CPTP 3.4 - Antipsychotics

Question 1

Name three positive symptoms associated with schizophrenia?

Answer 1

Hallucinations - aural/visual
Paranoia
Disorders of thought/disorganised behaviour

Question 2

Name three negative symptoms associated with schizophrenia?

Answer 2

Blunted emotions/anhedonia
Social withdrawal
Apathy/loss of energy

Question 3

What is the dopamine theory of schizophrenia?

Answer 3

Schizophrenia is caused by an OVER active dopamine system in the brain

Question 4

Name the three main dopamine pathways within the brain?

Answer 4

1. Nigrostriatal (substantia nigra - striatum)
2. Mesolimbic/mesocorticle (mibrain - limbic system//midbrain - cortex)
3. Tubeloinfundibular (hypothalamus - ANT’ pituitary)

Question 5

Describe prolactin regulation?

Answer 5

Tubuloinfundibular pathway
Suckling - induces the hypothalamus to secrete prolactin releasing factor which acts on the ANT’ pituitary which releases prolactin which acts on the mammary tissues.
Dopamine acts as a prolactin release INHIBITING factor on the ANT’ pituitary

Question 6

What effects does prolactin have on mammary tissues?

Answer 6

Milk production
Proliferation and differentiation of mammary tissue
Influences maternal behaviour

Question 7

Describe the nigrostriatal pathway and name some common clinical conditions associated?

Answer 7

Substantia nigra –> dorsal striatum
Part of the extra pyramidal motor system = involved in initiation and control of movement
Diseases include Parkinson’s and Huntington’s Chorea

Question 8

Describe the mesocorticle/mesolimbic pathways defective in schizophrenia?

Answer 8

Ventral tegmental area to:-

1. Ventral striatum and hippocampus
2. Frontal cortex

Question 9

What effects does Dopa have on the defective mesocorticle/mesolimbic pathways?

Answer 9

Dopa action on the ventral striatum and hippocampus = reward/addiction/sensory
Dopa action on the frontal cortex = cognition/mood/emotions

Question 10

In terms of defective mesocorticle/mesolimbic pathways, define schizophrenia?

Answer 10

INCREASED Dopa @ ventral striatum and hippocampus

DECREASED Dopa @ frontal cortex

Question 11

Describe anti-psychotic drug mechanism of action?

Answer 11

Affinity for Dopamine D2 receptors = therapeutic efficacy

Anti-psychotic drugs block D2 receptors in the limbic/corticle areas = D2 receptor ANTAGONISTS

Question 12

Describe H1 receptor mediated side effects?

Answer 12

Weight gain

Sedation

Question 13

Describe M1 receptor mediated side effects?

Answer 13

Dry mouth
Constipation
Blurred vision
Urinary incontinence

Question 14

Describe a1 receptor mediated side effects?

Answer 14

Postural hypotension

Question 15

What adverse effects are brought about by anti-psychotics with very high affinity for D2 receptors?

Answer 15

Nigrostriatal pathway blockage of D2 transmission = extra-pyramidal side effects including tremor/muscle rigidity/facial expression loss/tardative dyskinesia
Selective D2 antagonism = prolactin production - Galactorrhea/gynocomastia

Question 16

Name a typical anti-psychotic?

Answer 16

Haloperidol (butryophenones) = very specific D2 receptor antagonist = High extra pyramidal side effects and glactorrhea and gynocomastia

Question 17

Name two atypical anti-psychotics?

Answer 17

Clozapine
Olanzapine
They have differing affinity for D2 receptors

Question 18

Clozapine is associated with which medical condition?

Answer 18

Agranulocytosis - acute WBC count drop

Question 19

Which two anti-psychotics are associated with weight gain and metabolic syndromes including diabetes?

Answer 19

Respiradone

Olanzapine

Question 20

Which type of symptoms are atypical anti-psychotics better at treating and why?

Answer 20

Negative symptoms
Low affinity for D2 receptors
Higher affinity for D3/D4 receptors
Higher affinity for 5-HT2A receptors

Question 21

Describe the mechanism of actions of atypical anti-psychotics?

Answer 21

Much faster dissociation rate from the D2 receptor (Koff) - Loose binding
Drugs are displaced by phasic bursts of Dopa and therefore do not interfere with the Dopamine signalling in the striatal pathways - NO extra pyramidal side effects