Neurobiologic Theories and Psychopharmacology
Central Nervous System
Brain
consists of the cerebrum, cerebellum, brain stem, and limbic system
Cerebrum
divided into two hemispheres
cerebral hemispheres are divided into four lobes:
frontal
control the organization of thought, body movement, memories, emotions, and moral behavior
abnormalities are associated with schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and
dementia
parietal
interpret sensations of taste and touch and assist in spatial orientation
temporal
centers for the senses of smell and hearing and for memory and emotional expression
occipital
assist in coordinating language generation and visual interpretation, such as depth perception
all lobes and structures are found in both halves except for the pineal body, or gland, which is located between the hemispheres
Cerebellum
Brain Stem
Limbic System
area of the brain located above the brain stem and consists of:
thalamus
regulates activity, sensation, and emotion
hypothalamus
involved in temperature regulation, appetite control, endocrine function, sexual drive, and impulsive behavior associated with feelings of anger, rage, or excitement.
hippocampus and amygdala
involved in emotional arousal and memory
Disturbances in the limbic system have been implicated in a variety of mental illnesses:
memory loss that accompanies dementia
poorly controlled emotions and impulses seen with psychotic or manic behavior
Neurotransmitters
the chemical substances manufactured in the neuron that aid in the transmission of information throughout the body
either:
Excitatory - excite or stimulate an action in the cells
Inhibitory - inhibit or stop an action
fit into specific receptor cells embedded in the membrane of the dendrite
after being released either:
Reuptake - transported back from the synapse to the axon to be stored for later use
Metabolized and inactivated by enzymes, primarily monoamine oxidase (MAO)
Major Nuerotransmitters
Dopamine
Excitatory
Controls complex movements, motivation, cognition; regulates emotional response
Norepinephrine (noradrenaline)
Excitatory
Causes changes in attention, learning and memory, sleep and wakefulness, moods
Epinephrine (adrenaline)
Excitatory
Controls fight or flight response
Serotonin
Inhibitory
Controls food intake, sleep and wakefulness, temperature regulation, pain control, sexual behaviors, regulation of emotions
Histamine
Neuromodulator
Controls alertness, gastric secretions, cardiac stimulation, peripheral allergic responses
Acetylcholine
Excitatory or inhibitory
Controls sleep and wakefulness cycle; signals muscles to become alert
Neuropeptides
Neuromodulators
Enhance, prolong, inhibit, or limit the effects of principal neurotransmitters
Glutamate
Excitatory
Results in neurotoxicity if levels are too high
γ-Aminobutyric acid (GABA)
Inhibitory
Modulates other neurotransmitters
Psychoimmunology
a relatively new field of study, examines the effect of psychosocial stressors on the body’s immune system
compromised immune system could contribute to the development of a variety of illnesses, particularly in populations already genetically at risk
Psychopharmacology
use of medications to treat mental illness
medications directly affect the central nervous system (CNS) and subsequently behavior, perceptions, thinking, and emotions
Efficacy
refers to the maximal therapeutic effect that a drug can achieve.
Potency
describes the amount of the drug needed to achieve that maximum effect;
low-potency drugs require higher dosages to achieve efficacy
high-potency drugs achieve efficacy at lower dosages.
Half-life
is the time it takes for half of the drug to be removed from the bloodstream
shorter half-life may need to be given three or four times a day
drugs with a longer half-life may be given once a day
the time that a drug needs to leave the body completely after it has been
discontinued is about five times its half-life
Off-label use
a drug will prove effective for a disease that differs from the one involved in original testing and FDA approval
Black Box Warning
a drug is found to have serious or life-threatening side effects, even if such side effects are rare
Principles that Guide Pharmacologic Treatment
selected based on its effect on the client’s target symptoms; effectiveness is evaluated largely by its ability to diminish or eliminate the target symptoms
drugs must be given in adequate dosages for some time before their full effects are realized
dosage of medication is often adjusted to the lowest effective dosage
for the client
older adults require lower dosages of medications than do younger clients to experience therapeutic effects; take longer for a drug to achieve its full therapeutic effect
psychotropic medications are often decreased gradually (tapering) rather
than abruptly; potential problems with:
rebound
temporary return of symptoms
recurrence of the original symptoms
withdrawal
new symptoms resulting from discontinuation of the drug
Follow-up care is essential to ensure:
compliance with the medication regimen
to make needed adjustments in dosage
to manage side effects
Compliance with the medication regimen is often enhanced when the
regimen is as simple as possible in terms of both the number of medications prescribed and the number of daily doses
Antipsychotic Drugs
formerly known as neuroleptics
used to treat the symptoms of psychosis, such as:
delusions and hallucinations seen in schizophrenia
schizoaffective disorder
manic phase of bipolar disorder
Off-label:
treatment of anxiety and insomnia
aggressive behavio
delusions
hallucinations
other disruptive behaviors that sometimes accompany Alzheimer disease
primary medical treatment for schizophrenia and are also used in psychotic episodes of:
acute mania
psychotic depression
drug-induced psychosis
Second-generation antipsychotics can increase mortality rates in elderly clients with dementia-related psychosis
Mechanism of Action
work by blocking receptors of the neurotransmitter dopamine
Dopamine receptors: D2, D3, and D4 have been associated with mental illness
conventional, or first-generation, antipsychotic drugs are potent antagonists of these dopamine receptors
produces many extrapyramidal side effects because of the
blocking of the D2 receptors
atypical or second-generation antipsychotic drugs: clozapine (Clozaril)
relatively weak blockers for D2 resceptors; this account for the lower incidence of extrapyramidal side effects
inhibit the reuptake of serotonin increasing their effectiveness in treating the depressive aspects of schizophrenia
Examples:
Paliperidone (Invega)
chemically similar to Risperidone (Risperdal)
it is an extended-release preparation; take one daily dose in most cases = increase compliance
Iloperidone (Fanapt)
Asenapine (Saphris)
a sublingual tablet
avoid food or drink for 10 to 15 minutes after the medication dissolves
Lurasidone (Latuda)
third generation of antipsychotics are called dopamine system stabilizers
thought to stabilize dopamine output
preserve or enhance dopaminergic transmission when it is too low and reduce it when it is too high
results in control of symptoms without some of the side effects of other antipsychotic medications
Aripiprazole (Abilify)
the first drug of this type, was approved for use in 2002.
Cariprazine (Vraylar) and Brexpiprazole (Rexulti)
newer third-generation
used for schizophrenia, manic episodes, and
as adjunct medication in both bipolar disorder and depression
The most common side effects are:
sedation
weight gain
akathisia
headache
anxiety
nausea
Depot Injection
a time-release form of intramuscular medication for maintenance therapy
six (6) antipsychotics are available in this form, some of it are:
Risperidone (Risperdal Consta)
25 mg, is given every 2 weeks
Paliperidone (Invega Sustenna)
117 mg, is given every 4 weeks
Olanzapine pamoate (Zyprexa Relprevv)
given 210 mg every 2 weeks or 405 mg every 4 weeks
potential to cause postinjection delirium/sedation syndrome, characterized by:
sedation
confusion
disorientation
agitation, and
cognitive impairment, that can progress to:
ataxia
convulsions
weakness, and
hypertension, which can lead to arrest
client is monitored q3hrs post injection and must be:
alert
oriented
symptom-free
Two first-generation antipsychotics use sesame oil as the vehicle for these injections
medication is absorbed slowly over time
thus, less frequent administration is needed to maintain the desired therapeutic effects
examples:
Decanoate Fluphenazine (Prolixin)
duration of 7 to 28 days
Decanoate Haloperidol (Haldol)
duration of 4 weeks
After condition is stabilized with oral doses administration by depot injection is required every 2 to 4 weeks to maintain the therapeutic effect
it also includes third-generation antipsychotic:
Aripiprazole (Abilify Maintena)
slowly absorbed into the bloodstream because of
insolubility of aripiprazole particles
Side Effects
Extrapyramidal symptoms (EPS) includes:
acute dystonia
characterized by:
acute muscular rigidity and cramping
a stiff or thick tongue with difficulty swallowing
in severe cases:
laryngospasm
respiratory difficulties
likely to occur in:
first week of treatment
<40 years
males
receiving high-potency drugs:
haloperidol
thiothixene
Spasms or stiffness in muscle groups can produce:
torticollis
twisted head and neck
opisthotonus
tightness in the entire body with the head back and an arched neck
oculogyric crisis
eyes rolled back in a locked position
can be freightening to client; reason for them not to take the medication
immediate treatment of anticholinergic drugs is needed, such as:
IM benztropine mesylate (Cogentin)
IM/IV diphenhydramine (Benadryl)
a regularly scheduled oral anticholinergic may allow the client to continue taking the antipsychotic drug with no further
dystonia
benztropine
Recurrent dystonic reactions would necessitate a lower dosage or a change in the antipsychotic drug
pseudoparkinsonism or drug-induced parkinsonism
generic label of EPS
symptoms resemble those of Parkinson disease and includes:
a stiff, stooped posture
masklike facies
decreased arm swing
a shuffling, festinating gait (with small steps)
cogwheel rigidity (ratchet-like movements of joints)
drooling; tremor
bradycardia
coarse pill-rolling movements of the thumb and fingers while at rest
treated by:
changing to an antipsychotic medication that has a lower incidence of EPS
adding an oral anticholinergic agent or amantadine to increase transmission of dopamine
akathisia
an intense need to move about
may appear as:
restless or anxious and agitated
rigid posture or gait
lack of spontaneous gestures
reasosn for drug discontinuation:
feeling of internal restlessness
inability to sit still or rest
treated by:
change in antipsychotic medication
the addition of an oral agent such as:
beta-blocker
anticholinergic
benzodiazepine
therapies for these EPS include:
lowering the dosage of the antipsychotic
changing to a different antipsychotic
administering anticholinergic medication
WARNING!
Atypical Antipsychotics
Elderly patients with dementia-related psychosis are at an increased risk for death if treated with this mediaction.
cause of death may appear to be cardiovascular or infectious in nature
Geodon
Contraindicated in patients with a:
known history of QT prolongation
recent myocardial infarction
uncompensated heart failure
it should not be used with other QT-prolonging drugs
Neuroleptic Malignant Syndrome (NMS)
potentially fatal idiosyncratic reaction to an antipsychotic drug
major symptoms:
rigidity
high fever
autonomic instability such as:
unstable blood pressure
diaphoresis
pallor
delirium
elevated levels of enzymes
creatine phosphokinase
patient usually present as:
confused and often mute
may fluctuate from agitation to stupor
often occurs in the first 2 weeks of therapy or after an increase in dosage, but it can occur at any time
factors thtat increase the risk of NMS:
Dehydration
poor nutrition
concurrent medical illness
treatment:
immediate discontinuance of all antipsychotic medications
institution of supportive medical care to treat:
dehydration
hyperthermia
to treat the client with other antipsychotic drugs requires full discussion between the client and the physician to weigh the relative risks against the potential benefits of therapy.
Tardive dyskinesia (TD)
syndrome of permanent involuntary movements
most commonly caused by the long-term use of conventional antipsychotic drugs
pathophysiology is still unclear
symptoms include:
involuntary movements of the tongue, facial and
neck muscles, upper and lower extremities, and truncal musculature
characterized by:
Tongue thrusting
protruding
lip smacking
blinking
grimacing
other excessive unnecessary facial movements
after its development, it becomes irreversible
decreasing or discontinuing antipsychotic medications can arrest its progression
antipsychotic medications can mask the beginning symptoms of TD
increased dosages of the antipsychotic medication cause the initial symptoms to disappear temporarily
as it worsen, they “break through” the effect of the antipsychotic drug
drug treatment includes:
Valbenazine (Ingrezza)
dosage range of 40 to 80 mg
cause:
nausea
vomiting
headache
balance disturbances
Deutetrabenazine (Austedo, Teva)
from 12 to 48 mg daily
may caus:
NMS
increased depression
increased suicidality with Huntington chorea
first drugs to treat TD
are vesicular monoamine transporter 2 (VMAT2) inhibitors
decrease activity of monoamines, such as dopamine, serotonin, and norepinephrine, thereby decreasing the abnormal movements associated with Huntington chorea and TD
effects of the drugs include:
somnolence
QT prolongation
akathisia
restlessness
goal for antipsychotics:
prevent TD through:
keeping maintenance dosages as low as possible
changing medications
monitoring the client periodically for initial signs of TD through:
standardized assessment tool - Abnormal Involuntary
Movement Scale
Anticholinergic Side Effects
often occur with the use of antipsychotics and include:
orthostatic hypotension
dry mouth
can be alleviated through using of:
calorie-free beverages
hard candy
constipation
can be prevented through using of:
stool softeners
adequate fluid intake
inclusion of grains and fruit in the diet
urinary hesitance or retention
blurred near vision
dry eyes
photophobia
nasal congestion
decreased memory
side effects usually decrease within 3 to 4 weeks but do not entirely remit
client taking anticholinergic agents for EPSs may have increased problems with anticholinergic side effects
Other Side Effects
increase blood prolactin levels, and may cause:
breast enlargement and tenderness in men and
women
diminished libido
erectile and orgasmic dysfunction
menstrual irregularities
increased risk for breast cancer
weight gain
mostly on 2nd generation, except:
Ziprasidone (Geodon)
significant on:
Clozapine (Clozaril)
Olanzapine (Zyprexa)
mechnism is unknown; is associated with:
increased appetite
binge eating
carbohydrate craving
food preference changes
decreased satiety in some clients
histamine antagonism stimulates appetite
genetics make client more prone to weight gain and metabolic syndrome:
cluster of conditions that increase the risk for:
heart disease
diabetes
stroke
The syndrome is diagnosed when three or more
of the following are present:
Obesity
excess weight, increased body mass index (BMI), and increased 81 abdominal girth because of fat deposits
common in clients with schizophrenia, further increasing the risk for type 2 diabetes mellitus and cardiovascular disease
Increased blood pressure
High blood sugar level
High cholesterol
with at least 150 mg/dL of triglyceride; less than 40 mg/dL of high-density lipoprotein for women and 50 mg/dL for men
recommended that:
clients taking antipsychotics be involved in an
educational program to control weight and decrease BMI
found that clients had greater success when staff provided information and practical support when it was needed
cardiovascular adverse effects
may include:
postural hypotension
palpitations
tachycardia
increase QT intervals
may be caused by drugs such as:
thioridazine (Mellaril)
droperidol (Inapsine)
mesoridazine (Serentil)
QT interval longer than 500 ms is considered dangerous and is associated with:
life-threatening dysrhythmias
sudden death
in rare cases, it can cause torsade de pointes
rapid heart rhythm of 150 to 250 beats/minute
present as “twisted” appearance on the electrocardiogram
other drugs:
Thioridazine and Mesoridazine
used to treat psychosis
Droperidol
most often used as an adjunct to anesthesia or to produce sedation.
Sertindole (Serlect)
never approved in the US to treat psychosis
used in Europe and was subsequently withdrawn from the market because of the number of cardiac dysrhythmias and deaths that it caused
WARNING!
Droperidol, Thioridazine, and Mesoridazine
lengthen the QT interval, leading to potentially life-threatening cardiac dysrhythmias or cardiac arrest
Clozapine
cause agranulocytosis
potentially life-threatening event
characterized by:
fever
malaise
ulcerative sore throat
leukopenia
may not manifest immediately
occur up to 24 weeks after the initiation of therapy
clients must have:
baseline WBC count (> 3,500/mm3) and differential before initiation of treatment
WBC count every week throughout treatment and for 4 weeks after discontinuation of clozapine
neutrophil count (ANC) is 2,000/mm3
Client Teaching
Nurse informs clients taking antipsychotic medication about the types of
side effects that may occur
encourages clients to report such problems to the physician instead of discontinuing the medication
Nurse teaches the client methods of managing or avoiding unpleasant side effects and maintaining the medication regimen
Drinking sugar-free fluids and eating sugar-free hard candy ease dry mouth
The client should avoid calorie-laden beverages and candy
promote dental caries, contribute to weight gain, and do little to relieve dry mouth
Methods to prevent or relieve constipation include:
exercising and increasing water and bulk-forming foods in the diet
Stool softeners are permissible, but the client should avoid laxatives
Use of sunscreen is recommended because photosensitivity can
cause the client to sunburn easily
Clients should monitor the amount of sleepiness or drowsiness they feel
Should avoid driving and performing other potentially dangerous
activities until their response times and reflexes seem normal
If the client forgets a dose of antipsychotic medication, he or she can take the missed dose if it is only 3 or 4 hours late
dose is more than 4 hours overdue or the next dose is due, the client can omit the forgotten dose
nurse encourages clients who have difficulty remembering to take their medication to use:
chart and to record doses when taken
pillbox that can be prefilled with accurate doses for the day or week
Antidepressant Drugs
primarily used in the treatment of:
major depressive illness
anxiety disorders
the depressed phase of bipolar disorder
psychotic depression
Off-label:
chronic pain
migraine headaches
peripheral and diabetic neuropathies
sleep apnea
dermatologic disorders
panic disorder
eating disorders
mechanism of action is not completely understood; interact with the two neurotransmitters:
norepinephrine and serotonin
regulating mood, arousal, attention, sensory processing, and appetite
divided into 4 groups:
Tricyclic and the related cyclic antidepressants
available in the 1950s
first choice of drugs to treat depression; even it cause varying
degrees of:
sedation
orthostatic hypotension
anticholinergic side effects
potentially lethal if taken in an overdose
Selective serotonin reuptake inhibitors (SSRIs)
first available in 1987
release of fluoxetine (Prozac)
Prozac Weekly
first and only medication that can be given once a week
for maintenance therapy for depression
It contains 90 mg of fluoxetine with an enteric coating that delays release into the bloodstream
replaced the cyclic drugs as the first choice in treating depression
equal in efficacy and produce fewer troublesome side effects
SSRIs and clomipramine are effective in the treatment of obsessive-compulsive disorder (OCD)
MAO inhibitors (MAOIs)
discovered to have a positive effect on people with depression
low incidence of sedation and anticholinergic effects; must be used with extreme caution:
hypertensive crisis occurs with ingestion of foods containing tyramine
MAOIs cannot be given in combination with other MAOIs, tricyclic antidepressants, meperidine (Demerol), CNS depressants, many antihypertensives, or general anesthetics
potentially lethal in overdose and pose a potential risk in clients
with depression who may be considering suicide
Other antidepressants:
desvenlafaxine (Pristiq)
venlafaxine (Effexor)
bupropion (Wellbutrin)
duloxetine (Cymbalta)
trazodone (Desyrel)
nefazodone (Serzone)
Preferred Drugs for Clients at High Risk for Suicide
SSRIs, venlafaxine, nefazodone, and bupropion are often better
choices
carry no risk of lethal overdose
SSRIs are effective only for mild and moderate depression
Evaluation of the risk for suicide must continue even after treatment with antidepressants is initiated
May feel more energized but still have suicidal thoughts
which increases the likelihood of a suicide attempt
Often takes weeks before the medications have a full therapeutic effect
clients may become discouraged and tired of waiting to feel better
can result in suicidal behavior
Mechanism of Action
precise mechanism is not known, but much is known about their action on the CNS
major interaction is with the monoamine neurotransmitter systems in the
brain, particularly norepinephrine and serotonin
released throughout the brain and help regulate arousal, vigilance, attention, mood, sensory processing, and appetite
Norepinephrine, serotonin, and dopamine are removed from the synapses after release by reuptake into presynaptic neurons
reloaded for subsequent release or metabolized by the enzyme MAO
Cyclic compounds may take 4 to 6 weeks to be effective
MAOIs need 2 to 4 weeks for effectiveness
SSRIs may be effective in 2 to 3 weeks
Side Effects of Selective Serotonin Reuptake Inhibitors
have fewer side effects compared to the cyclic compounds
enhanced serotonin transmission can lead to several common side effects such as:
anxiety
agitation
akathisia
treated with a beta-blocker, such as:
propranolol (Inderal)
benzodiazepine
nausea
can be minimized through taking medications with food usually
insomnia
may continue to be a problem even if the client takes the medication in the morning
sedative–hypnotic or low-dosage trazodone may be needed
sexual dysfunction
diminished sexual drive
difficulty achieving an erection or orgasm
SSRIs cause less weight gain than other antidepressants
Less common side effects include:
sedation
particularly with paroxetine (Paxil)
indicate the need for a change to another antidepressant
sweating
indicate the need for a change to another antidepressant
hand tremor
diarrhea
managed with symptomatic treatment
headaches
usually be managed with symptomatic treatment
Side Effects of Cyclic Antidepressants
Cyclic compounds have more side effects
individual medications in this category vary in terms of the intensity of side effects
cyclic antidepressants block cholinergic receptors, resulting in anticholinergic effects such as:
dry mouth
constipation
urinary hesitancy or retention
dry nasal passages
blurred near vision
more severe anticholinergic effects such as:
agitation
delirium
ileus
particularly in older adults
Other common side effects include:
orthostatic hypotension
sedation
weight gain
tachycardia
Clients may develop tolerance to anticholinergic effects, but these side effects are common reasons that clients discontinue drug therapy
Clients taking cyclic compounds frequently report:
sexual dysfunction similar to problems experienced with SSRIs
weight gain too
Side Effects of Monoamine Oxidase Inhibitors
most common side effects:
daytime sedation
difficult to treat
necessitate a change in medication
insomnia
difficult to treat
necessitate a change in medication
weight gain
dry mouth
orthostatic hypotension
sexual dysfunction
potential for a life-threatening hypertensive crisis if the client s takes sympathomimetic drug or ingests food that contain tyramine:
Mature or aged cheeses or dishes made with cheese
Aged meats
Italian broad beans (fava), bean curd (tofu), banana peel, overripe fruit, and avocado
All tap beers and microbrewery beer
Sauerkraut, soy sauce or soybean condiments, or marmite
Yogurt, sour cream, peanuts, brewer’s yeast, and monosodium glutamate (MSG)
increased serum tyramine levels may cause:
severe hypertension
hyperpyrexia
tachycardia
diaphoresis
tremulousness
cardiac dysrhythmias
Drugs that may cause potentially fatal interactions:
SSRIs
certain cyclic compounds
buspirone (BuSpar)
dextromethorphan
opiate derivatives:
meperidine
Side Effects of Other Antidepressants
nefazodone
sedation
headaches
cause dry mouth
nausea
trazodone
sedation
headaches
cause priapism
a sustained and painful erection that necessitates immediate treatment and discontinuation of the drug
may also result in impotence
mirtazapine
sedation
bupropion and desvenlafaxine
cause loss of:
appetite
nausea
agitation
insomnia
Venlafaxine
may cause:
dizziness
sweating
sedation
plus the aforementioned cause of loss
Drug Interactions
Serotonin Syndrome (Serotonergic Syndrome)
uncommon but potentially serious drug interaction
result from taking an MAOI and an SSRI at the same time
also occur if the client takes one of these drugs too close to the end of therapy with the other
NOTE: one drug must clear the person’s system before initiation of therapy with the other
Symptoms include:
agitation
sweating
fever
tachycardia
hypotension
rigidity
hyperreflexia
extreme reactions:
coma
death
Client Teaching
take SSRIs first thing in the morning unless sedation is a problem
paroxetine most often causes sedation
if client forgets a dose of an SSRI, he or she can take it up to 8 hours after the missed dose
should take it within 3 hours of the missed dose or omit the dose for that day
to minimize side effects, clients generally should take cyclic compounds at night in a single daily dose when possible
exercise caution when driving or performing activities requiring sharp, alert reflexes until sedative effects can be determined
clients taking MAOIs need to be aware that a life-threatening hyperadrenergic crisis can occur if they do not observe certain dietary restrictions
should receive a written list of foods to avoid while taking MAOIs
The nurse should make clients aware of the risk for serious or even fatal drug interactions when taking MAOIs and instruct them:
not to take any additional medication, including OTC preparations, without checking with the physician or pharmacist
WARNING!
Nefazodone
cause rare but potentially life-threatening liver damage, which could lead
to liver failure
Bupropion
may cause seizures at a rate four times that of other antidepressants
risk for seizures increases when:
doses exceed 450 mg/day (400 mg SR)
increases are sudden or in large increments
has a history of seizures, cranial trauma, excessive use of or withdrawal from alcohol, or addiction to opiates, cocaine, or stimulants
uses over-the-counter (OTC) stimulants or anorectics
has diabetes being treated with oral hypoglycemics or insulin
Mood-Stabilizing Drugs