By,

Akash R. Ghorpade
M.Sc Psychiatric Nurse
 INDEX
Sr. no. Content Page no.
1. Introduction
1
2. History of Psychotropic drugs
4
3. Definition
6
4. Factors affecting action of drug
7
5. Classification of Psychotropic drugs.
10
6. Classification:
a. Anti- Psychotics drugs /Neuroleptics 11

b. Anti-depressants 49

Anxiolytics (Anti- Anxiety drugs)/

c. 85
Hypno- sedatives

d. Mood stabilizers/ Anti- Maniac drugs 125

e. CNS Stimulants 148

7. Conclusion
198
8. References
199
 PSYCHOTROPIC DRUGS
 INTRODUCTION:
 Drug therapy can be defined as the attempted treatment or remediation of a
physical or mental disease or defect. There are many types of therapy, include
mental health therapy, physical therapy, and occupational therapy. Essentially
any form of treatment is therapy, and drug therapy is treatment that involves
using medications, usually on a consistent basis to treat disease.
 Drug therapy can take a lot of different forms. People who get strep
throat might have antibiotic therapy for a few weeks to cure the condition. A
person with a heart defect or who has had heart surgery
requires prophylactic drug treatment with antibiotics prior to having dental
procedures, and this helps to prevent developing serious illness in the heart
called bacterial endocarditic. When someone has cancer, they might
have chemotherapy, the administration of drugs to kill cancer cells.
 Sometimes the term drug therapy is used in context of taking medications to
treat mental illnesses. This is often how it’s understood, even though this
definition of drug therapy is far too narrow. Many forms of mental illness
benefit from medications that have often been specifically designed to help
restore people to better mental function.
 Unlike taking antibiotics or using something like chemotherapy, drug therapy
for mental conditions has long endured stigma. It is still difficult for many
people to understand that mental illness is indeed physical illness. This has
made a number of people extremely reluctant to try drug therapy even when

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 they are miserable. It is viewed as weak to need medicines for mental
conditions.
 This attitude is changing but it may still be pervasive among certain sectors of
the population. In particular, those who grew up when few drug therapies were
available for mental illness may be reluctant to endorse them now. This is
unfortunate because attitudes of these people may influence the degree to their
children will seek drug therapy or they may make people use medicines feel as
though they are doing something wrong.
 Suspicion about drug therapy doesn’t have to stem from the idea that drugs
represent weakness. It can also come from people’s inherent distrust of the
intent of pharmaceutical companies, and some of this distrust is justified. It is a
profit-based industry. Despite this fact, there are many drug therapies that are
lifesaving and are able to fully restore wellness in those who are very ill. One
common behavior among the many, who take medicines, particularly if they
are suspicious about them, is that they will discontinue them as soon as they
feel better. This is greatly damaging under many circumstances. Failure to take
all antibiotics, for instance, may cause an infection to worsen. Certainly,
discontinuation of psychiatric medications will result in a return of symptoms.

 ERA OF PSYCHIATRIC DRUGS:

 The era of modern psychiatric medications was inaugurated by the accidental
discovery and rapid widespread use of the anti-psychotic or anti-schizophrenia
drug, chlorpromazine (Thorazine). Antidepressants such as amitriptyline
(Elavil) and imipramine (Tofranil) began to be widely used about the same time
around the middle of the twentieth century, as did anti-anxiety agents such as
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 chlordiazepoxide (Librium) and diazepam (Valium). Since that time there has
been fairly steady progress in the development of psychiatric medications that
are safer to use and less likely to produce bothersome side effects. All the drugs
that are commonly prescribed were introduced into psychiatry from the 1950’s
onwards. Some people talk of this period in the 1950’s and the introduction of
this new ranges of drug, as a revolution, the psycho-pharmacological
revolution. The way psychiatry is practiced today is not very different from the
way it was practiced 50 or 100 years ago. What is different however, is the way
that psychiatry views itself, and particularly its drug treatments. Most drugs
that were in use prior to the 1950’s were various forms of sedatives. In the
19th Century, Opium and Bromides were used. In the 1920’s and 1930’s various
Barbiturates were synthetized and these became probably the most popular
drugs in the first half of the 20th Century. Paraldehyde was also used
extensively, and from the 1930’s some stimulants started to be used.
 A psychiatric medication is a licensed psychoactive drug taken to exert an
effect on the chemical makeup of the brain and nervous system. Thus, these
medications are used to treat mental disorders. Usually prescribed
in psychiatric settings, these medications are typically made
of synthetic chemical compounds, although some are naturally occurring, or at
least naturally derived. Since the mid-20th century, such medications have been
leading treatments for a broad range of mental disorders and have decreased
the need for long-term hospitalization therefore lowering the cost of mental
health care.

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 HISTORY OF PSYCHOTROPIC DRUGS:

AYURVEDA: (for Sympathy & Kindness)

400 BC
Used Dhatura and roots of Serpentina plant mixed
with oil (ghee).

1853 SEDATIVE: Bromide used as a sedative- hypnotic.

1882 HYPNOTIC: Paraldehyde used a hypnotic.

BARBITURATES: used for sedation. Phenobarbital

1903
introduced in 1912.

MALARIAL TREATMENT FOR GENERAL

1917 PARALYSIS OF INSANE (GPI): received a Nobel
prize (Julius Von Wagner Jauregui).

BARBITURATE INDUCED COMA: ‘Jacob Klaesi’

1922 introduced Barbiturate induced coma for treatment of
psychosis.

INSULIN- SHOCK TREAMENT: ‘Manfred Sakel’

1927
introduced insulin- shock treatment for schizophrenia.

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1931 RESERPINE: First report of successful treatment of
psychosis by (Ganesh Sen and Kartik Bose)

LOBOTOMY: Frontal lobotomy for treatment of

1936
psychiatric disorders (Egas Moniz and Almenda Lima).

AMPHETAMINES: Amphetamines used in treatment

1937
of behavioral disorder of children (C Bradley)

ELECTRO CONVULSIVE THERAPY: used for the

1938
treatment of psychosis (Ugo Cerletti and Lucio Bini)

LITHIUM: Lithium used in mania (John F Cade), did

1949
not receive much attention even in Australia.

IMIPRAMINE: Tricyclic anti- depressants (TCA) for

1958 treatments of depression (Thomas Kuhn) &

HALOPERIDOL: synthesized in Belgium (Janssen)

CHLORDIAZEPOXIDE: used in and anti- anxiety

1960
agent in Sternback.

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 DEFINITION OF PSYCHOTROPIC DRUGS:

1. Psychotropic drug is any drug that has primary effects on behavior, experience,
or other psychological functions
- (Logman Dictionary of Psychology &Psychiatry).

2. Psychotropic or psychoactive drugs can also be defined as chemical that affects

the brain & nervous system, alter feelings & emotions. These drugs also affect
the consciousness in various ways. A broad range of these drugs is used in
emotional & mental illnesses.

 TERMINOLOGIES USED IN PSYCHOPHARMACOLOGYLY:

1. Psychopharmacology: It is the study of the effects of drugs on affect, cognition,

and behavior

2. Efficacy: It refers to the maximal therapeutic that a drug can achieve.

3. Potency: It describe the amount of the drug needed to achieve the maximum

effect.

4. Half-life: It is the time taken for half of the drug to be removed from the blood

stream.

5. Agonist: A drug that binds to and activates a receptor

6. Antagonist: A drug that binds to but does not activate (block) a receptor.

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 CHARACTERISTICS OF PSYCHOTROPIC DRUGS:

 (According to Hollister, 1983)

1. It should cure the underlying pathology causing the disorder or symptoms

under focus, so that the drug can be stopped after sometime.
2. It should not have any side effects or toxicity in the therapeutic range.
3. It should benefit all the patients suffering from that disorder.
4. It should have rapid onset of action.
5. There should not be tolerance to the drug so that some dose is effective for
long duration of time.
6. There should be longer dependence on the drug and no withdrawal
symptoms on stopping the drug.
7. It should not be fatal/ lethal in overdoses.
8. It can be given in both In- patient and out- patient settings.

 FACTORS AFFECTING ACTION OF DRUG:

 Variation in response to the same dose of a drug between different patients
and even in the same on different occasions is a rule rather than exception.
Once or more of the following categories of differences among individuals
are responsible for the variations in drug response.

1. Individual differ in pharmacokinetic handling of drug attain varying

plasma/ target site concentration of the drug. This is more marked for
disposed by metabolism than for drugs excreted unchanged.

7
2. Variations in number or state of receptors, coupling protein or other
component of response effectuation.

3. Variations in neurogenic/hormonal tone or concentrations of specific

constituents.

a) BODY SIZE
It influences the concentration of the drug attained at the site of action.
The average adult dose refers to the individuals of medium built.
 Individual dose= BW (Kg)/70 * average adult dose
 Individual dose=BSA (m*m)/1.7 *average adult dose
 BSA (m*m*m) = BM(KG)* Height (cm)* 0.007184

b) AGE
The dose of a drug for children is often calculated from the adult dose
 Child dose= (Age/Age+12) adult dose............ (Young ‘s formula)
 Child dose= (Age/20) adult dose…................... (Dilling’s formula)

c) SEX
Female have smaller body size and require doses that are on the lower side
of the range. Subjective effects of the drugs may differ in females because of
their mental makeup. A number of anti-hypertensives interferes with sexual
function in male but not in female. Gynecomastia is a side effect that can
occur only in men. Ketoconazole causes loss of libido in men but not in
women.

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d) RACE
Race can be a factor affecting drug action, since enzyme systems; body
chemistry; and stature may vary. Among human being racial differences have
been observed e.g., Black require higher and Mongols require lower
concentrations of atropine and ephedrine to dilate their pupil.

e) GENETICS
The dose of a drug produces the same effect may vary by 4-6-fold among
different individual. This is mainly because of differing rate of drug metabolism
as the amount and isoform pattern of drug metabolizing enzyme is genetically
controlled. There are also differences in the target organ sensitivity.

f) ROUTE OF ADMINISTRATION
It governs the speed and intensity of drug response. A drug may have entirely
different uses through different routine. E.g., Magnesium sulfate given orally
causes purgation; applied on inflamed areas - decrease swelling; while
intravenously it produces CNS depression and hypotension.

g) Environment factor and time of administration

Several environment factors affect drug responses; exposure to insecticide,
carcinogens, tobacco smoke and consumption of charcoal broiled meat are
inducing drug metabolism. Type of diet and temporal relation between drug
ingestion and meal can alter drug absorption.

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h) Pathological factor
 Gastrointestinal diseases
 Liver disease
 Kidney disease
 Congestive heart failure
 Thyroid disease
 Autoimmune disorders

 CLASSIFICATION OF PSYTROPIC MEDICATIONS:

(There are 8 main groups of psychiatric medications)

1. Anti- Psychotics/ Neuroleptics: For the treatment of psychotic issues such

as ‘Schizophrenia’.
2. Anti- Depressants: Used for treating depression.
3. Anti- Anxiety/ Anti- Panic/ Hypno- Sedatives/ CNS Depressants: Treats
chronic anxiety (Panic attacks) to Acute (generalized anxiety).
4. Mood stabilizers/ Anti- Maniac drugs: Treats bipolar disorder,
schizophrenia, and borderline personality disorder.
5. CNS Stimulants: Treats Attention deficit hyperactivity disorder.
6. Anti- Epileptics/ Anti- Convulsant: Agents used to treat epileptic seizures.
7. Anti-Parkinsonian: Agents used in treatment of Parkinson’s disease.
8. Miscellaneous Drugs: Used in Child psychiatry, Eating disorders, Vitamins,
Dopamine or Calcium channel blockers.

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 ANTI- PSYCHOTICS / NEUROLEPTICS

■ INTRODUCTION:
 Antipsychotics are drugs used to treat various symptoms of psychosis, such as
those caused by psychotic disorders or schizophrenia. Antipsychotics are also
used as mood stabilizers in the treatment of bipolar disorder, even if no
symptoms of psychosis are present.
 Antipsychotics are sometimes referred to as neuroleptic drugs and some
antipsychotics are branded "major tranquilizers”. Neuroleptic: synonym for
antipsychotic drug; originally indicated drug w/antipsychotic efficacy but with
neurologic (extrapyramidal motor) side effects.
 These are used to treat symptoms of psychosis, such as delusions and
hallucinations. They work by blocking the receptors of the neurotransmitter
Dopamine.
 Antipsychotic drugs are the primary medical treatment for Schizophrenia and
are also used in psychotic episodes of acute mania, psychotic depression, and
drug-induced psychosis. • Persons with dementia who have psychotic
symptoms sometimes respond to low doses of antipsychotics. • Short-term
therapy with antipsychotics may be useful for transient psychotic symptoms,
such as those seen in some persons with borderline personality disorder.

■ CLASSIFICATION
 Typical anti-psychotics
 Atypical antipsychotic

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1. Typical Antipsychotics, or First-Generation Antipsychotic Drugs.
The typical, or conventional, antipsychotics were first developed in the
1950s. Haldol (haloperidol) and Thorazine (chlorpromazine) are the best-
known typical antipsychotics. They continue to be useful in the treatment
of severe psychosis and behavioural problems when newer medications
are ineffective. However, these medications do have a high risk of side
effects, some of which are quite severe. In response to the serious side
effects of many typical antipsychotics, drug manufacturers developed
another category referred to as atypical antipsychotics.

2. Atypical Antipsychotics, or Second-Generation Antipsychotic Drugs.

These new medications were approved for use in the 1990s. Clozapine,
asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole,
ziprasidone, zotepine, and aripiprazole are atypical antipsychotic drugs.
With the discovery of clozapine in 1959, it became evident that this drug
was less likely to produce extrapyramidal effects (physical symptoms
such as tremors, paranoia, anxiety, dystonia, etc. as a result of improper
doses or adverse reactions to this class of drug) in humans at clinically
effective doses than some other types of antipsychotics. Clozapine was
categorized as the first atypical antipsychotic drug. This category of drugs
has also been of great value in studying the pathophysiology of
schizophrenia and other psychoses.

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 Commonly prescribed Typical and Atypical antipsychotic medications:

 Typical antipsychotics include:

 Haldol (haloperidol)
 Loxitane (loxapine)
 Mellaril (thioridazine)
 Moban (molindone)
 Navane (thiothixene)
 Prolixin (fluphenazine)
 Serentil (mesoridazine)
 Stelazine (trifluoperazine)
 Trilafon (perphenazine)
 Thorazine (chlorpromazine)

 Atypical antipsychotics include:

 Abilify (aripiprazole)
 Clozaril (clozapine)
 Geodon (ziprasidone)
 Risperdal (risperidone)
 Seroquel (quetiapine)
 Zyprexa (olanzapine)

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■ Chemical classification of typical anti-psychotics

Phenothiazines (first-generation antipsychotics):

The phenothiazines are the largest chemical group, comprising more than 40
compounds (only the most relevant are listed below) grouped under three
subtypes. Drugs in this group share the same three-ring structure with different
side chains joined at the nitrogen atom of the middle ring. The activity of the group
can be affected by substitutions at position 2 or 10. The phenothiazines are
categorized into three subclasses based on substitutions at position 10: aliphatic,
piperidine, and piperazine phenothiazines. Table 1 is a selection of the most
commonly prescribed phenothiazines, the list also specifies potency according to
side chain subtype.

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Non-phenothiazine (first-generation antipsychotics):

15
 Receptor Affinity Profile:

(Adapted from Hahn, Albers and Reist. Psychiatry, 2008 Edition).

ACTIVITIES

D2 Activity 5HT2 Activity Muscarinic Alpha-1 Antihistamine

Drugs
Activity adrenergic Activity

Activity

Chlorpromazine very high

very high very high very high very high
(Thorazine)

Fluphenazine moderate
very high moderate low low
(Prolixin)

Perphenazine high
very high very high low moderate
(Trilafon)

Trifluoperazine moderate
very high high low moderate
(Stelazine)

Thioridazine very high

very high very high very high very high
(Mellaril)

Haloperidol low
very high moderate low low
(Haldol)

Thiothixene high
very high low low moderate
(Navane)

Loxapine very high

high very high moderate high
(Loxitane)

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 Adverse effect profile:

Sedating Anticholinergic Extrapyramidal Hypotensive

Drug
effect effect side effects effects

IM- High
Chlorpromazine High High Low
P0- Moderate

Fluphenazine Low Low Very high Low

Haloperidol Very low Very low Very high Very low

Loxapine Moderate Low Moderate Moderate

Molindone Very low Low Moderate Low

Perphenazine Low Low High Low

Pimozide Low Low High Very low

Thioridazine High High Low High

Thiothixene Low Low High Low

Trifluoperazine Low Low High Low

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 Mechanism of Action
The exact mechanism of action of antipsychotic drugs is unknown. According to
the dopamine theory of schizophrenia, positive symptoms are the result of
overactivity in the mesolimbic dopamine pathway. This is in part based on the
observation that drugs that increase dopaminergic availability (L-DOPA, cocaine,
amphetamines) can trigger psychotomimetic effects in individuals not affected by
schizophrenia. As the image below shows, first-generation antipsychotics are D2
antagonists. As a result, they reduce dopaminergic neurotransmission in the four
dopamine pathways.

 Effects of first-generation antipsychotics on the four dopamine pathways

1. Mesocortical pathway.
Research on schizophrenia pathophysiology suggests that a dysfunction of this
pathway is associated with cognitive impairments and disturbances of
emotions and affect (negative symptoms). Blockade of the meso-cortical
pathway by high doses of first-generation antipsychotics can induce secondary
negative symptoms and cognitive effects.

2. Mesolimbic pathway: Antipsychotic effects

As explained earlier, overactivity of this pathway is thought to be involved in
the pathophysiology of positive symptoms of schizophrenia. Blockade of D2
receptors in the mesolimbic pathway has been proposed as a possible
mechanism of antipsychotic action of first-generation agents.

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3. Nigrostriatal pathway: Extrapyramidal Symptoms
Antagonism of D2 receptors in the nigrostriatal pathway is associated with
increased risk of extrapyramidal symptoms.

4. Tuberoinfundibular pathway: Hyperprolactinemia

Dopamine acts as a prolactin-inhibiting factor, D2 blockade increases prolactin
levels by promoting its release in the pituitary gland.

 SIDE EFFECTS AND ADVERSE DRUG REACTIONS

1. Extrapyramidal Effects: Dystonia’s, akathisia, tardive dyskinesia,

Parkinson’s-like symptoms, unwanted movements, ataxia, muscle
breakdown, rigidity, tremors, and seizures are some major effects of this
category of drugs. Neuroleptic malignant syndrome may occur as well.

2. Effects on the Central Nervous System: Drowsiness, sedation, and hypnosis

occur. Confusion, vertigo, syncope, disturbed sleep, nightmares, and
agitation are also reported by various studies. Dementia, amnesia, and loss
of memory are some adverse effects. Suicidal ideation in old and young with
increased mania, anxiety, agitation, violent behavior, and depression can
also be seen in people taking these drugs.

3. Effects on the Cardiovascular System: Cardiomyopathy is noted in nine out

of every 100,000 people using clozapine. Alteration in electrocardiogram

19
 (ECG) readings, chest pain, angina, myocarditis, palpitation, tachycardia,
edema, phlebitis, and arrhythmias are serious adverse effects. Myocardial
infarction (heart attack) occurs in only 1% of people using this category of
drug. Orthostatic hypotension—the medical name for the fuzzy feeling you
get when standing up to quickly—is very common.

4. Hepatic (Liver) Effects: These agents increase the serum concentration of

alkaline aminotransferase. Reversible liver cell hyperplasia, increase in
bilirubin, jaundice, drug induced hepatitis, and necrosis have been recorded
in studies.

5. Gastrointestinal Effects: Constipation, dry mouth, anorexia, weight gain,

increases in pancreatic enzymes, epigastric distress, abdominal cramps,
dyspepsia, heartburn, and nausea are some common adverse effects.

6. Genitourinary (Urinary and Reproductive) Effects: Impotence, delayed

and premature ejaculation, testicular swelling, priapism, increased or
decreased libido, virginal itching, enuresis, polyuria, breast engorgement,
galactorrhea, and anorgasmia have been reported.

7. Pregnancy and Lactation: Antipsychotic drugs can be used in pregnant

females since they have shown no teratogenic (development of the fetus or
embryo) effects in animal studies. Drugs like clozapine and olanzapine have
shown no harm to the fetus. However, during lactation, the metabolites may
be disturbed in the milk and could harm the newborn.

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8. Other Effects: Cases of blurred vision, hot flashes, dry throat, nasal
congestion, severe hyperglycemia, numbness, chills, glaucoma, leukopenia,
neutropenia, hyperlipidemia, agranulocytosis, and respiratory depression
have been reported.

 Key Concept: Dopamine-2 Receptor Blockade in The Basal Ganglia Results in

Extra pyramidal Motor Side Effects (EPS).

- Dystonia

- Neuroleptic malignant syndrome

- Parkinsonism

- Tardive dyskinesia

- Akathisia

- Increased prolactin secretion (common with all; from dopamine blockade)

- Weight gain (common, antihistamine effect?)

- Photosensitivity (v. common w/ phenothiazines)

- Lowered seizure threshold (common with all)

- Leucopenia, agranulocytosis (rare; w/ phenothiazines)

- Retinal pigmentopathy (rare; w/ phenothiazines)

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 MECHANISMS OF ACTION OF TYPICAL NEUROLEPTICS

 Dopamine-2 receptor blockade in meso-limbic and meso-cortical systems for

antipsychotic effect.

 Dopamine-2 receptor blockade in basal ganglia (Nigro-striatal system) for

EPS

 Dopamine-2 receptor super sensitivity in nigrostriatal system for tardive

dyskinesia.

 LONG TERM EFFECTS OF D2 RECEPTOR BLOCKADE

 Dopamine neurons reduce activity.

 Postsynaptic D-2 receptor numbers increase (compensatory response).

 When D2 blockade is reduced, DA neurons resume firing and stimulate

increased # of receptors >> hyper-dopamine state >> tardive dyskinesia

 MANAGEMENT OF EPS

 Dystonia and parkinsonism: anticholinergic antiparkinsonian drugs.

 Neuroleptic malignant syndrome: muscle relaxants, DA agonists,

supportive.

 Akathisia: benzodiazepines, propranolol.

 Tardive dyskinesia: increase neuroleptic dose; switch to clozapine.

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1. OLANZAPINE
 Name of the drug:
 Trade Name : Tab. Olanzapine
 Pharmacological Name: Olanzapine

 Drug classes:
 Antipsychotic
 Dopaminergic blocking agent

 Available forms:
 Tablets Available : 2.5, 5, 7.5, 10, 15, 20 mg;
 Orally disintegrating tablets : 5, 10, 15, 20 mg;
 Powder for injection : 10 mg

 Dosage:
 ADULTS
 Schizophrenia: Initially, 5–10 mg PO daily, increase to 10 mg PO daily
within several days; may be increased by 5 mg/day at 1-wk intervals to
achieve desired effect. Do not exceed 20 mg/day.

 Bipolar mania: 10–15 mg/day PO; adjust at 5-mg intervals as needed, not
less than q 24 hr. Maximum dose, 20 mg/day. For maintenance, 5–
20 mg/day PO. The initial dose is 10 mg of olanzapine when combined with
lithium or valproate.

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  Agitation: 10 mg IM; range 5–10 mg IM; dose may be repeated in 2 hr if
needed, safety of > 30 mg/24 hr not established.

 PEDIATRIC PATIENTS
 Safety and efficacy not established in patients < 18 yr.

 GERIATRIC PATIENTS
 5 mg IM.

 DEBILITATED PATIENTS
 Start with initial dose of 5 mg; 2.5 mg IM.

 Indications:
 Treatment of schizophrenia
 Treatment of acute mixed or manic episodes associated with bipolar 1
disorder and maintenance of bipolar 1 disorder as monotherapy, or
combined with lithium or valproate
 Treatment of agitation associated with schizophrenia and bipolar 1 mania
(injection)
 Unlabeled use: Dementia related to Alzheimer's disease

 Contraindications:
 Allergy to olanzapine,
 Myeloproliferative disorders,
 Severe CNS depression,

24
  Comatose states,
 Lactation.

 Therapeutic action:
Mechanism of action not fully understood; blocks dopamine receptors in the
brain, depresses the RAS; blocks serotonin receptor sites; anticholinergic,
antihistaminic (H1), and alpha-adrenergic blocking activity may contribute to
some of its therapeutic (and adverse) actions; produces fewer extra-
pyramidal effects than most antipsychotics.

 Pharmacokinetics:

Route Onset Peak Duration

Oral Varies 6 hr Weeks

IM Rapid 15–45 min Weeks

 Metabolism: Hepatic; T1/2: 30 hours

 Distribution: Crosses placenta; enters breast milk
 Excretion: Feces, urine

 Cautions:
 Use cautiously in elderly or debilitated patients, or with
 CV or cerebrovascular disease, dehydration, seizure disorders, Alzheimer's
disease,

25
  Prostate enlargement, narrow-angle glaucoma, history of paralytic ileus or
breast cancer,
 Pregnancy; phenylketonuria (if using orally disintegrating tablets, contain
phenylalanine).

 Adverse effects:
 CNS: Somnolence, dizziness, nervousness, headache, akathisia, personality
disorders, tardive dyskinesia, neuroleptic malignant syndrome
 CV: Orthostatic hypotension, peripheral edema, tachycardia
 GI: Constipation, abdominal pain
 Respiratory: Cough, pharyngitis
 Other: Fever, weight gain, joint pain, development of diabetes mellitus

 Drug-drug Interactions
 Increased risk of orthostatic hypotension with anti-hypertensive, alcohol,
benzodiazepines; avoid use of alcohol and use caution with anti-
hypertensive
 Increased risk of seizures with anti-cholinergic, CNS drugs
 May decrease effectiveness of levodopa, dopamine agonists
 Decreased effectiveness with rifampin, omeprazole, carbamazepine,
smoking
 Increased risk of toxicity with fluvoxamine

26
 Nursing considerations:
 Assessment
 History: Allergy to olanzapine, myeloproliferative disorders, severe CNS
depression, comatose states, history of seizure disorders, lactation; CV
or cerebrovascular disease, dehydration, Alzheimer's disease, prostate
enlargement, narrow-angle glaucoma, history of paralytic ileus or breast
cancer, elderly or debilitated patients, pregnancy
 Physical Examination: T, weight; reflexes, orientation, IOP, ophthalmologic
examination; P, BP, orthostatic BP, ECG; R, adventitious sounds; bowel
sounds, normal output, liver evaluation; prostate palpation, normal urine
output; CBC, urinalysis, LFTs, renal function tests

 Interventions
 Do not dispense more than 1-wk supply at a time.
 Peel back foil on blister pack of disintegrating tablets; do not push through
foil; use dry hands to remove tablet and place in mouth.
 Prepare solution for IM injection using 2.1 mL sterile water for injection.
Resulting solution contains 5 mg/mL. Solution should be clear yellow. Use
within 1 hr of reconstitution. Discard any unused portion.
 Monitor for the many possible drug interactions before beginning therapy.
 WARNING: Monitor elderly patients for dehydration and institute
remedial measures promptly; sedation and decreased sensation of thirst
related to CNS effects of drug can lead to dehydration.
 Encourage patient to void before taking the drug to help
decrease anticholinergic effects of urinary retention.

27
  Monitor for elevations of temperature and differentiate between infection
and neuroleptic malignant syndrome.
 Monitor for orthostatic hypotension and provide appropriate safety
measures as needed.

 Teaching points
 Take this drug exactly as prescribed; do not change dose without consulting
your health care provider.
 Peel back foil on blister pack of disintegrating tablets; do not push through
foil; use dry hands to remove tablet, place entire tablet in mouth.
 This drug cannot be taken during pregnancy. If you think you are pregnant
or wish to become pregnant, contact your health care provider.
 You may experience these side effects: Drowsiness, dizziness, sedation,
seizures (avoid driving, operating machinery, or performing tasks that
require concentration); dizziness, faintness on arising (change positions
slowly, use caution); increased salivation (if bothersome, contact your health
care provider); constipation (consult with your health care provider for
appropriate relief measures); fast heart rate (rest and take your time if this
occurs).
 Report lethargy, weakness, fever, sore throat, malaise, mouth ulcers,
and flulike symptoms

28
2. HALOPERIDOL
 Name of the drug:
 Trade Name :- Tab. Haldol
 Pharmacological Name :- Haloperidol

 Drug classes:
 Antipsychotic
 Butyrophenones

 Available forms:
 Tablets :- 0.5 mg, 1 mg, 2 mg, 5 mg, 10 mg, 20 mg.
 Oral concentrate :- 2 mg/ml.
 Haloperidol injection :- 5 mg/ml.
 Haloperidol decanoate injection: 50 mg/ml, 100 mg/ml.

 Route/Dosage:
 PO (Adults): 0.5–5 mg 2–3 times daily. Patients with severe symptoms may
require up to 100 mg/day.
 PO (Geriatric Patients or Debilitated Patients): 0.5–2 mg twice daily
initially; may be gradually increased as needed.
 PO (Children 3–12 year or 15–40 kg): 50 mcg/kg/day in 2–3 divided doses;
may increase by 500 mcg (0.5 mg)/day q 5–7 days as needed (up to 75
mcg/kg/day for nonpsychotic disorders or Tourette’s syndrome or 150
mcg/kg/day for psychoses).

29
  IM (Adults): 2–5 mg q 1–8 hour (not to exceed 100 mg/day).
 IV (Adults): 0.5–5 mg, may be repeated q 30 min
 Haloperidol Deaconate:
IM (Adults): 10–15 times the previous daily PO dose but not to exceed 100
mg initially, given monthly (not to exceed 300 mg/mo).

 Contra-indications:
 Nausea and vomiting from surgery or chemotherapy.
 Hypersensitivity
 Angle-closure glaucoma
 Bone marrow depression
 CNS depression
 Severe liver or cardiovascular disease (Q-T interval prolonging conditions)
 Hypersensitivity.

 Action:
Alters the effects of dopamine in the CNS. Also has anti-cholinergic and alpha-
adrenergic blocking activity.

 Pharmacokinetics:
ROUTE ONSET PEAK DURATION

PO 2 hr 2–6 hr 8–12 hr

IM 20–30 min 30–45 min 4–8 hr†

IM (deaconate) 3–9 days Unknown 1 month

30
 Absorption: Well- absorbed following PO/IM administration. Decanoate salt
is slowly absorbed and has a long duration of action.
 Distribution: Concentrates in liver. Crosses placenta; enters breast milk.
 Protein Binding: 90%.
 Metabolism and Excretion: Mostly metabolized by the liver.
 Half-life: 21–24 hr.

 Caution:
 Debilitated patients (dose reduction required);
 Cardiac disease; Diabetes; Respiratory insufficiency;
 Prostatic hyperplasia; CNS tumors;
 Intestinal obstruction; Seizures;
 Lactation:

 Side Effects:
 CNS: SEIZURES, extrapyramidal reactions, confusion, drowsiness,
restlessness, tardive dyskinesia.
 EENT: blurred vision, dry eyes.
 Resp: respiratory depression.
 CV: hypotension, tachycardia.
 GI: constipation, dry mouth, anorexia, drug-induced hepatitis, ileus, weight
gain.
 GU: urinary retention.
 Derma: diaphoresis, photosensitivity, rashes.
 Endo: galactorrhea, amenorrhea.

31
  Hemat: anemia, leukopenia.
 Metab: hyperpyrexia.
 Miscellaneous: NEUROLEPTIC MALIGNANT SYNDROME,
hypersensitivity reactions.

 Drug Interactions:
 Drug–Drug: ↑ hypotension with antihypertensives, nitrates, or acute
ingestion of alcohol.
 ↑ anticholinergic effects with drugs having anticholinergic properties,
 including antihistamines, antidepressants, atropine, phenothiazines,
quinidine, and disopyramide. ↑ CNS depression with other CNS
depressants,
 Including alcohol, antihistamines, opioid an algesics,
and sedative/hypnotics.
 Concurrent use with epinephrine may result in severe hypotension and
tachycardia. May ↓ therapeutic effects of levodopa.
 Acute encephalopathic syndrome may occur when used with lithium.
Dementia may occur with methyldopa.

 Nursing Responsibility
 Assessment:

 Assess mental status (orientation, mood, behavior) prior to and periodically

during therapy.

32
 Assess positive (hallucination, delusions) and negative (social isolation)
symptoms of schizophrenia.
 Monitor blood pressure (sitting, standing, lying) and pulse prior to and
frequently during the period of dose adjustment. May cause QT interval
changes on ECG.
 Observe patient carefully when administering medication, to ensure that
medication is actually taken and not hoarded.
 Monitor intake and output ratios and daily weight. Assess patient for signs
and symptoms of dehydration (decreased thirst, lethargy,
hemoconcentration), especially in geriatric patients.
 Assess fluid intake and bowel function. Increased bulk and fluids in the diet
help minimize constipating effects.
 Monitor patient for onset of akathisia (restlessness or desire to keep moving),
which may appear within 6 hr of 1st dose and may be difficult to distinguish
from psychotic agitation. Benztropine may be used to differentiate agitation
from akathisia. Observe closely for extrapyramidal side effects
(parkinsonian—difficulty speaking or swallowing, loss of balance control,
pill rolling of hands, mask-like face, shuffling gait, rigidity, tremors;
and dystonic—muscle spasms, twisting motions, twitching, inability to
move eyes, weakness of arms or legs). Trihexyphenidyl or Benztropine may
be used to control these symptoms. Benzodiazepines may alleviate akathisia.
 Monitor for tardive dyskinesia (uncontrolled rhythmic movement of mouth,
face, and extremities; lip smacking or puckering; puffing of cheeks;
uncontrolled chewing; rapid or worm-like movements of tongue, excessive
eye blinking). Report immediately; may be irreversible.

33
  Monitor for development of neuroleptic malignant syndrome (fever,
respiratory distress, tachycardia, seizures, diaphoresis, hypertension or
hypotension, pallor, tiredness, severe muscle stiffness, loss of bladder
control). Report symptoms immediately. May also cause leukocytosis,
elevated liver function tests, elevated CPK.

 Lab Test Considerations:

 Monitor CBC with differential and liver function tests periodically during
therapy.

 IV: Haloperidol decanoate should not be administered IV.

 Patient/Family Teaching:

 Advise patient to take medication as directed. Take missed doses as soon as

remembered, with remaining doses evenly spaced throughout the day. May
require several weeks to obtain desired effects. Do not increase dose or
discontinue medication without consulting health care professional. Abrupt
withdrawal may cause dizziness; nausea; vomiting; GI upset; trembling; or
uncontrolled movements of mouth, tongue, or jaw.
 Inform patient of possibility of extrapyramidal symptoms and tardive
dyskinesia. Caution patient to report symptoms immediately.
 Advise patient to change positions slowly to minimize orthostatic
hypotension.
 May cause drowsiness. Caution patient to avoid driving or other activities
requiring alertness until response to medication is known.

34
  Caution patient to avoid taking alcohol or other CNS depressants
concurrently with this medication.
 Advise patient to use sunscreen and protective clothing when exposed to the
sun to prevent photosensitivity reactions. Extremes of temperature should
also be avoided, because this drug impairs body temperature regulation.
 Instruct patient to use frequent mouth rinses, good oral hygiene, and
sugarless gum or candy to minimize dry mouth.
 Advise patient to notify health care professional of medication regimen prior
to treatment or surgery.
 Instruct patient to notify health care professional promptly if weakness,
tremors, visual disturbances, dark-colored urine or clay-colored stools, sore
throat, or fever is noted.
 Encourage continued participation in psychotherapy.
 Provide positive reinforcement for medication compliance.
 Refer to local support group.
 Emphasize the importance of routine follow-up exams to monitor response
to medication and detect side effects.

3. CLOZAPINE
 Name of the drug:
 Trade Name :- Tab. Clozaril
 Pharmacological Name :- Clozapine
 Drug classes:
 A-typical Antipsychotic
 Dopaminergic blocking agent

35
 Available forms:
 Tablets Available :- 25; 100mg

 Dosage
 For schizophrenia
 Initial dose: - 12.5 mg orally once or twice a day.
 Maintenance dose: - If the first dose is well- tolerated, dosages may then be
titrated in daily increments of 25 mg to 50 mg for approximately two weeks
until a daily dose of 300 to 450 mg is achieved.
 Maximum dose: 900 mg per day.

 Reduction of the risk of recurrent suicidal behavior in patients with

schizophrenia or schizoaffective disorder:
 Initial dose: 12.5 mg orally once or twice a day.
 Maintenance dose: If the first dose is well- tolerated, dosages may then be
titrated in daily increments of 25 mg to 50 mg for approximately two weeks
until a daily dose of 300 to 450 mg is achieved.
 Maximum dose: 900 mg per day

 Indications:
 Clozapine is used principally in treating treatment – resistant schizophrenia
 It is also used for reducing the risk of suicide in patient judged to belong to
a high-risk group with chronic risk for suicide behavior
 Clozapine work well against positive symptoms and negative symptoms of
schizophrenia

36
  Psychosis in Parkinson’s.

 Contra- indication:
 Severe cardiac disorder
 Active liver disease.
 Severe renal impairment.
 History of agranulocytosis or neutropenia.
 Bone marrow disorders.
 Paralytic ileus.
 Alcoholic and toxic psychoses.
 History of circulatory collapse.
 Drug intoxication
 Coma or CNS depression.
 Uncontrolled epilepsy.
 Pregnancy or breastfeeding.

 Cautions:
 Other drugs that increase the QT interval.
 Cardiovascular disease.
 Older patients.
 Neutropenia and potentially fatal agranulocytosis.
 Avoid drugs that depress leucopoiesis.

37
 Therapeutic action:
Clozapine is classified as an atypical antipsychotic drug because its profile of
binding to serotonergic as well as dopamine receptor its effect on various
dopamine mediated behaviors also differ from those exhibited by more typical
antipsychotics. And clozapine interferes to a lower extent with the binding of
dopamine at D1; D2; D3; and D5 receptor, and has a high affinity for the D4
receptor; but it does not induce catalepsy nor inhibit apomorphine- induced
stereotype in animal models as is seen with conventional neuroleptics.

 Side effect:
 Constipation;
 Dry mouth, blurred vision;
 Drooling, especially at night;
 Increased sweating;
 Drowsiness, dizziness, spinning sensation; or
 Sleep problems.

 To make sure you can safely take clozapine, tell your doctor if you have any of
these other conditions:
 Heart disease, heart rhythm disorder, high blood pressur
 History of heart attack or stroke
 A personal or family history of long qt syndrome
 Epilepsy or other seizure disorder
 Lung disease
 Cardiomyopathy

38
  Liver or kidney disease
 Diabetes or Glaucoma
 A history of bone marrow or blood cell disorders
 An enlarged prostate or urination problems

 Nursing Considerations
 Differential blood counts must be normal on commencement and monitored
regularly.
 Due to potential for myocarditis and cardiomyopathy, patients should have:
 Full physical examination and medical history;
 Specialist examination if there are any cardiac problems;
 Investigations for myocarditis or cardiomyopathy in the presence of
tachycardia.
 Stop taking if cardiomyopathy or myocarditis is suspected.
 Use with caution in conjunction with drugs causing constipation.
 Withdraw drug over 14 days to prevent rebound psychosis.

 Patient teaching
 Patients must immediately report symptoms of infection, especially flu-like
symptoms.
 Avoid hot baths or showers as hypotension can occur.
 Oral hygiene is important to avoid oral candidiasis.
 Avoid overexposure to the sun as heatstroke can occur.

39
4. CHLORPROMAZINE HYDROCHLORIDE
 Name of the drug:
 Trade Name :- Tab. Chlorpromazine
 Pharmacological Name :- Chlorpromazine hydrochloride

 Drug classes:
 Antipsychotic
 Phenothiazine

 Available forms:
 Tablets
 Parental

 Dose & Indication:

 Treat psychotic disorders such as schizophrenia or manic-depression, and
severe behavior
 IM: Initial Dose 25 to 50 mg. The dose may be repeated in one hour.
Subsequent doses may be increased and given every 2 to 4 hours as needed.
 Oral: Initial Dose: 10 to 25 mg orally 3 times a day. Total daily doses should
be increased in 20 to 50 mg increments every 3 or 4 days until symptoms are
controlled.
 Usual Maintenance Dose: 200 mg/day orally

40
 Usual Adult Dose for Mania
 Oral: 10 mg orally 3 to 4 times a day or 25 mg orally 2 to 3 times a day.
More severe cases: 25 mg orally 3 times a day.
 IM: 25 mg injection one time. If necessary, may give additional 25 to 50 mg
injection in 1 hour.

 Usual Adult Dose for Nausea/Vomiting

 Oral: 10 to 25 mg every 4 to 6 hours as needed.
 IM: 25 mg one time.

 Nausea/Vomiting During Surgery:

 IM: 12.5 mg one time. May repeat in 30 minutes if necessary and if no
hypotension occurs.
 IV: 2 mg at 2-minute intervals. Do not exceed 25 mg. Dilute to 1 mg/ml.

 Usual Adult Dose for Light Sedation prior to a medical or surgical

procedure:
 Oral: 25 to 50 mg, 2 to 3 hours before the operation.
 IM: 12.5 to 25 mg, 1 to 2 hours before operation.

 Usual Adult Dose for Hiccups

 Oral: 25 to 50 mg 3 to 4 times a day.
 IM: If symptoms persist for 2 to 3 days, give 25 to 50 mg IM.
 IV infusion: use slow IV infusion: 25 to 50 mg in 500 to 1000 mL of saline.

41
  Usual Adult Dose for Porphyria
 Oral: 25 to 50 mg 3 to 4 times a day.
 IM: 25 mg injection 3 to 4 times a day until patient can take oral therapy.

 Usual Adult Dose for Tetanus

 IM: 25 to 50 mg given 3 to 4 times daily,
 IV: 25 to 50 mg diluted to at least 1 mg/mL and administered at a rate of 1
mg/min.

 Usual Pediatric Dose for Schizophrenia

 6 months and older:
 Oral: 0.5 to 1 mg/kg/dose orally every 4 to 6 hours; older children may
require 200 mg/day or higher
 intramuscular or intravenous: 0.5 to 1 mg/kg/dose every 6 to 8 hours
Maximum recommended doses
 less than 5 years (less than 22.7 kg): 40 mg/day
 5 years and older: (22.7 to 45.5 kg): 75 mg/day

 Action:
Chlorpromazine acts as an antagonist (blocking agent) on different
postsynaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and
D4 - different antipsychotic properties on productive and unproductive
symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, anti-
depressive and anti-aggressive properties as well as an attenuation of extra
pyramidal side-effects, but also leading to weight gain, fall in blood pressure,

42
 sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors,
sedation, antiemesis, vertigo, fall in blood pressure and weight gain),
alpha1/alpha2-receptors (ant sympathomimetic properties, lowering of blood
pressure, reflex tachycardia, vertigo, sedation, hypersalivation and
incontinence as well as sexual dysfunction, but may also attenuate pseudo
parkinsonism - controversial)

 Side effects:

 Nervous system
 sedation,
 drowsiness and
 rarely seizures.
 Tardive dyskinesia,
 dystonia,
 pseudoparkinsonism
 Fever,
 Seizures

 Psychiatric
 excitability, and
 reversible catatonic states

 Hematologic
 agranulocytosis (which occurs in about one out of 10,000 patients).
 Hemolytic anemia

43
  thrombocytopenia, and
 eosinophilia

 Cardiovascular
 Hypotension
 ECG changes include prolongation of the PR interval, prolongation of QTc
segments, diffuse T-wave flattening, and ST segment depression

 Hypersensitivity

 Cautions:
 This medicine may cause drowsiness, dizziness, or fainting. Stand up slowly.
 Do not drive, operate machinery, or do anything else that could be
dangerous until you know how you react to this medicine.
 Do not become overheated in hot weather or during exercise or other
activities since heat stroke may occur while you are using this medicine.
 This medicine may cause increased sensitivity to the sun. Avoid exposure to
the sun or sunlamps until you know how you react to this medicine
 Do not drink alcohol while you are taking this medicine.
 Do not breast-feed while taking this medicine.

 Pharmacokinetics:
 Readily absorbed from the GI tract.
 Bioavailability varies due to first-pass metabolism by the liver.

44
  Elimination through kidney
 Half-life 30 hours.

 Side effects:
 CNS: Agitation, coma, convulsions, extreme sleepiness, fever, restlessness
 CVS: difficulty breathing, irregular heart rate, low blood pressure,
 GI: -difficulty swallowing, dry mouth, intestinal blockage
 Skin: -rashes; sensitivity to light

 Drug Interaction:
 Benzothiazine: Antipsychotics may diminish the stimulatory effect of
Amphetamines. Monitor effectiveness of amphetamine therapy when altering
concurrent antipsychotic therapy as antipsychotic agents may impair the
stimulatory effect of amphetamines.
 Amitriptyline: Increased risk of cardiotoxicity and arrythmias.
 Amphetamine: Decreased anorexic effect, may increase psychotic symptoms.

 Nurses responsibility
 Check: blood-pressure, pulse rate,
 laboratory-tests (liver function tests, kidney-values, blood cell counts,
 ECG changes
 Maintain input& output chart

45
5. TRIFLUOPERAZINE HYDROCHLORIDE
 Name of the drug
 Trade Name :- Tab. Unicalm
 Pharmacological Name :- Trifluperazine

 Drug classes
 Antipsychotic
 Phenothiazine

 Available forms
 Tablets And
 Intra muscular

 Dosage
 Orally: 15 to 20 mg per day
 IM: 1 to 2 mg

 Indication:
 Schizophrenia,
 Emotional withdrawal,
 Anxiety,
 Tension,
 Hallucinations and suspiciousness.

46
 Contra-indication
 Coma
 Blood discases
 Liver damage

 Therapeutic Action:
Trifluoperazine blocks postsynaptic mesolimbic dopaminergic D1 and D2
receptors in the brain; depresses the release of hypothalamic and hypophyseal
hormones and is believed to depress the reticular activating system thus
affecting basal metabolism, body temperature, wakefulness, vasomotor tone,
and emesis

 Pharmacokinetics:
 Metabolism :- Hepatic
 Half life :- 10-20 hours

 Side effects:
 CNS:- drowsiness; dizziness; blank facial expression ;agitation; unusual,
slowed, or uncontrollable movements of any part of the body; difficulty
falling asleep or staying asleep; headache; difficulty urinating.
 CVS:- tachycardia; slight ECG change
 GI:- constipation; nausea; changes in appetite; weight gain:- dry mouth;
weakness
 RS:- breast milk production; missed menstrual periods; decreased sexual
ability in men difficulty urinating; breast enlargement

47
 Drug Interactions:
This drug may reduce the effectiveness of oral anticoagulant (blood thinning)
drugs.

 Cautions:
 Trifluoperazine increases the level of prolactin, a hormone that stimulates
the mammary glands in the breast, in the blood.
 Propranolol increases the concentration of trifluoperazine. The blood
pressure-lowering effects of guanethidine may be diminished by
trifluoperazine.

 Nurses responsibility:
 Instruct the patient to take sips of water frequently to relieve dryness of
mouth
 Advise him to get up from bed/ chair very slowly
 Differentiate between akathisia & agitation and inform physician
 Take all seizure precaution
 Advise the patient not to drive car or operate any machinery

48
 ANTI-DEPRESSANTS

 Introduction:

Antidepressants are those drugs, which are used for the treatment of depressive
illness. These are also called as mood elevators or thymoleptics. Antidepressants
are a class of drugs that reduce symptoms of depressive disorders by correcting
chemical imbalances of neurotransmitters in the brain. Chemical imbalances may
be responsible for changes in mood and behavior. Neurotransmitters are vital, as
they are the communication link between nerve cells in the brain.
Neurotransmitters reside within vesicles found in nerve cells, which are released
by one nerve and taken up by other nerves. Neurotransmitters not taken up by
other nerves are taken up by the same nerves that released them. This process is
called "reuptake." The prevalent neurotransmitters in the brain specific
to depression are serotonin, dopamine and norepinephrine (also called
noradrenaline). In general, antidepressants work by inhibiting the reuptake of
specific neurotransmitters, hence increasing their levels around the nerves within
the brain, such as selective serotonin reuptake inhibitors (SSRIs), antidepressants
that will affect serotonin levels in the brain.

 Indication:
 Dysthymic disorder
 Major depression with melancholia or psychotic symptoms
 Depression associated with organic disease
 Alcoholism

49
  Schizophrenia
 Mental retardation
 Depressive phase of bipolar disorder
 Depression accompanied by anxiety
 Anxiety disorders
 Bulimia nervosa
 Peptic ulcer
 Migraine

 Classification:

1. Selective Serotonin Reuptake Inhibitors (SSRIs)

2. Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)
3. Tricyclic Antidepressants (TCAs)
4. Monoamine Oxidase Inhibitors (MAOIs)
5. Atypical Antidepressants

 Mechanism of Actions:
There are three basic molecules, known chemically as monoamines, that are
believed to be involved in mood regulation. These primarily work as
neurotransmitters, which literally transmit nerve signals to their corresponding
receptors in the brain. Antidepressants work by influencing these
neurotransmitters, which include:

 Dopamine, which plays a central role in decision-making, motivation,

arousal, and the signalling of pleasure and reward

50
  Norepinephrine, which influences alertness and motor function and helps
regulate blood pressure and heart rate in response to stress
 Serotonin, the neurotransmitter whose role it is to regulate mood, appetite,
sleep, memory, social behaviour, and sexual desire.

 Actions:

1. Selective Serotonin Reuptake Inhibitors (SSRIs):

 There are a number of antidepressants that work by preventing the
reabsorption (reuptake) of neurotransmitters into the body. Collectively
known as reuptake inhibitors, they prevent the reuptake of one or more
neurotransmitters so that more are available and active in the brain.
 Selective serotonin reuptake inhibitors (SSRIs) work by specifically
inhibiting the reuptake of serotonin. SSRIs are a newer class of
antidepressants first developed during the 1970s.
 SSRIs tend to have fewer side effects than older antidepressants but are still
known to nausea, insomnia, nervousness, tremors, and sexual dysfunction.4
 In addition to treating depressions, SSRIs are also sometimes used to treat
obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD),
eating disorders, and premature ejaculations. They have also proved helpful
during stroke recovery.

 Examples include:
 Celexa (citalopram)
 Lexapro (escitalopram)
 Luvox (fluvoxamine)
 Paxil (paroxetine)

51
  Prozac (fluoxetine)
 Vibryd (vilazodone)
 Zoloft (sertraline)

2. Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs):

 Serotonin and norepinephrine reuptake inhibitors (SNRIs) work in a similar
way to SSRIs except that they inhibit the reuptake of both norepinephrine
and serotonin. The first SNRI was FDA-approved in December 1993.
Increasing norepinephrine levels in tandem to serotonin levels can be
particularly useful or people with psychomotor retardation (the slowing of
physical movement and thought).
 Common side effects of SNRIs include nausea, drowsiness,
fatigue, constipation, and dry mouth.5
 Some SNRIs, like Cymbalta, can also be used to treat chronic pain, a
condition closely linked to the development of depression. They have also
proven useful in treating generalized anxiety, post-traumatic stress disorder
(PTSD), social anxiety disorder (SAD), panic disorder, and nerve pain
associated with fibromyalgia.

 Examples of SNRIs include:

 Cymbalta (duloxetine)
 Effexor (venlafaxine)
 Fetzima (levomilnacipran)3
 Pristiq (desvenlafaxine)
 Savella (milnacipran)

52
3. Tricyclic Antidepressants (TCAs):

 Tricyclic antidepressants (TCAs) are an older class of drug first discovered

in the 1950s. They were named after their chemical structure, which is
composed of three interconnected rings of atoms.
 TCAs work similarly to reuptake inhibitors in that they block the absorption
of serotonin and norepinephrine into nerve cells, as well as another
neurotransmitter known as acetylcholine (which helps regulate the
movement of skeletal muscles).
 Ludiomil (maprotiline) belongs to the same class of the drug but is more
appropriately described as a tetracyclic antidepressant (TeCA) due to its
fourth atomic ring. Common symptoms include constipation, dry mouth,
blurry vision, drowsiness, dizziness, and weight gain. In some cases,
irregular heartbeats, low blood pressure, and seizures can also occur.
 In addition to their use in depression, tricyclic antidepressants can help treat
chronic pain.
 They were also once commonly used in children with attention deficit
hyperactivity (ADHD) but have since been replaced with more effective
drug agents with fewer side effects.
 Examples of TCAs include:

 Anafranil (clomipramine)
 Asendin (amoxapine)
 Elavil (amitriptyline)
 Norpramin (desipramine)
 Pamelor (nortriptyline)
 Sinequan (doxepin)

53
  Surmontil (trimipramine)
 Tofranil (imipramine)
 Vivactil (protriptyline)

4. Monoamine Oxidase Inhibitors (MAOIs):

 One of the first classes of antidepressants developed were monoamine
oxidase inhibitors (MAOIs). This antidepressant class, first discovered in the
1950s, inhibits the action of an enzyme called monoamine oxidase, whose
role it is to break down monoamines. By blocking this effect, more
neurotransmitters are available for use in mood regulation.
 MAOIs are less commonly used due to potentially severe reactions
with foods high in tyramine.7 If taken inappropriately, MAOIs can cause
tyramine levels to rise, triggering critical increases in blood pressure.
 To avoid this, MAOI treatment usually involves dietary restrictions. Other
side effects include nausea, dizziness, drowsiness, restlessness, and
insomnia.
 Despite the risks, MAOIs have proven useful in treating agoraphobia, social
phobia, bulimia, PTSD, borderline personality disorder, and bipolar
depression. Even so, its use is usually reserved for when other
antidepressant options have failed.

 Examples of MAOIs include:

 Emsam (selegiline)
 Marplan (isocarboxazid)
 Nardil (phenelzine)
 Parnate (tranylcypromine)

54
5. Atypical Antidepressants:
 There are also other fairly new antidepressants that do not fit into any If the
above-listed categories. Broadly described as atypical antidepressants, they
affect serotonin, norepinephrine, and dopamine levels in unique ways.
 Side effects can vary by drug type but may include dizziness, dry mouth,
insomnia, nausea, vomiting, constipation, blurry vision, weight gain, and
sexual dysfunction.

 Examples include:

 Oleptro (trazodone) and Brintellix (vortioxetine): Serotonin antagonist

and reuptake inhibitors (SARIs) used for major depression that both
inhibits serotonin reuptake and block adrenergic receptors
 Remeron (mirtazapine): A noradrenergic antagonist used for major
depression, that blocks receptors of the stress hormone epinephrine
(adrenaline) on the brain
 Symbax: Combines the SSRI fluoxetine with the antipsychotic drug
fluoxetine to treat bipolar depression or treatment-resistant depression
 Wellbutrin (bupropion): Classified as a dopamine reuptake inhibitor,
used to treat depression and seasonal affective disorder as well as a
smoking cessation aid.

55
 Antidepressants and risk of suicide:
 Most antidepressants are generally safe, but the Food and Drug Admnistration
(FDA) requires that all antidepressants carry black box warnings, the strictest
warnings for prescriptions. In some cases, children, teenagers and young adults
under 25 may have an increase in suicidal thoughts or behavior when taking
antidepressants, especially in the first few weeks after starting or when the dose
is changed.

 Anyone taking an antidepressant should be watched closely for worsening

depression or unusual behavior. If you or someone you know has suicidal
thoughts when taking an antidepressant, immediately contact your doctor or
get emergency help.

 Keep in mind that antidepressants are more likely to reduce suicide risk in the
long run by improving mood.

 Mechanism of action:
The exact mechanism is unknown. It increases the catecholamine level in brain.
The tricyclic antidepressants are also called as Mono Amine Reuptake
Inhibitors (MARI). TCAs and MAIOs have the same effect. The main mode of
action is by blocking the reuptake of nor-epinephrine and /or serotonin and/or
dopamine it will increase functional level of nor-epinephrine and serotonin and
dopamine. It takes about 5 to 10 days for MAIOs and 2 to3 weeks for TCAs to
bring down depressive symptoms. SSRIs act by inhibiting the re-uptake of
serotonin and increasing its levels at the receptor site.

56
 Neurotransmitters and the catecholamine hypothesis:
 Neurotransmitters pass along signal
 Smaller number of neurotransmitters causes depression

 Some foods high in tyramine include:

 Aged cheeses, such as aged cheddar and Swiss; blue cheeses such as Stilton
and Gorgonzola; and Camembert. Cheeses made from pasteurized milk are
less likely to contain high levels of tyramine, including American cheese,
cottage cheese, ricotta, farm cheese and cream cheese.
 Cured meats, which are meats treated with salt and nitrate or nitrite, such as
dry-type summer sausages, pepperoni and salami.
 Fermented cabbage, such as sauerkraut and kimchee.
 Soy sauce, fish sauce and shrimp sauce.
 Yeast-extract spreads, such as Marmite.
 Improperly stored foods or spoiled foods.
 Broad bean pods, such as fava beans.

1. AMITRIPTYLINE HYDROCHLORIDE
 Name of the drug:
 Trade Name :- Tab. Tryptanol
 Pharmacological Name:- Amitriptyline hydrochloride

 Drug class:
 Anti-depressant
 TCA; tertiary amine

57
 Available forms:
 Injection: 10 mg/mL;
 Tablets: 10, 25, 50, 75, 100, 150 mg

 Dosages:
 ADULTS
 Depression, hospitalized patients: Initially, 100 mg/day PO in divided
doses: gradually increase to 200–300 mg/day as required. May be given IM
20–30 mg qid, initially only in patients unable or unwilling to take drug PO.
Replace with oral medication as soon as possible.
 Depression, outpatients: Initially, 75 mg/day PO, in divided doses; may
increase to 150 mg/day. Increases should be made in late afternoon or hs.
Total daily dosage may be administered HS. Initiate single daily dose
therapy with 50–100 mg HS; increase by 25–50 mg as necessary to a total of
150 mg/day. Maintenance dose is 40–100 mg/day, which may be given as a
single bedtime dose.
 Chronic pain: 75–150 mg/day PO.
 Prevention of cluster or migraine headaches: 50–150 mg/day PO.
 Prevention of weeping in MS patients with forebrain disease: 25–75 mg
PO.

 PEDIATRIC PATIENTS > 12 YR

 10 mg TID- PO and then 20 mg HS.

58
  GERIATRIC PATIENTS
 10 mg TID- PO with 20 mg HS.

 Indications:
 Relief of symptoms of depression (endogenous most responsive); sedative
effects may help when depression is associated with anxiety and sleep
disturbance.
 Control of chronic pain (e.g., intractable pain of cancer, central pain
syndromes, peripheral neuropathies, postherpetic neuralgia,
tic douloureux);
 Prevention of onset of cluster and migraine headaches;
 Treatment of pathologic weeping and laughing secondary to forebrain
disease (due to MS), insomnia.

 Contraindications:
 Hypersensitivity to any tricyclic drug; concomitant therapy with an MAOI;
recent MI; myelography within previous 24 hr or scheduled within 48 hr;
lactation.
 Electroshock therapy;
 Preexisting CV disorders (severe coronary heart disease, progressive heart
failure, angina pectoris, paroxysmal tachycardia);
 Angle-closure glaucoma,
 Increased IOP,
 Urinary retention, ureteral or urethral spasm;
 Seizure disorders;

59
  Hyperthyroidism;
 Impaired hepatic, renal function;

 Therapeutic actions:
Mechanism of action unknown; TCAs inhibit the reuptake of the
neurotransmitters nor-epinephrine and serotonin, leading to an increase in
their effects; anti-cholinergic at CNS and peripheral receptors; sedative.

 Pharmacokinetics:
Route Onset Peak Duration

Oral Varies 2–4 hr 2–4 wk

 Metabolism: Hepatic; T1/2: 10–50 hr

 Distribution: Crosses placenta; enters breast milk
 Excretion: Urine

 Side effects
 CNS: Disturbed concentration, sedation and anticholinergic (atropine-like)
effects, confusion (especially in elderly), hallucinations, disorientation,
decreased memory, feelings of unreality, delusions, anxiety, nervousness,
restlessness, agitation, panic, insomnia, nightmares, hypomania, mania,
exacerbation of psychosis, drowsiness, weakness, fatigue, headache,
numbness, tingling, paresthesia’s of extremities, incoordination, motor
hyperactivity, akathisia, ataxia, tremors, peripheral

60
 neuropathy, extrapyramidal symptoms, seizures, speech
blockage, dysarthria, tinnitus, altered EEG.
 CV: Orthostatic hypotension, hypertension, syncope, tachycardia,
palpitations, MI, arrhythmias, heart block, precipitation of CHF, CVA
 Endocrine: Elevated or depressed blood sugar, elevated prolactin levels,
inappropriate ADH secretion
 GI: Dry mouth, constipation, paralytic ileus, nausea, vomiting,
anorexia, epigastric distress, diarrhea, flatulence, dysphagia, peculiar taste,
increased salivation, stomatitis, glossitis, parotid swelling, abdominal
cramps, black tongue, hepatitis, jaundice (rare), elevated transaminase,
altered alkaline phosphatase
 GU: Urinary retention, delayed micturition, dilation of the urinary
tract, gynecomastia, testicular swelling; breast enlargement, menstrual
irregularity and galactorrhea; increased or decreased libido; impotence
 Hematologic: Bone marrow depression, including agranulocytosis,
eosinophilia, purpura, thrombocytopenia, leukopenia.
 Hypersensitivity: Rash, pruritus, vasculitis, petechiae, photosensitization,
edema (generalized, face, tongue), drug fever
 Withdrawal: Symptoms on abrupt discontinuation of prolonged therapy:
nausea, headache, vertigo, nightmares, malaise
 Other: Nasal congestion, excessive appetite, weight change; sweating,
alopecia, lacrimation, hyperthermia, flushing, chills

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 Drug-interaction:
 Increased TCA levels and pharmacologic (especially anticholinergic) effects
with cimetidine, fluoxetine.
 Increased TCA levels with methylphenidate, phenothiazines, hormonal
contraceptives, disulfiram.
 Hyper pyretic crises, severe seizures, hypertensive episodes and deaths with
MAOIs, furazolidone
 Increased antidepressant response and cardiac arrhythmias with thyroid
medication
 Increased or decreased effects with estrogens
 Delirium with disulfiram
 Sympathetic hyperactivity, sinus tachycardia, hypertension, agitation
with levodopa

 Nursing Responsibility

 Assessment
 History: Hypersensitivity to any tricyclic drug; concomitant therapy with an
MAOI; recent MI; myelography within previous 24 hr or scheduled within
48 hr; lactation; EST; preexisting CV disorders; angle-closure glaucoma,
increased IOP, urinary retention, ureteral or urethral spasm; seizure
disorders; hyperthyroidism; impaired hepatic, renal function; psychiatric
patients; manic-depressive patients; elective surgery
 Physical Examination: Weight; T; skin color, lesions; orientation, affect,
reflexes, vision and hearing; P, BP, orthostatic BP, perfusion; bowel sounds,

62
 normal output, liver evaluation; urine flow, normal output; usual sexual
function, frequency of menses, breast and scrotal examination; LFTs,
urinalysis, CBC, ECG
 Restrict drug access for depressed and potentially suicidal patients
 Give IM only when oral therapy is impossible.
 Do not administer IV.
 Administer major portion of dose at bedtime if drowsiness,
severe anticholinergic effects occur
 Reduce dosage if minor side effects develop; discontinue if serious side
effects occur.
 Arrange for CBC if patient develops fever, sore throat, or other sign of
infection.

 Teaching points:
 Take drug exactly as prescribed; do not stop abruptly or without consulting
health care provider.
 Avoid using alcohol, other sleep-inducing drugs, over-the-counter drugs.
 Avoid prolonged exposure to sunlight or sunlamps; use a sunscreen or
protective garments.
 You may experience these side effects: Headache, dizziness, drowsiness,
weakness, blurred vision (reversible; if severe, avoid driving and tasks
requiring alertness while these persist); nausea, vomiting, loss of appetite,
dry mouth (eat frequent small meals; use frequent mouth care and suck on
garless candies); nightmares, inability to concentrate, confusion; changes in
sexual function.

63
  Report dry mouth, difficulty in urination, excessive sedation.

2. IMIPRAMINE
 Name of the drug:
 Trade Name :- Tofranil
 Pharmacological Name :- Tablet. imipramine hydrochloride

 Drug classes:
 Anti-depressant
 TCA

 Available forms:
 Tablets (imipramine hydrochloride)—10, 25, 50 mg;
 capsules (imipramine pamoate) —75, 100, 125, 150 mg

 Doses:
 Depression:
Adults – 25mg three times a day increasing to 150mg-200mg a day in divided
doses. In severe cases (treated in hospital) the dose may be increased up to a
maximum of 100mg three times a day. The usual maintenance dose is between
50mg and 100mg a day in divided doses.
Elderly (over 60 years) - Initially 10mg a day increasing to 30-50mg a day.

 Nightly bedwetting: Children only, to be taken at bedtime (for no longer than

3 months and up to a maximum of 75mg a day.
64
 Indications:
 Depression
 Bedwetting in children.
 It increases the amount of certain natural substances in the brain.

 Contraindications:
 Recovery period after a heart attack
 Who are taking MAOIs,
 Hypersensitivity.

 Therapeutic Action:
Imipramine hydrochloride was the first tricyclic anti-depressant to be
discovered. Tricyclic antidepressants act to change the balance of naturally
occurring chemicals in the brain called neurotransmitters that regulate the
transmission of nerve impulses between cells. Mental well-being is partially
dependent on maintaining the correct balance between these brain chemicals.
Imipramine is thought to act primarily by increasing the concentration of
norepinephrine and serotonin (both chemicals that stimulate nerve cells) and,
to a lesser extent, by blocking the action of another brain chemical, acetylcholine

 Pharmacokinetics:
Route Onset Peak

Oral Varies 2–4 hours

65
  Metabolism: Hepatic; T ½: 8–16 hr
 Distribution: Crosses placenta; enters breast milk
 Excretion: Urine

 Side effects:
 Heart - Low/high blood pressure, fast heart rate, palpitations, heart attack,
abnormal heart rhythm, heart block, ECG changes, heart failure and stroke.
 Psychiatric - Confusion, hallucinations, disorientation, anxiety, restlessness,
agitation, sleeplessness, abnormal dreams and irritable mood.
 Central Nervous System - Numbness, tingling, incoordination, tremors,
seizures, alterations in EEG patterns and ringing in the ear.
 Eye - Blurred vision, visual disturbances and dilatation of pupil.
 Allergic Reactions - Skin rash, hives, itching, photosensitization, swelling in
the face and tongue and fever.
 Blood - Bone marrow depression.
 Gastrointestinal - Nausea, vomiting, dry mouth, loss of appetite,
constipation, stomach upset, diarrhea, intestinal obstruction, mouth ulcer,
abdominal cramps and black tongue.
 Genitourinary - Breast enlargement in the male, spontaneous milk secretion
in the female, increased or decreased sexual drive, impotence, testicular
swelling, elevation or depression of blood sugar levels, urinary retention and
dilation of the urinary tract.
 Other – Jaundice and hair loss.

66
 Warnings and Precautions:
 Caution should be exercised in patients with history of increased eye
pressure, prostate enlargement, difficulty in urinating, seizures, overactive
thyroid, liver, kidney or heart disease, any allergy, who are taking other
medications, during pregnancy and breast feeding.
 It may cause drowsiness or dizziness, do not drive a car or operate
machinery while taking this medication.
 Avoid alcohol consumption and smoking while taking this medication.
 Avoid exposure to sunlight; otherwise, it may cause skin sensitivity.

 Drug- interaction:
 Increased TCA levels and pharmacologic (especially anticholinergic) effects
with cimetidine, fluoxetine, ranitidine.
 Increased serum levels and risk of bleeding with oral anticoagulants
 Altered response, including arrhythmias and hypertension, with
sympathomimetics.
 Risk of severe hypertension with clonidine
 Hyper pyretic crises, severe convulsions, hypertensive episodes, and deaths
when MAO inhibitors are given with TCAs.
 Decreased hypotensive activity of guanethidine with imipramine

 Nursing responsibility
 Assessment
 History: Hypersensitivity to any tricyclic drug or to tartrazine; concomitant
therapy with an MAO inhibitor; EST with coadministration of TCAs; recent

67
 MI; myelography within previous 24 hr or scheduled within 48 hr;
preexisting CV disorders; seizure disorders; hyperthyroidism; angle-closure
glaucoma, increased intraocular pressure, urinary retention, ureteral or
urethral spasm; impaired hepatic, renal function; psychiatric patients;
elective surgery; pregnancy; lactation
 Physical Examination: Weight; T; skin color, lesions; orientation, affect,
reflexes, vision and hearing; P, BP, auscultation, orthostatic BP, perfusion;
bowel sounds, normal output, liver evaluation; urine flow, normal output;
usual sexual function, frequency of menses, breast and scrotal examination;
liver function tests, urinalysis, CBC, ECG .
 Limit drug access for depressed and potentially suicidal patients.
 Give IM only when oral therapy is impossible. Do not give IV.
 Give major portion of dose hs if drowsiness, severe anticholinergic effects
occur (note that elderly may not tolerate single daily dose therapy).
 Reduce dosage if minor side effects develop; discontinue if serious side
effects occur.
 Arrange for CBC if patient develops fever, sore throat, or other sign of
infection during therapy.

 Teaching points:
 Take drug exactly as prescribed. Do not stop taking drug abruptly or without
consulting your health care provider.
 Avoid prolonged exposure to sunlight or sunlamps; use a sunscreen or
protective garments.

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  These side effects may occur: headache, dizziness, drowsiness, weakness,
blurred vision (reversible; safety measures may need to be taken if severe;
avoid driving or performing tasks that require alertness); nausea, vomiting,
loss of appetite (small frequent meals, frequent mouth care may help); dry
mouth (sucking sugarless candies may help); disorientation, difficulty
concentrating, emotional changes; changes in sexual function, impotence,
changes in libido.
 Report dry mouth, difficulty in urination, excessive sedation, fever, chills,
sore throat, palpitations.

3. FLUOXETINE
 Name of the drug:
 Trade Name :- Tab. Fludac
 Pharmacological Name :- Fluoxetine

 Drug classes:
 Anti-depressant
 SSRIs

 Available forms:
 Capsule- 10mg; 20mg; 40mg; 90mg
 Tablets- 10, 20 mg;
 Liquid- 20 mg/5 mL;
 DR capsules- 90 mg

69
 Dosage:

 Usual Adult Dose for Premenstrual Dysphoric Disorder

 Initial dose: 20 mg orally once daily.

 Maintenance dose: 20 mg/day

 Usual Adult Dose for Depression

 Initial dose: 20 mg orally once a day in the morning.
 Maintenance dose: 20 to 80 mg/day in 1 to 2 divided doses.

 Usual Adult Dose for Obsessive Compulsive Disorder

 Initial dose: 20 mg orally once a day in the morning.
 Maintenance dose: 20 to 60 mg/day in 1 to 2 divided doses.
 Maximum dose: 80 mg/day.

 Usual Adult Dose for Panic Disorder

 Initial dose: 20 mg orally once a day in the morning.
Maintenance dose: 20 to 60 mg/day in 1 to 2 divided doses.
Maximum dose: 80 mg/day.

 Usual Adult Dose for Bulimia

 Initial dose: 60 mg orally once a day in the morning.

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 Indications:
 Depression,
 Obsessive compulsive disorder, and
 Bulimia nervosa.
 Eating disorders, and
 Panic attacks

 Contraindications:
 Hypersensitive to Monoamine oxidase inhibitors
 Severe renal failure
 Breast feeding
 Neuroleptic malignant syndrome

 Therapeutic Action:
Fluoxetine inhibits serotonin reuptake pumps in certain neuronal connections.
This action increases the naturally occurring serotonin neurotransmitter levels.
Increased serotonin levels cause changes in gene expression, which ultimately
do its intended therapeutic actions. However, increased serotonin in unwanted
areas of the brain causes side effects.

 Side effects:
 Serious side effect such as:
 Very stiff (rigid) muscles, high fever, sweating, fast or uneven heartbeats,
tremors, overactive reflexes;

71
  nausea, vomiting, diarrhea, loss of appetite, feeling unsteady, loss of
coordination;
 headache, trouble concentrating, memory problems, weakness, confusion,
hallucinations, fainting, seizure, shallow breathing or breathing that stops;
or
 severe skin reaction -- fever, sore throat, swelling in your face or tongue,
burning in your eyes, skin pain, followed by a red or purple skin rash that
spreads (especially in the face or upper body) and causes blistering and
peeling.
 Less serious side effects of fluoxetine may include:
 cold symptoms such as stuffy nose, sneezing, sore throat;
 drowsiness, dizziness, feeling nervous;
 mild nausea, upset stomach, constipation;
 increased appetite, weight changes;
 sleep problems (insomnia);
 decreased sex drive, impotence, or difficulty having an orgasm; or dry
mouth.

 Warning and Precautions:

Children, adolescents, and young adults (18 to 24 years of age) with major
depressive disorder and other psychiatric disorders may be at an increased risk
of suicidal thinking and suicidality with antidepressant use, particularly during
the first few months of treatment. Medical evidence has not shown this
increased risk to exist in adults older than 24 years of age, but adults 65 years

72
 of age and older taking antidepressants appear to have a decreased risk of

suicidality.

 Nurses Responsibility:
 Assessment
 History: Hypersensitivity to fluoxetine, impaired hepatic or renal function,
diabetes mellitus, lactation, pregnancy, seizures
 Physical examination: Weight, T; skin rash, lesions; reflexes, affect; bowel
sounds, liver evaluation; P, peripheral perfusion; urinary output, LFTs, renal
function tests
 Interventions Arrange for lower or less frequent doses in elderly patients
and patients with hepatic or renal impairment.
 BLACK BOX WARNING: Establish suicide precautions for severely
depressed patients. Limit quantity of capsules dispensed; high risk in
children and adolescents.
 Administer drug in the morning.
 Monitor patient for response to therapy for up to 4 wk before increasing
dose.
 Switch to once-a-week therapy by starting weekly dose 7 days after last 20
mg/day dose. If response is not satisfactory, reconsider daily dosing.

73
 Teaching points:
 It may take up to 4 weeks before the full effect occurs. Take in the morning.
If you feel sleepy or tired, you may take it at night. If you are taking the once-
weekly capsule, mark calendar with reminders of drug day.
 Do not take this drug during pregnancy. If you think that you are pregnant
or wish to become pregnant, consult your health care provider.
 Keep this drug, and all medications, out of the reach of children.
 You may experience these side effects: Dizziness, drowsiness, nervousness,
insomnia (avoid driving or performing hazardous tasks); nausea, vomiting,
weight loss (eat small frequent meals; monitor your weight loss); sexual
dysfunction; flulike symptoms.
 Report rash, mania, seizures, severe weight loss.

4. ISOCARBOXAZID
 Name of the drug:
 Trade Name :- Tab. Marplan
 Pharmacological Name :- Isocarboxazid

 Drug classes:
 Anti-depressant
 Monoamine Oxidase Inhibitor, Nonselective

 Available forms:
 Tablets :- 10mg

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 Dosage:
Depression
10 mg PO q6-12hr, increase by 10 mg/day q2-4d to 40 mg/day PO divided q6-
12hr by end of first week. After first week, may increase by up to 20 mg/week
to maximum 60 mg/day; decrease dose to maintenance dose once maximum
effect achieved.

 Indication:
 Depression

 Contraindication:
 Hypersensitivity
 Cerebrovascular Disorder
 Pheochromocytoma
 Liver Disease
 Renal Impairment
 Contraindicated MAOI-Other Drug Combinations

 Therapeutic Action:
Isocarboxazid works by irreversibly blocking the action of a chemical substance
known as monoamine oxidase (MAO) in the nervous system. MAO subtypes A
and B are involved in the metabolism of serotonin and catecholamine
neurotransmitters such as epinephrine, norepinephrine, and dopamine.
Isocarboxazid, as a nonselective MAO inhibitor, binds irreversibly to

75
 monoamine oxidase–A (MAO-A) and monoamine oxidase–B (MAO-B). The
reduced MAO activity results in an increased concentration of these
neurotransmitters in storage sites throughout the central nervous system (CNS)
and sympathetic nervous system. This increased availability of one or more
monoamines is the basis for the antidepressant activity of MAO inhibitors

 Pharmacokinetics: -
 Administration
 If hypertensive crisis occurs, withdraw drug immediately and give
phentolamine 5 mg I.V. slowly, as ordered.
 Ask patient about other drugs he's using. MAO inhibitors can cause
dangerous interactions with many drugs.
 Know that psychotropics should be withheld for 14 days after
isocarboxazid withdrawal
 Absorption: - Well absorbed from the gastrointestinal tract
 Metabolism: - Hepatic and rapid (by oxidation)

 Side effect:
 CNS: drowsiness, anxiety, forgetfulness, hyperactivity, lethargy, sedation,
syncope, headache, insomnia, sleep disturbance, tremor, myoclonic jerks,
paresthesia, dizziness, suicidal behavior or ideation (especially in child or
adolescent)
 CV: orthostatic hypotension, palpitations, hypertensive crisis
 GI: nausea, diarrhea, constipation, dry mouth

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  GU: urinary frequency, urinary hesitancy, erectile
dysfunction Hepatic: jaundice, hepatotoxicity
 Musculoskeletal: heavy feeling
 Skin: sweating
 Other: chills

 Drug interactions:
 Amphetamines, CNS depressants, dextromethorphan, dibenzoazepine
derivatives and other TCAs, other MAO inhibitors, SSRIs (such as fluoxetine,
paroxetine), sympathomimetics: hypertensive crisis, seizures, fever,
diaphoresis, excitation, delirium, tremor, coma, circulatory collapse
 Anesthetics: severe hypotension
 Antidepressants, bupropion, buspirone: hypertension
 Antihypertensives, beta-adrenergic blockers, thiazide diuretics: increased
hypotensive effect
 Dextromethorphan, tryptophan: hypertension, excitation, hyperpyrexia

 Cautions:
 Hyperthyroidism, seizure disorders, hypotension, diabetes mellitus,
myocardial ischemia, hypomania
 patients switching MAO inhibitors
 suicidal or drug-dependent patients
 elderly patients
 pregnant or breastfeeding patients
 children younger than age 16 (safety and efficacy not established).

77
 Nurse responsibility:
 Patient monitoring
 Monitor blood pressure frequently. Drug may cause hypertensive crisis.
 Watch for increased depression and suicidal ideation, especially in child or
adolescent.
 Monitor liver function tests. Assess for jaundice and signs and symptoms of
hepatic dysfunction; discontinue drug and notify prescriber if these occur.
 Patient teaching
 Explain importance of taking drug exactly as prescribed.
 Caution patient not to stop therapy suddenly. Dosage must be tapered.
 Instruct patient to immediately report occipital headache, palpitations, stiff
neck, nausea, sweating, dilated pupils, and photophobia (indications of
hypertensive crisis).
 Tell patient to immediately report rash, hives, itching, shortness of breath,
wheezing, cough, or swelling of face, lips, tongue, or throat.
 Advise patient (or caregiver, as appropriate) to monitor his mental status
carefully and immediately report increased depression or suicidal thoughts
or behavior (especially in child or adolescent).
 Stress importance of avoiding certain foods and beverages (especially those
containing tyramine) and over-the-counter preparations during and for 14
days after therapy. Inform patient that pharmacist can provide complete list
of foods to avoid.
 Instruct patient to tell all prescribers he's taking drug.
 Caution patient not drink alcohol or consume excessive amounts of caffeine.

78
  Advise patient to rise slowly from a lying or sitting position, to avoid
dizziness
 Caution patient to avoid driving and other hazardous activities until he
knows how drug affects concentration, vision, and alertness.
 Tell patient to discontinue drug at least 10 days before elective surgery.
 As appropriate, review all other significant and life-threatening adverse
reactions and interactions, especially those related to the drugs, tests, foods,
and behaviors mentioned above.

5. AMOXAPINE
 Name of the drug:
 Trade Name :- Tab. Demolox
 Pharmacological Name :- Amoxapine

 Drug classes:
 Anti-depressant agents,
 Second-Generation -tricyclic antidepressant

 Available forms:
 Tablets :- 25mg ; 50mg; 100mg; 150mg

 Dosage:

 PO (Adults): 50 mg 2–3 times daily, increase to 100 mg 2–3 times daily by

end of 1 week (not to exceed 300 mg daily in outpatients, 600 mg daily in

79
 divided doses in hospitalized patients). Once optimal dose is achieved, may
be given as a single bedtime dose; no single dose to exceed 300 mg.

 PO (Geriatric Patients): 25 mg 2–3 times daily, may be increased to 50 mg

2–3 times daily (not >300 mg/dl).

 Indications:

 Antidepressants
 Panic disorder,
 Obsessive-compulsive disorder,
 Attention-deficit/hyperactivity disorder,
 Enuresis (bed-wetting),
 Eating disorders such as bulimia nervosa,
 Cocaine dependency, and
 Depressive phase of bipolar (manic-depressive) disorder
 Used to support smoking cessation programs.

 Contraindications:

 Angle-closure glaucoma;

 Recent MI;

 Prolongation of QTc interval;

 Cardiac arrhythmia;

 Heart failure.

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 Therapeutic Action:
Amoxapine acts by decreasing the reuptake of norepinephrine and serotonin
(5-HT). Has significant anticholinergic properties. And also has antianxiety
effect related to sedative properties.

 Pharmacokinetics: -
 Absorption: Well, absorbed following oral administration.
 Distribution: Widely distributed; enters breast milk.
 Protein Binding: 92% bound to plasma proteins.
 Metabolism and Excretion: Extensively metabolized by the liver.
 Half-life: 8 hr.

ROUTE ONSET PEAK DURATION

PO within 1–2 wk 2–6 wk days–wks

 Side effects:
 CNS: NEUROLEPTIC MALIGNANT SYNDROME, fatigue, sedation,
extrapyramidal reactions, tardive dyskinesia.
 EENT: blurred vision, dry eyes, dry mouth.
 CV: ARRHYTHMIAS, hypotension, ECG changes.
 GI: constipation, increased appetite, weight gain, paralytic ileus.
 GU: testicular swelling, urinary retention.
 Derm: photosensitivity, rash.
 Endo: gynecomastia, sexual dysfunction.

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  Hemat: blood dyscrasias.
 Misc: fever.

 Cautions:
 Pre-existing cardiovascular disease;
 Prostatic hyperplasia (increased susceptibility to urinary retention);
 History of seizures (threshold may be lowered);
 May ↑ risk of suicide attempt/ideation especially during dose early
treatment or dose adjustment
 OB: Use only if clearly needed and maternal benefits outweigh risk to fetus;
 Lactation: May result in sedation in infant; discontinue drug or bottle feed;
 Pedi: Suicide risk, especially at initiation of therapy, may be greater in
children and adolescents;
 Geri: May be more susceptible to adverse effects; dosage reduction
required.

 Drug interaction:
 Dangerously high blood pressure has resulted from the combination of
tricyclic antidepressants, such as amoxapine, and members of another class
of antidepressants known as monoamine oxidase (MAO) inhibitors. Because
of this, amoxapine should never be taken in combination with MAO
inhibitors. Patient taking any MAO inhibitors, for example Nardil
(phenelzine sulfate) or Parmate (tranylcypromine sulfate), should stop the
MAO inhibitor then wait at least 14 days before starting amoxapine or any
other tricyclic antidepressant.

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  Amoxapine may decrease the blood pressure–lowering effects of clonidine.
Patients who take both drugs should be monitored for loss of blood-pressure
control and the dose of clonidine may be increased as needed.
 The sedative effects of amoxapine are increased by other central nervous
system depressants such as alcohol, sedatives, sleeping medications, or
medications used for other mental disorders such as schizophrenia.

 Nursing responsibility:
 Monitor mental status (orientation, mood, behavior) frequently. Assess for
suicidal tendencies, especially during early therapy.
 Monitor BP and pulse before and during initial therapy.
 Observe for onset of extrapyramidal side effects (akathisia—
restlessness; dystonia—muscle spasms and twisting motions; pseudo
parkinsonism—mask facies, rigidity, tremors, drooling, shuffling gait,
dysphagia, pill-rolling motions of hands).
 Monitor for tardive dyskinesia (lip smacking or puckering, puffing of
cheeks, rhythmic chewing or worm-like movement of tongue and mouth,
uncontrolled movements of extremities).
 Monitor for development of neuroleptic malignant syndrome (fever,
respiratory distress, tachycardia, convulsions, diaphoresis, hypertension or
hypotension, pallor, tiredness, severe muscle stiffness, loss of bladder
control).
 Assess for sexual dysfunction.

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 Lab Test Considerations:
 May cause ↑ serum prolactin levels.
 Monitor CBC and differential during chronic therapy. May rarely cause bone
marrow suppression.
 In chronic therapy, periodically monitor hepatic and renal function. Serum
glucose may be ↑ or ↓.

 Patient/Family Teaching:
 Instruct patient to take medication as directed. Abrupt discontinuation may
cause nausea, headache, and malaise.
 Inform patient of the possibility of extrapyramidal symptoms and tardive
dyskinesia. Instruct patient to report these symptoms immediately.
 May cause drowsiness and blurred vision. Caution patient to avoid driving
and other activities requiring alertness until response to drug is known.
 Orthostatic hypotension, sedation, and confusion are common during early
therapy, especially in geriatric patients. Protect patient from falls and advise
patient to make position changes slowly.
 Refer patient to nutritional or weight management program as appropriate
 Advise patient to avoid alcohol or other CNS depressant drugs during and
for 3–7 days after therapy.
 Consult health care professional if dry mouth persists for more than 2 wk.
 Advise patient to inform health care professional if breast enlargement or
sexual dysfunction occurs.

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 ANTI-ANXIETY DTUGS/ HYPNO-
SEDATIVES
 INTRODUCTION:
Anxiety is both a normal and useful response to potentially stressful or
dangerous situations. It helps by increasing our awareness of what's going on
around us and in other ways. Anxiety disorders are associated with certain
chemical imbalances in the brain involving neurotransmitters such as
serotonin, norepinephrine, and gamma amino-butyric acid or GABA. These
chemicals are associated with an individual's sense of well-being or with the
ability to relax. Anxiety medications can't cure an anxiety disorder, but by
altering the level of these chemicals, antidepressants and anti-anxiety drugs
help control the psychological symptoms. Drugs like beta-blockers block the
receptors that are associated with the physiological symptoms of anxiety.
An anxiolytic also anti-panic or antianxiety agent is a medication, or other
intervention, that reduces anxiety. This effect is in contrast
to anxiogenic agents, which increase anxiety. Anxiolytic medications have
been used for the treatment of anxiety disorder and its related psychological
and physical symptoms. Light therapy and other interventions have also been
found to have an anxiolytic effect

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 Classification of anxiolytic drugs:
 Benzodiazepines (BDZ).
 5HT agonists.
1A

 5HT reuptake inhibitors.

 Antidepressants
 beta-adrenergic blockers
 MAO inhibitors

 Several types of medication can treat the symptoms of anxiety. According to

the Anxiety and Depression Association of America (ADAA), the four major
classes of drugs for anxiety disorders are as follows:

1. Selective serotonin reuptake inhibitors:

 Although selective serotonin reuptake inhibitors (SSRIs) are a type
of antidepressant, doctors commonly prescribe them to people with anxiety
and obsessive-compulsive disorder (OCD).
 According to one article, doctors consider SSRIs to be the first-line drug
treatment for anxiety.
 SSRIs work by stopping nerve cells in the brain from reabsorbing serotonin,
which is a chemical that plays a vital role in mood regulation.
 These medications typically begin to take effect within 2 to 6 weeks trusted
Source, but they do not work for everyone.

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 People usually take SSRIs for up to 12 months trusted Source to treat anxiety,
then gradually reduce the dosage. These drugs are not habit-forming, meaning
that they do not usually lead to dependence.
 People should consult their doctor or physician before they start reducing or
stopping their medication.
 Examples of SSRIs for anxiety include:
 citalopram (Celexa)
 escitalopram (Lexapro)
 fluoxetine (Prozac)
 fluvoxamine (Luvox)
 paroxetine (Paxil, Pexeva)
 sertraline (Zoloft)

2. Serotonin-Norepinephrine reuptake inhibitor:

 Serotonin-norepinephrine reuptake inhibitors (SNRIs) are another class of
antidepressant that treats depression and anxiety. Doctors may also prescribe
them to treat some chronic pain conditions.
 These medications work by reducing the brain’s reabsorption of the chemical’s
serotonin and norepinephrine.
 As Compare with SSRIs, SNRIs can take several weeks to have an effect.
 Examples of SNRIs for anxiety are:
 duloxetine (Cymbalta)
 venlafaxine (Effexor XR)

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3. Tricyclic antidepressants:

 Tricyclic antidepressants (TCAs) are an older class of antidepressant drug.

Although they may be effective for the treatment of depression and anxiety,
doctors often prescribe SSRIs instead, as they cause fewer side effects.
 However, TCAs may be useful for some people, especially if other medications
do not provide relief.
 Examples of TCAs for anxiety include:
 amitriptyline (Elavil)
 imipramine (Tofranil)
 nortriptyline (Pamelor)

4. Benzodiazepines:
 Benzodiazepines are a type of sedative drug that reduces the physical
symptoms of anxiety, such as tense muscles. These drugs also encourage
relaxation, and their effects take place within a few minutes. Although they are
highly effective for short-term issues, doctors rarely prescribe benzodiazepines
 because they become less effective over time and can be addictive.
 Due to these risks, experts suggest that doctors do not prescribe the continuous
use of benzodiazepines for more than 1 month.
 Some people may take benzodiazepines to manage short-term anxiety. For
example, people with a fear of flying may take them before a flight.
 At, people may take a benzodiazepine alongside an SSRI for a few weeks until
the SSRI takes effect.

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  Examples of Benzodiazepines include:
 alprazolam (Xanax)
 chlordiazepoxide (Librium)
 diazepam (Valium)
 lorazepam (Ativan)

 Black Box Warning for Benzodiazepines from FDA:

 Benzodiazepines carry a black box warning. This is the most serious warning
from the Food and Drug Administration (FDA). A black box warning alerts
doctors and patients about drug effects that may be dangerous.
 Taking benzodiazepines with opioid drugs increases your risk for severe
sleepiness, respiratory depression, coma, and even death. Alprazolam
shouldn’t be taken with an opioid unless there are no other available
treatment options.
 Using benzodiazepines, even as prescribed, can lead to physical dependence
and withdrawal if you stop taking the drug suddenly. Withdrawal can be
life threatening.
 Taking benzodiazepines can also lead to misuse and addiction. Misuse of
[drug name] increases your risk of overdose and death.
 Only take benzodiazepines as your doctor prescribes.
 Talk with your healthcare provider if you have any concerns about safely
taking this drug.

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5. Beta- blockers:

 Beta-blockers are a common medication for people with high blood

pressure and heart conditions. However, doctors may prescribe them off-label
for anxiety in certain situations. Beta-blockers reduce the effects of
norepinephrine, meaning that they can relieve some of the physical symptoms
of anxiety. Examples of beta-blockers include atenolol (Tenormin) and
propranolol (Inderal).

6. Buspirone:
 This anti-anxiety medication may treat short- or long-term anxiety symptoms.
 Buspirone (BuSpar) works much more slowly than benzodiazepines and may
not treat all types of anxiety disorder, but it causes fewer side effects and has a
lower risk of dependency.

7. Monoamine oxidase inhibitors:

 Monoamine oxidase inhibitors (MAOIs) are one of the earliest types of

antidepressant. Doctors may prescribe them off-label to treat the symptoms of
panic disorder and social phobia.

 Types of MAOI include:

 isocarboxazid (Marplan)

 phenelzine (Nardil)

 selegiline (Emsam)

 tranylcypromine (Parnate).

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 Mechanism of Action:

Benzodiazepines act by binding to BZ receptors in the brain  enhance GABA

action on brain  chloride channels opening   chloride influx to the cell

 hyper- polarization  inhibition of brain.

1. CLONAZEPAM HYDROCHLORIDE
 Name of the drug
 Trade Name :- Tab. Clonazep
 Pharmacological Name :- Clonazipam Hydrochloride

 Drug classes
 Benzodiazepine
 Antiepileptic

 Available forms
 Tablets :- 0.5, 1, 2 mg;
 orally disintegrating tablets:- 0.125, 0.25, 0.5, 1, 2 mg

 Dosages
 ADULTS
Seizure disorders: Initial dose should not exceed 1.5 mg/day PO divided into
three doses; increase in increments of 0.5–1 mg PO every 3 days until seizures

91
 are adequately controlled or until side effects preclude further increases.
Maximum recommended dosage is 20 mg/day.

 Panic disorders: Initial dose 0.25 mg PO bid; gradually increase to a target

dose of 1 mg/day.

 PEDIATRIC PATIENTS > 10 YR OR 30 KG

Initially, 0.01–0.03 mg/kg/day PO; do not exceed 0.05 mg/kg/day PO, given
in two or three doses. Increase dosage by not more than 0.25–0.5 mg every third
day until a daily maintenance dose of 0.1–0.2 mg/kg has been reached, unless
seizures are controlled by lower dosage or side effects preclude increases.
Whenever possible, divide daily dose into three equal doses, or give largest
dose HS.

 Indications:
 Treatment of Lennox-Gas taut syndrome (petit mal variant),
 Akinetic and myoclonic seizures;
 May be useful in patients with absence (petit mal) seizures who have not
responded to succinimides; up to 30% of patients show loss of effectiveness
of drug, often within 3 months of therapy (may respond to dosage
adjustment),
 Treatment of panic disorder with or without agoraphobia
 Unlabeled uses: Periodic leg movements during
sleep, hypokinetic dysarthria, acute manic episodes, multifocal tic
disorders, neuralgias

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 Contraindications and cautions:
 Hypersensitivity to benzodiazepines,
 Psychoses,
 Acute narrow-angle glaucoma,
 Shock,
 Coma,
 Acute alcoholic intoxication with depression of vital signs;
 Pregnancy (risk of congenital malformations, neonatal withdrawal
syndrome), labor and delivery ("floppy infant" syndrome),
 Lactation (infants become lethargic and lose weight).
 Use cautiously with impaired liver or renal function, debilitation.

 Therapeutic Actions:
Exact mechanisms not understood; benzodiazepines potentiate the effects of
GABA, an inhibitory neurotransmitter

 Pharmacokinetics:
Route Onset Peak Duration

Oral Varies 1–2 hr Weeks

 Metabolism: Hepatic; T1/2: 18–50 hr

 Distribution: Crosses placenta; enters breast milk
 Excretion: Urine

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 Adverse effects:
 CNS: Transient, mild drowsiness initially; sedation, depression, lethargy,
apathy, fatigue, light-headedness, disorientation, anger, hostility, episodes
of mania and hypomania, restlessness, confusion,
crying, delirium, headache, slurred speech, dysarthria, stupor, rigidity,
tremor, dystonia, vertigo, euphoria, nervousness, difficulty in concentration,
vivid dreams, psychomotor retardation, extrapyramidal symptoms; mild
paradoxical excitatory reactions during first 2 week of treatment
 CV: Bradycardia, tachycardia, CV collapse, hypertension and hypotension,
palpitations, edema
 Dermatologic: Urticaria, pruritus, rash, dermatitis
 EENT: Visual and auditory disturbances, diplopia, nystagmus, depressed
hearing, nasal congestion
 GI: Constipation, diarrhea, dry mouth, salivation, nausea, anorexia,
vomiting, difficulty in swallowing, gastric disorders, hepatic
dysfunction, encopresis.
 GU: Incontinence, urinary retention, changes in libido, menstrual
irregularities
 Hematologic: Elevations of blood enzymes—LDH, alkaline phosphatase,
AST, ALT; blood dyscrasias: agranulocytosis, leukopenia
 Other: Hiccups, fever, diaphoresis, paresthesia’s, muscular
disturbances, gynecomastia.

 Drug-Interactions:

 Increased CNS depression with alcohol

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  Increased effect with cimetidine, disulfiram, omeprazole, hormonal
contraceptives
 Decreased effect with theophylline
 Risk of increased digoxin levels and toxicity; monitor patient carefully

 Nurses Responsibility
 Assessment
 History: Hypersensitivity to benzodiazepines; psychoses; acute narrow-
angle glaucoma; shock; coma; acute alcoholic intoxication; pregnancy;
lactation; liver or renal dysfunction, debilitation.
 Physical examination: Skin color, lesions; T; orientation, reflexes, affect,
ophthalmologic examination; P, BP; R, adventitious sounds; liver evaluation,
abdominal examination, bowel sounds, normal output; CBC, LFTs, renal
function tests

 Interventions:
 Monitor addiction-prone patients carefully because of their predisposition
to habituation and drug dependence.
 Monitor liver function and blood counts periodically in patients on long-
term therapy.
 WARNING: Taper dosage gradually after long-term therapy, especially in
patients with epilepsy; substitute another antiepileptic.
 Monitor patient for therapeutic drug levels: 20–80 ng/mL.

95
  If the patient has epilepsy, arrange for patient to wear medical alert
identification indicating the patient has epilepsy and is receiving drug
therapy.

 Teaching points
 Take drug exactly as prescribed; do not stop taking drug (long-term therapy)
without consulting health care provider.
 Avoid alcohol, sleep-inducing, or over-the-counter drugs.
 Avoid pregnancy; serious adverse effects can occur. Using barrier
contraceptives is advised while taking this drug.
 You may experience these side effects: Drowsiness, dizziness (may become
less pronounced; avoid driving or engaging in other dangerous activities);
GI upset (take drug with food); fatigue; dreams; crying; nervousness;
depression, emotional changes; bed-wetting, urinary incontinence.
 Report severe dizziness, weakness, drowsiness that persists, rash or skin
lesions, difficulty voiding, palpitations, swelling in the extremities.

2. DIAZEPAM
 Name of the drug
 Trade Name :- Inj. Calmpose
 Pharmacological Name:- Diazepam

 Drug classes
 Benzodiazepine

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  Antiepileptic
 Anxiolytic
 Skeletal muscle relaxant (centrally acting)

 Available forms:
 Tablets —2, 5, 10 mg;
 SR capsule —15 mg;
 oral solution —1 mg/mL, 5 mg/5 mL;
 rectal pediatric gel —2.5, 5, 10 mg;
 rectal adult gel —10, 15, 20 mg;
 injection —5 mg/mL

 Dosages:
 ADULTS
 Oral
 Anxiety disorders, skeletal muscle spasm, seizure disorders: 2–10 mg bid–
qid.
 Alcohol withdrawal: 10 mg tid–qid first 24 hr; reduce to 5 mg tid–qid, as
needed.
 Oral sustained-release
 Anxiety disorders: 15–30 mg/day.
 Alcohol withdrawal: 30 mg first 24 hr; reduce to 15 mg/day as needed.
 Rectal
 0.2 mg/kg PR; treat no more than one-episode 5 days. May be given a second
dose in 4–12 hr.

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 Parenteral:
 Usual dose is 2–20 mg IM or IV. Larger doses may be required for some
indications (tetanus). Injection may be repeated in 1 hr.
 Anxiety: 2–10 mg IM or IV; repeat in 3–4 hr if necessary.
 Alcohol withdrawal: 10 mg IM or IV initially, then 5–10 mg in 3–4 hr if
necessary.
 Endoscopic procedures: 10 mg or less, up to 20 mg IV just before procedure
or 5–10 mg IM 30 min prior to procedure. Reduce or omit dosage of opioids.
 Muscle spasm: 5–10 mg IM or IV initially, then 5–10 mg in 3–4 hr if
necessary.
 Status epilepticus: 5–10 mg, preferably by slow IV. May repeat q 5–10 min
up to total dose of 30 mg. If necessary, repeat therapy in 2–4 hr; other drugs
are preferable for long-term control.
 Preoperative: 10 mg IM.
 Cardioversion: 5–15 mg IV 5–10 min before procedure.

 PEDIATRIC PATIENTS:
 Oral
 6 months: 1–2.5 mg PO tid–qid initially. Gradually increase as needed
and tolerated rectal.
 < 2 yr: Not recommended.
 2–5 yr: 0.5 mg/kg.
 6–11 yr: 0.3 mg/kg.
 >12 yr: Adult dose; may give a second dose in 4–12 hr.

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  Parenteral:
Maximum dose of 0.25 mg/kg IV administered over 3 min; may repeat after
15–30 min. If no relief of symptoms after three doses, adjunctive therapy is
recommended.
 Tetanus (> 1 mo): 1–2 mg IM or IV slowly q 3–4 hr as necessary.
 Tetanus (> 5 yr): 5–10 mg q 3–4 hr.
 Status epilepticus (> 1 mo–< 5 yr): 0.2–0.5 mg slowly IV q 2–5 min up to a
maximum of 5 mg.
 Status epilepticus (> 5 yr): 1 mg IV q 2–5 min up to a maximum of 10 mg;
repeat in 2–4 hr if necessary.

 GERIATRIC PATIENTS OR THOSE WITH DEBILITATING DISEASE

 2–2.5 mg PO daily–bid or 2–5 mg parenteral initially; reduce rectal dose.
Gradually increase as needed and tolerated; use cautiously.

 Indications:
 Management of anxiety disorders or for short-term relief of symptoms of
anxiety
 Acute alcohol withdrawal; may be useful in symptomatic relief of acute
agitation, tremor, delirium tremens, hallucinosis
 Muscle relaxant: Adjunct for relief of reflex skeletal muscle spasm due to
local pathology (inflammation of muscles or joints) or secondary to
trauma; spasticity caused by upper motoneuron disorders (cerebral palsy
and paraplegia); athetosis, stiff-man syndrome
 Parenteral: Treatment of tetanus

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  Antiepileptic: Adjunct in status epilepticus and severe recurrent convulsive
seizures (parenteral); adjunct in seizure disorders (oral)
 Preoperative (parenteral): Relief of anxiety and tension and to lessen recall
in patients prior to surgical procedures, cardioversion,
and endoscopic procedures
 Rectal: Management of selected, refractory patients with epilepsy who
require intermittent use to control bouts of increased seizure activity
 Unlabeled use: Treatment of panic attacks

 Contraindications and cautions:

 Hypersensitivity to benzodiazepines;
 Psychoses,
 Acute narrow-angle glaucoma,
 Shock, coma,
 Acute alcoholic intoxication;
 Pregnancy (cleft lip or palate, inguinal hernia, cardiac defects,microcephaly,
pyloric stenosis when used in first trimester; neonatal withdrawal syndrome
reported in newborns);
 Lactation.
 Use cautiously with elderly or debilitated patients; impaired liver or renal
function; and in patients with a history of substance abuse.

 Therapeutic Actions:
Exact mechanisms of action not understood; acts mainly at the limbic system
and reticular formation; may act in spinal cord and at supra-spinal sites to

100
 produce skeletal muscle relaxation; potentiates the effects of GABA, an
inhibitory neurotransmitter; anxiolytic effects occur at doses well below those
necessary to cause sedation, ataxia; has little effect on cortical function.

 Pharmacokinetics
Route Onset Peak Duration

Oral 30–60 min 1–2 hr 3 hr

IM 15–30 min 30–45 min 3 hr

IV 1–5 min 30 min 15–60 min

Rectal Rapid 1.5 hr 3 hr

 Metabolism: Hepatic; T1/2: 20–80 hr

 Distribution: Crosses placenta; enters breast milk
 Excretion: Urine

 IV facts
 Preparation: Do not mix with other solutions; do not mix in plastic bags or
tubing.
 Infusion: Inject slowly into large vein, 1 mL/min at most; for children do
not exceed 3 min; do not inject intra-arterially; if injected into IV tubing,
inject as close to vein insertion as possible.
 Incompatibilities: Do not mix with other solutions; do not mix with any
other drugs.

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 Side effects:
 CNS: Transient, mild drowsiness initially; sedation, depression, lethargy,
apathy, fatigue, light-headedness, disorientation, restlessness,
confusion, crying, delirium, headache, slurred speech, dysarthria, stupor,
rigidity, tremor, dystonia, vertigo, euphoria, nervousness, difficulty in
concentration, vivid dreams, psychomotor
retardation, extrapyramidal symptoms; mild paradoxical excitatory
reactions, during first 2 wk of treatment, visual and auditory
disturbances, diplopia, nystagmus, depressed hearing, nasal congestion
 CV: Bradycardia, tachycardia, CV collapse, hypertension and hypotension,
palpitations, edema
 Dependence: Drug dependence with withdrawal syndrome when drug is
discontinued (common with abrupt discontinuation of higher dosage used
for longer than 4 mo); IV diazepam: 1.7% incidence of fatalities; oral
benzodiazepines ingested alone; no well-documented fatal overdoses
 Dermatologic: Urticaria, pruritus, skin rash, dermatitis
 GI: Constipation; diarrhea, dry mouth; salivation; nausea; anorexia;
vomiting; difficulty in swallowing; gastric disorders; elevations of blood
enzymes—LDH, alkaline phosphatase, AST, ALT; hepatic dysfunction;
jaundice
 GU: Incontinence, urinary retention, changes in libido, menstrual
irregularities
 Hematologic: Decreased hematocrit, blood dyscrasias

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  Other: Phlebitis and thrombosis at IV injection sites, hiccups, fever,
diaphoresis, paresthesia’s, muscular disturbances, gynecomastia; pain,
burning, and redness after IM injection

 Drug-Interactions:
 Increased CNS depression with alcohol, omeprazole
 Increased pharmacologic effects of diazepam if combined
with cimetidine, disulfiram, hormonal contraceptives
 Decreased effects of diazepam with theophylline’s, ranitidine

 Nurses Responsibility
 Assessment
 History: Hypersensitivity to benzodiazepines; psychoses, acute narrow-
angle glaucoma, shock, coma, acute alcoholic intoxication; elderly or
debilitated patients; impaired liver or renal function; pregnancy, lactation
 Physical: Weight; skin color, lesions; orientation, affect, reflexes, sensory
nerve function, ophthalmologic examination; P, BP; R, adventitious sounds;
bowel sounds, normal output, liver evaluation; normal output; LFTs, renal
function tests, CBC
 WARNING: Do not administer intra-arterially; may produce arteriospasm,
gangrene.
 Change from IV therapy to oral therapy as soon as possible.
 Do not use small veins (dorsum of hand or wrist) for IV injection.
 Reduce dose of opioid analgesics with IV diazepam; dose should be reduced
by at least one-third or eliminated.

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  Carefully monitor P, BP, respiration during IV administration
 WARNING: Maintain patients receiving parenteral benzodiazepines in bed
for 3 hr; do not permit ambulatory patients to operate a vehicle following an
injection.
 Monitor EEG in patients treated for status epilepticus; seizures may recur
after initial control, presumably because of short duration of drug effect.
 Monitor liver and renal function, CBC during long-term therapy.
 Taper dosage gradually after long-term therapy, especially in epileptic
patients.
 Arrange for epileptic patients to wear medical alert ID indicating that they
are epileptics taking this medication.
 Discuss risk of fetal abnormalities with patients desiring to become
pregnant.

 Teaching points:
 Take this drug exactly as prescribed. Do not stop taking this drug (long-term
therapy, antiepileptic therapy) without consulting your health care provider.
 Caregiver should learn to assess seizures, administer rectal form, and
monitor patient.
 Use of barrier contraceptives is advised while using this drug; if you become
or wish to become pregnant, consult with your health care provider.
 It is advisable to wear a medical alert ID indicating your diagnosis and
treatment (as antiepileptic).
 You may experience these side effects: Drowsiness, dizziness (may lessen;
avoid driving or engaging in other dangerous activities); GI upset (take drug

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 with food); dreams, difficulty concentrating, fatigue, nervousness, crying
(reversible).

3. LORAZEPAM
 Name of the drug:
 Trade Name :- Inj. Ativan
 Pharmacological Name :- Lorazepam

 Drug classes:
 Benzodiazepine
 Anxiolytic
 Sedative-hypnotic

 Available forms:
 Injection —2, 4 mg/mL;
 oral solution—2 mg/mL;
 tablets —0.5, 1, 2 Mg

 Dosages:
 ADULTS
 Oral
 Usual dose is 2–6 mg/day; range 1–10 mg/day given in divided doses
with largest dose HS. Insomnia due to transient stress: 2–4 mg given hrs.

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  Intra-muscular (IM)
 0.05 mg/kg up to a maximum of 4 mg administered at least 2 hr before
operative procedure.

 Intra vascular (IV)

 Initial dose is 2 mg total or 0.044 mg/kg, whichever is smaller. Do not
exceed this dose in patients older than 50 yr. Doses as high as 0.05 mg/kg
up to a total of 4 mg may be given 15–20 min before the procedure to those
benefited by a greater lack of recall. Continuous infusion 0.5–1 mg/hr
titrated, based on patient response.

 PEDIATRIC PATIENTS
Drug should not be used in children < 12 yr.

 GERIATRIC PATIENTS OR PATIENTS WITH HEPATIC DISEASE

Initially, 1–2 mg/day in divided doses. Adjust as needed and tolerated.

 Indications:
 Oral: Management of anxiety disorders or for short-term relief of symptoms
of anxiety or anxiety associated with depression; insomnia due to anxiety of
transient situational stress
 Parenteral: Preanesthetic medication in adults to produce sedation, relieve
anxiety, and decrease recall of events related to surgery; treatment of status
epilepticus

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  Unlabeled parenteral use: Management of status epilepticus,
chemotherapy-induced nausea and vomiting, acute alcohol withdrawal

 Contraindications and cautions:

 Hypersensitivity to benzodiazepines, propylene glycol, polyethylene glycol
or benzyl alcohol (parenteral lorazepam);
 Psychoses;
 Acute narrow-angle glaucoma;
 Shock; coma;
 Acute alcoholic intoxication with depression of vital signs;
 Pregnancy (crosses placenta; risk of congenital malformations and neonatal
withdrawal syndrome);
 Labor and delivery ("floppy infant" syndrome); and lactation.
 Use cautiously with impaired hepatic or renal function.

 Therapeutic action:
Exact mechanisms are not understood; acts mainly at subcortical levels of the
CNS, leaving the cortex relatively unaffected. Main sites of action may be the
limbic system and reticular formation; benzodiazepines potentiate the effects of
GABA, an inhibitory neurotransmitter; anxiolytic effects occur at doses well
below those necessary to cause sedation and ataxia.

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 Pharmacokinetics

Route Onset Peak Duration

Oral Intermediate 1–6 hr 12–24 hr

IM 15–30 min 60–90 min 12–24 hr

IV 1–5 min 10–15 min 12–24 hr

 Metabolism: Hepatic; T1/2: 10–20 hr

 Distribution: Crosses placenta; enters breast milk
 Excretion: Urine

 IV facts
 Preparation: Dilute lorazepam immediately before IV use. For direct IV
injection or injection into IV line, dilute with an equal volume of compatible
solution (sterile water for injection, sodium chloride injection, or 5% dextrose
injection); do not use if solution is discolored or contains a precipitate.
Protect from light.
 Infusion: Direct inject slowly, or infuse at maximum rate of 2 mg/min.

 Side-effects:
 CNS: Transient, mild drowsiness initially; sedation, depression, lethargy,
apathy, fatigue, light-headedness, disorientation, anger, hostility, episodes
of mania and hypomania, restlessness, confusion, crying,delirium,
headache, slurred speech, dysarthria, stupor, rigidity, tremor,
dystonia, vertigo, euphoria, nervousness, difficulty concentrating,

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 vivid dreams, psychomotor retardation, extrapyramidal symptoms; mild
paradoxical excitatory reactions during first 2 week of treatment
 CV: Bradycardia, tachycardia, CV collapse, hypertension and hypotension,
palpitations, edema
 Dermatologic: Urticaria, pruritus, rash, dermatitis
 EENT: Visual and auditory disturbances, diplopia, nystagmus, depressed
hearing, nasal congestion
 GI: Constipation, diarrhea, dry mouth, salivation, nausea, anorexia,
vomiting, difficulty in swallowing, gastric disorders, hepatic dysfunction
 GU: Incontinence, urinary retention, changes in libido, menstrual
irregularities
 Hematologic: Elevations of blood enzymes: LDH, alkaline phosphatase,
AST, ALT; blood dyscrasias—agranulocytosis, leukopenia

 Drug- Interactions:
 Increased CNS depression with alcohol and other sedating medications,
such as barbiturates and opioids
 Decreased effectiveness with theophylline’s
 Risk of toxicity if combined with probenecid, valproate; reduce lorazepam
dose by 50%

 Drug-herb
Kava kava increases the sedative effects of benzodiazepines; coma has been
reported with concurrent use

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 Nurses Responsibility
 History: Hypersensitivity to benzodiazepines, propylene glycol,
polyethylene glycol or benzyl alcohol; psychoses; acute narrow-angle
glaucoma; shock; coma; acute alcoholic intoxication with depression of vital
signs; pregnancy; lactation; impaired liver or renal function, debilitation
 Physical examination: Skin color, lesions; T; orientation, reflexes, affect,
ophthalmologic examination; P, BP; R, adventitious sounds; liver evaluation,
abdominal examination, bowel sounds, normal output; CBC, LFTs, renal
function tests
 Sublingual administration has more rapid absorption than PO, and
bioavailability compares to IM use.
 Do not administer intra-arterially; arterio-spasm or gangrene may result.
 Give IM injections of undiluted drug deep into muscle mass, monitor
injection sites.
 Do not use solutions that are discolored or contain a precipitate. Protect
drug from light, and refrigerate oral solute
 Intensol is a concentrated solution; it is recommended it be mixed with
water, juice, soda, applesauce, or pudding.
 WARNING: Keep equipment to maintain a patent airway readily available
when drug is given IV
 Refrigerate injection and oral solution (36° to 46° F).
 Reduce dose of opioid analgesics by at least half in patients who have
received parenteral lorazepam.

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  Keep patients who have received parenteral doses under close observation,
preferably in bed, up to 3 hr. Do not permit ambulatory patients to drive
following an injection
 WARNING: Taper dosage gradually after long-term therapy, especially in
patients with epilepsy.

 Teaching points:
 Take drug exactly as prescribed; do not stop taking drug (in long-term
therapy) without consulting health care provide
 You may experience these side effects: Drowsiness, dizziness (may be
transient; avoid driving or engaging in dangerous activities); GI upset (take
drug with food); nocturnal sleep disturbances for several nights after
discontinuing the drug if used as a sedative and hypnotic; depression,
dreams, emotional upset, crying.
 Report severe dizziness, weakness, drowsiness that persists, rash or skin
lesions, palpitations, edema of the extremities; visual changes; difficulty
voiding.

4. ALPRAZOLAM
 Name of the drug:
 Trade Name :- Inj.Anxit
 Pharmacological Name :- Alprazepam

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 Drug classes:
 Benzodiazepine
 Anxiolytic

 Available forms:
 Tablets—0.25, 0.5, 1, 2 mg;
 XR tablets—0.5, 1, 2, 3 mg;
 Intensol solution—1 mg/mL;
 Rapidly disintegrating tablets—0.25, 0.5, 1, 2 mg

 Indications:
 Management of anxiety disorders, short-term relief of symptoms of anxiety;
anxiety associated with depression.
 Treatment of panic attacks with or without agoraphobia
 Unlabeled uses: Social phobia, premenstrual syndrome, depression

 Contraindications:
 Hypersensitivity to benzodiazepines,
 Psychoses,
 Acute narrow-angle glaucoma,
 Shock,
 Coma,
 Acute alcoholic intoxication with depression of vital signs,
 Pregnancy (crosses the placenta; risk of congenital malformations, neonatal
withdrawal syndrome), labor and delivery ("floppy infant" syndrome),

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  Lactation (secreted in breast milk; infants become lethargic and lose weight).

 Therapeutic action:
Exact mechanisms of action not understood; main sites of action may be the
limbic system and reticular formation; increases the effects of gamma-
aminobutyrate, an inhibitory neurotransmitter; anxiety blocking effects occur
at doses well below those necessary to cause sedation, ataxia.

 Pharmacokinetics:

Route Onset Peak Duration

Oral 30 min 1–2 hr 4–6 hr

 Metabolism: Hepatic; T1/2: 6.3–26.9 hr

 Distribution: Crosses placenta; enters breast milk
 Excretion: Urine

 Adverse effects:
 CNS: Transient, mild drowsiness initially; sedation, depression, lethargy,
apathy, fatigue, light-headedness, disorientation, anger, hostility, episodes
of mania and hypomania, restlessness, confusion,
crying, delirium, headache, slurred speech, dysarthria, stupor, rigidity,
tremor, dystonia, vertigo, euphoria, nervousness, difficulty in concentration,
vivid dreams, psychomotor retardation, extrapyramidal symptoms; mild

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 paradoxical excitatory reactions during first 2 weeks of treatments,;
tachycardia, CV collapse, hypertension, hypotension, palpitations, edema
 Dermatologic: Urticaria, pruritus, rash, dermatitis
 EENT: Visual and auditory disturbances, diplopia, nystagmus, depressed
hearing, nasal congestion
 GI: Constipation, diarrhea, dry mouth, salivation, nausea, anorexia,
vomiting, difficulty in swallowing, gastric disorders, hepatic dysfunction
 GU: Incontinence, changes in libido, urinary retention, menstrual
irregularities
 Hematologic: Elevations of blood enzymes—LDH, alkaline phosphatase,
AST, ALT; blood dyscrasias—agranulocytosis, leukopenia

 Caution:
 Impaired liver or kidney function,
 Debilitation.

 Drug- Interactions:
 Increased CNS depression with alcohol, other CNS
depressants, propoxyphene
 Increased effect with cimetidine, disulfiram, omeprazole, isoniazid,
hormonal contraceptives, valproic acid
 Decreased effect with carbamazepine, rifampin, theophylline
 Possible increased risk of digitalis toxicity with digoxin
 Decreased anti-Parkinson effectiveness of levodopa with benzodiazepines
 Contraindicated with ketoconazole, itraconazole; serious toxicity can occur

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 Drug-food
Decreased metabolism and risk of toxic effects if combined with grapefruit
juice; avoid this combination

 Drug-alternative therapy
 Risk of coma if combined with kava therapy
 Additive sedative effects with valerian root

 Nurses Responsibility:
 Assessment
 History: Hypersensitivity to benzodiazepines; psychoses; acute narrow-
angle glaucoma; shock; coma; acute alcoholic intoxication with depression
of vital signs; labor and delivery; lactation; impaired liver or kidney function;
debilitation
 Physical: Skin color, lesions; T; orientation, reflexes, affect, ophthalmologic
examination; P, BP; liver evaluation, abdominal examination, bowel sounds,
normal output; CBC, LFTs, renal function tests
 Arrange to taper dosage gradually after long-term therapy, especially in
epileptic patients
 Do not administer with grapefruit juice.
 Taper drug slowly; decrease by no more than 0.5 mg every 3 days.

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 Teaching points:
Take this drug exactly as prescribed; take extended-release form once a day
in the AM; place rapidly disintegrating tablet on top of tongue, where it will
disintegrate and can be swallowed with saliva.
 Do not drink grapefruit juice while on this drug.
 Do not stop taking drug (in long-term therapy) without consulting health
care provider.
 Avoid alcohol, sleep-inducing, or over-the-counter drugs.
 You may experience these side effects: Drowsiness, dizziness (these
effects will be less pronounced after a few days, avoid driving a car or
engaging in other dangerous activities if these occur); GI upset (take drug
with food); fatigue; depression; dreams; crying; nervousness.
 Report severe dizziness, weakness, drowsiness that persists, rash or skin
lesions, difficulty voiding, palpitations, swelling in the extremities.

5. PHENOBARBITONE
 Name of the drug
 Trade Name :- Inj.Cardinal
 Pharmacological Name :-Phenobarbitone

 Drug classes
 Barbiturate (long acting)
 Sedative
 Hypnotic
 Antiepileptic

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 Available forms:
 Tablets — 15, 16, 16.2, 30, 60, 90, 100 Mg;
 Capsules —16 Mg;
 Elixir —15 mg/5 ml, 20 mg/5 ml;
 Injection —30, 60, 65, 130 mg/mL

 Dosages:
 ADULTS
 Oral
 Sedation: 30–120 mg/day in two to three divided doses. No more than
400 mg per 24 hr.
 Hypnotic: 100–200 mg HS.
 Antiepileptic: 60–100 mg/day.

 IM or IV
 Sedation: 30–120 mg/day IM or IV in two to three divided doses.
 Preoperative sedation: 100–200 mg IM, 60–90 min before surgery.
 Hypnotic: 100–320 mg IM or IV.
 Acute seizures: 200–320 mg IM or IV repeated in 6 hr if needed.

 PEDIATRIC PATIENTS
 Oral
 Sedation: 2 mg/kg/dose PO tid. 8–32 mg/dose
 Hypnotic: Determine dosage using age and weight charts.
 Antiepileptic: 3–6 mg/kg/day.

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  IM or IV
 Preoperative sedation: 1–3 mg/kg IM or IV 60–90 min before surgery.
 Antiepileptic: 4–6 mg/kg/day for 7–10 days to a blood level of 10–15
mcg/mL or 10–15 mg/kg/day IV or IM.
 Status epilepticus: 15–20 mg/kg IV over 10–15 min.

 GERIATRIC PATIENTS OR PATIENTS WITH DEBILITATING

DISEASE OR RENAL OR HEPATIC IMPAIRMENT
Reduce dosage and monitor closely—may produce excitement, depression,
confusion.

 Indications:
 Oral or parenteral: Sedative
 Oral or parenteral: Hypnotic, treatment of insomnia for up to 2 wk
 Oral: Long-term treatment of generalized tonic-clonic and cortical focal
seizures
 Oral: Emergency control of certain acute seizures (eg, those associated with
status epilepticus, eclampsia, meningitis, tetanus, and toxic reactions to
strychnine or local anesthetics)
 Parenteral: Preanesthetic
 Parenteral: Treatment of generalized tonic- clonic and cortical focal seizures
 Parenteral: Emergency control of acute seizures
(tetanus, eclampsia, epilepticus)

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 Contraindications:
 Hypersensitivity to barbiturates,
 Manifest or latent porphyria;
 Marked liver impairment;
 Nephritis;
 Severe respiratory distress;
 Previous addiction to sedative-hypnotic drugs (may be ineffective and may
contribute to further addiction);
 Pregnancy (fetal damage, neonatal withdrawal syndrome).

 Therapeutic action:
General CNS depressant; barbiturates inhibit impulse conduction in the
ascending RAS, depress the cerebral cortex, alter cerebellar function, depress
motor output, and can produce excitation, sedation, hypnosis, anesthesia, and
deep coma; at sub hypnotic doses, has anti-seizure activity, making it suitable
for long-term use as an antiepileptic.

 Pharmacokinetics:
Route Onset Duration

Oral 30–60 min 10–16 hr

IM, SC 10–30 min 4–6 hr

IV 5 min 4–6 hr

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  Metabolism: Hepatic; T1/2: 79 hr
 Distribution: Crosses placenta; enters breast milk
 Excretion: Urine

 IV facts
 Preparation: No further preparation is needed.
 Infusion: Infuse very slowly, each 60 mg over 1 min, directly IV or into
tubing or running IV; inject partial dose and observe for response before
continuing. It may require > 15 min to achieve peak levels in brain tissue.
Avoid overdosing by observing effects before continued dosing.
 Incompatibilities: Do not combine with chlorpromazine, codeine,
ephedrine, hydralazine, hydrocortisone, insulin, meperidine, methadone,
procaine, promazine, vancomycin.

 Adverse effects:
 CNS: Somnolence, agitation, confusion, hyperkinesia, ataxia, vertigo, CNS
depression, nightmares, lethargy, residual sedation (hangover), paradoxical
excitement, nervousness, psychiatric disturbance, hallucinations, insomnia,
anxiety, dizziness, thinking abnormality
 CV: Bradycardia, hypotension, syncope
 GI: Nausea, vomiting, constipation, diarrhea, epigastric pain
 Hypersensitivity: Rashes, angioneurotic edema, serum
sickness, morbilliform rash, urticaria; rarely, exfoliative dermatitis, Stevens-
Johnson syndrome

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  Local: Pain, tissue necrosis at injection site, gangrene; arterial spasm with
inadvertent intra-arterial injection; thrombophlebitis;
permanent neurologic deficit if injected near a nerve
 Respiratory: Hypoventilation, apnea, respiratory depression,
laryngospasm, bronchospasm, circulatory collapse
 Other: Tolerance, psychological and physical dependence, withdrawal
syndrome

 Drug-Interactions:
 Increased serum levels and therapeutic and toxic effects with valproic acid
 Increased CNS depression with alcohol
 Increased risk of nephrotoxicity with methoxyflurane
 Increased risk of neuromuscular excitation and hypotension with
barbiturate anesthetics
 Decreased effects of the following drugs: Theophyllines, oral anticoagulants,
beta-blockers, doxycycline, corticosteroids, hormonal contraceptives and
estrogens, metronidazole, phenylbutazones, quinidine, felodipine,
fenoprofen.

 Caution:
 Acute or chronic pain (drug may cause paradoxical excitement or mask
important symptoms);
 Seizure disorders (abrupt discontinuation of daily doses can result in
status epilepticus);
 Lactation (secreted in breast milk; drowsiness in nursing infants);

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  Fever,
 Hyperthyroidism,
 Diabetes mellitus,
 Severe anemia,
 Pulmonary or cardiac disease,
 Status asthmaticus,
 Shock,
 Uremia; impaired liver or renal function,
 Debilitation.

 Nursing responsibility
 History: Hypersensitivity to barbiturates, manifest or latent porphyria;
marked liver impairment; nephritis; severe respiratory distress; previous
addiction to sedative-hypnotic drugs; pregnancy; acute or chronic pain;
seizure disorders; lactation, fever; hyperthyroidism; diabetes mellitus;
severe anemia; cardiac disease; shock; uremia; impaired liver or renal
function; debilitation
 Physical: Weight; T; skin color, lesions; orientation, affect, reflexes; P, BP,
orthostatic BP; R, adventitious sounds; bowel sounds, normal output, liver
evaluation; LFTs, renal function tests, blood and urine glucose, BUN
 Monitor patient responses, blood levels (as appropriate) if any interacting
drugs listed above are given with phenobarbital; suggest alternative means
of contraception to women using hormonal contraceptives.
 WARNING: Do not give intra-arterially; may produce arteriospasm,
thrombosis, gangrene.

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  Administer IV doses slowly
 Administer IM doses deep in a large muscle mass
(gluteus maximus, vastus lateralis) or other areas where there is little risk of
encountering a nerve trunk or major artery
 WARNING: Monitor injection sites carefully for irritation, extravasation (IV
use). Solutions are alkaline and very irritating to the tissues.
 Monitor P, BP, respiration carefully during IV administration.
 Arrange for periodic lab tests of hematopoietic, renal, and hepatic systems
during long-term therapy.
 WARNING: Taper dosage gradually after repeated use, especially in
patients with epilepsy. When changing from one antiepileptic drug to
another, taper dosage of the drug being discontinued while increasing the
dosage of the replacement drug.

 Teaching points:
 This drug will make you drowsy and less anxious; do not try to get up after
you have received this drug (request assistance to sit up or move around).
 Take this drug exactly as prescribed; this drug is habit forming; its
effectiveness in facilitating sleep disappears after a short time.
 Do not take this drug longer than 2 weeks (for insomnia), and do not
increase the dosage without consulting the prescriber.
 Do not reduce the dosage or discontinue this drug (when used for epilepsy);
abrupt discontinuation could result in a serious increase in seizures.
 Wear a medical alert tag so that emergency medical personnel will know you
have epilepsy and are taking this medication.

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 Avoid pregnancy while taking this drug; use a means of contraception other
than hormonal contraceptives.
 You may experience these side effects: Drowsiness, dizziness, hangover,
impaired thinking (may lessen after a few days; avoid driving or engaging
in dangerous activities); GI upset (take drug with food); dreams, nightmares,
difficulty concentrating, fatigue, nervousness (reversible).
 Report severe dizziness, weakness, drowsiness that persists, rash or skin
lesions, fever, sore throat, mouth sores, easy bruising or bleeding,
nosebleed, petechiae, pregnancy.

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 MOOD STABILIZERS/ ANTI-MANIACS

 Introduction:

 Anti-manic agents are also called MOOD STABILIZERS.

 The first mood stabilizer to be used was lithium, and it is the only drug that was
developed specifically for use in bipolar disorder. Most the other drugs
classified as mood stabilizers are medications that were first used to treat
seizure disorders, such as epilepsy. They are known as "anticonvulsants," since
they are designed to inhibit or reduce the frequency of seizures. Interestingly,
they also help stabilize mood swings. Some heart-related medications called
calcium channel blockers are being studied for use in treating bipolar disorder
as mood stabilizers.
 Mood stabilizers are psychiatric medications that help control swings
between depression and mania. They’re prescribed to restore neurochemical
balance by decreasing brain activity.
 Mood stabilizer drugs are commonly used to treat people with bipolar mood
disorder and sometimes people with schizoaffective disorder and borderline
personality disorder. In some cases, they’re used to supplement other
medications, such as antidepressants, to treat depression.
 Mood stabilizers are medicines that treat and prevent highs (mania) and lows
(depression). They also help to keep your moods from interfering with work,
school, or your social life.

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 Bipolar disorder, formerly called manic depression, is a mental health condition
that causes extreme mood swings that include emotional highs (mania or
hypomania) and lows (depression).
 When you become depressed, you may feel sad or hopeless and lose interest or
pleasure in most activities. When your mood shifts to mania or hypomania (less
extreme than mania), you may feel euphoric, full of energy or unusually
irritable. These mood swings can affect sleep, energy, activity, judgment,
behavior and the ability to think clearly.
 Episodes of mood swings may occur rarely or multiple times a year. While most
people will experience some emotional symptoms between episodes, some may
not experience any.
 Although bipolar disorder is a lifelong condition, you can manage your mood
swings and other symptoms by following a treatment plan. In most cases,
bipolar disorder is treated with medications and psychological counselling
(psychotherapy).

 Mode of action:
The specific biochemical mechanism of action unclear. Anti-manic agents
produce many neurochemical changes in the area of brain. Changes may
affect nor epinephrine and serotonin. CNS involved in emotion. Decrease
activity of the nerve impulse, resulting in depression or increase in the nerve
impulse, causing mania. Lithium maintaining the sodium concentration in the
brain, thereby regulating the mood swings as well as impulse along the nerve
cells.

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 Types of mood stabilizer:

1. Lithium

 Lithium carbonate is the mood stabiliser that I'm on… Apart from the side effect
of it making me really thirsty, I've found it has really evened me out, brought
up my lows and made them not last as long and balanced the highs out, too.
 Lithium is a mood stabilizing medication commonly used to treat bipolar
disorder. It can be prescribed as:
 Lithium carbonate (Camcolit, Priadel, Liskonum
 Lithium citrate (Li-liquid, Priadel).

2. Anti-Convulsant:

 Some anticonvulsant medication can be used to help stabilize mood. You may
also hear these drugs referred to as anti-epileptic medication. Anticonvulsants
which are used as mood stabilizers include:

 Carbamazepine (Tegretol)
 lamotrigine (Lamictal)
 valproate (Depakote, Epilim).

127
 3. Antipsychotics:

 Some antipsychotic medications can be used as mood stabilizers, as part of the

treatment for bipolar disorder.

 The National Institute for Health and Care Excellence (NICE), the organization
that produces guidelines on best practice in healthcare, has guidelines for
treating bipolar disorder. These guidelines recommend using the following
antipsychotics as mood stabilizers:

 haloperidol (Dozic, Haldol, Haldol decanoate, Serenace)

 olanzapine (Zalasta, Zyprexa, ZypAdhera)
 quetiapine (Atrolak, Biquelle, Ebesque, Seroquel, Tenprolide, Zaluron)
 risperidone (Risperdal, Risperdal Consta).

1. SODIUM VALPROATE

 Name of the drug

 Trade Name :- Tab. Valparin
 Pharmacological Name:- Sodium Valproate

 Drug class:

 Antiepileptic

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 Available forms
 Tablets
 Oral liquid
 Modified-release tablets,
 Capsules, and
 Granules
 Injection

 Dosage:
 15mg/kg/day with a maximum of 60mg/kg/day orally

 Indication:
 All forms of epilepsy,
 Generalized epilepsy with absence seizures,
 Prophylaxis of febrile convulsion,
 Prophylaxis of post traumatic epilepsy,
 Status epileptics,
 Alcohol withdrawal,
 Mania,
 Nelsons syndrome,
 Tardive dyskinesias.

 Contra indications:
 Hypersensitivity to valproic acid,
 Hepatic disease or significant hepatic impairment.

129
 Therapeutic Action:
Sodium valproate works by stabilizing electrical activity in the brain, and so
reducing fits. Mechanism of action not understood: antiepileptic activity may
be related to the metabolism of the inhibitory neurotransmitter,
GABA; divalproex sodium is a compound containing equal proportions of
Valproic acid and sodium valproate.

 Side effects:

This is usually temporary and regrowth normally

Hair loss begins within a few months (although the hair may
become curlier than before)

Feeling sick, These may occur when you first start taking sodium
stomach valproate but soon disappear. Try eating small but
irritation frequent meals. Stick to simple foods
Diarrhea Drink plenty of water to replace lost fluids
If this happens, do not drive or use tools or machines.
Feeling sleepy
Do not drink alcohol

 Drug-Interactions:

 Divalproex, valproate, or valproic acid may interact with carbamazepine,

cimetidine, cyclosporine, drugs called beta blockers (such as propranolol),
midazolam, rifampin, some anesthetics, and triazolam. Tell all prescribers
you're taking this drug.
 Avoid alcohol while taking this drug.

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 Caution:
 Liver disorders,
 Kidney disorders,
 Immune disorder systemic lupus erythematous, or
 Diabetes,
 Pregnancy,
 Hyperammonemia
 Porphyria (a rare inherited blood disorder),
 Acute or severe liver problems or a family history of liver problems,
 Allergy to sodium valproate.

 Nurses Responsibility
 Take drug with or without meals.
 Don’t crush or break extended-release capsules. Swallow them whole.
 If you can’t swallow extended-release capsule whole, carefully open it,
sprinkle contents on cool applesauce, and immediately swallow contents
with a full glass of water without chewing.
 Monitor LFT & RFT

2. LITHIUM CARBONATE
 Name of the drug:
 Trade Name :- Tab.Lithosum - SR
 Pharmacological Name :- Lithium Carbonate

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 Drug classes
 Anti-maniac drug

 Available forms
 Capsules —150, 300, 600 mg;
 Tablets —300 mg;
 SR tablets —300 mg;
 CR tablets —450 mg;
 Syrup —300 mg/5 mL

 Dosages:
 ADULTS
 Acute mania: 600 mg PO tid or 900 mg slow-release form PO bid to produce
effective serum levels between 1 and 1.5 mEq/L. Serum levels should be
determined twice per wk in samples drawn immediately before a dose (at
least 8–12 hr after previous dose).
 Long-term use: 300 mg PO tid–qid to produce a serum level of 0.6–
1.2 mEq/L. Serum levels should be determined at least every 2 mo in
samples drawn immediately before a dose (at least 8–12 hr after previous
dose).
 Conversion from conventional to slow-release dosage forms: Give the
same total daily dose divided into two or three doses.

 PEDIATRIC PATIENTS
Safety and efficacy for children < 12 yr not established.

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 GERIATRIC PATIENTS AND PATIENTS WITH RENAL IMPAIRMENT
Reduced dosage may be necessary.

 Indications:
 Treatment of manic episodes of manic-depressive illness; maintenance
therapy to prevent or diminish frequency and intensity of subsequent manic
episodes
 Improvement of neutrophil counts in patients with cancer chemotherapy–
induced neutropenia and in children with chronic neutropenia and HIV
patients on zidovudine therapy (doses of 300–1,000 mg/day, serum levels of
0.5 and 1 mEq/L);
 Prophylaxis of cluster headache and cyclic migraine headache,
 Treatment of SIADH,
 Hypothyroidism (doses of 600–900 mg/day)

 Contraindications:
 Hypersensitivity to tartrazine;
 Significant renal or CV disease;
 Severe debilitation,
 Severe hydration;
 Sodium depletion,
 Patients on diuretics (lithium decreases sodium reabsorption,
and hyponatremia increases lithium retention);
 Pregnancy;
 Lactation.

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 Therapeutic Actions:
Mechanism is not known; alters sodium transport in nerve and muscle cells;
inhibits release of norepinephrine and dopamine, but not serotonin, from
stimulated neurons; slightly increases intra-neuronal stores of catecholamine’s;
decreases intra-neuronal content of second messengers and may thereby
selectively modulate the responsiveness of hyperactive neurons that might
contribute to the manic state.

 Pharmacokinetics
Route Onset Peak

Oral 5–7 days 10–21 days

 Metabolism: Hepatic; T1/2: 17–36 hr

 Distribution: Crosses placenta; enters breast milk
 Excretion: Urine

 Adverse effects:
Reactions are related to serum lithium levels. (Toxic lithium levels are close to
therapeutic levels. Therapeutic levels in acute mania range between 1 and
1.5 mEq/L; therapeutic levels for maintenance are 0.6–1.2 mEq/L) < 1.5 mEq/L
 CNS: Lethargy, slurred speech, muscle weakness, fine hand tremor
 GI: Nausea, vomiting, diarrhea, thirst
 GU: Polyuria = 1.5–2 mEq/L (mild to moderate toxic reactions)

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 CNS: Coarse hand tremor, mental confusion, hyperirritability of muscles,
drowsiness, incoordination
 CV: ECG changes
 GI: Persistent GI upset, gastritis, salivary gland swelling, abdominal pain,
excessive salivation, flatulence, indigestion 2–2.5 mEq/L (moderate to
severe toxic reactions)
 CNS: Ataxia, giddiness, fasciculations, tinnitus, blurred
vision, clonic movements, seizures, stupor, coma
 CV: Serious ECG changes, severe hypotension with cardiac arrythmias
 GU: Large output of dilute urine
 Respiratory: Fatalities secondary to pulmonary complications > 2.5 mEq/L
(life-threatening toxicity)
 General: Complex involvement of multiple organ systems, including
seizures, arrythmias, CV collapse, stupor, coma

 Reactions unrelated to serum levels:

 CNS: Headache, worsening of organic brain syndromes, fever, reversible
short-term memory impairment, dyspraxia
 CV: ECG changes; hyperkalemia associated with ECG changes; syncope;
tachycardia-bradycardia syndrome; rarely, arrhythmias, CHF,
diffuse myocarditis, death
 Dermatologic: Pruritus with or without rash; maculopapular, acneiform,
and follicular eruptions; cutaneous ulcers; edema of ankles or wrists
 Endocrine: Diffuse nontoxic goiter;
hypothyroidism; hypercalcemia associated with hyperparathyroidism;

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 transient hyperglycemia; irreversible nephrogenic diabetes insipidus,
which improves with diuretic therapy; impotence or sexual dysfunction
 GI: Dysgeusia (taste distortion), salty taste; swollen lips; dental caries
 Other: Weight gain (5–10 kg); chest tightness; swollen or painful joints, eye
irritation, worsening of cataracts, disturbance of visual
accommodation, leukocytosis.

 Drug-Interactions:
 Increased risk of toxicity with thiazide diuretics due to decreased renal
clearance of lithium—reduced lithium dosage may be necessary
 Increased plasma lithium levels with indomethacin and some
other NSAIDs—phenylbutazone, piroxicam, ibuprofen, as well
as fluoxetine and methyldopa
 Increased CNS toxicity with carbamazepine
 Encephalopathic syndrome (weakness, lethargy, fever, tremulousness,
confusion, extrapyramidal symptoms, leukocytosis, elevated serum
enzymes) with irreversible brain damage when taken with haloperidol
 Greater risk of hypothyroidism with iodide salts
 Decreased effectiveness due to increased excretion of lithium with
urinary alkalinizes, including antacids, tromethamine

 Caution:
 Protracted sweating and diarrhea;
 Suicidal or impulsive patients;
 Infection with fever.

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 Nurses Responsibility
 History: Hypersensitivity to tartrazine; significant renal or CV disease;
severe debilitation, dehydration; sodium depletion, patients on diuretics;
protracted sweating, diarrhea; suicidal or impulsive patients; infection with
fever; pregnancy; lactation
 Physical examination: Weight and T; skin color, lesions; orientation, affect,
reflexes; ophthalmic examination; P, BP, R, adventitious sounds; bowel
sounds, normal output; normal fluid intake, normal output, voiding pattern;
thyroid, renal glomerular and tubular function tests, urinalysis, CBC and
differential, baseline ECG

 Interventions:
 Give with caution and daily monitoring of serum lithium levels to patients
with renal or CV disease, debilitation, or dehydration or life-threatening
psychiatric disorders.
 Give drug with food or milk or after meals.
 WARNING: Monitor clinical status closely, especially during initial stages
of therapy; monitor for therapeutic serum levels of 0.6–1.2 mEq/L.
 Individuals vary in their response to this drug; some patients may exhibit
toxic signs at serum lithium levels considered within the therapeutic range.
 Advise patient that this drug may cause serious fetal harm and cannot be
used during pregnancy; urge use of barrier contraceptives.
 Decrease dosage after the acute manic episode is controlled; lithium
tolerance is greater during the acute manic phase and decreases when manic
symptoms subside.

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  WARNING: Ensure that patient maintains adequate intake of salt and
adequate intake of fluid (2,500–3,000 mL/day).

 Teaching points:
 Take this drug exactly as prescribed, after meals or with food or milk.
 Eat a normal diet with normal salt intake; maintain adequate fluid intake (at
least 2.5 quarts/day).
 Arrange for frequent checkups, including blood tests. Keep all appointments
for checkups to get the most benefits with the least toxicity.
 Use contraception to avoid pregnancy. If you wish to become pregnant or
believe that you have become pregnant, consult your care provider.
 Discontinue drug, and notify care provider if toxicity occurs—diarrhea,
vomiting, ataxia, tremor, drowsiness, lack of coordination or muscular
weakness.
 You may experience these side effects: Drowsiness, dizziness (avoid driving
or performing tasks that require alertness); GI upset (eat frequent small
meals); mild thirst, greater than usual urine volume, fine hand tremor (may
persist throughout therapy; notify heath care provider if severe).
 Report diarrhea or fever.

3. CARBAMAZEPINE

 Name of the drug:

 Trade Name :- Tab.Teritol
 Pharmacological Name :- Carbamazepine

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 Drug classes:
 Anti-epileptic

 Available forms:
 Tablets —200 mg;
 Chewable tablets —100 mg;
 ER tablets —100, 200, 400 mg;
 ER capsules —100, 200, 300 mg;
 Suspension —100 mg/5 mL, 200 mg/10 mL

 Dosages:
Individualize dosage; a low initial dosage with gradual increase is advised.
 ADULTS
 Epilepsy: Initial dose, 200 mg PO bid on the first day; increase gradually by
up to 200 mg/day in divided doses q 6–8 hr, until best response isachieved.
Suspension:100 mg PO qid. Do not exceed 1,200 mg/day in patients > 15 yr;
doses up to 1,600 mg/day have been used in adults (rare). For maintenance,
adjust to minimum effective level, usually 800– 1,200 mg/day.
 Combination therapy: When added to existing antiepileptic therapy, do so
gradually while other antiepileptics are maintained or discontinued.
 Trigeminal neuralgia: Initial dose, 100 mg PO bid on the first day; may
increase by up to 200 mg/day, using 100-mg increments q 12 hr as needed.
Do not exceed 1,200 mg/day. For maintenance, control of pain can usually
be maintained with 400–800 mg/day (range 200–1,200 mg/day). Attempt to

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 reduce the dose to the minimum effective level or to discontinue the drug at
least once every 3 mo.
 Suspension: Start at 50 mg PO qid, increase by 50 mg PO qid as needed to
maximum dose (Equetro).
 Bipolar 1 disorder: 200–600 mg/day PO in divided doses; may be increased
in 200-mg/day increments. Do not exceed 1,600 mg/day.
 PEDIATRIC PATIENTS > 12 YR
 Use adult dosage. Do not exceed 1,000 mg/day in patients 12–15 yr;
1,200 mg/day in patients > 15 yr.
 PEDIATRIC PATIENTS 6–12 YR
 Initial dose, 100 mg PO bid on the first day. Increase gradually by adding
100 mg/day at 6- to 8-hr intervals until best response is achieved. Do not
exceed 1,000 mg/day. Dosage also may be calculated on the basis of 20–
30 mg/kg/day in divided doses tid–qid.
 PEDIATRIC PATIENTS < 6 YR
 Optimal daily dose, < 35 mg/kg/day.
 GERIATRIC PATIENTS
 Use caution:- Drug may cause confusion, agitation.

 Indications:
 Refractory seizure disorders: Partial seizures with complex symptoms
(psychomotor, temporal lobe epilepsy), generalized tonic-clonic (grand mal)
seizures, mixed seizure patterns or other partial or generalized seizures.
Reserve for patients unresponsive to other agents with seizures difficult to

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 control or who are experiencing marked side effects, such as excessive
sedation
 Trigeminal neuralgia (tic douloureux): Treatment of pain associated with
true trigeminal neuralgia; also beneficial in glossopharyngeal neuralgia
 Treatment of acute manic and mixed episodes associated with bipolar 1
disorder (Equetro)
 Neurogenic diabetes insipidus (200 mg bid–tid);
 Certain psychiatric disorders, including schizoaffective illness, resistant
schizophrenia, and dyscontrol syndrome associated with limbic system
dysfunction; alcohol withdrawal (800–1,000 mg/day); restless leg syndrome
(100–300 mg/day hs); non-neuritic pain syndrome (600–1,400 mg/day);
hereditary or nonheriditary chorea in children (15–25 mg/kg/day).

 Contraindications:
 Hypersensitivity to carbamazepine or TCAs,
 History of bone marrow depression,
 Concomitant use of MAOIs,
 Lactation,
 Pregnancy.

 Therapeutic actions:
Mechanism of action not understood; antiepileptic activity may be related to its
ability to inhibit polysynaptic responses and block post-tetanic potentiation.
Drug is chemically related to the TCAs.

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 Pharmacokinetics:
Route Onset Peak

Oral Slow 4–5 hr

ER oral Slow 3–12 hr

 Metabolism: Hepatic; T1/2: 25–65 hr, then 12–17 hr

 Distribution: Crosses placenta; enters breast milk
 Excretion: Feces, urine

 Adverse effects:
 CNS: Dizziness, drowsiness, unsteadiness, disturbance of coordination,
confusion, headache, fatigue, visual hallucinations, depression with
agitation, behavioral changes in children, talkativeness, speech disturbances,
abnormal involuntary movements, paralysis and other symptoms of
cerebral arterial insufficiency, peripheral neuritis and paresthesia’s,
tinnitus, hyperacusis, blurred vision, transient diplopia and
oculomotor disturbances, nystagmus, scattered punctate cortical lens
opacities, conjunctivitis, ophthalmoplegia, fever, chills.
 CV: CHF, aggravation of hypertension, hypotension, syncope and collapse,
edema, primary thrombophlebitis, recurrence of thrombophlebitis,
aggravation of CAD, arrhythmias and AV block; CV complications
 Dermatologic: Pruritic and erythematous rashes, urticaria, Stevens-
Johnson syndrome, photosensitivity reactions, alterations in
pigmentation, exfoliative dermatitis, alopecia,

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 diaphoresis, erythema multiforme anthodium, purpura, aggravation of
lupus erythematosus
 GI: Nausea, vomiting, gastric distress, abdominal pain, diarrhea,
constipation, anorexia, dryness of mouth or pharynx, glossitis, stomatitis;
abnormal LFTs, cholestatic and hepatocellular jaundice, hepatitis, massive
hepatic cellular necrosis with total loss of intact liver tissue
 GU: Urinary frequency, acute urinary retention, oliguria with hypertension,
renal failure, azotemia, impotence, proteinuria, glycosuria, elevated BUN,
microscopic deposits in urine
 Hematologic: Hematologic disorders (severe bone marrow depression)
 Respiratory: Pulmonary hypersensitivity characterized by
fever, dyspnea, pneumonitis or pneumonia

 Drug- Interactions:
 Increased serum levels and manifestations of toxicity with
erythromycin, troleandomycin, cimetidine, danazol, isoniazid, propoxyphe
ne, verapamil; dosage of carbamazepine may need to be reduced
(reductions of about 50% recommended with erythromycin)
 Increased CNS toxicity with lithium
 Increased risk of hepatotoxicity with isoniazid (MAOI qualities); because of
the chemical similarity of carbamazepine to the TCAs and because of the
serious adverse interaction of TCAs and MAOIs, discontinue MAOIs for
minimum of 14 days before carbamazepine administration
 Decreased absorption with charcoal

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  Decreased serum levels and decreased effects of carbamazepine with
barbiturates
 Increased metabolism but no loss of seizure control
with phenytoin, primidone
 Increased metabolism of phenytoin, valproic acid
 Decreased anticoagulant effect of warfarin, oral anticoagulants; dosage
of warfarin may need to be increased during concomitant therapy but
decreased if carbamazepine is withdrawn
 Decreased effects of nondepolarizing muscle relaxants, haloperidol
 Decreased antimicrobial effects of doxycycline

 Cautions:
 History of adverse hematologic reaction to any drug (increased risk of
severe hematologic toxicity);
 Glaucoma or increased IOP;
 History of cardiac, hepatic, or renal damage;
 Psychiatric patients (may activate latent psychosis).

 Nursing considerations
 Assessment
 History: Hypersensitivity to carbamazepine or TCAs; history of bone
marrow depression; concomitant use of MAOIs; history of
adverse hematologic reaction to any drug; glaucoma or increased IOP;
history of cardiac, hepatic, or renal damage; psychiatric history; lactation;
pregnancy

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  Physical examination: Weight; T; skin color, lesions; palpation of lymph
glands; orientation, affect, reflexes; ophthalmologic examination
(including tonometry, fundoscopy, slit lamp examination); P, BP, perfusion;
auscultation; peripheral vascular examination; R, adventitious sounds;
bowel sounds, normal output; oral mucous membranes; normal urinary
output, voiding pattern; CBC including platelet, reticulocyte counts and
serum iron; LFTs, urinalysis, BUN, thyroid function tests, EEG

 Interventions:
 Use only for classifications listed. Do not use as a general analgesic. Use only
for epileptic seizures that are refractory to other safer agents.
 Give drug with food to prevent GI upset.
 Do not mix suspension with other medications or elements—precipitation
may occur.
 WARNING: Reduce dosage, discontinue, or substitute other antiepileptic
medication gradually. Abrupt discontinuation of all antiepileptic medication
may precipitate status epilepticus.
 Suspension will produce higher peak levels than tablets—start with a lower
dose given more frequently.
 Ensure that patient swallows ER tablets whole—do not cut, crush, or chew.
 Arrange for frequent LFTs; discontinue drug immediately if hepatic
dysfunction occurs.
 WARNING: Arrange for patient to have CBC, including
platelet, reticulocyte counts, and serum iron determination, before initiating
therapy; repeat weekly for the first 3 month of therapy and monthly

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 thereafter for at least 2–3 yr. Discontinue drug if there is evidence of marrow
suppression, as follows:
Erythrocytes < 4 million/mm3

Hct < 32%

Hgb < 11 gm/Dl
Leukocytes < 4,000/mm3
Platelets < 100,000/mm3

Reticulocytes < 0.3% (20,000/mm2)

Serum iron 150 g/100 mL

 Arrange for frequent eye examinations, urinalysis, and BUN determinations.

 Arrange for frequent monitoring of serum levels of carbamazepine and
other antiepileptics given concomitantly, especially during the first few
weeks of therapy. Adjust dosage on basis of data and clinical response.
 Counsel women who wish to become pregnant; advise the use of barrier
contraceptives.
 Evaluate for therapeutic serum levels (usually 4–12 mcg/mL).

 Teaching points:
 Take drug with food as prescribed. Swallow extended-release tablets whole,
do not cut, crush, or chew them. If using Equetro capsules, they may be
opened and contents sprinkled over soft food, such as 1 teaspoon of
applesauce.

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 Do not discontinue this drug abruptly or change dosage, except on the
advice of your physician.
 Avoid alcohol, sleep-inducing, or over-the-counter drugs; these could cause
dangerous effects.
 Arrange for frequent checkups, including blood tests, to monitor your
response to this drug. Keep all appointments for checkups.
 Use contraceptives at all times; if you wish to become pregnant, you should
consult your physician.
 Wear a medical alert tag at all times so that any emergency medical
personnel will know that you have epilepsy and are taking antiepileptic
medication.
 You may experience these side effects: Drowsiness, dizziness, blurred vision
(avoid driving or performing other tasks requiring alertness or visual
acuity); GI upset (take the drug with food or milk; eat frequent small meals).

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 CNS STIMULANTS

 INTRODUCTION:
Stimulants are a substance which tends to increase behavioral activity when
administered. Stimulants are commonly used in treating ADHD but also have
other uses. Some of those uses are narcolepsy, also, obesity, fatigue and
sometimes depression.. Stimulants such as amphetamines, methyl phenidate
(Ritalin-a little different than an amphetamine), and other stimulants are
commonly prescribed, mostly with children and teens, but also with adults.The
work by increasing the level of nor-epinephrine and dopamine in the brain;
some also trigger release of these chemicals from storage areas in cells. Different
stimulants have slightly different mechanisms for raising the level of these
neurotransmitters. Stimulants (also often referred to as psychostimulants or
colloquially as uppers) is an overarching term that covers
many drugs including those that increase activity of the central nervous
system and the body,[1] drugs that are pleasurable and invigorating, or drugs
that have sympathomimetic effects. Stimulant, any drug that excites any bodily
function, but more specifically those that stimulate the brain and
central nervous system. Stimulants induce alertness, elevated mood,
wakefulness, increased speech and motor activity and decrease appetite. Their
therapeutic use is limited, but their mood-elevating effects make some of them
potent drugs of abuse. The major stimulant drugs are amphetamines and
related compounds, methylxanthines (methylated purines), cocaine, and
nicotine. Amphetamines achieve their effect by increasing the amount and

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activity of the neurotransmitter norepinephrine (noradrenaline) within the
brain. They facilitate the release of norepinephrine by nerve cells and interfere
with the cells’ reuptake and breakdown of the chemical, thereby increasing its
availability within the brain. The most commonly used amphetamines
are methamphetamine (Methedrine), amphetamine sulfate (Benzedrine),
and dextroamphetamine sulfate (Dexedrine). Amphetamines were first used in
the 1930s to treat narcolepsy and subsequently became prescribed
for obesity and fatigue. Their heavy or prolonged use causes irritability,
restlessness, hyperactivity, anxiety, excessive speech, and rapid mood swings.
Still higher doses or chronic use can cause agitation, tremor, confusion, and, in
the most serious cases, a state resembling paranoid schizophrenia. Moreover,
letdown effects of deep depression and physical exhaustion may occur after
only a single dose of moderate strength wears off. With repeated use, tolerance
develops, so that a user needs to take larger doses, but the accompanying
dependence is not strong enough to be termed a physical addiction.
Amphetamines are widely abused, in some cases by workers or students
seeking enhanced physical energy and mental acuity to fulfill demanding
tasks. Certain drugs related to the amphetamines have the same mode of action
but are somewhat milder stimulants. Among them are phenmetrazine
(Preludin) and methylphenidate (Ritalin). The latter drug is widely used to
“slow down” hyperactive children and improve their ability to concentrate.

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 Prescription Stimulants:
Illicit drugs are not the only stimulants out there, as prescription amphetamines
have become popular drugs of abuse in recent years. These drugs include
Ritalin, Adderall, and Concerta. They are often prescribed to treat attention
deficit hyperactivity disorder (ADHD), a condition that affects an individual’s
ability to focus and control impulses. According to the Center for Disease
Control and Prevention (CDC), 11 percent of people 4-17 years old had been
diagnosed with ADHD as of 2011.
 Specific Prescription Stimulants
 Ritalin
 Adderall
 Concerta
 Dexedrine
 Vyvanse
 Other Prescription Drug Classes
 Opiates
 Benzodiazepines
 Barbiturates
 Narcotic Drugs
 Prescription Drugs

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 Classification of Stimulants:
Central nervous system stimulants can be divided into three groups:
1. Convulsants and Respiratory Stimulants: Bicuculline, Picrotoxin,
Pentylenetetrazol, and Doxapram are the drugs of this group. These drugs
have no clinical application and are often used in poisons, in intensive care
settings, and for research. Their mechanism of action is unknown.
2. Psychotomimetic Drugs/ Hallucinogens: These drugs
produce hallucinations by altering the perception of the surrounding
environment. Drugs in this group include lysergic acid, psilocybin, and
mescaline.
3. Psychomotor Stimulants: These psychotropic medications stimulate the
central nervous system (CNS) by boosting the release of certain chemicals
in the brain. They include:
 Adderall (amphetamine and dextroamphetamine)
 Dexedrine (dextroamphetamine)
 Ritalin (methylphenidate)

 Mechanism of action
These drugs achieve their beneficial effects by increasing the levels of
dopamine, serotonin, and norepinephrine in the brain. Dopamine, one of the
most important neurotransmitters, is related to concentration, attention, and
feelings of reward and pleasure. Norepinephrine plays an important role in
alertness. Some stimulant drugs also increase the level of glutamate, a
neurotransmitter associated with behavioral control and inhibition. People
experiencing attention deficit hyperactivity (ADHD) often have low levels

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 of glutamate. Methylxanthines inhibit the phosphodiesterase enzymes. This
increases intracellular cyclic adenosine monophosphate. Moreover, they
also block adenosine receptors and increase the movement of extracellular
calcium. Nicotine, at high doses, produces ganglionic stimulation. It binds
with all nicotinic receptors. Varenicline has a similar action to nicotine.
Amphetamine exerts effects by promoting the release of monoamines
(serotonin, dopamine, and norepinephrine). Amphetamine may also inhibit
the function of monoamine oxidase. Cocaine inhibits the activity of
transporters that promote the reuptake of monoamines.

 Therapeutic uses:
1. ADHD: In both children and adults, ADHD is the most common reason
for a stimulant prescription. By one estimate, 8% of children experience
ADHD, while 2% to 5% of adults are diagnosed. While it may seem odd
to prescribe a stimulant drug to someone with hyperactivity, these drugs
actually increase a person's ability to control their urges and behaviors.
Overall, the effect is calming and leads to improved focus in school and
at work.
2. Narcolepsy: Stimulant drugs are also prescribed for the treatment
of narcolepsy. People with narcolepsy have sudden attacks of extreme
sleepiness, impairing basic functioning and preventing them from doing
simple tasks such as driving or working a regular job. Stimulants help the
person maintain alertness throughout the day.

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 3. Exogenous Obesity: Amphetamines are used for
exogenous obesity (obesity from consuming too many calories).
4. Headache: Caffeine is sometime used to treat headaches. It may use in
combination with various analgesics to relieve pain, stress, tension, and
fatigue.

 Drug interactions:
It is important to disclose any other drugs or medications that you ingest
with your doctor before taking a stimulant, as adverse drug interactions can
occur. Certain substances may lose their effectiveness or negatively interact
if taken with stimulants:
 Antidepressants should be avoided since their use with psychomotor
stimulants produces exaggerated cardiovascular effects.
 Anticoagulants interfere with the metabolism of psychomotor stimulants.
 Amphetamines increase the effects of the neurotransmitter
norepinephrine, which aids in the body’s stress response.

 Phenothiazine (chlorpromazine), an antipsychotic, counteracts the effects

of psychomotor stimulants.

 Amphetamines may antagonize the outcomes of antihypertensives (blood

pressure medication).

 Amphetamines may decrease the rate absorption of phenytoin (an

anticonvulsant).

 Insulin requirements may decrease while using amphetamines.

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1. AMPHETAMINE SULFATE
 Name of the drug:
 Trade Name :- Tab. Adderall
 Pharmacological Name:- Amphetamine Sulphate

 Drug classes:
 CNS Stimulant

 Available forms:
 Tablets—5mg; 7.5mg; 10mg; 12.5mg; 15mg; 20mg

 Dosage:
 Adults: 5-20 mg 1-3 times/day.
 Children over 12 years, initial: 5 mg b.i.d.; increase in increments of 10
mg/day at weekly intervals until optimum dose is reached.
 Children, 6-12 years, initial: 2.5 mg b.i.d.; increase in increments of 5 mg at
weekly intervals until optimum dose is reached (maximum is 60 mg/day).
Attention deficit disorders in children.
 3-6 years, initial: 2.5 mg/day; increase by 2.5 mg/day at weekly intervals
until optimum dose is achieved (usual range 0.1-0.5 mg/kg/dose each
morning).
 6 years and older, initial: 5 mg 1-2 times/day; increase in increments of 5
mg/week until optimum dose is achieved (rarely over 40 mg/day). The dose
of Adderall is 5-30 mg per day.

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 Indications:
 Attention Deficit Hyperactivity Disorder
 Need for Comprehensive Treatment Program

 Contraindications:
 Advanced arteriosclerosis,
 Symptomatic cardiovascular disease,
 Moderate to severe hypertension,
 Hyperthyroidism,
 Known hypersensitivity or idiosyncrasy to the sympathomimetic amines,
 Glaucoma.
 Agitated states.
 Patients with a history of drug abuse.
 During or within 14 days following the administration of monoamine
oxidase inhibitors (hypertensive crises may result).

 Mechanism of Action:

Amphetamines are non-catecholamine sympathomimetic amines with CNS

stimulant activity. The mode of therapeutic action in ADHD is not known.
Amphetamines are thought to block the reuptake of norepinephrine and
dopamine into the presynaptic neuron and increase the release of these
monoamines into the extra neuronal space.

155
 Pharmacokinetics:
The half-life of racemic amphetamine is 12–13 hours and is excreted renally,
with a significant portion unaltered. Metabolism takes place mostly in liver.
Deamination into phenylacetone happens via CYP2C and renders the
compounds inert. Phenylacetone is then further metabolized into benzoic
acid and hippuric.

 Side effects:
 Headache
 upset stomach
 trouble sleeping
 decreased appetite
 unpleasant taste in your mouth
 nervousness
 dizziness
 sexual dysfunction
 vomiting
 itching
 diarrhoea or constipation
 dry mouth
 weight loss
 mood swings

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 Drug Interactions:
 Acidifying agents -Gastrointestinal acidifying agents (guanethidine,
reserpine, glutamic acid HCl, ascorbic acid, fruit juices, etc.) lower
absorption of amphetamines.
 Urinary acidifying agents -(ammonium chloride, sodium acid phosphate,
etc.) Increase the concentration of the ionized species of the amphetamine
molecule, thereby increasing urinary excretion. Both groups of agent’s lower
blood levels and efficacy of amphetamines.
 Adrenergic blocker -Adrenergic blockers are inhibited by amphetamines.
 Alkalinizing agents -Gastrointestinal alkalinizing agents (sodium
bicarbonate, etc.) increase absorption of amphetamines. Co-administration
of ADDERALL and gastrointestinal alkalizing agents, such as antacids,
should be avoided.
 Antidepressants, tricyclic -Amphetamines may enhance the activity of
tricyclic or sympathomimetic agents; d-amphetamine with desipramine or
protriptyline and possibly other tricyclics cause striking and sustained
increases in the concentration of d-amphetamine in the brain; cardiovascular
effects can be potentiated.

 Nurses Responsibility
Report to doctor if have following symptoms
 New or worse behavior and thought problem.
 New or worse bipolar illness.
 New or worse aggressive behavior or hostility.

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2. METHYLPHENIDATE HYDROCHLORIDE
 Name of the drug
 Trade Name :- Tab.Ritalin
 Pharmacological Name:- Methylphenidine Hydrochloride

 Drug class:
 CNS Stimulant

 Available forms:
 Tablets—5, 10, 20 mg;
 Chewable tablets—2.5, 5, 10 mg;
 SR tablets—20 mg;
 ER tablets—10, 18, 20, 27, 36, 54 mg;
 ER capsules—20, 30 mg (Metadate CD); and 20, 30, 40 mg (Ritalin LA)

 Dosages:
 ADULTS
Individualize dosage. Administer orally in divided doses bid or tid,
preferably 30–45 min before meals; dosage ranges from 10–60 mg/day PO.
If insomnia is a problem, drug should be taken before 6 PM. Timed-release
tablets have a duration of 8 hr and may be used when timing and dosage are
adjusted to the 8-hr daily regimen.

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  PEDIATRIC PATIENTS 13-17 YR
Initially 18 mg/day PO taken in the morning without regard to food; titrate
to a maximum 72 mg/day PO. Do not exceed 2 mg/kg/day. Tablets must
be swallowed whole and should not be cut, crushed, or chewed (Concerta).

 PEDIATRIC PATIENTS > 6 YR

Start with small oral doses (5 mg PO before breakfast and lunch with gradual
increments of 5–10 mg weekly). Daily dosage > 60 mg not recommended.

 Indications:
 Narcolepsy
 Attention-deficit disorders, hyperkinetic syndrome, minimal brain
dysfunction in children or adults with a behavioral syndrome characterized
by the following symptoms:
 Moderate to severe distractibility, short attention span, hyperactivity,
emotional lability, and impulsivity, not secondary to environmental factors
or psychiatric disorders
 Treatment of depression in the elderly,
 Cancer and stroke patients;
 Alleviation of neurobehavioral symptoms after traumatic brain injury;
 Improvement in pain control and sedation in patients receiving opiates

 Contraindications
 Hypersensitivity to methylphenidate;
 Marked anxiety,

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  Tension, and agitation;
 Glaucoma;
 Motor tics,
 Family history or diagnosis of Tourette syndrome;
 Severe depression of endogenous or exogenous origin;
 Normal fatigue states.

 Therapeutic actions:
Mild cortical stimulant with CNS actions similar to those of the amphetamines;
efficacy in hyperkinetic syndrome, attention-deficit disorders in children
appears paradoxical and is not understood

 Pharmacokinetics:

Route Onset Peak Duration

Oral Varies 1–3 hr 4–6 hr

 Metabolism: Hepatic; T1/2: 1–3 hr (6.8 hr ER)

 Distribution: Crosses placenta; may enter breast milk
 Excretion: Urine

 Adverse effects:
 CNS: Nervousness, insomnia, dizziness, headache, dyskinesia, chorea,
drowsiness, Tourette syndrome, toxic psychosis, blurred vision,
accommodation difficulties

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  CV: Increased or decreased pulse and BP; tachycardia, angina, cardiac
arrhythmias, palpitations
 Dermatologic: Rash, urticaria,
fever, arthralgia, exfoliative dermatitis, erythema multiforme with
necrotizing vasculitis and thrombocytopenic purpura, loss of scalp hair
 GI: Anorexia, nausea, abdominal pain, weight loss
 Hematologic: Leukopenia, anemia
 Other: Tolerance, psychological dependence, abnormal behavior with abuse

 Drug- Interactions:
 Decreased effects of guanethidine; avoid this combination
 Increased effects and toxicity of methylphenidate with MAOIs
 Increased serum levels of phenytoin, TCAs, oral anticoagulants, SSRIs with
methylphenidate; monitor for toxicity
 Seizure disorders;
 Hypertension;
 Drug dependence,
 Alcoholism;
 Emotional instability;
 Lactation,
 Pregnancy.

 Nurses Responsibility
 Assessment

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  History: Hypersensitivity to methylphenidate; marked anxiety, tension, and
agitation; glaucoma; motor tics, Tourette syndrome; severe depression;
normal fatigue state; seizure disorders; hypertension; drug dependence,
alcoholism, emotional instability; pregnancy, lactation
 Physical examination: Weight; T; skin color, lesions; orientation, affect,
ophthalmologic examination (tonometry); P, BP, auscultation; R,
adventitious sounds; bowel sounds, normal output; CBC with differential,
platelet count, baseline ECG

 Interventions:
 Ensure proper diagnosis before administering to children for behavioral
syndromes; drug should not be used until other causes or concomitants of
abnormal behavior (learning disability, EEG abnormalities, neurologic
deficits) are ruled out.
 Interrupt drug dosage periodically in children to determine if symptoms
warrant continued drug therapy.
 Monitor growth of children on long-term methylphenidate therapy.
 Ensure that all timed-release tablets and capsules are swallowed whole, not
chewed or crushed.
 Dispense the smallest feasible dose to minimize risk of overdose.
 Give before 6 PM to prevent insomnia.
 Monitor CBC and platelet counts periodically in patients on long-term
therapy.
 Monitor BP frequently early in treatment.

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 Teaching points:
 Take this drug exactly as prescribed. Timed-release tablets and capsules
must be swallowed whole, not chewed or crushed. Metadate CD capsules
may be opened and entire contents sprinkled on soft food—do not chew or
crush granules.
 Take drug before 6 PM to avoid nighttime sleep disturbance.
 Avoid alcohol and over-the-counter drugs, including nose drops, cold
remedies; some over-the-counter drugs could cause dangerous effects.
 You may experience these side effects: Nervousness, restlessness, dizziness,
insomnia, impaired thinking (may lessen; avoid driving or engaging in
activities that require alertness); headache, loss of appetite, dry mouth.
 Keep drug in secure place; do not share with others.
 Report nervousness, insomnia, palpitations, vomiting, rash, fever.

3. DEXTROAMPHETAMINE
 Name of the drug:
 Trade Name :- Tab.Dextrostat
 Pharmacological Name:- Dextroamphetamine

 Drug classes:
 CNS Stimulant
 Amphetamine

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 Available forms:
 Tablets —5, 10, 15 mg;
 SR capsules—5, 10, 15 mg

 Dosages:
 ADULTS
 Narcolepsy: Start with 10 mg/day PO in divided doses; increase in
increments of 10 mg/day at weekly intervals. If insomnia or anorexia occurs,
reduce dose. Usual dosage is 5–60 mg/day PO in divided doses. Give first
dose on awakening, additional doses (one or two) q 4–6 hr; long-acting forms
can be given once a day.
 PEDIATRIC PATIENTS
 Narcolepsy: 6–12 year: Condition is rare in children < 12 yr; when it
does occur, initial dose is 5 mg/day PO. Increase in increments of 5 mg at
weekly intervals until optimal response is obtained.
>12 yr: Use adult dosage.

 Attention- deficit disorder: < 3 year: Not recommended. 3–

5 yr: 2.5 mg/day PO. Increase in increments of 2.5 mg/day at weekly
intervals until optimal response is obtained.
> 6 yr: 5 mg PO daily–bid. Increase in increments of 5 mg/day at weekly
intervals until optimal response is obtained. Dosage will rarely exceed
40 mg/day. Give first dose on awakening, additional doses (one or two) q
4–6 hr. Long-acting forms may be used once a day.

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 Indications:
 Narcolepsy
 Adjunct therapy for abnormal behavioral syndrome in children (attention-
deficit disorder, hyperkinetic syndrome) that includes psychological, social,
educational measures.

 Contraindications:
 Hypersensitivity
to sympathomimetic amines, tartrazine (Dexedrine and DextroStat);
 Advanced arteriosclerosis,
 Symptomatic CV disease,
 Moderate to severe hypertension,
 Hyperthyroidism,
 Glaucoma,
 Agitated states.

 Therapeutic actions:
Acts in the CNS to release norepinephrine from nerve terminals; in higher
doses also releases dopamine; suppresses appetite; increases alertness, elevates
mood; often improves physical performance, especially when fatigue and
sleep-deprivation have caused impairment; efficacy in hyperkinetic syndrome,
attention-deficit disorders in children appears paradoxical and is not
understood.

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 Pharmacokinetics:

Route Onset Peak Duration

Oral Rapid 1–5 hr 8–10 hr

 Metabolism: Hepatic; T1/2: 10–30 hr

 Distribution: Crosses placenta; enters breast milk
 Excretion: Urine

 Adverse effects:
 CNS: Overstimulation, restlessness, dizziness, insomnia, dyskinesia,
euphoria, dysphoria, tremor, headache, psychotic episodes
 CV: Palpitations, tachycardia, hypertension
 Dermatologic: Urticaria
 Endocrine: Reversible elevations in serum thyroxine with heavy use
 GI: Dry mouth, unpleasant taste, diarrhea, constipation, anorexia and
weight loss
 GU: Impotence, changes in libido
 Other: Tolerance, psychological dependence, social disability with abuse

 Drug- Interactions:
 WARNING: Hypertensive crisis and increased CNS effects if given within
14 days of MAOIs; do not give dextroamphetamine to patients who are
taking or who have recently taken MAOIs

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  Decreased duration of effects if taken with
urinary alkalinizes (acetazolamide, sodium bicarbonate), furazolidone
 Decreased effects if taken with urinary acidifiers
 Decreased efficacy of antihypertensive drugs (guanethidine) given with
amphetamines

 Cautions:
 History of drug abuse;
 Pregnancy;
 Lactation

 Nurses Responsibility
 Assessment
 History: Asses Hypersensitivity to sympathomimetic amines, tartrazine;
advanced arteriosclerosis, symptomatic CV disease, moderate to severe
hypertension, hyperthyroidism, glaucoma, agitated states, history of drug
abuse; lactation, pregnancy, use of MAOI in the last 14 days

 Physical examination: Weight; T; skin color, lesions; orientation, affect,

ophthalmic examination (tonometry); P, BP, auscultation; R, adventitious
sounds; bowel sounds, normal output; thyroid function tests, blood and
urine glucose, baseline ECG.

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 Interventions:
 Ensure proper diagnosis before administering to children for behavioral
syndromes. Drug should not be used until other causes (learning disability,
EEG abnormalities, neurologic deficits) are ruled out.
 Interrupt drug dosage periodically in children being treated for behavioral
disorders to determine if symptomatic response still validates drug therapy.
 Monitor growth of children on long-term amphetamine therapy.
 Dispense the lowest feasible dose to minimize risk of overdosage; should be
in a light-resistant container.
 Ensure that patient swallows SR tablets whole; do not cut, crush, or chew.
 Give drug early in the day to prevent insomnia.
 Monitor BP frequently early in therapy.

 Teaching points:
 Take this drug exactly as prescribed. Do not increase the dosage without
consulting your health care provider. If the drug appears ineffective, consult
your health care provider.
 Do not crush or chew sustained-release or long-acting tablets.
 Take drug (especially sustained-release form) early in the day to avoid
insomnia.
 Avoid pregnancy while taking this drug. This drug can cause harm to the
fetus.
 You may experience these side effects: Nervousness, restlessness, dizziness,
insomnia, impaired thinking (may diminish in a few days; avoid driving.

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 ANTIPARKINSONIAN

 INTRODUCTION
Anti-Parkinson drugs are medicines that relieve the symptoms of Parkinson's
disease and other forms of parkinsonism. Anti-Parkinson drugs are used to
treat symptoms of parkinsonism, a group of disorders that share four main
symptoms: tremor or trembling in the hands, arms, legs, jaw, and face; stiffness
or rigidity of the arms, legs, and trunk; slowness of movement (bradykinesia);
and poor balance and coordination. Parkinson's disease is the most common
form of parkinsonism and is seen more frequently with advancing age. Other
forms of the disorder may result from viral infections, environmental
toxins, carbon monoxide poisoning, and the effects of treatment
with antipsychotic drugs.
Although Parkinson's disease can't be cured, treatments are available to help
reduce symptoms and maintain quality of life. These include supportive
therapies such as physiotherapy, occupational therapy and psychological
counselling that help you cope with everyday life, or medication to control your
symptoms. Surgical procedures such as deep brain stimulation may be used
under the direction of the psychiatrist/ nurse practitioners/ clinal
psychologists.
Antiparkinsonian drugs are medicines used to treat the symptoms of
Parkinson's disease. The majority of the registered antiparkinsonian drugs in
Hong Kong are available in oral dosage forms e.g., tablets, capsules; while a few
of them are presented in injectable forms and transdermal patches.
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 Due to the chronic nature of Parkinson's disease (PD), a broad-based program
is needed that includes patient and family education, support-group services,
general wellness maintenance, exercise, and nutrition. At present, no cure for
the disease is known, but medications or surgery can provide relief from the
symptoms. While many medications treat Parkinson's, none actually reverses
the effects of the disease. Furthermore, the gold-standard treatment varies with
the disease state. People with Parkinson's, therefore, often must take a variety
of medications to manage the disease's symptoms.[1] Several medications
currently in development seek to better address motor fluctuations and
nonmotor symptoms of PD. However, none is yet on the market with specific
approval to treat Parkinson's.

 Oral antiparkinsonian drugs:

Antiparkinsonian drugs consist largely of the use of dopaminergics or
antimuscarinics in an attempt to restore the normal balance between dopaminergic
and cholinergic activity. Drugs with different actions may be necessary to achieve
optimum control of symptoms. The medications may include:

a) Levodopa: this drug is the most effective medication to control the symptoms
of Parkinson's disease. It is absorbed by the nerve cells in your brain and is
converted to dopamine. Levodopa is usually combined with a peripheral dopa-
decarboxylase inhibitor such as benderizine or carbidopa. Dopa-decarboxylase
inhibitors prevent the breakdown of levodopa in the gut, which allows effective
concentrations of dopamine to be achieved in the brain with lower doses of
levodopa, and also reduces side effects such as nausea and vomiting.

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b) Dopamine agonists: they act as a substitute for dopamine in the brain and have
a direct action on dopamine receptors. They are not as effective as levodopa in
improving the symptoms of Parkinson's disease. However, they are less likely
to cause muscle problems than levodopa and are used to treat early Parkinson’s
disease. Examples include pramipexole, ropinirole, bromocriptine and
cabergoline.

c) Monoamine oxidase-B (MAO-B) inhibitors: they block the effects of an

enzyme called monoamine oxidase-B in the brain that metabolizes or
breakdown brain dopamine. They are used as an alternative to levodopa for
treating early Parkinson’s disease. Examples include selegiline and rasagiline.

d) Catechol O-methyltransferase (COMT) inhibitors: they prevent the

peripheral breakdown of levodopa, by inhibiting an enzyme called catechol-O-
methyltransferase (COMT). Adding a peripheral COMT inhibitor can therefore
extend the duration and effect of levodopa in the brain, and allow lower and
less frequent doses of levodopa. They are usually prescribed for people in later
stages of Parkinson’s disease. Examples include entacapone.

e) Antimuscarinics: they have a weak antiparkinsonian effect compared with

levodopa. They reduce tremor and rigidity but have little effect on
bradykinesia. Antimuscarinic side effects, particularly cognitive impairment,
occur frequently and can limit their use. Examples include orphenadrine and
benztropine.

f) Amantadine: it is a weak dopamine agonist with some antimuscarinic activity.

It has mild antiparkinsonian effects compared with levodopa. It may be used
alone to provide short-term relief of symptoms of mild, early-stage Parkinson's
disease, and may also be given with levodopa therapy during the later stages
of the disease to control involuntary movements induced by levodopa.

171
 The key steps in the synthesis and degradation of dopamine and the sites of
action of various psychoactive substances at the dopaminergic synapse:

172
 Treatment approaches to newly diagnosed idiopathic PD:

173
1. TRIHEXYPHENIDYL Hydrochloride

 Name of the drug:

 Trade Name :- Tab.Dextrostat
 Pharmacological Name :- Dextroamphetamine

 Drug classes:
 CNS Stimulant
 Amphetamine

 Available forms:
 Tablets—5, 10, 15 mg;
 SR capsules—5, 10, 15 mg

 Dosage:
 Usual Adult Dose for Extrapyramidal Reaction
4 to 10 mg orally each day. The total daily dose is best tolerated when
administered in 2 or three equally separated doses.
 Usual Adult Dose for Parkinson's Disease
Initial: 1 mg/day; increase by 2 mg increments at intervals of 3 to 5 days
Usual dose: 6 to 10 mg/day in 3 to 4 divided doses; doses of 12 to 15 mg/day
may be required.Drug-induced extrapyramidal symptoms: Initial: 1
mg/day; increase as necessary to usual range of 5 to 15 mg/day in 3 to 4
divided doses.Use in combination with levodopa: Usual range: 3 to 6
mg/day in divided doses

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  Usual Pediatric Dose for Cerebral Spasticity
 Oral:
Children 2 to 17 years old:
Dystonia in cerebral palsy:
Initial: 0.1 to 0.2 mg/kg/day in three divided doses for 1 week; increase by
0.05 to 0.3 mg/kg/day in three divided doses for the second week;
thereafter, titrate up weekly by 0.05 to 0.5 mg/kg/day in three divided
doses as clinically tolerated
Maximum dose: 0.75 mg/kg/day

 Indications:
 Adjunct in Parkinsonism.
 Drug-induced extrapyramidal symptoms (EPS).

 Contraindications:
 Tardive dyskinesia.
 Narrow-angle glaucoma.

 Therapeutic Actions:
The indirect pathway of neurotransmission within the basal ganglia may be
related to imbalance between dopaminergic and cholinergic systems.
Trihexyphenidyl, a synthetic anticholinergic, acts as a competitive antagonist at
muscarinic receptors to decrease acetylcholine. It may also improve dystonia
through a direct relaxant effect on smooth muscle

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 Pharmacokinetics:
Trihexyphenidyl is rapidly absorbed after oral administration.] In a study of 8
adults being treated with doses of 2–8 mg/day, the average peak serum
concentration was 7.15 + 2.58 ng/mL, reached at an average of 1.32 + 0.58 hours
after a dose. Trihexyphenidyl is metabolized in the liver via hydroxylation. The
estimated elimination half-life in adults has been estimated at 5 to 10 hours, but
newer studies have reported much longer values of up to 33 hours. The average
onset of effect of trihexyphenidyl is seen within one hour after an oral dose in
adults. Peak effects typically occur within 2–3 hours, and the duration of effect
ranges from 6 to 12 hours.

 Side effects:
 Anticholinergic and antihistaminic effects,
 confusion,
 anhidrosis,
 excitement,
 nausea, vomiting,
 angle-closure glaucoma,
 hallucinations,
 neuroleptic malignant syndrome,
 heat stroke,
 drowsiness.

 Drug interaction:
 Potentiates CNS depression with alcohol, CNS depressants.

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  Antagonizes psychotropics.
 Additive anticholinergic effects with MAOIs.
 Paralytic ileus with phenothiazines, tricyclic antidepressants.

 Cautions:
 Cardiovascular, renal, or hepatic disorders.
 Hypertension.
 Psychosis.
 GI or GU obstruction.
 Exposure to extreme heat.
 Monitor intraocular pressure.
 Avoid abrupt cessation.
 Nursing mothers.

 Nurses Responsibility
 Observe for parkinsonian & extra pyramidal symptoms prior & during the
therapy
 Monitor intake- outer chart
 In presence of behavioral changes withhold the drug & report to the
consultant
 Instruct the patient to take the drug as directed
 Medication should be tapered gradually
 Advice the client not to drive & other activities require alertness
 Caution the patient to change positions slowly to minimize the orthostatic
hypotension

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  Instruct the patient to rinse the mouth frequently to prevent dry mouth
 Instruct the patient to avoid antacids within 1-2 hours of this medication
 Emphasize on routine follow up examination.

2. DIPHENHYDRAMINE
 Name of the drug
 Trade Name :- Tab. Benedryl
 Pharmacological Name :- Diphenhydramine

 Drug classes:
 CNS Stimulant
 Antihistamine
 Anti-motion sickness drug
 Sedative-hypnotic
 Antiparkinsonian
 Cough suppressant

 Available forms:
 Capsule soft gels—25 mg;
 Capsules—25, 50 mg;
 Tablets—25, 50 mg;
 Chewable tablets—12.5 mg;
 Elixir—12.5 mg/5 ml;
 Syrup—12.5 mg/5 ml;

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  Liquid—6.25, 12.5 mg/5 ml;
 Injection—10, 50 mg/ ml;
 Solution—12.5 mg/5 mL

 Dosages:
 ADULTS
 Oral: 25–50 mg q 4–8 hr PO.
 Motion sickness: Give full dose prophylactically 30 min before exposure
to motion, and repeat before meals and hs.
 Nighttime sleep aid: 25–50 mg PO hs.
 Cough suppression: 25 mg q 4 hr PO, not to exceed 150 mg in 24 hr.
 Parenteral: 10–50 mg IV or deep IM or up to 100 mg if required. Maximum
daily dose is 400 mg.
 PEDIATRIC PATIENTS > 10 KG OR 20 LB
 Oral: 12.5–25 mg tid–qid PO or 5 mg/kg/day PO or 150 mg/m2 per day
PO. Maximum daily dose 300 mg.
 Motion sickness: Give full dose prophylactically 30 min before exposure
to motion and repeat before meals and hs.
 Cough suppression:
2–6 yr: 6.25 mg q 4 hr, not to exceed 25 mg in 24 hr.
6–12 yr: 12.5 mg q 4 hr PO, not to exceed 75 mg in 24 hr.
 Parenteral: 5 mg/kg/day or 150 mg/m2 per day IV or by deep IM
injection. Maximum daily dose is 300 mg divided into four doses.

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  GERIATRIC PATIENTS:
More likely to cause dizziness, sedation, syncope, toxic confusional states,
and hypotension in elderly patients; use with caution.

 Indications:
 Relief of symptoms associated with perennial and seasonal allergic rhinitis;
vasomotor rhinitis; allergic conjunctivitis; mild,
uncomplicated urticaria and angioedema; amelioration of allergic reactions
to blood or plasma; dermatographias, adjunctive therapy in anaphylactic
reactions
 Active and prophylactic treatment of motion sickness
 Nighttime sleep aid
 Parkinsonism (including drug-induced parkinsonism
and extrapyramidal reactions), in the elderly intolerant of more potent
drugs, for milder forms of the disorder in other age groups, and in
combination with centrally acting anticholinergic antiparkinsonian drugs
 Syrup formulation: Suppression of cough due to colds or allergy

 Contraindications:
 Allergy to any antihistamines,
 Third trimester of pregnancy,
 Lactation.

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 Therapeutic actions:
Competitively blocks the effects of histamine at H1-receptor sites, has atropine-like,
antipruritic, and sedative effects.

 Pharmacokinetics:
Route Onset Peak Duration

Oral 15–30 min 1–4 hr 4–7 hr

IM 20–30 min 1–4 hr 4–8 hr

IV Rapid 30–60 min 4–8 hr

 Metabolism: Hepatic; T1/2: 2.5–7 hr

 Distribution: Crosses placenta; enters breast milk
 Excretion: Urine

 IV facts:
 Preparation: No additional preparation required.
 Infusion: Administer slowly each 25 mg over 1 min by direct injection or
into tubing of running IV.
 Incompatibilities: Do not combine
with amobarbital, amphotericin B, cephalothin,
hydrocortisone, phenobarbital, phenytoin, thiopental.
 Y-site incompatibilities: Do not mix with foscarnet.

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 Adverse effects:

SYSTEM SIDE-EFFECTS
CNS Drowsiness, sedation, dizziness, disturbed
coordination, fatigue, confusion, restlessness, excitation,
nervousness, tremor, headache, blurred vision, diplopia

CV Hypotension,palpitations, bradycardia,
tachycardia, extrasystoles

GI Epigastric distress, anorexia, increased appetite and weight

gain, nausea, vomiting, diarrhea or constipation

GU Urinary frequency, dysuria, urinary retention, early menses,

decreased libido, impotence

Hematologic Hemolyticanemia, hypoplastic anemia,

thrombocytopenia, leukopenia, agranulocytosis, pancytopenia

Respiratory
Thickening of bronchial secretions, chest tightness, wheezing,
nasal stuffiness, dry mouth, dry nose, dry throat, sore throat

Other
Urticaria, rash, anaphylactic shock, photosensitivity, excessive
perspiration

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 Drug- Interactions:
 Possible increased and prolonged anticholinergic effects with MAOIs.

 Cautions:
 Narrow-angle glaucoma,
 Stenosing peptic ulcer,
 Symptomatic prostatic hypertrophy,
 Asthmatic attack,
 Bladder neck obstruction,
 Pyloroduodenal obstruction,
 Pregnancy;
 Elderly patients who may be sensitive to anticholinergic effects.

 Nurses Responsibility
 Assessment
 History: Allergy to any antihistamines, narrow-angle
glaucoma, stenosing peptic ulcer, symptomatic prostatic hypertrophy,
asthmatic attack, bladder neck obstruction, pyloroduodenal obstruction,
third trimester of pregnancy, lactation
 Physical examination: Skin color, lesions, texture; orientation, reflexes,
affect; vision examination; P, BP; R, adventitious sounds; bowel sounds;
prostate palpation; CBC with differential

 Interventions:
 Administer with food if GI upset occurs.

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  Administer syrup form if patient is unable to take tablets.
 Monitor patient response, and arrange for adjustment of dosage to lowest
possible effective dose.

 Teaching points:
 Take as prescribed; avoid excessive dosage.
 Take with food if GI upset occurs.
 Avoid alcohol; serious sedation could occur.
 You may experience these side effects: Dizziness, sedation, drowsiness (use
caution driving or performing tasks requiring alertness); epigastric distress,
diarrhea or constipation (take drug with meals); dry mouth (use frequent
mouth care, suck sugarless lozenges); thickening of bronchial secretions,
dryness of nasal mucosa (use a humidifier).
 Report difficulty breathing, hallucinations, tremors, loss of coordination,
unusual bleeding or bruising, visual disturbances, irregular heartbeat.

3. BROMOCRIPTINE
 Name of the drug:
 Trade Name :- Tab.Parlodel
 Pharmacological Name:- Bromocriptine

 Drug classes:
 CNS Stimulant
 Amphetamine

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 Available forms:
 Tablets—5, 10, 15 mg;
 SR capsules—5, 10, 15 mg

 Dosages:
 Adult
 Hyperprolactinemia
Initial: 1.25 mg to 2.5 mg orally daily.
Titration: Add 2.5 mg orally, as tolerated, to the treatment dosage every 2
to 7 days.
Maintenance: 2.5 mg to 15 mg orally daily.

 Acromegaly
Initial: 1.25 mg to 2.5 mg orally once daily, with food, at bedtime for 3days.
Titration: Add 1.25 mg to 2.5 mg orally, as tolerated, to the treatment
dosage every 3 to 7 days.
Maintenance: 20 mg to 30 mg orally daily
Maximum dosage should not exceed 100 mg/day

 Parkinson's Disease
Initial: 1.25 mg twice daily with meals.
Titration: Add 2.5 mg/day, with meals, to dosage regimen every 14 to 28
days.
Maximum dosage: 100 mg/day.

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  Diabetes Mellitus Type II

For the Cycloset (R) trade name of bromocriptine only:

Initial: 0.8 mg orally daily taken within two hours after waking in the
morning with food
Titration: Increase by 0.8 mg weekly as tolerated
Maintenance: 1.6 to 4.8 mg orally daily taken within two hours after
waking in the morning with food
The maximum dosage should not exceed 4.8 mg daily.

 Pediatric Dose for Hyperprolactinemia

11 to 15 years old:
Initial: 1.25 mg to 2.5 mg orally daily.
Maintenance: 2.5 mg to 10 mg orally daily.

 Indications:
 Parkinson’s disease either alone or with other medications. It is also used for
 Galactorrhoea (abnormal milk production),
 Hypogonadism (reduced hormone production by sex hormones),
 Infertility,
 Suppressed lactation and
 Menstrual disorders

 Contraindications:
 Uncontrolled high blood pressure,
 Severe ischemic heart disease,

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  Breast cancer,
 During pregnancy and lactation and
 Hypersensitivity.

 Therapeutic actions:
The dopamine D2 receptor is a 7-transmembrane G-protein coupled receptor
associated with Gi proteins. In lactotrophs, stimulation of dopamine
D2 receptor causes inhibition of adenylyl cyclase, which decreases intracellular
cAMP concentrations and blocks IP3-dependent release of Ca2+ from
intracellular stores. Decreases in intracellular calcium levels may also be
brought about via inhibition of calcium influx through voltage-gated calcium
channels, rather than via inhibition of adenylyl cyclase. Additionally, receptor
activation blocks phosphorylation of p42/p44 MAPK and decreases
MAPK/ERK kinase phosphorylation. Inhibition of MAPK appears to be
mediated by c-Raf and B-Raf-dependent inhibition of MAPK/ERK kinase.
Dopamine-stimulated growth hormone release from the pituitary gland is
mediated by a decrease in intracellular calcium influx through voltage-gated
calcium channels rather than via adenylyl cyclase inhibition. Stimulation of
dopamine D2receptors in the nigrostriatal pathway leads to improvements in
coordinated muscle activity in those with movement disorders.

 Pharmacokinetics:
Oral absorption of Bromocriptine (Mesylate) is found to be 35% ±5. Volume of
distribution is found to be 1-3.7 l/kg and plasma protien binding is 96%.

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 Presystemic metabolism is noted to be 72.5% ±2.5 and metabolism is reported
Hepatic. Renal Excretion accounts for 6% and plasma half-life is 15 hr.

 Adverse effects:

SYSTEM SIDE-EFFECTS

Gastrointestinal Nausea, vomiting, gastric hemorrhage, abdominal

cramps, constipation and diarrhea.
Central Nervous
System Dizziness, headache, drowsiness, depression,
postural hypotension, hallucinations, confusion
Respiratory and psychosis.

Genitourinary

Nasal congestion and pleural effusion.

Urinary frequency, urinary incontinence, urinary

retention and increased Blood Urea Nitrogen.

 Drug- Interactions:
 The Cycloset brand of bromocriptine is used together with diet
and exercise to treat type 2 (non-insulin dependent) diabetes. Cycloset is not
for treating type 1 diabetes.

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  The Parlodel brand of bromocriptine is used to treat certain conditions
caused by a hormone imbalance in which there is too much prolactin in the
blood (hyperprolactinemia). Symptoms include lack of sexual development
in adolescents. Women may have missed menstrual periods, loss of interest
in sex,hot flashes, infertility, or unexpected breast milk production and
leakage from the nipples. Men may have enlarged breasts, decreased libido,
decreased facial or body hair, and loss of muscle. Parlodel is also used to
treat these disorders when they are caused by brain tumors that can produce
prolactin.

 Parlodel is sometimes used together with surgery or radiation in

treatingacromegaly, a condition caused by a pituitary gland tumor that
produces too much growth hormone.

 Parlodel is also used to treat symptoms of Parkinson's disease, such as

stiffness, tremors, muscle spasms, and poor muscle control.

 Cautions:
 Bromocriptine has been reported to cause heart attacks, strokes, high blood
pressure (hypertension), and low blood pressure (hypotension).
 At one point, bromocriptine was approved to suppress postpartum lactation
(to suppress breast milk production after childbirth for women who will not
be breastfeeding). However, bromocriptine is no longer approved for this
use, since the benefits of bromocriptine are not worth the risk of serious side
effects (such as strokes) for this use (see Parlodel and
Breastfeeding or Cycloset and Breastfeeding).

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 There have been some cases of lung problems in people who took
bromocriptine. In general, these problems slowly improved after
bromocriptine was stopped.
 It is not known whether bromocriptine is safe for people with liver or kidney
disease.
 Intense, unusual urges have been reported in people taking Parkinson's
disease medications. Examples include an intense desire to gamble or to
engage in risky sexual behavior. Let your healthcare provider know right
away if you experience any of these urges.
 People with Parkinson's disease have an increased risk for melanoma (a type
of skin cancer). At this time, it is not clear if this is caused by Parkinson's
disease medications or other factors. It is a good idea to have regular skin
checks to monitor for this problem.
 Bromocriptine can worsen psychosis and heart disease. If you have a history
of such problems, bromocriptine may not be a good choice for you.
 Let your healthcare provider know if you develop blue, numb fingers or toes
while taking bromocriptine. Your dosage may need to be reduced. Keeping
your fingers and toes warm can help prevent this problem.
 Bromocriptine can cause hallucinations (seeing, hearing, or feeling things
that are not really there) or other psychological problems. Let your
healthcare provider know if you develop hallucinations while taking
bromocriptine.
 Bromocriptine can potentially interact with several medications (see Drug
Interactions with Bromocriptine).

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  Bromocriptine is usually considered a pregnancy Category B medication.
This means that it is probably safe for use during pregnancy, although the
benefits may not outweigh the risks in many cases (see Parlodel and
Pregnancy or Cycloset and Pregnancy).
 Women should not take bromocriptine while breastfeeding. Therefore, if
you are breastfeeding or plan to start, discuss this with your healthcare
provider prior to taking the drug (see Parlodel and
Breastfeeding or Cycloset and Breastfeeding).
 Are allergic to bromocriptine mesylate, Parlodel, or any inactive
components used to make the medication. Your healthcare provider or
pharmacist has a list of the inactive ingredients.
 Are allergic to a class of drugs known as ergot alkaloids (bromocriptine is
one of these drugs).

 Nursing Responsibility
 Assessment
 Characteristic resting tremor of the extremities (may be worse on one side),
and possibly affecting the head and neck.
 Bradykinesia (slowness of movement).
 Muscle rigidity in performing all movements, as well as rest.
 Verbal fluency may be impaired.
 Signs of autonomic dysfunction (sleeplessness, salivation, sweating,
orthostatic hypotension).
 Depression, dementia.
 Masklike facies.

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  Poor balance, gait disturbances, speech problems.

 Diagnostic Evaluation:
 Diagnosis is based on observation of clinical symptoms and consideration of
patient’s age and history, confirmed by favorable response to levodopa
therapy.
 CT scanning and MRI may be performed to rule out other disorder.

 Pharmacologic Interventions:
 Various drugs can be used, often in combination to prolong effectiveness
because tolerance develops.
 Anticholinergics to reduce activation of cholinergic pathways, which are
thought to be overactive in dopamine deficiency.
 Amantadine, which may improve dopamine release in the brain.
 Levodopa, a dopamine precursor, combined with carbidopa, a decarboxylase
inhibitor, to inhibit destruction of L-dopa in the bloodstream, making more
available to the brain.
 Bromocriptine, a dopaminergic agonist that activates dopamine receptors in
the brain.
 Monoamine oxidase inhibitors as adjunct to levodopa therapy.
 Catecholamine-O-methyltransferase (COMT) inhibitors, as adjunct therapy
in combination with levodopa therapy; COMT is an enzyme that eliminates
dopamine from the brain.

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 Surgical Interventions:
 Medical pallidotomy to improve dyskinesia, rigidity, and tremor.
 Chronic deep brain stimulation through electrodes implanted into the
thalamus or globus pallidus to decrease tremor.
 Brain tissue transplants through the use of stem cells and genetically
engineered animal cells are a promising area of research.

 Nursing Intervention
 Monitor drug treatment to note adverse reactions and allow for dosage
adjustments. Monitor for liver function changes and anemia during drug
therapy.
 Monitor the patient’s nutritional intake and check weight regularly.
 Monitor the patient’s ability to perform activities of daily living.
 To improve mobility, encourage the patient to participate in daily exercise,
such as walking, riding stationary bike, swimming, or gardening.
 Advise the patient to perform stretching and postural exercises as outlined
by a physical therapist.
 Teach the patient walking techniques to offset parkinsonian shuffling gait
and tendency to lean forward.
 Encourage the patient to take warm baths and massage muscles to help relax
muscles.
 Instruct the patient to rest often to avoid fatigue and frustration.
 To improve the patient’s nutritional status, teach the patient to think through
the sequence of swallowing.

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  Urge the patient to make a conscious effort to control accumulation of saliva
(drooling) by holding head upright and swallowing periodically. Be alert for
aspiration hazard.
 Have the patient use secure, stabilized dishes and eating utensils.
 Suggest the patient eat smaller meals and additional snacks.
 To prevent constipation, encourage patient to consume foods containing
moderate fiber content (whole grains, fruits, and vegetables), and to increase
his or her water intake.
 Obtained a raised toilet seat to help the patient sit and stand.
 Teach the patient facial exercises and breathing methods to obtain
appropriate pronunciation, volume, and intonation.
 Teach the patient about the medication regimen and adverse reaction.

4. BENZTROPINE MESILATE
 Name of the drug:
 Trade Name :- Tab. Benedryl
 Pharmacological Name:- Diphenhydramine

 Drug classes
 CNS Stimulant
 Antihistamine
 Anti-motion sickness drug
 Sedative-hypnotic
 Antiparkinsonian

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  Cough suppressant

 Available forms
 Capsule soft gels—25 mg;
 Capsules—25, 50 mg;
 Tablets—25, 50 mg;
 Chewable tablets—12.5 mg;
 Elixir—12.5 mg/5 ml;
 Syrup—12.5 mg/5 ml;
 Liquid—6.25, 12.5 mg/5 ml;
 Injection—10, 50 mg/ ml;
 Solution—12.5 mg/5 ml.

 Dosages
 ADULTS
 Preparation : injection
 Strength: 5 – 6 mg
 Dose : arteriosclerotic , idiopathic and post encephalitic parkinsonism : the
usual daily dose is 1 to 2 mg with a range of 0.5 to 6 mg orally or parenterally.

 Indications:
 Drug induced parkinsonism, akathisia and acute dystonia
 Parkinson disease
 Idiopathic or secondary dystonia.

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 Contraindications:
 Narrow angle glaucoma because of its atropine like side effects , this drug is
contraindicated in children under 3 years of age , and should be used with
caution in order children.

 Therapeutic Actions:
Benztropine is a centrally acting anticholinergic agent resulting from the
combination of the tropine portion of the atropine molecule and the benzhydryl
portion of diphenhydramine. Animal studies have indicated that
anticholinergic activity of benztropine is approximately one half that of
atropine, while antihistaminic activity approaches that of pyrilamine. Its
anticholinergic effects have been established as therapeutically significant in
the management of Parkinsonism. benztropine antagonizes the effect of
acetylcholine, decreasing the imbalance between the neurotransmitter’s
acetylcholine and dopamine, which may improve the symptoms of early
Parkinson’s disease.

 Adverse effects:
SYSTEM SIDE-EFFECTS

CNS -Cognitive changes, nervousness, impaired memory, numbness of

fingers, listlessness and depression. mental confusing, excitement and
visual hallucinations with high doses.
Gastrointestinal

-Dry mouth, anorexia, constipation, nausea, vomiting, rarely paralytic

Ophthalmic: ileus.
Endocrine

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 Cardiovascular -Blurred vision, mydriasis
Hypersensitivity -Hyperthermia, anhidrosis, heat stroke, genitourinary
-Tachycardia
-Hypersensitivity

 Drug interaction:
Antipsychotic drugs such as phenothiazines or haloperidol tricyclic
antidepressants.
Pediatric use: - because of the atropine like side effects, cognentin should be
used with caution in pediatric patients over three years of age.

 Nurses responsibility
 Instruct the patient to rinse the mouth frequently to prevent dry mouth.
 Instruct the patient to take the drug as directed.
 Medication should be tapered gradually
 Caution the patient to avoid driving or other activities need alertness
 Observe for parkinsonian and extrapyramidal symptoms prior and during
the therapy
 Monitor intake output chart
 In presence of behavioral changes withhold the drug and report to the
consultant
 Emphasize on routine follow up examination.

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 CONCLUSION
Chronic co-administration of psychiatric drugs with known interaction
potential can be safely managed with dose changes, therapeutic interchanges
with similar products, and/or administration time adjustments. Newly
initiated combinations are the highest risk for adverse effects from drug
interactions; thus, first-dose monitoring is essential, along with the patient's
own personal report of the perceived benefit and side effects of therapy. When
considering drug-drug interactions with psychiatric agents, practitioners and
prescribers should consider the following survival tips: -

 Become an expert in the drugs used most often in one's own practice

 Pay special attention to those drugs with narrow therapeutic indices and
potential lethal doses

 Consult resources frequently

 Try to select agents that have a low degree of drug-interaction potential.

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 REFERENCES
1. Stuart GW, Laria MT. Principles and Practices of Psychiatric Nursing. IST ed.
Philadelphia: Mosby Publishers; 2001.
2. Kaplan HI, Sadock BJ. Synopsis of Psychiatry, Behavioral Sciences/ Clinical
Psychiatry. 9th ed. Hong Kong: William and Wilkinson Publishers ;1998.
3. Mary TC. Psychiatric Mental Health Nursing –Concept of Care 3rd ed.
Philadelphia: F.A. Davis Publishers ;2002
4. Ahuja N.A Short Text Book of Psychiatry 5th Ed. New Delhi: Jaypee Medical
Brothers Publishers .2002.
5. Dr. Bimla Kapoor; The Psychiatric nursing; Volume 2; second edition; Kumar
Publication; PP80-84.
6. R Sreevani; A Guide to Mental Health and Psychiatric nursing; Third edition;
Jaypee publication; Third Edition; PP103-104 therapies, pp 171-182
7. Capt.(rtd) Jacob alphonsa, hand book of psychiatric nursing, vikas publishing
house pvt ltd, New Delhi 1 st edition, 2003, drug therapy, pp 109 -116
8. Practical manual mental health nursing, IGNOU school of health sciences,
February 2001, types and administration of drugs (psychopharmacology and
role of nurse), pp 87-99
9. http://www.critpsynet.freeuk.com/moncrieff.htm
10.allpsych.com/psychology101/neurotransmitters.html
11.https://www.dana.org/media/detail.aspx?id=39884
12.webvision.med.utah.edu/book/part-iv-neurotransmitters-in-the-retina
13.www.goodreads.com › Health › Mental Health
14.www.madinamerica.com, anatomy-of-an-epidemic-down-under-PS
15.www.healthyplace.com, psychiatric-medication-cannot-cure-mental

199
 16. www.huffingtonpost.com, anatomy-of-an-epidemic-co_b_555572....

17. blogs.scientificamerican.com/. /are-psychiatric-medications-making

18. www.mind.org.uk/. /7996_making_sense_of_coming_off_psychiatry.

19. Stahl, S M. Stahl's Essential Psychopharmacology: Neuroscientific Basis and

Practical Applications. 3rd ed. New York: Cambridge University Press; 2008
20.Sadock, B J., V A. Sadock, and P Ruiz. Kaplan and Sadock's Comprehensive
Textbook of Psychiatry. 9th ed. Philadelphia: Lippincott Williams & Wilkins,
2009.
21. Grunder, G., H. Hippius, and A. Carlsson. "The 'Atypicality' of Antipsychotics:

A Concept Re-Examined and Re-Defined." Nat Rev Drug Discov 8.3 (2009): 197-
202.
22. Schatzberg, AF, Nemeroff, C. The American Psychiatric Publishing Textbook of

Psychopharmacology. 4th ed. American Psychiatric Publishing, 2010.

23. Taylor, D; Paton,C ; Kapur, S (Editors)The Maudsley Prescribing Guidelines in

Psychiatry, Wiley-Blackwell; 11th Edition,2011

24. Schatzberg, AF., Cole, JO, and DeBattista, C. Manual of Clinical
Psychopharmacology. 7th ed. American Psychiatric Publishing, 2010.

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THANK
YOU

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