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Objectives
1. To know the basis for the dopamine
hypothesis of schizophrenia
2. To understand the mechanism of
action of antipsychotic agents with
respect to their therapeutic and
adverse effects
2Rogie Royce Z. Carandang, RPh, MPH
Antipsychotics
• aka neuroleptics, major tranquilizers
• “Neuroleptics” because of their
tendency to cause movement
disorders
• “Major tranquilizers” vs minor
tranquilizers (anxiolytics)
3Rogie Royce Z. Carandang, RPh
Psychosis
• Symptoms of delusions,
hallucinations, and disorders of
thought
• Due to increase dopamine levels
(as in amphetamines, cocaine)
4
Rogie Royce Z. Carandang, RPh
Schizophrenia
• 1% of population, inheritable
• Characterized by positive and
negative symptoms, a pattern of
social and occupational deterioration,
and persistence of the illness for at
least 6 months
• 2 or more symptoms
6
Rogie Royce Z. Carandang, RPh
Positive Symptoms
1. Hallucinations
- auditory, visual, tactile, and/or
olfactory hallucinations, voices that are
commenting
2. Delusions
- grandiose, paranoid, thought
broadcasting, thought insertion
3. Bizarre behavior
- aggressive/agitated, odd clothing or
appearance, odd social behavior,
repetitive-stereotyped behavior 7
Rogie Royce Z. Carandang, RPh
Negative Symptoms
• Affective flattening, alogia, asociality
• POSITIVE symptoms respond more
consistently with medications.
NEGATIVE symptoms are less
responsive.
8Rogie Royce Z. Carandang, RPh
Adverse Effects
9Rogie Royce Z. Carandang, RPh
Receptor Blocked Side Effect
Dopamine D2 Parkinsonism/ EPS
Histamine H1 Sedation
Muscarinic M Dry mouth,
constipation, urinary
retention, blurring of
vision
Adrenergic α1 Orthostatic hypotension
Chemical Classification of Antipsychotics
1. PHENOTHIAZINES
• Aliphatic – chlorpromazine
• Piperidine – thioridazine
• Piperazine – fluphenazine,
perphenazine
2. Butyrophenones
• Haloperidol
3. Thioxanthenes
• Thiothixene
• Same structure as
Phenothiazine but N
replaced by C 10
Rogie Royce Z. Carandang, RPh
ChlorpromazineThioridazine
Phenothiazine Ring
Haloperidol
Chemical Classification of Antipsychotics
4. Dihydroindolines
• Molindone
5. Diphenylbutylpiperidines
• Primozide
6. Dibenzoxapine
• Clozapine, quetiapine
7. Benzisoxazole
• Risperidone
11Rogie Royce Z. Carandang, RPh
Clozapine
Typical vs Atypical Drugs
12Rogie Royce Z. Carandang, RPh
Typical/First Generation Atypical/Second Generation
Thioridazine (Mellaril, Melleril)
Chlorpromazine (Thorazine,
Laractyl, Psynor)
Perphenazine (Trilafon)
Thiothixene (Navane)
Fluphenazine (Prolixin, Modezine,
Sydepress)
Haloperidol (Haldol, Serenace)
Clozapine (Clozaril, Leponex)
Quetiapine (Seroquel)
Ziprasidone (Geodon, Zeldox)
Aripiprazole (Abilify)
Olanzapine (Zyprexa)
Risperidone (Risperdal)
Blocks D2 receptors only Blocks 5-HT2 > D2 receptors
Treats positive symptoms only Treats both positive and negative
symptoms
Causes movement disorders
(Parkinsonism)
Causes little or no movement
disorders
Low potency vs High potency Drugs
13Rogie Royce Z. Carandang, RPh
Low Potency High Potency
Phenothiazines
chlorpromazine,
thioridazine
Haloperidol decanoate
Fluphenazine decanoate
Sedation, hypotension,
anticholinergic effects
EPS
Movement Disorders
1. Extrapyramidal symptoms (EPS)
• aka neuroleptic-induced
parkinsonism
• Most common (15%)
• Coarse tremors, rigidity,
bradykinesia
• Risk: high potency
• Tx: lower dose, anticholinergics
(benztropine [Cogentin],
diphenhydramine, biperiden
[Akineton], trihexyphenydyl [Artane])
14Rogie Royce Z. Carandang, RPh
Movement Disorders
2. Acute Dystonia
- Muscular spasm, involuntary
movement
- Spasmodic torticollis, trismus,
tongue potrusion, ophisthotonos,
upward movement of eyes
(oculogyric crisis)
- Risk: high potency
- Tx: IM/IV anticholinergics
16Rogie Royce Z. Carandang, RPh
Movement Disorders
3. Neuroleptic malignant syndrome
(NMS)
• Idiosyncratic, life-threatening
• Motor: Muscular rigidity, dystonia,
agitation
• Autonomic: hyperpyrexia,
hypertension
• Risk: high dose, rapid dose
escalation
• Tx: discontinue meds, supportive,
dantrolene, bromocriptine
17Rogie Royce Z. Carandang, RPh
Movement Disorders
4. Akathisia
- Subjective feeling of muscular
discomfort
- Agitated, pace relentlessly,
alternately sit and stand
- Tx: Beta-blockers (propranolol), BZD
(lorazepam), clonidine
18Rogie Royce Z. Carandang, RPh
Movement Disorders
5. Tardive dyskinesia
- Choreoathethoid movements
- Tongue protrusion/twisting, lip
puckering
- Tx: lower dose, change meds
19Rogie Royce Z. Carandang, RPh
Other Adverse Effects
1. Agranulocytosis clozapine,
chlorpromazine
2. Retinal deposits and visual
impairment thioridazine
3. Prolonged QT interval, torsades de
pointes ziprasidone
20Rogie Royce Z. Carandang, RPh
Other Uses of Antipsychotics
1. Antiemetic (blocks dopamine
receptors) prochlorperazine
2. Intractable hiccups
chlorpromazine
3. Pruritus (anihistamine)
promethazine (Zinmet, Thaprozine)
21Rogie Royce Z. Carandang, RPh