NR546 Midterm Exam

Questions And Answers 2023 Update

A+
What should the PMHNP consider when prescribing chemical restraints? - Answer--
allergy status
-prior med hx for adverse drug reactions r/t the meds ordered in the chemical restraint
-state regulations regarding chemical restrains must be reviewed

Are the PMHNP and other staff liable if the client has an allergic reaction or adverse
side effects to the drugs used for chemical restraint? - Answer-No.
The client has been court-ordered to take the prescribed medications and the standing
order for chemical restraints is approved. The PMHNP and other staff are not liable if
the patient has an allergic reaction or adverse side effects.

How does reviewing the genetic makeup of a client help guide the PMHNP in selecting
medication for clients? - Answer--Genetic testing can assist by providing more
information on how clients may respond to certain psychotropic medications
-provides information on how a client may break down and metabolize medications
based on the cytochrome P450 system.

Tanrıkulu and Erbaş (2020) investigated identical twins to determine the presence of an
inherited link for schizophrenia and why one twin may develop schizophrenia when the
other does not. When two people have 100% identical DNA, why don't both persons
develop the exact illnesses? Studies of identical Danish twins found that if one twin had
schizophrenia, the other twin had a 50% lifetime risk of developing schizophrenia
(Lemvigh et al., 2020). Why is there only half the risk? - Answer-Both environmental and
psychosocial stressors can impact mental health. Although twins may have identical
genes, their gene expression may be different.

There may be an environmental exposure that turned a gene "on" that should have
been "off" for one twin to develop schizophrenia and not the other.

central sulcus - Answer-separates the frontal lobe from the parietal lobe

frontal lobe - Answer-associated with movement, intelligence, abstract thinking

broca's area - Answer-speech production

temporal lobe - Answer-involves object identification and auditory signals

cerebellum - Answer-coordination

wernicke's area - Answer-speech comprehension

occipital lobe - Answer-primary visual area

parietal lobe - Answer-keeps us alert to what is going on around us

sensory cortex - Answer-pain, heat, and other sensations

motor cortex - Answer-movement

hippocampus - Answer-involved in both memory and anxiety

nucleus accumbens - Answer-involved in the reward process

thalamus - Answer-involved in sensory organ and motor command processing

striatum - Answer-involved in complex motor actions, also links cognition to motor

actions

limbic system - Answer-includes circuits that are associated with pleasure and reward

basal ganglia - Answer-group of structures involved in voluntary motor movements

amygdala - Answer-involved in emotional regulation and perception of odors

corpus callosum - Answer-controls the communication between the two brain

hemispheres

white matter - Answer-contains nerve fibers that connect neurons from different regions
into functional circuits

grey matter - Answer-contains nerve cells and dendrites

brain tissue - Answer-made up of grey matter and white matter

dorsal striatum - Answer-involved in complex motor actions and linkage of cognition to

motor actions
-main input area for basal ganglia
*activated when anticipating or engaging in pleasure

The field of epigenetics is rapidly growing and can help explain how gene expression is:
- Answer-influenced by environmental factors and how epigenetics contributes to the
manifestation of mental illness

How does epigenetics impact a person's mental health? - Answer-internal or external

factors activate portions of the genome that result in the manifestation of mental health
symptoms
-activation is often a result of a stressful event, which, when combined with the genetic
risk, results in the disease
-genes being on or off
-occurrence of symptoms may be the result of inheritance of an abnormal gene or of
normal genes being "on" when they should be "off."

Types of epigenetic changes: - Answer-DNA Methylation

Histone modification
Non-coding RNA

The potential legal and ethical issues impacting mental health treatment must also be
taken into account, including: - Answer--informed consent
-competence to make healthcare decisions
-off-label prescribing

Informed consent - Answer-Clients have the right to receive enough information to make
decisions about treatment.
-must also be informed about potential risks associated with medications.
-have the right to refuse treatment
-cannot be forcibly medicated in non-emergencies. However, clients can be forcibly
medicated if they are violent toward themselves or others and when less restrictive
methods have failed

Compliance - Answer-A court order may be issued for a client to receive treatment
against their wishes if they are considered a danger to themselves or others.
-Examples: clients with schizophrenia or sex offenders
-Guardians can provide consent for clients who have limited cognitive capabilities or are
incompetent to make decisions
-PMHNPs are responsible for being knowledgeable about their state laws and abiding
by them.

Off-Label Prescribing - Answer-Some clients may benefit from the unapproved use of a
drug for symptom management.
-Example: many SSRIs used to tx anxiety and OCD but are not FDA approved for use
in this disorder.
-potentially raises ethical and legal concerns
-PMHNP must remain up to date with the latest recommendations for off-label
prescribing.

Incidence of mental illness-what factors are increasing the incidence - Answer-

Psychological and sociological factors

Lifestyle factors such as a client's smoking status, diet, exercise, history of medication
adherence, or history of addiction should be considered when prescribing psychotropic
medications
Adherence - Answer-Persistence
-taking med over intended time period
Compliance
-taking med as prescribed

left hemisphere - Answer--speech comprehension

-word recognition
-grammar
-sequential processing
-recognition of detail
-conscious mental processing

right hemisphere - Answer--prosody of speech

-emotional modulation
-visual-spatial skills
-recognition of facial expression
-music
-abstract mathematical skills
-holistic processing
-unconscious mental processing

Pharmacokinetics - Answer-the study of what happens to a drug from the time of

administration until the parent drug and all metabolites leave the body

CYP450 - Answer-CYP450 enzymes in the gut wall or liver convert drug substrate into a
biotransformed product in the bloodstream, responsible for degradating of a large # of
psychotropic drugs
-Not all ind. have same genetic form of CYP450 enzymes, determined with
pharmacogenetic testing
*Most individuals have "normal" rates of drug metabolism from the major CYP450
enzymes and are said to be "extensive metabolizers", most drug doses are set for these
individuals.
*genetic variants of these enzymes can make poor metabolizers or ultra rapid
metabolizers

Five of the most important:

CYP450 1A2, 2B6, 2D6, 2C9, 2C19, and 3A4.

ultra rapid metabolizers - Answer-elevated enzyme activity

subtherapeutic drug levels
poor efficacy with standard doses

genotyping - Answer-the patient for pharmacogenomic use

-genes for these CYP450 enzymes can now be readily measured and used to predict
which patients might need to have dosage adjustments
-measurement of genes for drug metabolism
most common targets of psychotropic drugs - Answer-G-protein receptors
-Drug actions at these receptors occur in a spectrum, from full agonist actions, to partial
agonist actions, to antagonism, and even to inverse agonism.

Pharmacokinetics concepts - Answer-absorption

distribution
metabolism
excretion

Flockhart Table - Answer-drug interactions that are mediated by cytochrome P450

enzymes

comprehensive list of drugs and the interactions related to the cytochrome P450 system

Neurotransmitters - Answer-chemicals released by neurons to send communication

across synaptic clefts to other neurons
-impact human emotion and behavior

Neurotransmission: - Answer-the chemical transmission of information between neurons

and their target cells
-the chemicals, or neurotransmitters, are released from their transport vesicles to bind
with receptor sites to perform their duties, which are excitatory or inhibitory
-neurotransmitter then either returned and stored for future use (reuptake) or inactivated
and dissolved by enzymes
-Types: Classic, Retrograde, Volume

Classic neurotransmission - Answer-neurons send electrical impulses from one part of

the cell to another part of the same cell via their axons
-one neuron hurling a chemical messenger, or neurotransmitter, at the receptors of a
second neuron
-electrical impulse converted chemical signal at the synapse in a process known as
excitation-secretion coupling, the first stage of chemical neurotransmission, then back
into electrical impulse in second neuron
-chemical information from the first neuron triggering a cascade of further chemical
messages within the second neuron to change that neuron's molecular and genetic
functioning

Retrograde neurotransmission - Answer-postsynaptic neurons "talk back" to their

presynaptic neurons
-second neuron to the first at the synapse between them
-Chemicals produced specifically as retrograde neurotransmitters at some synapses
include: endocannabinoids, gaseous neurotransmitter nitric oxide (NO), nerve growth
factor (NGF).
Volume neurotransmission - Answer-Neurotransmission without a synapse or
nonsynaptic diffusion neurotransmission
-Chemical messengers sent by one neuron to another can spill over to sites distant to
the synapse by diffusion
-neurotransmission can occur at any compatible receptor within the diffusion radius of
the neurotransmitter
-neurotransmission occurs in chemical "puffs"
-sophisticated "chemical soup."
-example: dopamine action in the prefrontal cortex, at the sites of autoreceptors on
monoamine neurons

Excitatory neurotransmitters: - Answer-increase the likelihood that the neuron will fire an
action potential

inhibitory neurotransmitters: - Answer-decrease the likelihood that a neuron will fire an

action

neurotransmitters that most impact mental health can be classified into four major
categories: - Answer-cholinergics
-acetylcholine

monoamines
-norepinephrine, dopamine, serotonin, histamine

amino acids
-gamma- amino-butyric acid and glutamate

neuropeptides

Inhibitors: VISA CKGQ - Answer-Valproate

Isoniazid
Sulfonamides
Amiodarone
Chloramphenicol
Ketoconazole
Grapefruit Juice
Quinidine

-decrease medication metabolism

Inducers: CRAP GPS - Answer-Carbamazepine

Rifampin
Alcohol
Phenytoin
Griseofulvin
Phenobarbital
Sulfonylureas

-increase medication metabolism

neurotransmitters that may be responsible for a client's symptoms of depression -

Answer-Imbalanced levels of acetylcholine, norepinephrine, serotonin, histamine, or
glutamate can contribute to symptoms of depression

client who is a poor metabolizer: - Answer-has a lower concentration of the necessary

enzyme to metabolize a drug, which results in higher blood concentrations of the drug.
-increase the risk of side effects and adverse reactions

Why is trazodone not used as a front-line antidepressant - Answer-Its antidepressant

that has a secondary effect of blocking histamine and adrenergic receptors
-causes sedation and somnolence and as a result
*often used as an adjunct in therapy when a depressed patient has difficulty sleeping

effect on neurotransmitters and side effects: Selective Serotonin Reuptake Inhibitors

(SSRIs) - Answer-Inhibits the reuptake of serotonin, which can cause nausea, agitation,
headache, and sexual dysfunction

effect on neurotransmitters and side effects: Serotonin and Norepinephrine Reuptake

Inhibitors (SNRIs) - Answer-Inhibits the reuptake of serotonin and norepinephrine, which
can cause nausea, sweating, insomnia, tremors, sexual dysfunction

effect on neurotransmitters and side effects: Tricyclic Antidepressants - Answer--Inhibits

the reuptake of serotonin and norepinephrine, which can cause sexual dysfunction
-Blocks norepinephrine receptors, which can cause hypotension and tachycardia
-Blocks histamine receptors, which can cause sedation and weight gain
-Blocks acetylcholine receptors, which can cause dry mouth, constipation, blurred
vision, and urinary retention

effect on neurotransmitters and side effects: Monoamine Oxidase Inhibitors (MAOIs) -

Answer-Increases norepinephrine and serotonin by inhibiting the enzyme that
inactivates it, which can cause sedation, dizziness, sexual dysfunction, and
hypertensive crisis

effect on neurotransmitters and side effects: Benzodiazepines - Answer-Increases the

receptor affinity for GABA, which can cause dependence and confusion

effect on neurotransmitters and side effects: Bupropion - Answer-Inhibits the reuptake of

norepinephrine and dopamine, which can cause insomnia, dry mouth, tremors, and
seizures

antagonist - Answer-causes a conformational change that stabilizes the receptor in the

baseline state and thus is "silent."
-blocks the action of a neurotransmitter

agonists - Answer-fully stimulate G-protein-linked receptors

partial agonists - Answer-stimulate receptors to a lesser degree than an agonist or

natural neurotransmitter

SSRIs, SNRIs, and tricyclic antidepressants increase ________ levels.

___________ do not impact serotonin levels. - Answer-increase serotonin levels.
Benzodiazepines do not impact serotonin levels.

Is nicotine an inducer or an inhibitor of the CYP 1A2 enzyme? - Answer-inducer

Nicotine is an inducer of the CYP 1A2 enzyme. Does the PMHNP anticipate Joshua
may need a higher or lower dose of olanzapine to achieve a therapeutic response? -
Answer-Higher
-Nicotine is an inducer of the CYP 1A2 enzyme, so it lowers the concentration of drugs.
Therefore, a higher dose of olanzapine may be needed to control his symptoms.

Ernesto, a 60-year-old, presents to the PMHNP with report of having anxiety, frequent
occurrences of feeling frozen in place and like his heart is pounding out of his chest, as
well as having difficulty sleeping.
The PMHNP suspects the client has an elevated level of which neurotransmitter? -
Answer-Norepinephrine
-responsible for the regulation of fight or flight responses and can impact mood and
sleep.

Which of the following is the best medication class for the PMHNP to prescribe for
Ernesto to address his elevated norepinephrine levels? - Answer-selective serotonin
reuptake inhibitor would block the reuptake of serotonin, leaving a larger amount of
serotonin available. Increasing the amount of serotonin would help regulate the feelings
of fear and anxiety. Reducing the occurrence of fear would help reduce the release of
norepinephrine.
A serotonin and norepinephrine reuptake inhibitor would prevent the reuptake of
norepinephrine, which would not reduce the level of norepinephrine as needed.
Benzodiazepines increase the levels of GABA and do not impact norepinephrine. A
monoamine oxidase inhibitor would increase levels of norepinephrine.

During a follow up appointment after 4 weeks, the PMHNP should assess for the need
to add which medication to Ernesto's treatment plan? - Answer-The nurse should
assess for sexual dysfunction and anticipate the potential need for a phosphodiesterase
inhibitor such as sildenafil (Viagra).
-After 4 to 6 weeks, the client should be experiencing full effects of the SSRI, so the
need for a short-term medication like a benzodiazepine or a beta blocker are not
anticipated. St. John's Wort is contraindicated with an SSRI and can cause serotonin
syndrome.
Glu - Answer-Glutamate
-amino acid
-excitatory neurotransmitter
-"workhorse" of the brain-can affect almost every neuron in the brain
-affects: energy, memory, learning, neural plasticity
-relay sensory info. and regulate spinal and motor reflexes
-too much: schizophrenia, epilepsy, mania
-receptors: NMDA, AMPA

GABA - Answer-inhibitory neurotransmitter

-decrease neuroexcitability across the brain
-"chill", take the edge off stress, help people calm down, relax, destress, sleep
-to little: may experience anxiety or schizophrenia
-slows down everything, even breathing
-affect executive function and motor coordination, increase risk for accidents
-Increased levels of gamma-aminobutyric acid have a calming effect.

5HT - Answer-Serotonin
-help regulate mood
-makes relaxed, comfortable, decreases stress, regulate sleep, arousal, libido,
aggression, pain perception

NE - Answer-norepinephrine
-monoamine neurotransmitter
-focus and productivity
-too much due to stress, meds, caffein, stimulants can cause: nervous, antsy, affect
focus

DA - Answer-dopamine
-monoamine neurotransmitter
-regulate mood
-associated with executive function, ability to perform well, be organized, emotional
intelligence
-movement and coordination
-to little: lose pleasure, interest, alertness, self-confidence, parkinson's disease
-to much: schizophrenia and psychosis
-reward center: can lead to addiction
-has own pathways

Ach - Answer-acetylcholine
-in CNS: affects arousal, motivation, attention, learning, REM sleep, impacts sleep, pain
perception, memory
-in PNS: makes you sweat and salivate
-link between brain and muscles
-not enough: Alzheimer's, Parkinson's, Schizophrenia
-too much: Depression
-Role in addiction
-Receptors: nicotinic & muscarinic

Histamine (Neurotransmitter) - Answer-Histamine impacts alertness, pain sensation,

and inflammatory responses; increased levels result in depression.

Melatonin (neurotransmitter) - Answer-Act at MT1-3 G-protein coupled receptors

Sleep/wake cycle
insomnia: melatonin agonists

Psychotropic drug metabolism may be impacted by factors such as: - Answer--age

-smoking
-caffeine intake
-other medications
-Some drugs or foods may inhibit or induce the rate of drug metabolism.

One-third of psychotropic drugs bind to a ______________, and one-third bind to

___________________. - Answer-neurotransmitter, G-protein-linked receptors.

The six main neurotransmitters are: - Answer-serotonin (5HT)

norepinephrine (NE)
dopamine (DA)
acetylcholine (Ach)
glutamate (Glu)
gamma-aminobutyric acid (GABA)

Signal transduction cascades can produce: - Answer-downstream (delayed) and/or

long-lasting effects
-explains why some psychopharmacological drugs do not provide an immediate
response but require time to see the drug effects

Signal transduction cascades - Answer-communication from the genome of the

presynaptic neuron to the genome of the postsynaptic neuron, and then back from the
genome of the postsynaptic neuron to the genome of the presynaptic neuron via
retrograde neurotransmission
-process involves long strings of chemical messages within both presynaptic and
postsynaptic neurons
-initial events occur in less than a second, but the long-term consequences are
mediated by downstream messengers that take hours to days to activate, yet can last
for many days or even for the lifetime of a synapse or neuron
-somewhat akin to a molecular "pony express"
Signal transduction cascades: Each molecular site within the cascade of transduction of
chemical and electrical messages is a potential location for: - Answer-a malfunction
associated with a mental illness
-also a potential target for a psychotropic drug

Retrograde - Answer-

transcription factor - Answer-A regulatory protein that binds to DNA and affects
transcription of specific genes.

antipsychotic meds - Answer-primarily used for schizophrenia & psychotic disorders

-also used as adjunctive meds for management of tx-resistant depression & other
conditions
-not curative
-decrease/control symptoms/improve quality of life

Schizophrenia - Answer-a disturbance that must last for 6 months or longer, including at
least one month of positive symptoms or negative symptoms
-neurodevelopmental, brain disorder
-psychological condition involving chronic or repeated episodes of psychosis
cause: combination of genetics and environmental factors
DX: based on clinical interview

psychosis - Answer-set of symptoms in which a person's mental capacity, affective

response, and capacity to recognize reality, communicate, and relate to others is
impaired

Symptoms of psychosis: - Answer--delusions & hallucinations (Hallmarks)

-disorganized speech
-disorganized behavior
-distortions of reality
-inappropriate or very strong emotions or apathy
-negative symptoms: diminished emotional expression and decreased motivation

area of the brain thought to be responsible for the positive symptoms of schizophrenia is
the ____________. one of the neuronal pathways known to be affected here is the
___________ from the _____________ and the _____________. - Answer-limbic
system, mesolimbic pathway, ventral tegmental area (VTA), nucleus accumbens

schizophrenia: the dopamine theory - Answer-suggests that in the mesolimbic pathway,

neurons from the VTA (ventral tegmental area) release higher than normal levels of
dopamine into the synaptic cleft at the NAC (nucleus accumbens).
-More dopamine binds to the D2 dopamine receptors in the NAC. This is thought to be
the cause of positive symptoms
Schizophrenia: dopamine and mesocortical system - Answer-area of the brain thought
to be responsible for negative symptoms of schizophrenia, prefrontal cortex
-mesocortical pathway goes from the VTA (ventral tegmental area) to the PFC
(prefrontal cortex)
-dysregulation of dopamine between these two areas of the brain results in the negative
and cognitive symptoms

Dopamine pathway: mesolimbic - Answer-location: Ventral tegmental area (VTA) within

midbreain to the nucleus accumbens (NA) in the limbic system

function: regulates emotional behaviors & associated with reward, motivation, pleasure

symptoms: overactivation causes (+) symptoms and may be a downstream

consequence of prefrontal cortex dysfunction & glutamate activity in the hippocampus

Dopamine pathway: mesocortical - Answer-location: ventral tegmental area (VTA) to the

prefrontal cortex (PFC). Specifically affecting dorsolateral prefrontal cortex (DLPFC) &
ventromedial prefrontal cortex (VMPFC)

function: regulates cognition, executive function, emotions, affect.

DLPFC-cognitive, (-) symptoms
VMPFC-affective & (-) symptoms

symptoms: hypoactivation of pathway may cause (-), cognitive, & affective symptoms

dopamine pathway: nigrostriatal - Answer-location: projects from substantia nigra (in

midbrain) to basal ganglia (striatum & globus pallidus)

function: part of extrapyramidal nervous system, controls posture & voluntary motor
movements

symptoms: imbalance of pathways causes movement disorders. Common disorders-

parkinson's and tremor.
Low dopamine in basal ganglia-akathisia & dystonia.
Hyperactivation of pathway-tics, dyskinesias, chorea.
Chronic blockade of D2 pathway-tardive dyskinesia.

dopamine pathway: tuberinfundibular - Answer-location: projects from hypothalamus to

anterior pituitary gland

function: dopamine inhibits prolactin release from pituitary

symptoms: disruption of pathway causes prolactin level to rise resulting in gynecomastia

& galactorrhea.
Females-amenorrhea
Both may get sexual dysfunction
neurobiological factors that contribute to psychosis and schizophrnia - Answer--genetics
-neuroanatomy
-neural networks
-neural signaling

neuroanatomy: symptoms associated with mesocortical and ventromedial prefrontal

cortex - Answer-negative and affective symptoms

neuroanatomy: symptoms associated with dorsolateral - Answer-cognitive symptoms

neuroanatomy: symptoms associated with orbitofrontal and connections to amygdala -

Answer-aggressive, impulsive symptoms

Worst toxin for someone who has at risk genes for schizophrenia - Answer-marijuana

Medications to treat psychosis are classified as either: - Answer-first generation

antipsychotics (FGAs) or second- generation antipsychotics (SGAs)

Antipsychotics are prescribed based on their: - Answer--pharmacological properties

-side effect profiles
-adverse effects according to the unique symptoms and needs of individuals across the
lifespan

First-generation antipsychotics (FGAs) - Answer-typical antipsychotics, non-selectively

blocks dopamine D2 receptors, specifically in mesolimbic pathway
-for the acute and chronic management of schizophrenia and psychosis
-Desired effect: improve (+) symptoms
-risk for developing hyperprolactinemia & extrapyramidal symptoms

Extrapyramidal symptoms (EPSs) - Answer-group of symptoms related to motor control

and coordination, caused by dopamine blockade or depletion in the basal ganglia
-dystonia
-akathisia
-parkinsonism
-bradykinesia
-tremors
-tardive dyskinesia

dystonia - Answer-Involuntary contractions of muscles; can cause pain

akathisia - Answer-Inner restlessness leading to repetitive motion (rocking, tapping

fingers).
parkinsonism - Answer-Combination of abnormal movements like those seen in
Parkinson's Disease, including tremor, slow movement, impaired speech, or muscle
stiffness
-akinesia, rigidity, tremor

bradykinesia - Answer-Slowness of movement

tardive dyskinesia - Answer-hyperkinetic movement disorder characterized by abnormal

facial and tongue movements and quick, jerky limb movements
-Can occur from long-term blockade of D2 receptors in the nigrostriatal DA pathway
-25% of clients will develop symptoms within 5 years of medication start
-Failure to discontinue typical antipsychotics prior to symptom onset can result in this
permanent condition

Hyperprolactinemia - Answer-when the serum prolactin level rises due to the blockade
of dopamine in the hypothalamus
-may be asymptomatic
-irregular menses
-male gynecomastia
-nipple discharge
-osteoporosis
-sexual dysfunction and infertility (both genders)

Neurolepsis - Answer-antipsychotic medication effects on psychotic clients, with respect

to cognition and behavior.
-Neurolepsis syndrome has three major features (PEA acronym)
Psychomotor slowing-extreme form of slowness or absence of motor movement
(nigrostriatal pathway)
Emotional quieting-worsening of (-) & cognitive symptoms (mesocortical pathways)
Affective indifference-worsening of affective symptoms (mesocortical pathway)

Additional adverse effects of excessive D2 receptor blockade (D2 antagonist actions)

include: - Answer--cardiac concerns: QT prolongation, torsades de pointes, and sudden
cardiac death
-blood dyscrasias (neutropenia, leukopenia, and agranulocytosis)
-esophageal dysmotility, aspiration
-increased fall risk

imbalance of dopamine (DA) and acetylcholine (ACh) can result in anticholinergic

effects such as: - Answer--dry mouth
-blurred vision
-racing heart
-constipation
-drowsiness
*due to muscarinic blockade
effects due to histamine blockade: - Answer-weight gain and drowsiness

effects due to α1-adrenergic blockade: - Answer-orthostatic hypotension, dizziness, and

drowsiness

Commonly prescribed antipsychotic medications for treatment of positive schizophrenic

symptoms - Answer-lowest to highest potency - FGAs
-chlorpromazine (low)
-mesoridazine (low)
-thioridazine (low)
-thiothixene (med)
-fluphenazine (med)
-haloperidol (high)

FGAs (typical antipsychotics) - Answer--Conventional

-Higher risk of extrapyramidal side effects (EPS)
-Treats positive symptoms
-Developed first

FGA meds - Answer--Haloperidol

-Thioridazine
-Thiothixene
-Fluphenazine
-Mesoridazine
-Chlorpromazine

Second Generation Antipsychotics (SGA) - Answer-Atypical, serotonin-dopamine

antagonists, maintain D2 antagonism but also have simultaneous serotonin 5HT2A
antagonism
-treat both positive and negative signs of psychosis
-classified by pharmacological properties related to their binding capacity, potency of
binding is responsible for medication efficacy and side effects
-Does not increase prolactin levels
-Lower risk of EPS

Due to the antagonism of serotonin, ______ generally have fewer EPS and prolactin
effects making them the first-line choice when prescribing medications for
schizophrenia. - Answer-Second Generation Antipsychotics (SGA)

SGA (atypical antipsychotics) categories: - Answer-Pines:

-olanzapine (zyprexa)
-quetiapine (seroquel)
-asenapine (saphris)
-clozapine (clozaril)

2 dones & a rone:

-risperidone (risperidol)
-paliperidone (invega)
-ziprasidone (geodon)
-iloperidone (fanapt)
-lurasidone (latuda)

2 pips & a rip:

-aripiprazole (abilify)
-brexpiprazole (rexulti)
-cariprazine (vraylar)

Pines - Answer--bind more potently to the 5HT 2A receptor than the D2.
-Sedation is common and relates to a high affinity for histamine.
-least risk of EPS but a high risk for weight gain and metabolic abnormalities

2 dones and a rone - Answer--more potently to the 5HT 2A receptor than to D2 or bine
equally between the 2 receptors.
-less sedating and cause less weight gain, but have a higher risk for hyperprolactinemia
and EPS

2 pips and a rip - Answer--pips: bind more potently to D2 receptors than to 5HT-2A,
have low risk of metabolic side effects and weight gain, but they have a potential for
EPS.
-rips binds equally to both D2 and 5HT-2A receptors, have low risk for metabolic
disorders

Extreme caution should be taken when prescribing antipsychotics for clients with
metabolic disorders. SGAs are associated with: - Answer-hyperglycemia and type 2
diabetes, dyslipidemia, and hypertension

Neuroleptic malignant syndrome (NMS) - Answer-Medical emergency, rare, sometimes

life-threatening reaction to antipsychotic medications
S/S:
-diaphoresis
-anxiety
-tachypnea
-muscle stiffness
-altered mental status
-tachycardia
-hyperthermia

Tx of Neuroleptic malignant syndrome (NMS) - Answer-stop the administration of

antipsychotic medications and provide supportive therapy. Treatment and
pharmacologic management may include hydration, benzodiazepines, and muscle
relaxants
The PMHNP must monitor for adverse effects in clients who are prescribed SGAs.
Which of the following physical exams and labs should be ordered or requested from
another provider? - Answer-BMI
-monthly x3 months then quarterly

Fasting lipids
-within first three months then check annually

Electrocardiogram
-baseline electrocardiogram should be obtained to evaluate for prolonged QT syndrome

BP

Fasting plasma glucose

-within first three months then check annually

Carbamazepine - Answer-glutamate, voltage-gated sodium and calcium channel

blocker
-Primary target symptoms: Seizures, unstable mood, mania, pain.
-Side Effects: SEDATION, dizziness, confusion, unsteadiness, headache, nausea,
vomiting, diarrhea, blurred vision, rash, benign leukopenia (up to 10%)
-Before starting: blood count, liver, kidney, and thyroid function tests
✽SUBSTRATE for CYP450 3A4 and an inducer of CYP450 3A4 thus, carbamazepine
induces its own metabolism, often requiring an upward dosage adjustment

Carbamazepine drug interactions - Answer--Enzyme-inducing antiepileptic drugs

(carbamazepine itself as well as phenobarbital, phenytoin, and primidone) may increase
the clearance of carbamazepine and LOWER its plasma levels
-CYP450 3A4 inhibitors, such as nefazodone, fluvoxamine, and fluoxetine, can
INCREASE plasma levels of carbamazepine

Olanzapine (zyprexa) - Answer-SGA - Atypical

serotonin-dopamine antagonist
Indication: schizophrenia age 13 and older, acute agitation, acute mania/mixed mania,
bipolar maintenance, bipolar depression, borderline personality disorder, PTSD
-Starting dose: Initial 5-10 mg once daily orally

Risk:
High metabolic risk
Highest risk for weight gain, sedation, blood dyscrasias, QT prolongation,
cardiovascular disease, cerebrovascular effects, hyperglycemia, and
hyperprolactinemia

quetiapine (seroquel) - Answer-SGA - Atypical

serotonin-dopamine antagonist
Indication: schizophrenia ages 13 and older, mania, bipolar maintenance, depression,
severe treatment-resistant anxiety, PTSD, behavioral disturbances in dementias,
Parkinson's disease, children, and adolescents.
-Starting dosing: initial 25 mg/day twice a day; increase by 25-50 mg twice a day each
day until desired efficacy is reached; maximum approved dose 800 mg/day

Risk:
Sedation
Moderate metabolic risk
Low EPS risk
Risk of orthostatic hypotension, blood dyscrasias (neutropenia, leukopenia, and
agranulocytosis), QT prolongation, weight gain, and renal and hepatic impairment

asenapine (Saphris) - Answer-SGA - Atypical

dopamine, serotonin, norepinephrine receptor antagonist
Indication: schizophrenia ages 10 and older, mania, bipolar, depression, impulse
control, PTSD, behavior disturbances in dementia and in children and adolescents
-Starting dosing: usual dosage range Schizophrenia and bipolar mania (sublingual): 10-
20 mg/day in 2 divided doses, Schizophrenia (transdermal): 3.8 mg/24 hours

Risk:
Low metabolic risk
Tardive dyskinesia (reduced risk compared to conventional antipsychotics)

clozapine (Clozaril) - Answer-SGA - Atypical

serotonin-dopamine antagonist
Indication: treatment-resistant schizophrenia, chronic SUICIDAL behavior in
schizophrenia or schizoaffective disorder, treatment-resistant bipolar disorder, violent
aggressive patients with psychosis and other brain disorders not responsive to other
treatments.
-Starting dosing: Initial 25 mg at night, increase 25-50 mg/day every 48-72 hours as
tolerated

Not indicated in acute presentation of schizophrenia

Special Comments: The Absolute Neutrophil Count (ANC) must be >1500/mm3 when
used and requires initial and weekly monitoring of WBC, granulocyte, and neutrophil
counts.

Risk:
High metabolic risk
Highest risk for weight gain.
Sedation
Low EPS risk.
BLACK BOX WARNING: may cause severe neutropenia
Contraindicated in liver disease and hepatic failure
Not a first-choice mediation for treating schizophrenia

risperidone (Risperidol) - Answer-SGA - Atypical

serotonin-dopamine antagonist
Indication: schizophrenia ages 13 and older, mania, autism, bipolar, depression,
impulse control, PTSD
-Starting dosing: usual is Oral: 2-8 mg/day for acute psychosis and bipolar disorder (0.5-
2mg for kids and elderly). In adults 1 mg/day orally in 2 divided doses, Increase each
day by 1 mg/day orally until desired efficacy is reached. (16mg/day max)

Risk:
Moderate metabolic risk
Highest risk of hyperprolactinemia
Risk of blood dyscrasias, QT prolongation, cardiovascular, and cerebrovascular effects
Sexual dysfunction

paliperidone (Invega) - Answer-SGA - Atypical

serotonin-dopamine antagonist
Indication: schizophrenia ages 12 and older, mania, bipolar, depression, impulse
control, PTSD, behavior disturbances in dementia and in children and adolescents.
-Starting dosing: 6 mg/day taken in morning, Can increase by 3 mg/day every 5 days
(max 12 mg/day)

Risk:
Moderate metabolic risk
Tardive dyskinesia (reduced risk compared to conventional antipsychotics)

ziprasidone (Geodon) - Answer-SGA - Atypical

dopamine and serotonin receptor antagonist
Indication: schizophrenia in ages 10 and older, acute agitation, mania, bipolar
maintenance/depression, impulse control, PTSD, behavioral disturbances in dementias
and in children and adolescents
-dosing:
• Schizophrenia: 40-200 mg/day (in divided doses) orally
• Bipolar disorder: 80-160 mg/day (in divided doses) orally
• 10-20 mg intramuscularly
-Special Comments: IM dosing in acute agitation associated with schizophrenia

Risk:
Low metabolic risk
Lowest risk for weight gain
Contraindicated in clients with QT, recent myocardial infarction, or uncompensated
heart failure
High incidence of rash/urticaria related to Stevens-Johnson syndrome and Drug
Reaction with Eosinophilia and Systemic Syndrome (DRESS)
iloperidone (Fanapt) - Answer-SGA - Atypical
dopamine-serotonin receptor antagonist
Indication: schizophrenia, mania, bipolar maintenance/depression, treatment-resistant
depression, impulse control, PTSD, behavioral disturbances in dementias and in
children and adolescents
-dosing: usual rangs 12-24 mg/day in 2 divided doses. Initial 2 mg in 2 divided doses on
day 1; 4 mg in 2 divided doses on day 2; 8 mg in 2 divided doses on day 3..etc..

Risk:
Moderate risk for weight gain, sedation
Low risk for hyperlipidemia

lurasidone (Latuda) - Answer-SGA - Atypical

dopamine, serotonin receptor antagonist
Indication: schizophrenia ages 13 and older, bipolar maintenance/depression, mania,
treatment-resistant depression, impulse control, PTSD, behavioral disturbances in
dementias and in children and adolescents
-Dosing: 40-80 mg/day for schizophrenia, 20-60 mg/day for bipolar depression
-should be taken with food, at least 350 calories, for maximum absorption.

Risk:
Low metabolic risk
Dose-dependent hyperprolactinemia

aripiprazole (Abilify) - Answer-SGA - Atypical

dopamine, serotonin receptor partial agonist
Indication: schizophrenia ages 13 and older, mania, autism, bipolar
maintenance/depression, depression, tourette's disorder, acute agitation, obsessive-
compulsive disorder, impulse control, PTSD, behavioral disturbances in dementias and
in children and adolescents
-Dosing:
• 15-30 mg/day for schizophrenia & mania
• 5-15 mg/day for autism
• 5-20 mg/day for Tourette's disorder

Risk:
Low metabolic risk
Low risk for weight gain
Low risk for orthostatic hypotension

Pearls
-less sedation than most other antipsychotics

brexpiprazole (Rexulti) - Answer-SGA - Atypical

Dopamine partial agonist
Indication: schizophrenia, treatment-resistant depression, mania, bipolar
maintenance/depression, impulse control, PTSD, behavioral disturbances in dementias
and in children and adolescents
-Dosing: schizophrenia 2-4 mg once daily, Depression: 2 mg once daily.

Special Comments: Considered procognitive

Risk:
Low metabolic risk
Akathisia
TD (reduced)

cariprazine (Vraylar) - Answer-SGA - Atypical

dopamine-serotonin partial agonist
Indication: schizophrenia, mania, bipolar maintenance/depression, depression, impulse
control, PTSD, behavioral disturbances in dementias and in children and adolescents
-Dosing:
• Schizophrenia: 1.5-6 mg once daily
• Bipolar mania: 3-6 mg once daily
• Bipolar depression: 1.5-3 mg once daily

Risk:
Low metabolic risk
Sedation
Akathisia, parkinsonism, TD (reduced)

Haloperidol - Answer-Typical FGA (conventional)

dopamine receptor antagonist
High potency
Indication: Psychotic disorders, tourette's syndrome, schizophrenia, bipolar disorder,
behavior disturbances in dementia
-Dosing: 1-40 mg/day orally, IR injection 2-5 mg each dose

Risks:
Neuroleptic-induced deficit syndrome
Akathisia
Parkinsonism
Tardive dyskinesia
Galactorrhea, amenorrhea
Weight gain and sedation

Thioridazine - Answer-Typical FGA (conventional)

dopamine and serotonin receptor antagonist
Low potency
Indication: Schizophrenic patients who fail to respond to treatment with other
antipsychotic drugs.
-Dosing: 200-800 mg/day in divided doses

Risks:
Neuroleptic-induced deficit syndrome
Akathisia
Priapism
Parkinsonims
Tardive dyskinesia
Galactorrhea, amenorrhea
Sedation & weight gain
QTc prolongation
Sexual dysfuction
Pigmentary retinopathy

Pearls:
-Generally, the benefits of thioridazine do not outweigh its risks for most patients
-Because of its effects on the QTc interval, thioridazine is not intended for use unless
other options (at least 2 antipsychotics) have failed
-Phenotypic testing may be necessary to detect 7% of Caucasian population whom
thioridazine is contraindicated due to a genetic variant leading to reduced activity of
CYP450 2D6

Thiothixene - Answer-Typical FGA (conventional)

-dopamine 2 antagonist
-High potency
Indication: Schizophrenia, bipolar disorder, other psychotic disorders.
-Dosing: 15-30 mg/day, initial 5-10 (max 60mg/day)

Risk:
Neuroleptic-induced deficit syndrome
Akathisia
Parkinsonism
Tardive dyskinesia
Sedation
Dry mouth, constipation, vision disturbance
hypotension

Fluphenazine - Answer-Typical FGA (conventional)

Blocks dopamine 2 receptors
-High potency
-Indication: Psychotic disorders, bipolar disorder
-Dosing: 1-20 mg/day oral, IM generally 1/3 to 1/2 the oral dose

Risks:
Neuroleptic-induced deficit syndrome
Akathisia
Priapism, sexual dysfunction
Parkinsonism
Tardive dyskinesia
Galactorrhea, amenorrhea
Dry mouth, constipation, urinary retention, blurred vision
weight gain
hypotension

Chlorpromazine - Answer-Typical FGA (conventional)

dopamine 2 antagonist
-Low potency
-Indication: Schizophrenia, severe agitation, ADHD, acute psychosis, nausea, vomiting,
acute intermittent porphyria, tetanus, intractable hiccups, bipolar disorder, restlessness
and apprehension before surgery.
-Dosing: 200-800 mg/day

Risks:
Neuroleptic-induced deficit syndrome
Akathisia
Priapism, sexual dysfunction
Sedation and weight gain
Dry mouth, constipation, urinary retention, blurred vision
hypotension
Tardive dyskinesia
Galactorrhea, amenorrhea

medications noted for decreased risk of death by suicide - Answer-Clozapine

-Reduction in risk of recurrent suicidal
behavior in patients with schizophrenia

Carla is a 35-year-old woman that is currently taking olanzapine for her diagnosed
schizophrenia. She has gained 30 pounds in the last 6 months and her waist
circumference is 37 inches. She requests a change in medications. Which of the
following medications is less associated with weight gain? - Answer-aripiprazole
-associated with the lowest risk weight gain.

Alex is a returning client who reports leaking fluid from his nipples. Which of the
following is most likely responsible for these undesirable side effects? - Answer-
Risperidone
-highest risk for galactorrhea, due to hyperprolactinemia.

Prescribing Considerations (antipsychotics) - Answer--Start with lowest dose, eval

tolerance, then titrate dose
-no evidence that high antipsychotic doses are more effective than standard doses
-Dose adjustments should be made after two weeks of taking medication
-Establish efficacy and an effective med dose before switching to a long-acting
injectable (LAI). dose of LAI will be same as the effective oral dose.
-Most antipsychotic side effects and adverse effects are dose-related.

When prescribing, document the _____________ at every visit. - Answer-targeted

symptoms, response, and any adverse effects

Many persons with schizophrenia are treated successfully in an ______________,

though some clients may require ________________ for initial treatment and
subsequent treatment of psychotic episodes - Answer-outpatient setting, inpatient
hospitalizations

Why begin with monotherapy? (antipsychotics) - Answer-The use of multiple

antipsychotics can increase the risk of QT prolongation.
-Combinations considered only after single med have provided inadequate response.

If antipsychotics switched too quickly - Answer-can develop agitation, activation,

insomnia, and experience withdrawal
-due to the binding differences in each medication subcategory
*Cross titration over several days to weeks is required to prevent side effects

Clients are more likely to experience side effects when changing from a medication in
one ___________ to a medication in another ____________ - Answer-subcategory,
subcategory
(ex: pine to done)

special considerations: Pregnancy (antipsychotics) - Answer--Risk of withdrawal

symptoms in the newborn: extrapyramidal symptoms may be present at delivery.
-atypical antipsychotics appear more harmful than typical antipsychotics due to
increased risk of gestational metabolic complications, increased gestational age weight,
and increased birth weight.
-Avoid Clozapine, Ziprasidone, olanzapine, risperidone, and quetiapine, especially in
the third trimester

special considerations: breast feeding (antipsychotics) - Answer-All antipsychotics are

assumed to be secreted in breast milk.
-recommended drug is discontinued or the infant bottle feeds.

special considerations: Older Adult (antipsychotics) - Answer-2019 American Geriatric

Society (AGS) Beers Criteria recommendations:
Avoid the use of haloperidol, ziprasidone, and olanzapine due to an increased risk of
cerebrovascular accident (CVA), cognitive decline, and death in persons with dementia
and with dementia-related psychosis.

special consideration: children (antipsychotics) - Answer-Black box warnings:

-Aripiprazole: Increased risk of suicide in children.
-Quetiapine: Increased risk of suicidal ideation and suicidal behavior in
adolescents/young adults during the initial 1-2 months of treatment

special considerations: caution (antipsychotics) - Answer--Olanzapine - exercise caution

in suspected alcohol withdrawal, stimulant intoxication, or anticholinergic intoxication
-High and repeated doses of amphetamines or cocaine can mimic positive symptoms of
paranoid schizophrenia

legal issues/considerations when prescribing antipsychotics - Answer-informed consent

-required due to serious side effects

challenges
-psychosis can be an obstacle
-provide education before obtaining a signature in outpatient setting

contingency planning
-establish a plan with client and family for emergencies
-designate a mental healthcare proxy if possible

Prescribing Pearls - Answer--Use the lowest effective dose and slow dosage titration.
-Avoid agents with anticholinergic properties.
-Avoid combining benzodiazepines with intramuscular olanzapine due to an increased
risk of sudden death.
-Avoid the combination of intramuscular benzodiazepines with clozapine due to a risk of
respiratory failure.

Terence is a 23-year-old male who presented to the emergency department (ED) with
hallucinations.
He is highly agitated, and nonpharmacological treatment methods have not been able to
calm his behaviors. His agitation continues to escalate which is interfering with their
ability to gain an accurate history and assessment.
Limited information is available regarding his past medical and psychiatric history.
The attending providers are unclear whether his presentation is due to a mental health
disorder with a need to intervene or an underlying non-psychiatric medical condition.
The PMHNP is called to assist in calming the client.

Which of the following statements is inaccurate regarding the management of Terence's

agitation? - Answer-Aggressive pharmacological intervention should be done early to
fully sedate this client so that a full evaluation can occur.

Rationale: Aggressive pharmacological intervention (such as full sedation) interferes

with the ability to perform a full evaluation, including history and physical examination.
Terence requires medication that will support the completion of an evaluation and
differential diagnosis without putting the patient or staff at risk. Early aggressive
pharmacological treatment can result in masking underlying conditions.
Terence continues to be uncooperative. He has become violent and is threatening to
leave. He reports hearing voices and states that he will kill everybody in the room. As
staff attempt to apply restraints, Terence swings his fists and almost injures a nurse.
Which of the following medications is the most appropriate to administer to Terence? -
Answer-Olanzapine (Zyprexa) 10mg IM

Rationale: Terence is uncooperative and is threatening harm and requires immediate

support. Oral medication will likely be rejected or refused. A more desirable medication
would have a short onset to support the safety of all involved. Administering intranasal
Versed may put the staff and the patient at risk. Further, midazolam and other
benzodiazepines administered by themselves promote sedation; they do not treat the
underlying disease, which is causing agitation or psychosis. Administering medication
via intramuscular injection is the best option. Of the choices, olanzapine is the most
appropriate medication because it has a rapid onset of action and potent antihistamine
actions. Although ziprasidone is an option, the dose listed is excessive.

Terence is now calm, and his workup has been completed. Physical differential
diagnoses have been ruled out, and a diagnosis of new-onset schizophrenia is
suspected based on history gained from the family and the physical examination.
Terence is admitted for initial stabilization. Which of the following will you prescribe for
his initial treatment? - Answer-Aripiprazole (Abilify)

Rationale: Aripiprazole (Abilify) is the best choice of initial treatment for Terence.
Second-generation antipsychotics (SGAs) are prescribed initially due to the effect on
both D2 and 5HT2A. When initiating medication, it is important to consider metabolic
risk, especially in a young patient such as Terence. Aripiprazole has low metabolic risks
and low weight gain. Olanzapine has a high metabolic risk. Haloperidol is an FGA.
Clozapine is not an appropriate choice for first-line treatment. Clozapine treatment has a
serious risk of severe neutropenia and low absolute neutrophil count. Because of the
risk of agranulocytosis, this medication is available only through a restricted program
(REMS) and is prescribed for treatment-resistant schizophrenia.

all forms of psychosis are linked to the neurotransmitter systems: - Answer-dopamine,

serotonin, and glutamate

Dopamine Theory - Answer-Hyperactive dopamine at D2 receptors in the mesolimbic

pathway

Glutamate theory - Answer-NMDA receptor hypofunction

Serotonin theory - Answer-5HT2A receptor hyperfunction in the cortex

Alogia - Answer-dysfunction of communication

-poverty of speech

asociality - Answer-lack of interest in social interactions

anhedonia - Answer-a diminished ability to experience pleasure

avolition - Answer--lack of motivation

-reduced ability to complete everyday tasks

match each symptom to hypothetically malfunctioning brain circuits: positive symptoms -

Answer-mesolimbic

match each symptom to hypothetically malfunctioning brain circuits: negative symptoms

- Answer-mesocortical/prefrontal cortex

nucleus accumbens reward circuit

match each symptom to hypothetically malfunctioning brain circuits: cognitive symptoms

- Answer-dorsolateral prefrontal cortex

match each symptom to hypothetically malfunctioning brain circuits: aggressive

symptoms - Answer-orbitofrontal cortex

amygdala

match each symptom to hypothetically malfunctioning brain circuits: affective symptoms

- Answer-ventromedial prefrontal cortex

polygenic risk score - Answer-add up all the abnormal genes an individual has amongst
the known few hundred risk genes, suggesting how much risk there might be for
developing schizophrenia.

Barnes Akathisia Rating Scale (BARS) - Answer-rating scale to assess the severity of
drug-induced akathisia.
-includes objective and subjective items such as the level of the patient's restlessness

Abnormal Involuntary Movement Scale (AIMS) - Answer-tool used to monitor

involuntary movements and tardive dyskinesia in clients who take antipsychotic
medication
-best practice/recommendation to document the AIMS at minimum every 6 months for
patients taking an antipsychotic agent/dopamine blocker

Low-potency medications - Answer--require higher doses to achieve efficacy

-have more anticholinergic, antihistaminic, and α1- properties, can result in more
sedation

Targeting mesolimbic/mesostriatal dopamine D2 receptors causes: - Answer-

antipsychotic actions
Targeting dopamine D2 receptors in Mesolimbic/mesostriatal and mesocortical
pathways causes: - Answer-secondary negative symptoms

Targeting tuberoinfudibular dopamine D2 receptors causes: - Answer-elevation of

prolactin
-associated with gynecomastia, galactorrhea, amenorrhea

Targeting nigrostriatal dopamine D2 receptors causes: - Answer-motor side effects

-can cause drug induced parkinsonism

overactivity of the mesolimbic dopamine system - Answer-may mediate the positive

symptoms of psychosis

any abnormal motor symptoms caused by D2 receptor blockers are lumped together
and called collectively: - Answer-extrapyramidal symptsom (EPS)
-motor side effects of D2 antagonists

caused by chronic blockade of D2 receptors in the nigrostriatal dopamine pathway -

Answer-tardive dyskinesia (TD)
-tx: interventions that lower dopamine neurotransmission, inhibiting the vesicular
monoamine transporter type 2 (VMAT2) lowers the "go" signals - deuterated
tetrabenazine (deutetrabenazine), Valbenazine (most selective and potent) ,

the most common side effect of drugs that target D2 receptors for psychosis - Answer-
Drug induced parkinsonism (DIP)
-akinesia, bradykinesia, rigidity, and tremor
*anticholinergics-drugs that block muscarinic cholinergic receptors

adding 5HT2A antagonism: - Answer-improve side effects of D2 blockade and enhance

the antipsychotic efficacy of D2 blockade

Sedative-hypnotic agents - Answer-benzodiazepine & barbiturates, clinical indications

for use:
-sedation & anxiolysis
-treatment of insomnia
-general anesthesia
-seizures
-alcohol withdrawal states
-as adjunctive management with neuromuscular blockage/muscle relaxation
-to induce or maintain sleep

sedative-hypnotic medications: use - Answer--1 in 8 adults

-Higher incidence in older adults
-Often co-prescribed with opioids
sedative-hypnotic medications: misuse - Answer--Taken outside of prescriptive
guidelines
-Taken without prescription
-polysubstance Abuse
-Are common as second drugs of abuse, often taken with opioids and/or alcohol
-Increased respiratory and CNS depression
-Increased risk of emergency department visits

sedative-hypnotic medications: Withdrawal - Answer--May be severe

-Signs and symptoms include psychosis, hallucinations, delirium, seizures
-Mild signs and symptoms: irritability, tremor, anxiety, palpitations, insomnia, nausea,
vomiting, diaphoresis, headache

Benzodiazepine intoxication - Answer-Can resemble alcohol intoxication: unsteady gait,

cognitive impairment, discoordination, slurred speech
-Overdose may lead to respiratory depression and stupor/coma

Anxiety - Answer-response to situations that are perceived as stressful or dangerous

-increases alertness, heart rate, and respirations, preparing the body to respond to
perceived threatening environmental stimuli
*when symptoms of anxiety persist and become intense or excessive, a diagnosis of an
anxiety disorder may be warranted, and treatment is required

anxiety disorder - Answer--affects more women than men

-one of the most common mental health concerns in the United States
-about 25% of people develop pathological anxiety during their lifetime
-can be debilitating and negatively impact the quality of life

Types of anxiety disorders - Answer--separation anxiety disorder

-selective mutism
-specific phobias (animal, natural environment, blood-injection-injury, situational, other)
-social anxiety disorder
-panic disorder
-agoraphobia
-generalized anxiety disorder
-substance/medication-induced anxiety disorder
-anxiety disorder due to another medical condition

Other closely related disorders include:

-obsessive-compulsive disorder
-acute stress disorder
-posttraumatic stress disorder.

Neurobiological factors that contribute to anxiety - Answer-Genetics

-(GAD) has genetic heritability of approximately 30%
-Children of parents with GAD are twice as likely to experience anxiety as those who do
not have a positive family history
-stressful life events are environmental components with potential to impact genetic
expression

Neuroanatomy
-fear has emotional and physical components
-amygdala interprets stress or fear and sends a distress signal to the hypothalamus,
hypothalamus initiates the fight-or-flight response by activating the sympathetic nervous
system, adrenal glands send out adrenaline to prepare the body to fight or flee in the
presence of a threat, hypothalamus activates the hypothalamic-pituitary-adrenal (HPA)
axis-release of cortisol. A quick elevation of these stress hormones can increase
survival in the case of a short-term threat; however, ongoing activation of the system in
the presence of chronic fear or anxiety can increase morbidity
-hippocampus, where memories are stored, is also involved in the fear response.
Memories can trigger fear by activating the amygdala, causing persons to re-experience
a traumatic past event as occurs in post-traumatic stress disorder (PTSD)

Neural networks
-brain contains a system of neural circuits referred to as cortico-striato-thalamo-cortical
(CSTC) feedback loops or "worry loops."
-Different types of anxiety or worry are linked to malfunctions in the circuit
-panic and phobia, are thought to be regulated through the connections between the
amygdala and the prefrontal cortex, fear-overactivation of the CSTC circuits

Neural signaling
-neurotransmitters (NT) are regulated within the CTSC feedback loops,serotonin,
gamma-aminobutyric acid (GABA), dopamine, norepinephrine, and glutamate which
also help regulate the amygdala.
-GABA is the chief inhibitory NT. GABA is the "chill" to glutamate, which is the excitatory
NT.
-GABA works within the CTSC to inhibit the anxiety response.

symptom(s) may occur in response to sympathetic stimulation from fear: - Answer--

hyperventilation
-hypertension
-hyperglycemia
-chest pain

Rationale: Fear can trigger an adaptive respiratory response which can exacerbate
asthma or other chronic breathing disorders. This explains client reports of not being
able to breathe during a panic attack. Sympathetic nervous stimulation causes
increased heart rate, dry mouth, constipation, urinary retention, and increased blood
sugar. When autonomic nervous system symptoms become chronic, there is an
association with hypertension, cardiac ischemia, myocardial infarction, and sudden
death.
Anxiety: Medication management - Answer-Antidepressants
-SSRIs
-SNRIs

Anxiolytics
-azrapirones
-benzodiazepines

Other
-alpha 2 delta ligands
-beta blockers
-histamine receptor agonists

Selective serotonin reuptake inhibitors (SSRI) are the first-line drugs to treat which
anxiety disorder(s)? - Answer--generalized anxiety disorder
-panic disorder
-obsessive-compulsive disorder
-post-traumatic stress syndrome
-social anxiety disorder

Rationale: SSRIs are the first-line drugs to treat all anxiety disorders.

SSRIs - Answer-Selective serotonin reuptake inhibitors (SSRIs) are used for the
treatment of all anxiety disorders. They act by preventing the reuptake of 5-HT by
synapses in the brain.
Drugs
-citalopram (Celexa)
-escitalopram (Lexapro)
-fluoxetine (Prozac)
-fluvoxamine (Luvox, Luvox CR)
-paroxetine (Paxil, Paxil CR)
-sertraline (Zoloft)

SSRI's: Adverse effects and monitoring - Answer--anorexia

-diarrhea
-headache
-weight gain
-sexual side effects
-serotonin syndrome
Monitoring: akathisia, increased anxiety, suicidal ideation

SSRI's: clinical pearls - Answer--Dosage should be started at half the recommended

dose for depression, increase dosage after 2-4 weeks as needed to control anxiety.
-SSRIs should not be stopped abruptly because it can result in rebound anxiety.
SNRI's - Answer-Serotonin-norepinephrine reuptake inhibitors (SNRIs) are used to treat
all anxiety disorders except OCD.
-preventing the reuptake of 5-HT and norepinephrine (NE) by synapses in the brain.
Compared with venlafaxine and desvenlafaxine, which have serotonin reuptake
inhibition (SRI) activity and dose-related affinity for norepinephrine reuptake inhibition
(NRI) primarily, duloxetine has more balanced SRI and NRI activities. Levomilnacipran
has higher activity at NRI than SRI.
-desvenlafaxine (Pristiq)
-duloxetine (Cymbalta)
-venlafaxine (Effexor, Effexor XR)
-levomilnacipran (Fetzima)

SNRIs: adverse effects and monitoring - Answer--elevated blood pressure

-sweating
-anxiety
-dizziness
-insomnia
-constipation
-serotonin syndrome
Monitoring: increased anxiety and suicidal ideations

SNRIs: contraindication - Answer-liver problems

hypertension

SNRIs: clinical pearls - Answer--Due to the presence of norepinephrine, SNRIs can

exacerbate anxiety.
-Dosage should be started at half the recommended dose for depression to minimize
side effects.

Buspirone - Answer-Azapirones are Federal Drug Administration (FDA) approved for

short-term anxiety treatment and are used alone or as an adjunct to antidepressants.
-bind to serotonin and dopamine receptors in the brain and increase norepinephrine
metabolism in the brain.
-Buspirone (Buspar)

Buspirone: adverse effects - Answer--dizziness

-headache
-sedation
-nervousness
-nausea

Buspirone: contraindications - Answer--severe renal impairment

-severe hepatic impairment
-concurrent use of monoamine oxidase inhibitors (MAOIs)
Buspirone: clinical pearls - Answer--Buspirone is not habit-forming, does not have
abuse potential, causes withdrawal reactions, or potentiates alcohol and sedative-
hypnotic effects.
-It is prescribed for two or three times a day due to the short half-life; it is not prescribed
as needed (PRN).
-It has a gradual onset of action of 2 weeks, but over time provides the same efficacy as
a benzodiazepine.
-BuSpar may decrease sexual side effects when used in combination with an SSRI.

Alpha 2 Delta Ligands - Answer-used off-label for general anxiety disorder (GAD).
-bind with glutamate calcium channel blockers (Glu-CB) to inhibit the release of several
neurotransmitters. --Pregabalin has anxiolytic properties with selective binding to the α-
2-delta subunit of voltage-gated calcium channels.
-pregabalin (Lyrica)
-gabapentin (Neurontin)

Alpha 2 Delta Ligands: adverse effects - Answer--sedation

-dizziness
-impaired attention
-confusion
-dry mouth
-constipation
-blurred vision
-possible weight gain

Alpha 2 Delta Ligands: Precautions & Contraindications - Answer-Precautions:

-suicidal ideation
-substance abuse
-heart failure
-renal impairment

Contraindications:
-myopathy
-avoid prescribing concurrently with benzodiazepines (BZOs)

Alpha 2 Delta Ligands: clinical pearls - Answer--works quickly to reduce anxiety

symptoms
-pregabalin reduces anxiety with a similar onset to alprazolam.

Beta blockers - Answer-can be used to treat somatic anxiety effects such as tachycardia
and physical tension symptoms.
-block the effects of norepinephrine and epinephrine.
-propranolol (Inderal)
-atenolol (Tenormin)

Beta Blockers: adverse effects - Answer--dizziness, vertigo

-fatigue
-hypotension
-decreased libido and sexual dysfunction

Beta Blockers: Precautions & Contraindications - Answer-Precautions:

-Use with caution in clients with asthma or heart failure; beta-adrenergic blockade can
reduce heart rate and cause bronchoconstriction.
-can blunt signs of hypoglycemia in diabetics
-can mask clinical signs of hyperthyroidism

Contraindications:
-first-degree heart block
-bradycardia

Beta blockers: clinical pearls - Answer--not FDA-approved for the treatment of anxiety
but are commonly used.
-often used for test anxiety, performance anxiety, and social anxiety because these
drugs are nonsedating.
-may be prescribed after a traumatic event to help prevent a permanent fear response.

Histamine Receptor Antagonists - Answer-used for the treatment of anxiety and skeletal
muscle tension associated with psychoneurosis, for anxiety symptoms associated with
alcohol withdrawal, and for anxiety related to cardiac impairment.
-act by blocking histamine 1 receptors.
-hydroxyzine (Atarax)

Histamine Receptor Antagonists: adverse effects - Answer--sedation

-dry mouth
-tremor

Histamine Receptor Antagonists: monitoring & contraindications - Answer-Monitoring

-hepatic status
-potassium level
-QT interval

Contraindications:
-severe hepatic impairment
-QT prolongation

Histamine Receptor Antagonists: clinical pearls - Answer--It is unclear if efficacy is due

to an anxiolytic effect or a sedative effect.
-Caution clients about potential sedation when prescribing.
-When used concurrently with another central nervous system (CNS) depressant, the
depressant dose should be reduced to half.
-Elderly clients are more sensitive to the sedative and anticholinergic side effects of
hydroxyzine.
appropriate first-line medication treatment information for anxiety disorder's:
Generalized anxiety disorder: - Answer-Generalized anxiety disorder:
SSRIs
SNRIs
buspirone
Drug Therapy at least 1 year

appropriate first-line medication treatment information for anxiety disorder's: obsessive-

compulsive disorder - Answer-Obsessive-compulsive disorder
fluoxetine
fluvoxamine
sertraline
paroxetine
clomipramine
Drug therapy for at least 1 year

appropriate first-line medication treatment information for anxiety disorder's: PTSD -

Answer-Post-traumatic stress disorder
paroxetine
sertraline

Josie is a 36-year-old who was diagnosed with generalized anxiety disorder. She was
prescribed paroxetine (Paxil) 12 weeks ago. She has been taking the medication as
prescribed, and although she has tolerated the medication well, she has not achieved
relief of anxiety symptoms with increases in dosing at each follow-up visit. Place the
following medications in order of what would be prescribed next for Josie. - Answer-The
correct order of prescription is:
escitalopram (Lexapro)
duloxetine (Cymbalta)
buspirone (BuSpar)
pregabalin (Lyrica)
hydroxyzine (Atarax)
alprazolam (Xanax)
Rationale: Use a stepwise plan to change drug treatment if the initial medication was
either ineffective or poorly tolerated. Paroxetine requires a taper while you start the new
medication. Do not stop abruptly due to discontinuation syndrome. Switching Rx can be
helpful in switching medications.
Switch medications.Switch from one SSRI to another.Switch from SSRI to
SNRI.Augment with buspirone.Augment with pregabalin.
If standard drugs are not effective, nonstandard drugs approved for other anxiety
disorders may be used.hydroxyzinebenzodiazepine (if clinically justified) are for short-
term use only

Benzodiazepines (BZOs) - Answer-Controlled substance

enhance gamma-aminobutyric acid's (GABA's) inhibitory effects in the brain by acting
on GABA receptors outside of the receiving neuron to open a channel that allows
negatively charged chloride ions to pass into the neuron
-negative ions "supercharge" the neuron making it less responsive to neurotransmitters
that would normally excite it.
-also react at specific benzodiazepine receptors on the GABA neuron. Benzodiazepine
receptor subtypes have slightly different actions:
*Alpha one is responsible for sedative effects.
*Alpha two is responsible for anti-anxiety effects.
*Alpha one, alpha two, and alpha five are responsible for anticonvulsant effects.

Benzodiazepines use - Answer-short-term relief of acute anxiety

-do not treat underlying cause
not intended for long-term
-risk of tolerance, dependence, uncomfortable withdrawal

Benzodiazepines (BZO): adverse effects - Answer-oversedation

-drowsiness, poor concentration, incoordination, muscle weakness, dizziness and
mental confusion
-increased risk of accidents, falls, and injury.

memory impairment
-cause "blackouts"
-lack of concentration and attention, impair learning

depression
-inability to feel pleasure or pain.
-increase suicide risk

tolerance and dependence

-can occur in as little as 2 weeks
-psychologically and physically addictive

Paradoxical Effects
-increased anxiety, irritability, hyperactivity, aggression, insomnia, nightmares,
hallucinations at the onset of sleep, cases of assault and homicide have been reported

Benzodiazepines (BZO): Patient education - Answer--rationale for benzodiazepine

prescription
-expected length of treatment (short term only)
-avoiding alcohol
-adverse effects
-risks of tolerance and dependence
-avoiding driving while taking this medication

Benzodiazepines Safety and Prescribing Guidelines - Answer-Set ground rules:

-Client uses only one pharmacy.
-BZO should be prescribed by only one provider.
-Check the state prescription monitoring program (PMP) controlled substance database.
-No early refills.

Do not prescribe if the client is concurrently taking:

-opioids
-other benzodiazepines
-z-drugs (medications for sleep)
-muscle relaxants
-marijuana

Schedule regular follow-up:

-frequency based on client risk, older and younger clients clients with history of
substance use disorder
-Required components during follow-up:
*symptom assessment
*PMP prescription monitoring review
*urine drug screening
*care plan with informed consent
*appropriate documentation

Prescribe for short course only

-2-4 weeks
-Longer treatment requires a clear, written plan with a rationale

abrupt cessation of benzodiazepines - Answer-can lead to severe withdrawal symptoms

-seizures and death

Excitatory neurotransmitters, including ________,________,_________,_________, are

necessary for alertness, memory, muscle tone, coordination, emotional responses,
endocrine gland secretions, heart rate, and blood pressure control. - Answer-
norepinephrine, serotonin, acetylcholine, and dopamine

will induce calm but will also affect higher-level thinking - Answer-Benzodiazepines
(BZOs)

__________ increase GABA's inhibitory activity, leading to the decreased output of

excitatory neurotransmitters resulting in the adverse effects related to their use -
Answer-Benzodiazepines (BZOs)

alprazolam IR (Xanax) - Answer-Short-acting

Use: GAD, panic disorder
Half-life: 12-15 hours
Equivalence: 0.5 mg
Dosage:
-anxiety: 0.75-1.5mg/day in divided doses; max dose 4 mg/day
-panic: 1.5mg/day in divided doses; dosing may exceed 4 mg, increase slowly

-rapid onset, less sedating

-can cause sedation, fatigue, forgetfulness, hypersalivation
-useful adjunct to SSRI/SNRI
-recommended use: lowest effective dose for shortest period of time
-risk for respiratory depression, especially when taken with CNS depressants
-contraindicated in angle-closure glaucoma
-tapered dosing when discontinuing, risk of seizures with withdrawal

lorazepam (Ativan) - Answer-Short-acting

Use: agitation, anxiety
Half-life: 10-20 hours
Equivalence: 1 mg

Dosage:
2-6 mg/day; BID-TID dosing; max 10 mg/day
elderly: 1-2 mg/day in divided doses

-rapid onset
-can cause sedation and fatigue (anterograde anesthesia)
-safe with liver disease; use lower dosage with liver and renal impairment
-increased risk of drug hangover due to longer half-life
-increased depressive effects with opioids- do not prescribe together
-caution with sleep apnea
-contraindicated in angle-closure glaucoma, breastfeeding, and pregnancy
-tapered dosing when discontinuing

clonazepam (Klonopin) - Answer-Long-acting

Use: panic disorder
Half-life: 30-40 hours
Equivalence: 0.5 mg

Dosage:
0.5-2 mg/day in divided doses or at bedtime
starts at 0.25 mg and increases slowly

-rapid onset and less sedating, but does cause some sedation and fatigue
-longer duration of action
-only Category C benzodiazepine; not recommended with breastfeeding
-increases salivation
-contraindicated with liver disease
-easier to taper dosing than other BZOs due to the long half-life
diazepam (Valium) - Answer-Long-acting
Use: acute myocardial infarction-related anxiety, night terrors, alcohol withdrawal
Half-life: 20-50 hours
Equivalence: 10 mg

Dosage: 2-10 mg two times to four times daily

-rapid onset
-available in rectal gel
-can cause sedation, fatigue, forgetfulness, and confusion
-contraindicated in angle closure glaucoma
-risk of dependence after 12 weeks
-risk for seizures with rapid discontinuation; taper 2 mg every 3 days

The PMHNP is prescribing alprazolam for a client with panic disorder. The PMHNP
should be concerned if the client is also prescribed which medication? - Answer-
zolpidem

Rationale: Alprazolam presents a risk for respiratory depression, especially when taken
concurrently with another central nervous system depressant like zolpidem. SSRIs,
SNRIs, and buspirone may be taken with alprazolam.

BZO Tapering and Deprescribing - Answer-Withdrawal symptoms tend to occur faster

with shorter-acting agents (within 2 to 3 days) than with longer-acting agents (within 5 to
10 days).

The Ashton Model (UK plan)Links to an external site. recommends reducing daily
dosing by 10-20% every 1-2 weeks.

lifespan and lifestyle factors that are foundational to safe prescribing: Pregnancy -
Answer--Paroxetine is contraindicated, risk of atrial septal defects
-Hydroxyzine is contraindicated in the 1st trimester.
-Benzodiazepines cross the placenta, increased risk of neonatal complications even
with therapeutic doses, use during pregnancy can cause:
*intrauterine growth restriction
*oversedation at birth can cause floppiness, difficulty breathing, and difficulty feeding
*potential for learning disabilities, autism, and attention-deficit/hyperactivity disorder
(ADHD)
*neonatal withdrawal syndrome

which benzodiazepine is safe in lactation - Answer-

lifespan and lifestyle factors that are foundational to safe prescribing: Breast feeding -
Answer-Contraindicated when breastfeeding:
-gabapentine
-benzodiazepines
-histamine receptor agents
-alpha 2 ligands

lifespan and lifestyle factors that are foundational to safe prescribing: Older adult -
Answer-decline in renal and liver function may contribute to the prolonged elimination of
medications leading to increased sedative effects and fall risk
-Consider decreasing the dosage of sedative-hypnotics
-taper whenever possible

2019 American Geriatric Society (AGS) Beers Criteria include the following
recommendations:
-avoid barbiturates (increased dependence, tolerance, risk of overdose)
-avoid benzodiazepines (increased sensitivity, decreased metabolism)
-avoid gabapentin and pregabalin (falls due to sedation)
-avoid hydroxyzine (clients with dementia, cognitive impairment, delirium, lower urinary
symptoms, or benign prostatic hyperplasia [BPH])

lifespan and lifestyle factors that are foundational to safe prescribing: Children - Answer-
-Anxiety disorders often begin in childhood and are often comorbid with depression or
bipolar disorder.
-For children and adolescents, psychotherapy is the first choice of treatment. SSRIs
may be used for severe symptoms or when psychotherapy is not effective.
*There is an increased risk of suicide in clients less than 30 years using SSRIs.
-Gabapentin is not approved for anxiety in children, it may only be used for seizures.

Sofia presents to the PMHNP with a report of being overwhelmed with stress and worry.
Sofia reports she has always dealt with these feelings, but it has been worse since she
has taken a more advanced role in her work with significant responsibility. She has
difficulty relaxing and is often fatigued. The PMHNP diagnoses Sofia with generalized
anxiety disorder. - Answer-sertraline 25 mg po once daily.

Rationale: Anxiety can often be treated with antidepressants. The best choice for Sofia
is the SSRI, sertraline because it is half the recommended dose for depression. The
duloxetine dosage listed is an appropriate dose for depression. When treating anxiety,
the dosage should start at 30 mg and be titrated up. Buspirone is not the first drug of
choice and it is typically used short-term. A benzodiazepine should not be the first drug
of choice.

Sofia was prescribed sertraline 25 mg po once daily. Sofia's dosage was increased to
50 mg after week 1, increased to 100 mg after week 2, and increased to 150 mg after
week 3. At Sofia's 4-week follow-up visit, she is tolerating the medication well and
symptoms are slightly improved. Which is the best action by the PMHNP? - Answer-
increase the sertraline dose to 200 mg

Rationale: The PMHNP should increase the sertraline dose to the maximum dose of
200 mg because the client has slightly improved symptoms. It may take several months
for the client to see full relief, so it is best to wait before adding additional drugs or
switching drugs.

At Sofia's 12-week follow-up visit, the client is taking the maximum dose of sertraline
and is experiencing improvement in symptoms, but not full relief from symptoms. Which
is the best action by the PMHNP? - Answer-augment with buspirone

Rationale: The client has improvement in symptoms, but not full relief, so the best action
is to augment the current therapy. Buspirone offers anxiety relief but does not have the
effects of a CNS depressant or cause dependence like benzodiazepines. Buspirone
does take approximately 4 weeks to reach full therapeutic effects. If the client did not
experience an improvement in symptoms, switching to another SSRI would be the best
action.

Jill, a 23-year-old graduate student, presents with reports of panic attacks and worry
"my whole life." She reports that she can bring on panic attacks herself when she
worries. This happens almost every day and some days it is so bad she cannot go to
work or school. She was offered a few Xanax by a friend, and she wants a prescription
because "they really help." The PMHNP diagnoses Jill with Generalized Anxiety
Disorder (GAD). Which is the best medication for the PMHNP to prescribe? - Answer-
escitalopram

Rationale: Escitalopram is the only listed SSRI that is the appropriate drug class for
GAD. Bupropion is an SNRI. Medications that contain norepinephrine can increase
anxiety. Jill has chronic anxiety, not acute anxiety. Benzodiazepines should be
prescribed only for short-term use, less than 4 weeks as an adjunct until the SSRI
achieves efficacy. Buspirone seems like a good choice because this medication targets
5HT1A; however, this medication is used as an adjunct therapy, not monotherapy.

Mary Ann is a 55-year-old woman who scheduled an appointment with the PMHNP a
month before a planned vacation to Hawaii. Mary Ann states, "I have been on a plane
once before, and I had a major panic attack. It was terrible." She is concerned about
having another panic attack on the long transpacific flight. She is in good health and is
not taking any medications. Which is the best choice for the PMHNP to prescribe? -
Answer-alprazolam #4 tabs PRN

Rationale: Alprazolam #4 tabs PRN is the best choice for anxiety in a specific high-
anxiety situation such as flying. Benzodiazepines can be prescribed for PRN use.
Limiting the number of pills is appropriate to help prevent misuse and diversion of the
medication. In this case, medication was provided for departure and return. Using daily
medication is not necessary since Mary Ann does not have chronic anxiety. Providing
an SSRI PRN is not appropriate as it may take up to 6 weeks for efficacy.

Andrea is a 65-year-old woman who presents for care because "her nerves are a
mess." Her husband was diagnosed this week with Stage IV pancreatic cancer and has
less than a month to live. Andrea can not eat or sleep. She cries constantly and "her
heart is broken." Andrea is on no medications. Which is the best choice for the PMHNP
to prescribe? - Answer-citalopram daily and alprazolam #15 tabs PRN

Rationale: Citalopram and alprazolam are the best choices. Starting an SSRI with a
PRN benzodiazepine is appropriate to help cope while waiting for the full effects of
citalopram. Venlafaxine, an SNRI, contains norepinephrine which can increase anxiety.
Trazadone may help with sleep, but the dosing required for depression and anxiety
would result in increased sedation, which can increase fall risk in older adults.
Mirtazapine is appropriate for the loss of appetite, but the complaint is less than 1 week.
Mirtazapine is associated with weight gain and is not a first-line treatment for anxiety.

Worry - Answer-the second core symptom shared across the spectrum of anxiety
disorders
-hypothetically linked to cortico-striato-thalamo-cortical (CSTC) feedback loops from the
prefrontal cortex (CSTC "worry loops")
-can include anxious misery, apprehensive expectations, catastrophic thinking, and
obsessions

Amygdala and fear - Answer-affect or feeling of fear may be regulated via the reciprocal
connections the amygdala shares with key areas of prefrontal cortex that regulate
emotions, namely the orbitofrontal cortex and the anterior cingulate cortex

motor responses of fear - Answer-Motor responses of fear are regulated in part by

connections between the amygdala and the periaqueductal gray area of the brainstem

endocrine reactions to fear - Answer-part due to connections between the amygdala

and the hypothalamus, causing changes in the HPA (hypothalamic-pituitary-adrenal)
axis, and thus of cortisol levels.

Affect of fear - Answer-regulated by reciprocal connections between the amygdala and

the anterior cingulate cortex (ACC) and the amygdala and the orbitofrontal cortex (OFC)

autonomic and cardiovascular responses are mediated by: - Answer-connections

between the amygdala and the locus coeruleus, home of the noradrenergic cell bodies
-When autonomic responses are repetitive, inappropriately or chronically triggered as
part of an anxiety disorder, this can lead to increases in atherosclerosis, cardiac
ischemia, hypertension, myocardial infarction, and even sudden death

The known neurobiological regulators of the amygdala: - Answer-neurotransmitters

GABA, serotonin, norepinephrine, and the voltage-gated calcium channels
-known anxiolytics act upon these same neurotransmitters hypothetically in order to
mediate their therapeutic actions

neurotransmitters and regulators that modulate CSTC circuit - Answer--serotonin

-GABA
-dopamine
-norepinephrine
-glutamate
-voltage-gated ion channels

Excessive amygdala activity is theoretically reduced by: - Answer-benzodiazepines

-enhance phasic inhibition of GABA (γ-aminobutyric acid) by positive allosteric
modulation of postsynaptic GABA receptors
-blunt fear-associated outputs

modulate excessive output from worry loops - Answer-benzodiazepines

-enhancing the actions of inhibitory interneurons in CSTC circuits
-reduce symptoms of worry

also known as α2δ ligands since they bind to the α2δ subunit of presynaptic N and P/Q
VSCCs, block the release of excitatory neurotransmitters such as glutamate that occurs
when neurotransmission is excessive, as postulated in the amygdala to cause fear
(Figure 8-17A) and in CSTC circuits to cause worry - Answer-Gabapentin and
pregabalin

key neurotransmitter that innervates the amygdala as well as all the elements of CSTC
circuits - Answer-Serotonin
-regulate both the symptoms of fear and worry

Noradrenergic hyperactivity in anxiety - Answer-Norepinephrine is another

neurotransmitter with important regulatory input to the amygdala, and to the prefrontal
cortex and thalamus in CSTC circuits

__% of the population will develop an anxiety disorder - Answer-30%

Treatment for anxiety disorder subtypes: Generalized Anxiety Disorder - Answer-SSRIs,

SNRIs, benzodiazepines, buspirone, and α2δ ligands such as pregabalin and
gabapentin

Other "off-label" treatments for anxiety can

include mirtazapine, trazodone, vilazodone, tricyclic antidepressants, or even sedating
antihistamines such as hydroxyzine.

Treatment for anxiety disorder subtypes: PTSD - Answer-psychopharmacological

treatments
-not as effective as these same treatments are in anxiety disorders
-more effectively aimed at comorbidities: depression, insomnia, substance abuse, and
pain
Benzodiazepines are to be used with caution
-limited evidence from clinical trials for efficacy in PTSD
-many PTSD patients abuse alcohol and other substances
unique treatment for PTSD is the administration of α1 antagonists at night to prevent
nightmares

The amygdala hypothetically plays a central role in the _______________. Cortico-

striato-thalamo-cortical (CSTC) circuits are thought to play a key role in mediating the
symptom of __________. - Answer-fear response, worry

________,_________,_________,________ are all key modulators of the hypothetical

fear and worry circuits - Answer-Serotonin, norepinephrine, alpha-2 delta ligands and
GABA

Amygdala-centered circuit - Answer-Fear

-panic
-phobia

cortico-striato-thalamo-corical (CSTC) circuit - Answer-worry

-anxious misery
-apprehensive expectation
-obsession

Gabapentin - Answer-Anxiolytic
glutamate voltage-gated calcium channel blocker, Anticonvulsant; alpha 2 delta ligand
at voltage-sensitive calcium channels
-Indication: Partial seizures with or without secondary generalization, postherpetic
neuralgia, restless leg syndrome, neuropathic pain/chronic pain, anxiety, bipolar
disorder.
-Dosing: 900-1800 mg/day in 3 divided doses

Risks: CNS side effects:

Sedation
Ataxia
fatigue
nystagmus
tremor

Pearls:
-Most use if off-label
-Off-label use for first-line treatment of neuropathic pain may be justified

Pregabalin - Answer-Anxiolytic
glutamate voltage-gated calcium channel blocker, Anticonvulsant; alpha 2 delta ligand
at voltage-sensitive calcium channels
-Indication: Diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia,
neuropathic pain associated with spinal cord injury, partial onset seizures, peripheral
neuropathic pain, GAD, panic disorder, social anxiety disorder.
-Dosing: IR: 150-600 mg/day in 2-3 doses, CR: 330 mg once per day
Risks: CNS side effects:
Sedation

Pearls:
-First treatment approved for fibromyalgia
-Off-label use for GAD, panic disorder, and social anxiety disorder may be justified in
the USA

Buspirone - Answer-Anxiolytic
serotonin receptor partial agonist
-Indication: Anxiety, depression, treatment-resistant depression
-Dosing: usual 20-30 mg/day. Initial 15 mg twice a day; increase in 5 mg/day increments
every 2-3 days until desired efficacy reached (max 60 mg/day)

Risks:
Dizziness
Headache
Nervousness
Sedation

Pearls:
-Do not use if patient taking an MAOI
-generally reserved as an augmenting agent to treat anxiety

Hydroxyzine - Answer-Anxiolytic
histamine receptor antagonist
-Indication: Anxiety and tension associated with psychoneurosis, pruritus, sedation,
hysteria, withdrawal symptoms, delirium tremens, nausea and vomiting, insomnia.
-Dosing:
• Anxiety: 50-100 mg 4 times a day
• Sedative: 50-100 mg oral, 25-100 mg intramuscular injection
• Pruritus: 75 mg/day divided into 3-4 doses

Risks: Blocking histamine 1 receptors can cause sedation

Pearls:
-preferred anxiolytic for patients with dermatitis or skin symptoms such as pruritis

Alprazolam - Answer-Anxiolytic
BENZODIAZEPINE
GABA positive allosteric modulator
-Indication: Generalized anxiety disorder, other anxiety disorders, panic disorder,
premenstrual dysphoric disorder, irritable bowel syndrome, insomnia, acute mania,
acute psychosis, catatonia.
-Dosing:
• Anxiety: alprazolam IR: 1-4 mg/day (start at 0.75-1.5, 3 divided doses)
• Panic: alprazolam IR: 5-6 mg/day (start at 1.5, 3 divided doses)
• Panic: alprazolam XR: 3-6 mg/day (start at 0.5-1 QD AM)

Risks:
-Sedation, fatigue, depression
-Dizziness, ataxia, slurred speech, weakness
-Forgetfulness, confusion
-Hyperexcitability, nervousness

Pearls:
-not recommended during pregnancy, especially during first trimester
-Recommended either D/C drug or bottle feed

Lorazepam - Answer-Anxiolytic
BENZODIAZEPINE
GABA positive allosteric modulator
-Indication: Anxiety disorder, status epilepticus, preanesthetic, insomnia, muscle spasm,
alcohol withdrawal psychosis, headache, panic disorder, acute mania, acute psychosis,
delirium, catatonia.
-Dosing: oral initial 2-3 mg/day in 2-3 doses (max 10mg.day), Injection: 4 mg
administered slowly, Catatonia: 1-2 mg per dose

Risks:
-Sedation, fatigue, depression
-dizziness, ataxia, slurred speech, weakness
-forgetfulness, confusion
-hyperexcitability, nervousness

Pearls:
-not recommended during pregnancy, especially during first trimester
-Recommended either D/C drug or bottle feed
-most popular and useful benzodiazepines for treatment of agitation
-often used to induce pre-operative anterograde amnesia to assist in anesthesiology

Clonazepam - Answer-Anxiolytic
BENZODIAZEPINE
GABA positive allosteric modulator
-Indication: Panic disorder, lennox-gastaut syndrome, akinetic seizure, myoclonic
seizure, absence seizure, atonic seizure, other seizure disorders, acute mania, acute
psychosis, insomnia, catatonia.
-Dosing:
•Seizures 1.5 mg divided into 3 doses, raise by 0.5 mg every 3 days until desired effect
(up to 20 mg/day)
•Panic start at 0.25mg divided into 2 doses, raise to 1mg after 3 days (max 4 mg/day)
Risks:
-Sedation, fatigue, depression
-dizziness, ataxia, slurred speech, weakness
-forgetfulness, confusion
-hyperexcitability, nervousness

Pearls:
-not recommended during pregnancy, especially during first trimester
-Recommended either D/C drug or bottle feed
-Easier to taper than some other benzodiazepines because of long half-life (elimination
half-life approximately 30-40 hours)

Diazepam - Answer-Anxiolytic
BENZODIAZEPINE
GABA positive allosteric modulator
-Indication: Anxiety, acute agitation, tremor, delirium tremens, HALLUCINOSIS in acute
alcohol withdrawal, skeletal muscle spasm, spasticity, athetosis, stiff-person syndrome,
convulsive disorder, status epilepticus, insomnia, catatonia.
-Dosing:
•Oral (anxiety, muscle spasm, seizure): 2-10 mg, 2-4 times/day.
•Oral (alcohol withdrawal): initial 10 mg, 3-4 times/day for 1 day; reduce to 5 mg, 3-4
times/day, continue prn

Risks:
-Sedation, fatigue, depression
-dizziness, ataxia, slurred speech, weakness
-forgetfulness, confusion
-hyperexcitability, nervousness

Pearls:
-not recommended during pregnancy, especially during first trimester
-Recommended either D/C drug or bottle feed
-often the first-choice benzodiazepine to treat status epilepticus, and is administered
either intravenously or rectally

Propranolol - Answer-Anxiolytic
Beta blocker, antihypertensive
-Indication: Migraine, tremor, hypertension, angina pectoris, cardiac arrhythmias,
myocardial infaction, hypertrophic subaortic stenosis, pheochromocytoma, akathisia,
parkinsonian tremor, violence, aggression, PTSD, GAD, prevention of variceal bleeding,
CHF, tetralogy of fallot, hyperthyroidism.
-Dosing: 40-400 mg/day

Risks:
-bradycardia
-hypotension
-dizziness
-hypoglycemia
-weight gain
-bronchospasm, cold/flu symptoms, sinusitis, pna's
-sexual dysfunction

Pearls:
-May worsen depression, but helpful for anxiety

medication can be prescribed after an acute trauma to prevent a permanent fear

response - Answer-both β blockers and opioids
-potentially mitigate the conditioning of the original traumatic memory