist; nonbenzodiazepine, nonbarbiturate CNS depressant
  • Acts similar to facilitate GABA-mediated CNS depression in the limbic, thalamic, and hypothalamic regions
  • Preserves stage 3 of sleep and has only minor effects on REM sleep
  • The only indication for zolpidem is for short-term insomnia management (7 to 10 days)
  • Available in sublingual tablets (Edluar) and oral spray (Zolpimist)
    • In January 2013, the FDA lowered the recommended dose due to adverse effects observed especially among women

Zolpidem (Ambien, Edluar, Intermezzo) - Administration Alerts

  • Because of rapid onset, give immediately before bedtime.
  • Pregnancy category B.

Zolpidem (Ambien, Edluar, Intermezzo) - Pharmacokinetics

  • Onset: 7–27 min
  • Peak: 0.5–2.3 h
  • Duration: 6–8 h

Zolpidem (Ambien, Edluar, Intermezzo) - Adverse Effects

  • Daytime sedation, confusion, amnesia, dizziness, depression with suicidal thoughts, nausea, and vomiting.
  • Associated with adverse neuropsychiatric reactions, such as hallucinations, sensory distortion, sleepwalking, and nocturnal eating.
  • Women have significantly higher serum zolpidem concentration than men.
  • Adverse reactions are dose-dependent.
  • Lactating women should not take this drug.
  • Drug–Drug: Drug interactions with zolpidem include an increase in sedation when used concurrently with other CNS depressants, including alcohol
  • Phenothiazines augment CNS depression.
  • Herbal/Food: When taken with food, absorption is slowed significantly, and the onset of action may be delayed.
  • Treatment of Overdose: Generalized symptomatic and supportive measures should be applied with immediate gastric lavage where appropriate
  • IV fluids should be administered as needed
  • Use of flumazenil (Romazicon) as a benzodiazepine receptor antagonist may be helpful

Nonbenzodiazepine, Nonbarbiturate CNS Depressants Considerations

  • Assess for common side effects of CNS depression
  • Assess neurological status, level of consciousness
  • Monitor vital signs, observe respiratory patterns particularly during sleep
  • Monitor patient's intake of stimulants, such as caffeine and nicotine
  • Monitor affect and emotional status

Nursing Considerations for Drugs for Anxiety and Insomnia

  • Assessment
  • Potential nursing diagnoses
  • Reason for drug
  • Monitoring vital signs
  • Cautions and contraindications
  • Possible drug interactions (health, drug history, lab reports)

Nursing Diagnoses

  • Risk for injury related to drug therapy
  • Deficient knowledge related to drug therapy
  • Ineffective individual coping

Planning: Patient will

  • Experience therapeutic effects depending on drug
  • Be free of adverse effects
  • Demonstrate an understanding of the drug's activity
  • Accurately describe drug side effects and precautions
  • Demonstrate proper self-administration technique

Implementation

  • Interventions and rationales
  • Administration of drug
  • Observing for adverse effects
  • Patient education and discharge planning

Evaluation

  • Effectiveness of drug therapy
  • Evaluate the achievement of goals and expected outcomes

Nursing Practice Application: Pharmacotherapy for Anxiety or Sleep Disorders

Baseline assessment prior to administration:

  • Obtain a complete health history including hepatic, renal, respiratory, cardiovascular or neurologic disease, mental status, narrow-angle glaucoma, and pregnancy or breast-feeding
  • Obtain a drug history including allergies, current prescription and OTC drugs, herbal preparations, and caffeine and alcohol use
  • Be alert to possible drug interactions
  • Assess stress and coping patterns (e.g., existing or perceived stress, duration, coping mechanisms or remedies)
  • Obtain a sleep history (e.g., quality and quantity of sleep, restlessness or frequent wakefulness, snoring or apnea, remedies used for sleep, concerns)
  • Evaluate appropriate laboratory findings (e.g., hepatic or renal function studies)
  • Obtain baseline vital signs and weight
  • Assess the patient’s risk for falls
  • Assess the patient’s ability to receive and understand instruction
  • Include the family and caregivers as needed

Potential Nursing Diagnoses

  • Anxiety
  • Disturbed Sleep Pattern
  • Fatigue
  • Ineffective Coping
  • Activity Intolerance
  • Deficient Knowledge (drug therapy)
  • Risk for Injury, related to adverse effects of drug therapy
  • Risk for Falls, related to adverse effects of drug therapy

Assessment throughout administration:

  • Assess for desired therapeutic effects (e.g., statements of improvement in anxiety, appetite, ability to carry out ADLs, and sleep patterns normalized
  • Continue periodic monitoring of liver and renal function studies
  • Assess vital signs and weight periodically or if symptoms warrant
  • Assess for and promptly report adverse effects: excessive dizziness, drowsiness, light-headedness, confusion, agitation, palpitations, tachycardia, and musculoskeletal weakness

Implementation: Interventions and (Rationales)

Ensuring therapeutic effects:

  • Continue assessments as described earlier for therapeutic effects(If the drug is given for anxiety, the patient reports decreased anxiety, improved sleep and eating habits, improved coping, and ability to carry out ADLs without anxiety
  • If the drug is given for sleep, the patient reports the ability to fall and remain asleep and improved daytime wakefulness
  • Encourage the patient to keep a sleep diary of usual bedtime, the time involved trying to fall asleep, the quality and quantity of sleep, and daytime sleepiness
  • Collaboration: Assist the patient in developing healthy coping strategies and sleep habits with referral to appropriate health care providers as needed
  • Diverse Patients: Teach ethnically diverse patients to observe for optimal therapeutic effects and to report promptly

Minimizing adverse effects:

  • Continue to monitor vital signs, mental status, and coordination and balance periodically
  • Be particularly cautious with older adults who are at increased risk for falls(Drugs used for anxiety and sleep may cause excessive drowsiness and dizziness, increasing the risk of falls and injury
  • Teach the patient to rise from lying or sitting to standing slowly to avoid dizziness or falls(If dizziness occurs, the patient should sit or lie down and not attempt to stand or walk until the sensation passes
  • Ensure patient safety, especially in older adults
  • Observe for light-headedness or dizziness
  • Monitor and assist with ambulation as needed(Dizziness and drowsiness for a prolonged period may occur, depending on the drug’s half-life
    • Daytime drowsiness may impair walking or the ability to carry out usual ADLs
  • Subtle changes to mental alertness, cognitive functioning, or motor coordination may occur, even in the absence of sleepiness
  • Safety: Instruct the patient to call for assistance prior to getting out of bed or attempting to walk alone, and to avoid driving or other activities requiring mental alertness or physical coordination until the effects of the drug are known
  • Assess for changes in level of consciousness, disorientation or confusion, or agitation(Neurologic changes may indicate overmedication or effects of sleep deprivation
  • Instruct the patient or caregiver to immediately report increasing lethargy, disorientation, confusion, changes in behaviour or mood, slurred speech, or ataxia
  • Have caregivers observe for nighttime behavioral activities such as sleepwalking, sleep-eating or sleep- driving if nonbenzodiazepine sedative-hypnotic drugs are given, and report immediately
    The patient may not remember or be aware of these activities
  • Assess for changes in visual acuity, blurred vision, loss of peripheral vision, seeing rainbow halos around lights, acute eye pain, or any of these symptoms accompanied boy nausea and vomiting and report immediately(Increased intraoptic pressure in patients with narrow-angle glaucoma may occur in patients taking benzodiazepines
  • nstruct the patient to immediately report any visual changes or eye pain
  • Monitor affect and emotional status(Drugs may increase risk of mental depression, especially in patients with suicidal tendencies
  • Teach the patient about the need for continued monitoring, especially if pre-existing depression is present
  • Encourage appropriate lifestyle changes: lowered caffeine intake including OTC medications that contain caffeine, increased exercise during the day but not immediately before bedtime, limited or no alcohol intake, and smoking cessation
  • Advise the patient to discuss all OTC medications with the health care provider to ensure that caffeine or alcohol is not included in the formulation
  • Avoid abrupt discontinuation of therapy
  • Instruct the patient to take the drug exactly as prescribed and to not stop it abruptly
  • Overdosage may occur if the patient takes additional doses when drowsy or disoriented from medication effects

Nonpharmacologic methods and patient understanding

  • Drug therapy is used for the shortest amount of time possible
  • Developing other coping skills or improved sleep hygiene may lessen the need for drug therapy
  • The patient should be able to state the reason for the drug; appropriate dose and scheduling; what adverse effects to observe for and when to report; and the anticipated length of medication therapy
    *Teach patients to not open, chew, or crush extended release tablets; swallow them whole with plenty of waterSublingual forms of the drug should be allowed to dissolve under the tongue; water should not be taken