Antipsychotics

Question 1

What are antipsychotics?

Answer 1

• Drugs that reduce psychomotor excitement

* Controls symptoms of psychosis

Question 2

Therapeutic uses of antipsychotics

Answer 2

1. Hallucination
2. Delusions
3. Agitation
4. Psychomotor excitement
   - Mania
   - Schizophrenia
   - Psychosis 2ndary to medical condition
5. Prophylaxis – prevent relapse of psychotic illness/episodes

Question 3

MOA of antipsychotics

Answer 3

• Blockade of DA pathways - reduces irrational behavior, agitation and aggressiveness along with psychotic symptomology
• In schizophrenia, DA overactivity is not the only abnormality
- Monoaminergic (5-HT) and aminoacid (glutamate) neurotransmitter systems may also be affected
• Only positive symptoms (hallucinations, aggression etc.) are linked with DA overactivity
• Negative symptoms (apathy, cognitive deficit etc.) are not necessarily linked with DA, however reduction of dopaminergic neurotransmission is the major mechanism of antipsychotic action.

Question 4

Effect of DA antagonism on CVS

Answer 4

Hypotension (primarily postural) - d/t central and peripheral action on sympathetic tone

QT prolongation

Suppression of T wave (ECG)

Arrythmia (overdose)

Question 5

Effect of DA antagonism on endocrine system

Answer 5

Increased prolactin release - d/t blockage of DA which has an inhibitory action on pituitary lactotrophs - gynaecomastia and galactorrhea, amenorrhea, hyperprolactinemia

Deacreased ADH - increased urine volume

Impair glucose tolerance - aggravate diabets, weight gain

Question 6

Name the two classes of anti-psychotics

Answer 6

Typical

Atypical

Question 7

What are typical antipsychotics? Give examples

Answer 7

•	Work primarily through inhibition of D2 receptor – extrapyramidal side effects
•	Reduced tendency to induce neurologic movement disorder 
•	Examples: 
a)	Chlorpromazine
b)	Thioridazine
c)	Fluphenazine
d)	Haloperidol
e)	Zuclopentixol

Question 8

What are atypical antipsychotics?

Answer 8

•	Second generation anti-psychotics with weak dopamine blocking potential but strong 5-HT2 antagonistic activity. 
•	Minimal extrapyramidal SE and tardive dyskinesia 
•	Examples
a)	Risperidone 
b)	Clozapine 
c)	Olanzapine 
d)	Aripiprazole
e)	Quetiapine 
f)	Amisulpride

Question 9

Which class is used as the first line treatment?

Answer 9

Atypical antipsychotics

Question 10

Chlorpromazine (receptors involved and SEs)

Answer 10

• Receptor involved: alpha1, H1, muscarinic cholinergic
• SE: sedation (blockade of alpha1 and histamine), hypotension (a1), anticholinergic (dry mouth, constipation, urinary incontinence), EPSE

Question 11

Haloperidol (receptors involved and SEs)

Answer 11

• Receptor involved: dopamine receptor

* SE: high risk of EPSE

Question 12

Risperidone (receptors involved and SEs)

Answer 12

• Receptors involved: 5-HT2, D2 and alpha1

* SE: mild sedation, hypotension

Question 13

Olanzapine (receptors involved and SEs)

Answer 13

• Receptors involved: D2 (weak), anticholinergic, H1 (strong)
• SE: sedation (H1), dry mouth, constipation, weight gain, metabolic syndrome (worsens diabetes)

Question 14

Quetiapine (receptors involved and SEs)

Answer 14

• Receptors: 5-HT, D2, A1 and 2, H1, D2 (low)
• SE: sedation, postural hypotension, urinary retention/incontinence
- Extremely minimal EPSE and hyperprolactinaemic SE as D2 blocking activity is low

Question 15

Aripiprazole (receptors involved and SEs)

Answer 15

• Receptors: partial dopamine agonist at D2 receptor, but antagonist at 5-HT2 receptor
• SE: nausea, dyspepsia, constipation, light-headedness

Question 16

Clozapine

Answer 16

(used when unresponsive to other medication)
• Receptors: D2 (weak), 5-HT2 (strong), H1, alpha and muscarinic
• SE: sedation, potent anticholinergic, hypersalivation, agranulocytosis, bloody dyscrasia, precipitation of diabetes, myocarditis

Question 17

What monitoring is to be done when patient is on clozapine?

Answer 17

•	Regular blood tests are mandatory for a patient on clozapine to monitor the white cell count
-	First 6 months – weekly
-	Next 6 months – fortnightly 
-	Thereafter – every 4 weeks 
-	For one month after cessation
•	ECG

Question 18

List the extrapyramidal SE seen with conventional antipsychotics

Answer 18

1. Acute dystonia – painful contractions of muscles in neck, jaw or eyes (more common in men)
2. Parkinsonism – reduced facial movements, shuffling gait, stiffness, tremor
3. Akathisia – involuntary restlessness (typically in the legs)
4. Tardive dyskinesia – involuntary grimacing movements of the face, tongue or upper body

Question 19

List the general side effects seen with the use of atypical antipsychotics

Answer 19

1. Weight gain - worst with clozapine and olanzapine
2. Hyperglycaemia and type 2 diabetes - can induce this along with insulin resistance
3. Metabolic syndrome the above two + dyslipidemia and HTN
4. Stroke - caution with elderly patients and in dementia

Question 20

Treating acute dystonia

Answer 20

Stop antipsychotic AND/OR give anticholinergic

Question 21

Treatment of parkinsonism

Answer 21

Change antipsychotic - to something less D2 related

Question 22

Treating Akathisia

Answer 22

Reduce/ change antipsychotic

Question 23

Treating tardive dyskinesia

Answer 23

Sometimes reducing antipsychotics make it worse - not treatable

Therefore, prevent it rather than let it develop.

Question 24

Choosing antipsychotic

Answer 24

No real difference in efficacy

Consider previous use of antipsychotic - use what has helped before

Consider preexisting comobrbidties - diabetes, overwieght, parkinsons

Consider patient concerns for SE.

Question 25

Use of depot

Answer 25

a) Detained patients who lack insight and will not take oral regularly
b) Informal patients who recognise they can be irregular taking tablets or who prefers infrequent injection