Antipsychotics

Question 0

Haloperidol

Answer 0

Acts mainly on D2 receptors
Some effects on 5HT2 and alpha-1 receptors.
Negligible effects on D1.

Question 1

Chlorpromazine and Thioridazine

Answer 1

Block alpha 1 more potently than D2
Block Serotonin 5HT2 receptors relatively strongly.
Affinity for D1 is relatively weak.

Question 2

Pimozide and Amisulpride

Answer 2

Acts mainly on D2 receptors.

Question 3

Clozapine

Answer 3

Binds more to D4,5HT2,alpha1, and H1 receptors than D2 or D1 receptors.

Question 4

Risperidone

Answer 4

Potent in blocking D2 and 5HT2 receptors.

Question 5

Olanzepine

Answer 5

More potent as 5HT2 receptors antagonists. Lesser potency at D1, D2 and alpha 1.

Question 6

Quetiapine

Answer 6

Lower potency compound with relatively similar antagonism of 5HT2, D2, alpha 1 and 2 receptors.

Question 7

Similarity between olanzepine, clozapine and quetiapine?

Answer 7

Inhibits H1 histamine receptors.

Consistent with their sedative properties.

Question 8

Aripiprazole

Answer 8

Partial agonist effects at D2 and 5HT1a receptors.

Question 9

All effective antipsychotics block _____

Answer 9

D2 receptors.

Question 10

Advantages of atypical antipsychotics

Answer 10

Lower doses, reduced side effects, higher effectiveness especially on negative symptoms, better compliance.
Less chance of extra pyramidal side effects.

Question 11

Discuss metabolic effects of atypical agents

Answer 11

Aripiprazole 1kg/yr
Olanzepine and Clozapine >6kg/yr
Risperidone and Quetiapine >6kg/yr
Amisulpride 1.5kg/yr

Question 12

Discuss disadvantages of atypical agents

Answer 12

Risperidone and olanzepine increase risk of stroke when used for behavioral control in dementia.
Olanzepine + Prediabetes increases risk of conversion to type 2 diabetes by 6 fold. From a former 10% chance. Stopping Olanzepine causes 70% to reconvert.
Idiosyncratic toxicity.

Question 13

Nigrostriatal system

Answer 13

Motor control : difficulty in urinating, rigidity, as seen in Parkinson’s disease.

Question 14

Mesolimbic system

Answer 14

Behavioral effects - over activity leads to abnormal behaviour in rats.

Question 15

Tubero-infundibular system

Answer 15

Endocrine control. Dopamine agonists decrease prolactin release. The antagonists effect may stimulate it.

Question 16

Dopamine Hypothesis

Answer 16

Amphetamine, Levodopa, Bromocriptine and Apomorphine, increased D2 binding in the brain, D2 antagonists control disorder. Evidence of genetic variation in D4 receptors was discovered with some antipsychotics having high affinity for D4. LSD produces hallucinations and behavioural disturbance. Some antipsychotics act on 5HT receptors as antagonists. 5HT has a modulatory effect on dopaminergic neurons.

Question 17

Modes of action of antipsychotics

Answer 17

Inhibition of D2 with some action of D4
5HT2 receptor blockade (increase negative symptoms)
Histamine blockade H1 ( drowsiness)
Alpha adrenoceptor blockade. (Postural hypotension)

Question 18

Classes of Antipsychotics

Answer 18

Phenothiazines eg chlorpromazine and pimozide.
Butyrophenone eg Haloperidol
Thioxanthene derivatives eg Thiothixene
Atypical agents eg Aripiprazole, Clozapine, Risperidone, Quetiapine, Amisulpride, Olanzepine.

Question 19

Autonomic nervous system effects

Answer 19

Loss of accommodation, mouth and difficulty urinating due to muscarinic cholinoreceptor blockade.
Orthostatic hypotension, impotence, failure to ejaculate due to alpha adrenoceptor blockade.

Question 20

Central nervous system effects

Answer 20

Parkinson’s like symptoms, akathisia and dystonia due to dopamine receptor blockade.
Tardive dyskinesia due to super sensitivity if dopamine receptors.
Toxic confusional state due to muscarinic blockade.

Question 21

Endocrine system effects

Answer 21

Amenorrhea, galactorrhea, infertility, hyperprolactinemia due to dopamine receptor blockade.
Weight gain due to H1 and 5HT2 blockade.