Antipsychotic Medications

Question 1

Name some typical antipsychotics

Answer 1

Haloperidol
Chlorpromazine
Sulpiride
Thioridazine

Question 2

What occurs at high doses of the typical antipsychotics?

Answer 2

Immobility, rigidity and sleep i.e. Neurolepsis

Question 3

What occurs at low doses of typical antipsychotics?

Answer 3

An antipsychotic effects especially treating the postive symptoms. May even make negative symptoms worse

Question 4

What is the mechanism of the typical antipsychotics?

Answer 4

They have 100 fold more potent as D2 receptors over D1 and act to antagonise them.

Question 5

What is the clincal efficacy of an typical antipsychotic correlated to?

Answer 5

The affinity to D2 receptors over D1

Question 6

What percentage of patients show no improvement on typical Aps?

Answer 6

25-30%

Question 7

What percentage of patients show partial respite to typical antipsychotics?

Answer 7

25%

Question 8

What are the ADRs to typical antipsychotics?

Answer 8

Extrapyramidal side effects
Sedation
Hypotension
Tachycardia
Neuroleptic malignancy syndrome (idiosyncratic reactions)
Prolonged QT (haloperidol)
Hyperprolactinaemia

Question 9

Name the extrapyramidal side effects?

Answer 9

Akinesia
Acute dystonia
Tardative dyskinesia
Parkinsonism

Question 10

What is akinesia and how many patients of typical APs get it?

Answer 10

~20%
Restlessness in mainly lower legs and drive to move
Slow onset

Question 11

What is tardative dyskinesia and how many patients get it on typical aPs?

Answer 11

Involuntary movements of the Lower face muscles and tongue (80%) and limbs
It is irreversible and due to long term typical AP therapy
~50% get this

Question 12

What is acute dystonia and how many patients get it?

Answer 12

Contraction of muscle group to maximum which is normally self limiting. Onset is within hours and reminds to anticholingeric medication (procyclidine)
~10% get this

Question 13

What are the characteristic symtoms f Parkinson’s induced by typical APs how many patients get this?

Answer 13

Most common EPSE with onset in days/months
Tremor, bradykinesia, rigidity
~50% get severe but ~100% get mild

Question 14

Why does Parkinsonism occur in typical AP treatment?

Answer 14

Decreasing dopamine within the brain also affects the nigrostriatal pathway. Thus, modulation of striatal outputs from the SNc is impaired.

Question 15

What are the effects of typical APs in the tubuloinfundibular pathway?

Answer 15

Dopamine normally inhibits prolactin release. Therefore, typical APs = hyperprolactinaemia which causes sexual dysfunction, lactation and infertility.

Question 16

What receptors do atypical APs act on?

Answer 16

Mainly D2 and 5-HT2A but can also act on cholinerigc, adrenergic, histaminergic receptors

Question 17

Name some atypical APs

Answer 17

Clozapine
Quitiapine
Olanzipine
Aripiprazole
Risperidone

Question 18

What antipsychotics is good for L-DOPA induced psychosis?

Answer 18

Quitiapine

Question 19

Why are atypical APs better at treating schizophrenia?

Answer 19

Work better for negative symptoms (?due to to the dirty nature and lack of specificity of drugs). May also improve cognitive symptoms

Question 20

Advantages of atypical APs?

Answer 20

Treat negative symptoms
Less EPSE
Less NMS

Question 21

Disadvantage of atypical APs?

Answer 21

Do not work as quickly as typical
Variable effect from patient to patients
Weight gain (due to histamine receptor antagonism)
No as selective for D2

Question 22

What atypical AP is particular bad for weight gain?

Answer 22

Olanzipine

Question 23

Why does the dopamine theory nor provide the full story for the pathogenesis on schizophrenia?

Answer 23

1. Ampethamine do not = negative symptoms
2. D2 antags do not treat negative symptoms
3. Time course of antipsychotic action different from dopamine antagonists (antagonists = 30 mins, APs = 2-3 weeks)
4. Atycoals act on many receptors and are more effective for negative symptoms

Question 24

What is the discontinuation rate for treatments of schizophrenia.Why?

Answer 24

10% per month
Mainly due to ADRs, would rather risk another psychotic episode
Therefore, medication with fewer ADRs are important

Question 25

What are some other treatments for schizophrenia?

Answer 25

Psychological interventions (CBT, family therapy) these are labour intensive but cost effective in long term as reduced hospitalisation Support, advice and education Social therapy in aiding find work and accommodation ?ECT for severe catatonia

Question 26

What is the treatment regime for schizophrenia

Answer 26

Atypical forest choice. Normally 2 tried before clozapine therapy Typical used rarely in the treatment of acute uncooperative patients where rapid onset is needed Depot injections of typical/atypical recombined in an attempt to improve adherence and reduce relapse

Question 27

Define treatment resistant schizophrenia...what is recommended in this case?

Answer 27

Lack of satisfactory clinical improvement despite the sequential use of at least 2 antipsychotics (which should be atypical) for 6-8 weeks ?clozapine use in these patients

Question 28

What percentage of patients who are treatment resistant respond to clozapine?

Answer 28

~60%

Question 29

What are some main ADRs of clozapine?

Answer 29

``` Agranulocytosis (0.5-2%) Excess salivation Transient hyperthermia Myocarditis PE Weight gain Sedation Constipation GI upset ```

Question 30

Since clozapine causes agranulocytosis what must occur?

Answer 30

Administration as inpatient initially Blood samples taken every week for 18 weeks Then every 2 weeks for a year Monetary thereafter This is inconvenient for patients and expensive

Question 31

What are some characteristics of risperidone?

Answer 31

Low dose = atypical | High dose = Typical