Antipsychotics

Question 1

Psychosis?

Answer 1

Abnormal mental condition described as “loss of contact with
reality”
* Psychotic patients may exhibit some personality changes and
thought disorders, unusual or bizarre behaviour, as well as
difficulty making social interactions; also, impairment in
carrying out daily activities

Question 2

Schizophrenia

Answer 2

a type of psychosis characterised by:
* delusions, hallucinations and thought disorder (positive symptoms),
together with
* social withdrawal, blunted emotional responses often dementia
(negative symptoms).

Question 3

Schizophrenia aetiology?

Answer 3

Aetiology: unknown, but it is generally agreed that dopamine
hyperactivity underlies at least the positive symptoms of
schizophrenia.

Question 4

Schizophrenia adolescnce?

Answer 4

‣ Most cases of schizophrenia begin in adolescence/ young adult life
and tend to either follow a relapsing and remitting course or to be
chronic and progressive.

Question 5

Schizophrenia treatment goals?

Answer 5

Treatment Goals
* Reduce severity of psychotic symptoms
* Prevent recurrences of symptomatic episodes and associated
deterioration of functioning

Question 6

Schizophrenia drug treatment?

Answer 6

Drug Treatment
Neuroleptics/antipsychotic drugs
* Block postsynaptic dopamine D2 receptors → antipsychotic action.
* Most neuroleptics also block cholinergic, α-adrenergic, serotonin
and histamine receptors → adverse effects.

Question 7

Neuroleptics Classification ?

Answer 7

Typical/Conventional Antipsychotics
&
Atypical/Second-Generation Antipsychotics

Question 8

Typical/Conventional Antipsychotics

Answer 8

First-generation
Phenothiazines (chlorpromazine, fluphenazine); butyrophenones
(haloperidol ); thioxanthines (flupenthixol).

Question 9

Typical/Conventional Antipsychotics site of action

Answer 9

Act primarily by blocking D2 receptors.

Question 10

Typical/Conventional Antipsychotics potency?

Answer 10

Low potency neuroleptics e.g. chlorpromazine: less
affinity for dopamine receptors and more for α-adrenergic,
muscarinic and histaminergic receptors.
‣ High potency e.g. haloperidol: higher affinity for dopamine
receptors and less for α-adrenergic and muscarinic
receptors.

Question 11

Typical/Conventional Antipsychotics choice of drug?

Answer 11

• Choice of drug: AE profile, route of administration, patient
  previous response to drug.

Question 12

Atypical/Second-Generation Antipsychotics?

Answer 12

Clozapine, olanzapine, risperidone, quetiapine
* block dopamine receptors more selectively than conventional
antipsychotic.
* are less likely to cause extrapyramidal side effects,
* ↑ prolactin release slightly (except risperidone)
‣ The risk of metabolic syndrome is greater with SGAs that with
conventional antipsychotics

Question 13

Atypical/Second-Generation Antipsychotics extrapyramidal s/e?

Answer 13

Extrapyramidal Side Effects
Blockade of dopamine receptors may cause:
‣ Parkinsonism, especially in older patients; tardive dyskinesia,
akathisia, hyperprolactinaemia.
- Parkinsonian symptoms relieved by administration of
antimuscarinic drugs.

Question 14

Chlorpromazine MOA?

Answer 14

Low potency; blockade of D2 receptors&raquo_space; 5HT2A receptors

Question 15

Chlorpromazine Effects?

Answer 15

Effects
− Improves disturbed thought and blunted affect.
− Changes withdrawal and autistic behaviour
− Reduces hallucinations.
− Potent sedative → effective for restless aggressive patients and
patients who are difficult to control.

Question 16

Chlorpromazine dose?

Answer 16

Dose
− initiate with 25 mg tds po, gradually ↑ until symptoms are controlled
− once stabilised administer as single bedtime dose
− usual maintenance dose is 75 - 300 mg

Question 17

Chlorpromazine A/E?

Answer 17

AE: extrapyramidal symptoms incl. Parkinsonism (seldom);
anticholinergic effects, sedation, weight gain.

Question 18

Haloperidol MOA?

Answer 18

The most potent D2 antagonist, blockade of D2 receptors&raquo_space; 5HT2A
Used for both acute and chronic schizophrenia.

Question 19

Haloperidol Dose?

Answer 19

Dose
− 5 - 10 mg IM or PO; repeat q 4 - 6 h
− common maintenance dose 4 mg PO at bedtime
− haloperidol decanoate available as IM depot ‣25 - 150 mg
q 28 days (3 - 5 wk range)

Question 20

Haloperidol A/E?

Answer 20

AE: akathisia (motor restlessness), extrapyramidal symptoms,
anticholinergic effects

Question 21

Clozapine MOA?

Answer 21

Weak D2-receptor antagonist, blockade of 5HT2A-R > blockade
of D2-R
‣ Used in patients unresponsive to other antipsychotics
‣ Improves both the negative and positive symptoms.
‣ Has few or no motor AEs, minimal risk of causing tardive
dyskinesia

Question 22

Clozapine Dose?

Answer 22

Dose
12.5 mg PO OD or BD, increased daily in increments of 25
− 50 mg/day, if well-tolerated over 14 - 21 days up to 300 mg
daily in divided doses; max 900 mg/day.

Question 23

Clozapine A/E?

Answer 23

AE: raised BP, occasionally convulsions, sedation, hypotension,
tachycardia, weight gain, agranulocytosis (1%) - monitor WBCs.

Question 24

Depot Antipsychotic Drugs

Answer 24

Long-acting; useful for eliminating drug non-adherence.
* Haloperidol decanoate: 25 - 150 mg im q 28 days
* Fluphenazine decanoate:12.5 - 50 mg im q 2 - 4 wk
‣ Depot injections of typical antipsychotics may give rise to
higher incidence of extrapyramidal reactions than oral
preparations.