Lecture - 3 Agents Used To Manage Schizophrenia June 2014

Post Basic Psychiatric
Nursing Programme
Psychopharmacology
Managing
Schizophrenia
Presenter:
Novlette Mattis-Robinson
(R.Ph, BPharm. , MPH/HP/HE)
1
ANTIPSYCHOTICS
Psychotropic agents used to manage
schizophrenia and other psychotic
and neurologic illnesses
Previously called Tranquilizers
somnolence, relaxation, sedation
Other Names -:
Neuroleptics
Dopamine Antagonists
2
ANTIPSYCHOTICS
The first antipsychotic agents were
introduced in the early to mid 1950s
rauwolfia alkaloid, reserpine and the
Phenothiazines (Chlorpromazine)
Reserpine was problematic but the
Chlorpromazine was very impressive
Antipsychotics have reduced the
number of hospital beds occupied by
patients diagnoses with Schizophrenia.
3
ANTIPSYCHOTICS
The major use treat Schizophrenia
Also used to treat Agitation and
Psychosis associated with psychiatric
and / or organic disorders.
They have little or no abuse potential
not classified as controlled
substances.
4
CAUSES OF
SCHIZOPHRENIA
The actual cause is uncertain
Multiple theories that provide partial
explanations
Theories include;
Dopamine hypothesis
Genetics
Neurodevelopmental
Psychosocial
5
CAUSES OF
SCHIZOPHRENIA
Dopamine Theory
Postulates that dopamine hyperactivity in
the brain is responsible for psychotic
symptoms
Other neurotransmitters involved are 5hydroxytryptamine (Serotonin / 5-HT) and
Glutamate
Genetic Theory
History in first degree relative 10 % risk
History in both parents risk to 40%
6
CAUSES OF
SCHIZOPHRENIA
Neurodevelopmental
Occurs as a result of utero disturbances
during pregnancy (eg. complications,
neonatal hypoxia). Studies have linked
prenatal conditions to risk of
schizophrenia.
Evaluation continues
Psychosocial
Various socioeconomic influences (stress,
poor interpersonal skills, family conflicts)
7
TREATMENT OF
SCHIZOPHRENIA
No known cure exist for Schizophrenia
Treatment Options
Psychotherapy
Pharmacotherapy
Antipsychotic Medications
Typical or First Generation
Atypical or Second Generation
8
ANTIPSYCHOTICS
(Chemical Classes)
Phenothiazines e.g. Chlorpromazine
Butyrophenones e.g. Haloperidol
Thioxanthenes - e.g. Zuclopenthixol
Dibenzoxazepines - e.g. Loxapine
Dihydrolindoles - e.g. Molindone
9
ANTIPSYCHOTICS
(Chemical Classes)
Diphenylbutylpiperidines e.g. Pimozide
Benzamides e.g. Sulpride
Thienobenzodiazepines e.g.
Olanzapine
Dibenzothiazepines e.g. Quetiapine
10
EXAMPLES OF TYPICAL
ANTIPSYCHOTICS
Chlorpromazine - LARGACTIL
Fluphenazine - MODECATE
Haloperidol - HALDOL
Loxapine - LOXITANE
Mesoridazine - SERENTIL
Pimozide - ORAP
Trifluoperazine - STELAZINE
Thioridazine - MELLARIL
11
TYPICAL
ANTIPSYCHOTICS
Mechanism of Action
Primarily through blockade of Dopamine
receptors
Other receptors are involved (see diagram)
Efficacy
When in equivalent dose (equipotent),
efficacy is similar
Typical Antipsychotics are usually as
effective as Atypicals for +ve symptoms
but less effective for ve symptoms
12
TYPICAL
ANTIPSYCHOTICS
Potency
Classified by their potency for the
dopamine receptors (DA) (high,
moderate, low)
High potency agents have higher affinity
for DA and are associated with higher risk
for EPS
Low potency agents have less affinity for
DA and are associated with more effects
from histamine, muscarinic and
adrenergic receptors
13
TYPICAL
ANTIPSYCHOTICS
Adverse Effects
Dopamine Receptor Blockade
Hyperprolactinemia
Parkinsonism
Alpha adrenergic blockade

Postural hypotension
Orthostatic hypotension
14
TYPICAL
ANTIPSYCHOTICS
Muscarinic Receptor Blockade
Anticholinergic effects (dry mouth,
constipation, blurred vision, urine retention)
Thioridazine is the most potent
antimuscarinic phenothiazine)
Histamine Receptor Blockade

Sedation
Increased appetite (may cause weight gain)
15
TYPICAL ANTIPSCHOTICS
OTHER EFFECTS
Blockade of norepinephrine reuptake
Blockade of serotonin receptors
Inhibition of growth hormone release
(think about use in children)
Impairment of mechanisms related to
temperature regulation
16
CLASSIFICATION OF
ADVERSE EFFECTS
Neurological
Sedation
Extrapyramidal
Seizures
Neuroleptic Malignant Syndrome (NMS)
Cardiovascular
Orthostatic Hypotension
17
CLASSIFICATION OF
ADVERSE EFFECTS
Endocrine
Menstrual irregularities
Galactorrhoea
Decreased glucose tolerance
Haematological
Agranulocytosis
Hepatic
Cholestatic Jaundice
18
EXTRAPYRAMIDAL
SYNDROME (EPS)
Results from the blockade of post
synaptic dopamine receptors on the
nigrostriatal tract of the brain
imbalance in cholinergic and
dopaminergic systems.
Four (4) categories of EPS
Acute Dystonic Reactions
Akathisia
Parkinsonism
Tardive Dyskinesia
19
EXTRAPYRAMIDAL
SYNDROME (EPS)
Acute Dystonia
Abnormal involuntary movements
especially around mouth, jaw, face, and
neck.
Reactions characterized by painful muscle
spasms, fixed upward gaze, neck twisting,
arching of the back and clenched jaws
(trismus and laryngospasm)
Usually occurs within the first 72 hrs of
starting antipsychotic therapy
20
EXTRAPYRAMIDAL
SYNDROME (EPS)
Acute Dystonia contd
High potency antipsychotics are more
likely to produce these reactions
Treatment anticholinergics e.g.
Benztropine, antihistamine e.g.
Diphenhydramine
Parenteral therapy is preferred to
initiate therapy
21
EXTRAPYRAMIDAL
SYNDROME (EPS)
Akathisia
A subjective feeling of motor
restlessness where the patient
cannot sit or lie still
The patient often paces and
become agitated and / or
aggressive
A compulsion to be in motion
22
EXTRAPYRAMIDAL
SYNDROME (EPS)
Akathisia contd
May occur days to weeks after
therapy
Treatment decrease dose of
antipsychotic agent, switch to
low potency agent, use
Propranolol 20 60 mg daily
23
EXTRAPYRAMIDAL
SYNDROME (EPS)
Parkinsonism
Characterised by tremor, rigidity and
akinesia or bradykinesia
Occurs weeks to months after therapy
and more common in elderly females
Treatment anticholinergic agents eg.
Benztropine 2 mg and Trihexiphendyl 2
mg
24
EXTRAPYRAMIDAL
SYNDROME (EPS)
Tardive Dyskinesia
Characterized by a rhythmic involuntary
movement of the tongue, lips, jaw, face,
extremities and sometimes the trunk
Occurs months to years after therapy
began and may be irreversible
Protrusion of tongue, puckering of
mouth, chewing motions, lip smacking,
puffing of cheeks
25
EXTRAPYRAMIDAL
SYNDROME (EPS)
Tardive Dyskinesia
More common in women and persons
older than 50 yrs
Persons with brain damage and mood
disordes are at higher risks
Treatment prevention, early diagnosis
and mgt. Benzodiazepines e.g. Diazepam,
lithium and Carbamazepine may help
26
NEUROLEPTIC MALIGNANT
SYNDROME (NMS)
Life threatening
Symptoms hyperpyrexia (107 F),
agitation, stupor, sweating, respiration
these usually develop rapidly over a
24 72 hr period
Lab results increased WBC, CPK, liver
enzymes and renal shutdown
Can miss Dx in early stages (high
potency agents mostly)
27
EXTRAPYRAMIDAL
SYNDROME (EPS)
Management discontinue the
drugs immediately and start
supportive care / measures
Supportive measures monitor
vitals, renal output, keep patient cool
There is no known treatment
28
EXAMPLES OF ATYPICAL
ANTIPSYCHOTICS
Aripiprazole - ABILIFY
Clozapine - CLOZARIL
Olanzapine - ZYPREXA
Quetiapine - SEROQUEL
Resperidone - RISPERDAL
Ziprasidone - GEODON
Paliperidone - INVEGA
29
GUIDELINES
American Psychiatric Association (APA)
recommends using an Atypical first
(EPS)
Response to meds is not immediate,
maximum treatment response may be
6 months or longer
Post response, maintain therapy for 6
months minimum prevent or reduce
risk no relapse
30
CHOICE OF
ANTIPSYCHOTIC
Depends on patients previous
experiences
Adverse effects
Medical condition (concomitant)
Medication interactions
Patients preference
Cost
Dosage form available
31
MANAGEMENT OF
SCHIZOPHRENIA WITH
ANTIPSYCHOTICS
Assists with many aspects of thinking
and emotions
By themselves do not allow most
patients to function fully in society
Intensive training in social skills
Dopamine hypothesis does not account
for all the pathology of Schizophrenia
(weeks required to attain Tx benefits)
TYPICAL
ANTIPSYCHOTICS
Generally
Highly lipid soluble
Highly protein bound (92 - 99%)
Large volume of distribution
Variable Bioavailability
Relatively short plasma half life (10-20 hrs)
Metabolites may be found in urine weeks
after last dose of drugs (drugs hidden in
tissues)
MAJOR SIDE EFFECTS OF

TYPICAL ANTIPSYCHOTICS
Four (4) classical side effects
by which the agents are compared
Sedation (low potency agents)

Hypotension
Extrapyramidal Side Effects
(high potency)
Anticholinergic Side effects
ATYIPICAL
ANTIPSYCHOTICS
These agents have a greater affinity
for the 5HT receptors
Classification as Atypical is based on
three clinical observations
2
Effectiveness against negative symptoms

Effectiveness in patients refractory to
treatment with typical
Seldom induce motor-related side effects
REFERENCES
Shuster, Joel; Psychopharmacologic
agents, Remington, The Science and
Practice of Pharmacy, 21st Ed.Chapter
82, pg 1509-1516.
Katzung and Trevor; Pharmacology
Examination and Board Review, 6 th
Edition
Lippincotts Illustrated Reviews
Pharmacology 4th
36

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Post Basic Psychiatric

Alpha adrenergic blockade

Histamine Receptor Blockade

MAJOR SIDE EFFECTS OF

Sedation (low potency agents)

Effectiveness against negative symptoms

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