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ANTIPSYCHOTIC
What do antipsychotics treat?
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Psychotic Disorders (Psychosis)
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Abnormal Thinking and Perceptions
Loss of Contact with Reality
Delusions (false beliefs)
Hallucinations
ANTIPSYCHOTIC DRUGS
CLINICAL USE
1. Treatment of schizophrenia
 Reduce some of the positive symptoms
 Hyperactivity
 Bizarre behavior
 Hallucinations and delusions
 Facilitate functioning in both out and
inpatient environments
ANTIPSYCHOTIC DRUGS
CLINICAL USE
1. Treatment of schizophrenia
 Beneficial effects may take several
weeks to develop
 Individual patients may respond best
to specific drugs
ANTIPSYCHOTIC DRUGS
CLINICAL USE
1. Treatment of schizophrenia
 Negative symptoms
 Older drugs do not have much effect
 Newer atypical drugs improve some
 Emotional blunting
 Social withdrawal
ANTIPSYCHOTIC DRUGS
CLINICAL USE
2. Other psychiatric and neurologic
indications
 Psychotic symptoms of other psychotic
disorders
 Tourette’s syndrome and other tic
disorders
ANTIPSYCHOTIC DRUGS
CLINICAL USE
2. Other psychiatric and neurologic
indications
 Toxic psychoses caused by overdosage
of certain CNS stimulants
 Alzheimer’s and Parkinsonism
ANTIPSYCHOTIC DRUGS
CLINICAL USE
2. Nonpsychiatric indications
 Antiemetic action
 Phenothiazines except thioridazine
 Antipruritics
9
Extra Pyramidal
Symptoms
EPS
ANTIPSYCHOTIC DRUGS
1.
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Reversible neurologic effects
Occurs most frequently
 Haloperidol
 Fluphenazine
 Trifluoperazine
Less frequent with clozapine
Less common with the newer drugs
EPS
(Extra Pyramidal Symptoms)
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EPS include:
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Acute Dystonias: happens within hours
Parkinsonism: develops gradually (Days –
Weeks)
Tardive Dyskinesia: chronic development
Tardive Dystonia: chronic development
Akathisia
Parkinsonian Syndrome
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Parkinsonian Syndrome
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Tremors
Rigidity
Cogwheeling
Bradykinesia
May resemble Depression:
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Slowing in thinking
Decreased initiative
Masked face
Treatment of EPS
BRAND NAME
GENERIC NAME
Akineton
Artane
Biperiden
Trihexyphenidyl
Symmetrel
Amantadine
1
Akathisia
Restless Pacing
Akathisia
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Akathisia: Inability to sit
still
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A feeling of restlessness,
A need to keep moving,
Difficult to differentiate from
illness-related behaviors
Akathisia
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Appear Anxious:
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Treatment:
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May misidentify akathisia as anxiety
Anxiety can aggravate akathisia
Lowering the dosage of the
medication
Anticholinergics: not always effective
Propranolol: 10 to 80 mg/d
Clonidine: 0.1 to 0.8 mg/d
BDZ
Tardive Dyskinesia
TD
ANTIPSYCHOTIC DRUGS
2.
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Tardive dyskinesia
Choreoathetoid movements of the
muscle of the lips and buccal cavity
Maybe irreversible
Tend to develop after years of therapy
May appear as early as 6 months
ANTIPSYCHOTIC DRUGS
2.
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Tardive dyskinesia
Antimuscarinic drugs that improve
extrapyramidal effects increase the
severity of symptoms
No effective drug for treatment
Switching to clozapine does not
exacerbate the condition
Neuroleptic Malignant Syndrome
NMS
NMS
(Neuroleptic Malignant Syndrome)
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A rare but potentially fatal
complication
Main clinical findings:
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Hyperthermia
Severe muscular rigidity
Autonomic instability:
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Pulse/ BP/ Breathing/ Sweating
Changing levels of consciousness
Unstable vital signs
NMS
(Neuroleptic Malignant
Syndrome)
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Lab tests:
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Creatine Phosphokinase (CPK)
Leukocytosis (increased WBC)
Increased Myoglobin and
Myoglobinuria
Mortality: 20 – 30 %
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May be higher when depot forms are
used
NMS
(Neuroleptic Malignant Syndrome)
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Treatments
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Stop the antipsychotics
Supportive and symptomatic TX
Medications:
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Dantrolene
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Bromocriptine
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Amantadine
Metabolic Syndrome
Monitoring and Management
Equipment
ANTIPSYCHOTIC DRUGS
3.
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Autonomic effects
Result from blockade of peripheral
muscarinic receptors and alpha
adrenoceptors
 Strongest autonomic effects
 Thioridazine
 Weakest
 Haloperidol
ANTIPSYCHOTIC DRUGS
3.
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Autonomic effects
Intermediate autonomic effects
 Clozapine and most atypical
antipyschotics
ANTIPSYCHOTIC DRUGS
Autonomic effects
 Atropine-like effects
 Dry mouth
 Constipation
 Urinary retention
 Visual problems
 Not with ziprasidone and aripiprazole
ANTIPSYCHOTIC DRUGS
3.
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Autonomic effects
Alpha receptor blockade
 Postural hypotension
 All atypical drugs
Failure to ejaculate
 Phenothiazines
ANTIPSYCHOTIC DRUGS
4.
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Endocrine
Dopamine D2 receptor blockade in
the pituitary
 Hyperprolactinemia
 Gynecomastia
ANTIPSYCHOTIC DRUGS
6.
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Sedation
More marked sedation
 Chlorpromazine-ClozapineOlanzapine-Thioridazine
Less sedating among the older drugs
 Fluphenazine and haloperidol
Least sedating among newer drugs
 Aripiprazole
ANTIPSYCHOTIC DRUGS
7.
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Miscellaneous toxicities
Visual impairment due to retinal
deposits
 Thioridazine
At high doses, fatal ventricular
arrhythmias
 Thioridazine
ANTIPSYCHOTIC DRUGS
TOXICITY
7. Miscellaneous toxicities
 Arrhythmias
 Ziprasidone
 Agranulocytosis, seizure at high doses
 Clozapine
ANTIPSYCHOTIC DRUGS
TOXICITY
8. Overdosage toxicity
 Usually fatal
 Hypotension
 Fluid replacement
 Seizures
 Diazepam or phenytoin
 Cardiotoxicity is difficult to treat