Antipsychotics

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AntipsychoticsRogie Royce Z. Carandang, RPh, MPH

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)

Rogie Royce Z. Carandang, RPh

Psychosis

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

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

Negative Symptoms

• Affective flattening, alogia, asociality

• POSITIVE symptoms respond more

consistently with medications.

NEGATIVE symptoms are less

responsive.

Adverse Effects

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

ChlorpromazineThioridazine

Phenothiazine Ring

Haloperidol

Chemical Classification of Antipsychotics

4. Dihydroindolines

• Molindone

5. Diphenylbutylpiperidines

• Primozide

6. Dibenzoxapine

• Clozapine, quetiapine

7. Benzisoxazole

• Risperidone

Clozapine

Typical vs Atypical Drugs

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

Low Potency High Potency

Phenothiazines

chlorpromazine,

thioridazine

Haloperidol decanoate

Fluphenazine decanoate

Sedation, hypotension,

anticholinergic effects

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])

Low potency vs High potency Drugs

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

Movement Disorders

3. Neuroleptic malignant syndrome

• Idiosyncratic, life-threatening

• Motor: Muscular rigidity, dystonia,

agitation

• Autonomic: hyperpyrexia,

hypertension

• Risk: high dose, rapid dose

escalation

• Tx: discontinue meds, supportive,

dantrolene, bromocriptine

Movement Disorders

4. Akathisia

- Subjective feeling of muscular

discomfort

- Agitated, pace relentlessly,

alternately sit and stand

- Tx: Beta-blockers (propranolol), BZD

(lorazepam), clonidine

Movement Disorders

5. Tardive dyskinesia

- Choreoathethoid movements

- Tongue protrusion/twisting, lip

puckering

- Tx: lower dose, change meds

Other Adverse Effects

1. Agranulocytosis clozapine,

chlorpromazine

2. Retinal deposits and visual

impairment thioridazine

3. Prolonged QT interval, torsades de

pointes ziprasidone

Other Uses of Antipsychotics

1. Antiemetic (blocks dopamine

receptors) prochlorperazine

2. Intractable hiccups

chlorpromazine

3. Pruritus (anihistamine)

promethazine (Zinmet, Thaprozine)

End of Lecture!

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Antipsychotics

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