Anxiety Lecture (Behavior)

Where is serotonin found in the body

90% in GI

10% in brain

Enterochromaffin Cells

GI tract cells that contain serotonin

Raphe Nuclei

Structure in the brainstem than contains serotonin

Can serotonin cross BBB

No

How does serotonin affect the body

Head - Depression, Anxiety, Memory, Impulse, Sex

Red - Platelets and bleeding

Fed - GI Motility and Nause

Where is norepinephrine found in the brain

Locus coreuleus

How does norepinephrine effect the body

Concentration,

attention,

energy

Tachycardia,

hypertension,

glucose utilization,

decrease GI motility

What type of neurotransmitter is norepinephrine

Excitatory

What type of neurotransmitter is glutamate

Excitatoryu

What type of neurotransmitter is GABA

Inhibtory

Effect of GABA on the body

Relaxation,

euphoria,

decrease muscle contraction,

slows breathing

Protective for seizure

What effect does GABA have on anxiety

More GABA decreases anxiety

What type of neurotransmitter is histamine

Excitatory but sometimes inhibitory (Stimulates GABA)

What medication are considered anxiolytics

Selective serotonin reuptake inhibitors (SSRI’s)/Serotonin-norepinephrine reuptake inhibitors (SNRI’s)

Benzodiazepines

Azapirone

Antihistamines

Gabapentin (Neurontin): off label

Barbiturates

Alprazolam (Xanax)

Benzodiazepine

Lorazepam (Ativan)

Benzodiazepine

Diazepam (Valium)

Benzodiazepine

Clonazepam (Klonopin)

Benzodiazepine

Chlordiazepoxide (Librium)

Benzodiazepine

Clorazepate (Tranxene)

Benzodiazepine

Temazepam (Restoril)

Benzodiazepine

Midazolam (Versed)

Benzodiazepine

Triazolam (Halcyon)

Benzodiazepine

MOA of Benzodiazepines

Binds to GABA receptors

Increases frequency of GABA channels opening

More GABA decreases neural excitability

Reduces communication between neurons and produces a calming effect on many functions of the brain

How are benzodiazepines metabolized generally

CYP450

Who will have delayed metabolism of benzodiazepines

Elderly

Hepatic Dysfunction

What benzodiapines can be given IM / IV

Lorazepam (Ativan)

Midazolam (Versed)

Diazepam (Valium)

Indications for Benzodiapines

Anxiety

Insomnia

Agitation

Alcohol withdrawal

What benzodiazepine is used for sedation

: Midazolam (Versed)

What benzodiazepines are used for Anticonvulsants

Diazepam (Valium)

, lorazepam (Ativan)

midazolam (Versed)

What benzodiazepine is used for muscle relaxant

Diazepam (Valium )

What is the dosing stragey with benzodiazepines

Start with a benzodiazepine like lorazepam (Ativan) or Clonazepam (Klonopin) that is taken at a low dose to begin with, then titrated up

Continue meds for 2-6 weeks followed by a 1-2 week taper.

During this 6 week period, initiate SSRI

Side Effects of Benzodiazpeines

Sedation / Impaired Concentration (#1)

Dizzness

Ataxia

Anterograde Amnesia

Memory Los

Poor attention

Impaired to visuopartail awareness

Delirium

Disinhbitiion with paradoxical agitation / aggression

What medications can cause OD with benzo

ETOH

Opioids

Presentation of Benzo Withdrawal

Increased anxiety/irritability

Tremor or shakiness, muscle twitching

Sweating

Tachycardia, HTN

Insomnia

Seizures/delirium

What benzo has a particular severe withdrawal

Alprazolam (Xanax)

What determines the severity of benzo withdrawl

Short half life = Worse

How are benzos tapered

Decrease 25% each week

What is the main sign of benzo OD

Respiratory Depression

What agents can cause respiratory depression

Benzos

ETOH

Opioids

Barbiturates

TCAs

Flumazenil (Romazicon)

Benzodiazepine receptor antagonist

MOA of Flumazenil (Romazicon)

Can block and reverse CNS effect of benzos, but NOT of other sedatives like ETOH, opioids, or barbiturates

Side Effect of Flumazenil (Romazicon)

Seizures (#1)

N/V

Dizzy

Agitation

Emotional Lability

What medication has the street name footballs

Xanax

What should be done if prescribing benzos outpatient

Consider a UDS prior to initial order

Caution if any substance abuse history

Utilize a controlled substances contract

Educate patient about risks of combining with alcohol or other medications which may be CNS/respiratory depressants

Consider random UDS’s to look for other substances as well as diversion of medication

What should be done if prescribing benzos inpatient

Obtain a UDS

Caution if any substance abuse history

Advise patient of short- term nature, likely will not be prescribed on discharge

Orders should include a note to nursing to hold if sedated

Separate timing of orders for benzos from other medications that could be CNS/respiratory depressants

Indications for alprazolam (Xanax)

Panic Disorder

GAD

Socail Phobia

Benefits to alprazolam (Xanax)

Fast onset  quick relief of acute anxiety

Short half life

Often dosed multiple times a day up to (Q4H)

Less sedating than other benzos

Downsides to Using alprazolam (Xanax)

Euphoria or high reported  abuse potential

Serious problem with w/d symptoms

Indications for lorazepam (Ativan)

Anxiety

ETOH Withdrawal

Adjunct in acute psychotic agitiation

Benefits to lorazepam (Ativan)

IM, IV and PO form

No active metabolites

Moderate half-life

What benzo should be used if patient has serious or multiple comorbidities

lorazepam (Ativan)

lorazepam (Loreev XR)

Extended release lorazepam

Indication for lorazepam (Loreev XR)

patients who are taking Ativan TID scheduled dosing

Indications for clonazepam (Klonopin)

Panic Disorder

Social Phobia

GAD

Substitution for Short-Acting Benzo in Treatment of Withdrawal

Benefits to Using clonazepam (Klonopin)

Long half life

Does NOT provide euphoria

Rapid onset  prompt relief

Contraindication for clonazepam (Klonopin)

LIVER DISEASE

Downside for Using clonazepam (Klonopin)

Increased cognitive side effects

Cannot use with liver disease

Indications for Diazepam (Valium)

Anxiety,

ETOH withdrawal,

adjunctive treatment of muscle spasm and movement disorders

Benefit to Using Diazepam (Valium)

Very long half-life

Downside to Using Diazepam (Valium)

accumulation of active metabolites especially in the elderly and medically incapacitated

P450 metabolism so be careful in hepatic disease

Indications for Chlordiazepoxide (Librium)

Anxiety

ETOH Withdrawal

Benefit to Using Chlordiazepoxide (Librium)

Very long half

Downsides for Chlordiazepoxide (Librium)

Long half-life and P450 metabolism ensures drug will accumulate with multiple dosing

Elderly and medically incapacitated can become suddenly obtunded

Particular concern when using for alcohol withdrawal

Buspirone (BuSpar)

Azaspirone

MOA of Buspirone (BuSpar)

Complex MOA

Partial serotonin 1A agonist

No involvement with GABA

No withdrawal/addiction

No anti-seizure or muscle relaxant properties

Limited sedation

Indications for Buspirone (BuSpar)

GAD

Augment treatment for Depression / OCD

Side Effects of Buspirone (BuSpar)

Headache (#1)

Dizziness

GI Upset

Fatigue

Insomina

What can decrease efficacy of Buspirone (BuSpar)

Taken benzodiazepines before

When does Buspirone (BuSpar) take effect

2-4 weeks

gabapentin (Neurontin)

GABA analog calcium-channel modulator

Why is pregabalin not used for anxiety

More side effects

Higher dependence potential

Indication for Gabapentin

addition to SSRI treatment for a partial response to initial treatment

patients who cannot tolerate SSRI

Contraindication for Gabapentin for Anxiety

Opioid Use Disorder

Side Effects of Gabapentin

Sedation

Dizziness

hydroxyzine (Atarax, Vistaril)

Histamine receptor antagonist

Indication for Hydroxyzine

Anxeity

Insomnia

Side Effects for Hydroxyine

anticholinergic side effects

May prolong QTc

Barbiturates MOA

Increase duration of GABA channels opening

Indications for Barbiturates

seizures,

anxiety disorders,

insomnia

Phenobarbital(Luminal and Solfoton)

Barbiturates

pentobarbital (Nembutal)

Barbiturates

Why is Barbiturates not used often

risk of abuse/death

Who is anxiety disorders more common in

Women

What is responible for physiologic effects of anxity

Autonomic nervous system

Physiologic Symptoms of Anxiety

Headache

Perspiration

Palpitations

Tight Chest

Stomach upset

Restlessness

Anxiety

A response to a threat that is unknown, internal, vague

Fear

An emotional response to a real or perceived imminent threat

Selectivity of attention

Notice certain things about their environment while selectively overlooking others in an effort to prove they are justified in their anxiety

How does anxiety effect mental status

Affects thinking and learning

Can cause confusion and distortions of perception

Decreased ability to relate one item to another (make associations)

Selectivity of attention

How are neurotransmitters effects in anxious disorders

Increased norepinephrine activity

Decreased gamma aminobutyric acid (GABA)

Serotonin?

How many symptoms are needed for a panic attack

4 or more

What is the timing for a panic attack

developed abruptly and reached a peak within minutes

Symptoms of a Panic Attack

PANICSS

Palpitations

Abdominal distress

Numbness, Nausea

Intense fear of death

Choking, Chills, Chest pain

Sweating, Shaking

SOB

Panic Disorder

characterized by the recurrent spontaneous, unexpected occurrence of panic attacks

What is the timing of panic disorder

Attack followed by at least 1 month of:

Worry of repeat panic attack/maladaptive behavior

What can trigger a panic attack

excitement,

physical exertion,

sex,

moderate emotional trauma

What tends to be the concern of patients with a panic attack

death from cardiac or respiratory problem

Rumination

Compulsively focused attention on the symptoms of one's distress, and on its possible causes and consequences, as opposed to its solutions

Stammering

Speaking with many pauses and repetitions