NCM106: PHARMACOLOGY
CNS Drugs
ANTIPSYCHOTIC
Antipsychotic drugs are used mainly for the treatment of psychosis, a
severe mental disorder characterized by disordered thought
processes (disorganized and often bizarre thinking);
blunted or inappropriate emotional responses; bizarre behavior
ranging from hypoactivity to hyperactivity with agitation,
aggressiveness, hostility, and combativeness; social withdrawal in
which a person pays less-than-normal attention to the environment
and other people; deterioration from previous levels of occupational
and social functioning (poor self care and interpersonal skills);
hallucinations; and paranoid delusions.
Schizophrenia
Positive symptoms are characterized by central nervous system
(CNS) stimulation and include agitation, behavioral disturbances,
delusions, disorganized speech, hallucinations, insomnia, and paranoia.
Negative symptoms are characterized by lack of pleasure
(anhedonia), lack of motivation, blunted affect, poor grooming and
hygiene, poor social skills, poverty of speech, and social withdrawal.
SCHIZOAFFECTIVE DISORDER – is a condition in which the patient
exhibits symptoms of both schizophrenia and mood disorder.
Schizophrenia
The disorder is caused by imbalances in neurotransmitters in specific brain
areas. This theory suggests the possibility of overactive dopaminergic
pathways in the basal nuclei, an area of the brain that controls the motor
activity. The basal ganglia with associated nuclei are responsible for starting
and stopping synchronized motor activity such as leg and arm motions during
walking..
Symptoms of schizophrenia seem to be associated with the dopamine 2
receptor. The basal nuclei are particularly rich in D2 receptors whereas the
cerebrum contains very few. All antipsychotic drugs act by entering
dopaminergic synapses and competing with dopamine. By blocking a majority
of the D2 receptors, antipsychotic drugs reduce the symptoms of
schrizophrenia.
Antipsychotic Medications
Antipsychotic drugs are derived from several chemical groups. These
drugs may be broadly categorized as “typical,” conventional, or first-
generation agents (phenothiazines and older nonphenothiazines, such
as Haloperidol (Haldol) with similar pharmacologic actions, clinical
uses, and adverse effects), or as ―atypical” or second-generation agents,
which can also be called newer nonphenothiazines.
Mechanism of Action
Phenothiazines
PROTOTYPE DRUG: Chlorpromazine Hydrochloride (Thorazine)
THERAPEUTIC CLASS: Conventional Antipsychotic, schizophrenia
drug
PHARAMCOLOGIC CLASS: D2 dopamine receptor anatagonist;
phenothiazine
ACTIONS: It provides symptomatic relief of positive symptoms of
schizophrenia and control manic symptoms in patients with
schizoaffective disorder. Many patients must take chlorpromazine for
7 0r 8 weeks before they experience improvement. Extreme agitation
may be treated with IM/IV injections which begin to act within
minutes. It can also control severe nausea and vomiting.
Phenothiazines
Fluphenazine decanoate and enanthate (Prolixin Decanoate;
Prolixin Enanthate)
Fluphenazine hydrochloride (Prolixin, Permitil)
Perphenazine (Trilafon)
Prochlorperazine (Compazine)
Trifluoperazine (Stelazine)
Nonphenothiazines
PROTOTYPE: Haloperidol (Haldol)
First-Generation ―Typical‖ Antipsychotics
Frequently used, potent, long-acting drug. It is well absorbed after oral
or intramuscular (IM) administration, is metabolized in the liver, and is
excreted in urine and bile. It may cause adverse effects similar to those
of the phenothiazines. Usually, it produces a relatively low incidence
of hypotension and sedation and a high incidence of extrapyramidal
effects.
Loxapine (Loxitane), Molindone (Moban), Pimozide (Orap),
Thiothixene (Navane)
Side Effects
NMS
Neuroleptic malignant syndrome—fever (may be confused with heat
stroke), muscle rigidity, agitation, confusion, delirium, dyspnea,
tachycardia, respiratory failure, acute renal failure
A rare but potentially fatal reaction that may occur hours to months
after initial drug use. Symptoms usually develop rapidly over 24–72
hours. Treatment includes stopping the antipsychotic drug,
giving supportive care related to fever and other symptoms, and drug
therapy (dantrolene, a skeletal muscle relaxant, and amantadine or
bromocriptine, dopamine-stimulating drugs).
Second-Generation “Atypical” Antipsychotics
PROTOTYPE: Clozapine (Clozaril)
Clozapine is chemically different from the older antipsychotic drugs. It blocks
both dopamine and serotonin receptors in the brain. It is indicated for clients
with schizophrenia, including those who have exhibited recurrent suicidal
behavior.
Advantages of clozapine include improvement of negative symptoms, without
causing the extrapyramidal effects associated with older antipsychotic drugs.
Clozapine
The reason for the second-line status of clozapine is its association
with Agranulocytosis, a life-threatening decrease in white blood cells
(WBCs), which usually occurs during the first 3 months of therapy.
Weekly WBC counts are required during the first 6 months of
therapy; if acceptable WBC counts are maintained, then WBC counts
can be monitored every other week. In addition, clozapine is
reportedly more likely to cause constipation, dizziness, drowsiness,
hypotension, seizures, and weight gain than other atypical drugs.
Olanzapine (Zyprexa), Quetiapine (Seroquel), Risperidone
(Risperdal), Ziprasidone (Geodon), Aripiprazole (Abilify)
Nursing Management
1. Supervise ambulation to prevent falls or other injuries if the client is drowsy or elderly
or has postural hypotension.
2. Several measures can help prevent or minimize hypotension, such as having the client
lie down for approximately an hour after a large oral dose or an injection of
antipsychotic medication; applying elastic stockings; and instructing the client to
change positions gradually, elevate legs when sitting, avoid standing for prolonged
periods, and avoid hot baths (hot baths cause vasodilation and increase the incidence
of hypotension). In addition, the daily dose can be decreased or divided into smaller
amounts.
3. Dry mouth and oral infections can be decreased by frequently brushing the teeth;
rinsing the mouth with water; chewing sugarless gum or candy; and ensuring an
adequate fluid intake. Excessive water intake should be discouraged because it may
lead to serum electrolyte deficiencies.
4. The usual measures of increasing fluid intake, dietary fiber, and exercise can help
prevent constipation.
DRUGS FOR BIPOLAR DISORDERS
Mania at the opposite pole from depression occurs in individual with
bipolar disorder who experiences a period of depression followed by a
period of mania.
BIPOLAR DISORDER – involves extremes of depression alternating
with hyperactivity and excitement. This condition may reflect a
biochemical imbalance followed by overcompensation on the part of
neurons and their inability to reestablish stability.
THERAPEUTIC ACTIONS
Lithium alters sodium transport in nerve and muscle cells; inhibits the
release of norepinephrine and dopamine but not serotonin from
stimulated neurons; increases the intraneuronal stores of
norepinephrine and dopamine slightly and decreases intraneuronal
content of second messengers. This last mode of action may allow it to
selectively modulate the responsiveness of hyperactive neurons that
might contribute to the manic state.
PHARMACOKINETICS
Lithium is readily absorbed from the GI tract, reaching peak levels in 30
minutes-3 hours. It follows the same distribution pattern in the body as water.
It slowly crosses the blood-brain barrier. Lithium is excreted from the kidney,
although about 80% is reabsorbed. During period of sodium depletion or
dehydration, the kidney reabsorbs more lithium into the serum, often leading
to toxic levels.
Patients must be encouraged to maintain hydration while taking this drug.
Lithium crosses placenta and enters breast milk and has been associated with
congenital abnormalities.
CONTRAINDICATIONS
1. Presence of hypersensitivity to lithium (to prevent hypersensitivity
reactions).
2. Significant renal or cardiac disease (could be exacerbated by the toxic
effects of the drug
3. History of leukemia, metabolic disorders including sodium depletion,
dehydration and diuretic use (it depletes sodium reabsorption and severe
hyponatremia may occur). Hyponatremia leads to lithium retention and
toxicity.
4. Pregnancy and lactation (potential for adverse effects on the fetus or
neonate). While using lithium, women of childbearing age should be advised to
use birth control
5. Protacted diarrhea or excessive sweating
6. Suicidal or impulsive patients and in patients who have infection with fever
(could be exacerbated by the toxic effects of the drug).
Nursing Management
1. obtain baseline: renal, cardiac, thyroid
2. Monitor WBC for Leukocytopenia and Agranulocytosis
3. Increase fluid intake
4. Avoid excessive exercises and warm environment
5. Assess for signs of lithium toxicity
6. Therapeutic level of lithium: 0.5 to 1.5meq/L
Maintenance dose - 0.6 to 1.2 meq/L
Elderly - 0.5 to 1.0 meq/L
Antidepressant Drugs
Depression is a mental health issue that starts most often in early adulthood. It’s also
more common in women. However, anyone at any age may deal with depression.
Signs and Symptoms
Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRIs are the most commonly prescribed class of antidepressants. An
imbalance of serotonin may play a role in depression. These drugs fight
depression symptoms by decreasing serotonin reuptake in the brain. This
effect leaves more serotonin available to work in the brain.
• Sertraline (Zoloft)
• Fluoxetine (Prozac, Sarafem)
• Citalopram (Celexa)
• Escitalopram (Lexapro)
• Paroxetine (Paxil, Pexeva, Brisdelle)
• Fluvoxamine (Luvox)
Common side effects of SSRIs include:
• nausea
• trouble sleeping
• nervousness
• tremors
• sexual problems
SSRI’s can also be indicated to:
• obsessive-compulsive disorder (OCD)
• panic disorder
• bulimia
• post-traumatic stress disorder (PTSD)
• premenstrual dysphoric disorder (PMDD)
• hot flashes caused by menopause
• anxiety
How SSRI’s Work
Serotonin is one of many brain chemicals that transmit messages between
brain cells. It has been called the ―feel-good chemical‖ because it causes a
relaxed state of well-being. Normally, serotonin circulates in the brain and then
absorbs into the bloodstream.
Depression is linked with low levels of serotonin (as well as low levels of
dopamine, norepinephrine, and other brain chemicals). SSRIs work by
preventing blood from absorbing some of the serotonin from brain. This leaves
a higher level of serotonin in the brain, and increased serotonin can help
relieve depression.
SSRIs don’t cause the body to make more serotonin, however. They simply help
the body use what it has more effectively.
PHARMACOKINETICS
SSRIs are well absorbed from the GI tract, metabolized in the liver and
excreted in the urine and
feces. The half-life varies widely with the drug being used.
CAUTION
Patients with impaired renal or hepatic functions (could alter
metabolism and excretion of drug leading to toxic effects).
Severely depressed/suicidal patients especially children, adolescents
and young adults (risk of increased suicidality).
Pregnancy (associated with congenital anomalies)
NURSING CONSIDERATIONS
1. Assess for any known allergies to SSRIs (avoid hypersensitivity
reactions)
2. Severe depression, angle-closure glaucoma, bipolar disorder (could
be exacerbated by these drugs).
3. Assess impaired liver and renal functions (could alter metabolism
and excretion of the drug)
4. Assess female patients if pregnant or breastfeeding
5. Assess vital signs, weight, skin color and lesions, affect, orientation
and reflexes, vision, bowel sounds (baseline status for beginning
therapy and fort potential adverse effects.
Tricyclic antidepressants (TCAs)
TCAs are often prescribed when SSRIs or other antidepressants don’t
work. It isn’t fully understood how these drugs work to treat
depression.
TCAs include:
amitriptyline
amoxapine
clomipramine (Anafranil)
desipramine (Norpramin)
doxepin
imipramine (Tofranil)
Side Effects
Common side effects of TCAs can include:
Constipation
Dry mouth
Fatigue
The more serious side effects of these drugs include:
Low blood pressure
Irregular heart rate
Seizures
How TCA’s Work
Tricyclic antidepressants help keep more serotonin and norepinephrine available to the
brain. These chemicals are made naturally by the body and are thought to affect the mood.
By keeping more of them available to your brain, tricyclic antidepressants help elevate
your mood.
Some tricyclic antidepressants are also used to treat other conditions, mostly in off-label
uses. These conditions include obsessive compulsive disorder (OCD) and chronic
bedwetting. In lower doses, cyclic antidepressants are used to prevent migraines and to
treat chronic pain. They are also sometimes used to help people with panic disorder.
Tricyclic antidepressants treat depression, but they have other effects on your body as
well. They can affect automatic muscle movement for certain functions of the body,
including secretions and digestion. They also block the effects of histamine, a chemical
found throughout your body. Blocking histamine can cause effects such as drowsiness,
blurred vision, dry mouth, constipation, and glaucoma. These may help explain some of the
more troublesome side effects associated with these drugs.
PHARMACOKINETICS
TCAs are well absorbed from the gastrointestinal tract, reaching peak levels in
2-4 hours. They are highly bound to plasma proteins and are lipid soluble; this
allows then to be distributed widely in the tissues including the brain. The
TCAs cross the placenta and enter breast milk.
CAUTIONS
Patients with preexisting cardiovascular disorders (because of the cardiac
stimulatory effect of the drug and with any condition that would be
exacerbated by the anticholinergic effects).
CAUTION
Angle-closure glaucoma, urinary retention, prostate hypertrophy, GI
or gentourinarysurgery
Psychiatric patients (may exhibit worsening of psychoses or paranoia).
Manic-depressive patients (may shift to a manic state)
Children, adolescent and young adults (risk of suicidality).
History of seizures and elderly(seizure threshold may
decreased secondary to stimulation of the receptor sites)
Hepatic or renal disease (could interfere with metabolism and
excretion of these drugs and lead toxic levels
Interactions
1. Alcohol – decreases effectiveness, increases sedation
effects
2. Tricyclic antidepressants can increase the effects of
Epinephrine in the heart. This can lead to high blood
pressure and problems with heart rhythm.
NURSING CONSIDERATIONS
1. Assess for any known allergies of these drugs (to avoid hypersensitivity
reactions)
2. Assess liver or kidney function (could alter metabolism and excretion of the
drug).
3. Assess Glaucoma, benign prostatic hypertrophy, cardiac dysfunction, GI
obstruction, surgery or recent myocardial infarction (all of which could be
exacerbated by the effects of the drug).
4. Assess for history of seizures/psychiatriuc problems/suicidal thoughts,
myelography within the past 24 hours or in the next 48 hours or is taking
MAOIs (to avoid potentially severe adverse reactions).
5. Assess vital signs, weight, skin color and lesions, affect, orientation,
reflexes, vision and bowel sounds on abdominal examination (This
determines baseline status before beginning therapy and for any potential
adverse effects).
Monoamine Oxidase Inhibitors (MAOIs)
MAOI’s are older drugs that treat depression. They work by stopping the
breakdown of norepinephrine, dopamine, and serotonin. They’re more difficult
for people to take than most other antidepressants because they interact with
prescription drugs, nonprescription drugs, and some foods. They also can’t be
combined with stimulants or other antidepressants.
MAOIs include:
Isocarboxazid (Marplan)
Phenelzine (Nardil)
Selegiline (Emsam), which comes as a transdermal patch
Tranylcypromine (Parnate)
SIDE EFFECTS
nausea
dizziness
drowsiness
trouble sleeping
Restlessness
INTERACTIONS
Foods – avoid Tyramine rich foods and beverages(aged cheese, soy sauce,
tofu, draft beer)
Other Antidepressant drugs
It can dangerously cause high levels of serotonin (serotonin syndrome)
PHARMACOKINETICS
The MAOIs are well absorbed from the GI tract, reaching peak levels
in 2-3 hours. They are metabolized in the liver primarily by acetylation
and are excreted in the urine. Patients with liver or renal impairment
and those known as ―slow acetylators‖ may require lowered doses to
avoid exaggerated effects of the drugs.
NURSING CONSIDERATIONS
1. Assess for any known allergies to these drugs (avoid hypersensitivity reactions)
2. Assess impaired liver and renal functions (could alter metabolism and excretion of
drug).
3. Cardiac dysfunction, GI or GU obstruction(could be exacerbated by the drug)
4. Seizure disorders, psychiatric conditions or suicidality and occurence of myelopathy
within the past 24 hours or in the next 48 hours to avoid the possibility of severe
reactions.
5. Determine whether female patients are pregnant/breastfeeding (should not be used
during pregnancy and lactation).
6. Assess vital signs, weight, skin color and lesions, affect, orientation and reflexes, vision
and bowel sounds (determine baseline status and for any potential adverse effects
before beginning therapy
ANXIETY
Anxiety - is a state of ―apprehension, tension or uneasiness that stems from the
anticipation of danger, the source with is largely unknown or unrecognized.
Situational Anxiety -is the anxiety experienced by people faced with a stressful
environment
- it may be intense, though patients often learn coping mechanisms to deal with
stress seeking conventional intervention.
Generalized Anxiety Disorder (GAD) - is a difficult to control, excessive anxiety that lasts
6 months or more.
- it focuses on a variety of life events/activities and interferes with normal day-
to-day functions.
Panic Disorder - characterized by intense feelings of immediate apprehension,
fearfulness, terror or impending doom, accompanied by ↑ ANS activity.
Anxiety Related Disorders
Phobias - are fearful feelings attached to situation or objects. Common phobias: fear of
snakes, spiders, crowd ( social anxiety)and heights
Obsessive Compulsive Disorder - involves recurrent, intrusive thoughts/repetitive
behaviors that interfere with normal activities/relationship
Post Traumatic Stress Disorder (PTSD) - a type of situational anxiety that develops in
response to re-experiencing a previous life event
Signs and Symptoms
restlessness, fatigue, muscle tension, nervousness, inability to focus/concentrate, and
overwhelming sense of dread and sleep disturbance.
BENZODIAZEPINES USED AS ANXIOLYTICS
1. Alprazolam (Xanax)
2. Chlordiazepoxide (Librium)
3. Clorazepam (Klonopin)
4. Clorazepate (Tranxene)
5. Diazepam (Valium)
6. Lorazepoam (Ativan)
PHARMACOKINETICS
The benzodiazepines are well absorbed from the GI tract, with peak levels achieved in 30
minutes to 2 hours. They are lipid soluble and well distributed throughout the body,
crossing the placenta and entering breast milk. Patients with liver disease must receive a
smaller dose and bemonitored closely. Excretion primarily through the urine.
CONTRAINDICATIONS AND CAUTIONS
1. Allergy to any benzodiazepine to prevent hypersensitivity reactions
2. Psychosis which could be exacerbated by sedation
3. Acute narrow-angle glaucoma
4. Shock,coma or alcoholic intoxication
5. Pregnancy because a predictable syndrome of cleft lip/palate, inguinal hernia, cardiac
defects, microcephaly or pyloric stenosis occurs when they are taken in the first
trimester
6. Breastfeeding is contraindicated becasue of potential adverse effects on the neonate
7. Elderly/debilitated patients because of possible unpredictable reaction.
Note:
The risk of CNS depression increases if benzodiazepines are taken with alcohol or other
CNS depressants, so much combinations should be avoided.
BARBITURATES AS ANXIOLYTICS-HYPNOTICS
• Drugs derived from barbituric acid
• Former mainstay drug used for the treatment of anxiety and for sedation and sleep
induction
• Associated with potentially severe adverse effects and many drug-drug interactions,
which make it less desirable than some of the newer agents
• Overdose results in profound respiratory depression, hypotension and shock
THERAPEUTIC ACTIONS
Barbiturates are general CNS depressants that inhibit neuronal impulse conduction in the
ascending RAS, depress the cerebral cortex, alter the cerebellar function, depress motor
output. They can cause sedation, hypnosis, anesthesia and in extreme cases coma
PHARMACOKINETICS
Barbiturates are absorbed well, reaching peak levels in 20-60 minutes. They
are metabolized in the liver to varying degrees, depending on the drug, and
excreted in the urine.
The long-acting barbiturates tend to be metabolized slower and excreted to a
greater degree unchanged in the urine. They are known to induce liver enzyme
systems, increasing the metabolism of barbiturate broken down by that system
as well as that of any other drug that may be metabolized by that enzyme
system.
ADVERSE EFFECTS
• Drowsiness, somnolence, lethargy, ataxia, vertigo, a feeling of a ―hangover‖, thinking abnormalities,
paradoxical excitement, anxiety and hallucinations, nausea, vomiting, constipation, diarrhea and
epigastric pain, hypoventilation, laryngospasm
• Cardiovascular effects: bradycardia, hypotension (IV administration) and syncope
• Hypersensitivity reactions: rash, serum sickness and Steven-Johnson sydrome
NURSING CONSIDERATIONS
• Assess for contraindications or cautions: Known allergies to prevent hypersensitivity reactions
• Assess for baseline status before beginning the therapy and for the occurrence of any potential
adverse effects.(Vital signs, weight, tissue perfusion: skin color and lesions, affect, orientation, reflexes,
bowel sounds)
