PHARM - Antipsychotic Drugs - Week 10

Question 1

Name 9 ways neurotransmitter function can be modulated in CNS disorders.

Answer 1

Axon potential
NT synthesis
NT storage
NT metabolism
NT release
NT reuptake
NT degradation
NT receptor
Ionic conductance (receptor induced)

Question 2

What percentage of the population has schizophrenia.

Answer 2

1%

Question 3

Does schizophrenia affect individuals equally across all cultures and/or socioeconomic groups?

Answer 3

Yes

Question 4

Does schizophrenia develop in early or late age?

Answer 4

Early age

Question 5

True or false

Schizophrenia has no genetic link.

Answer 5

False, there is a genetic link

Question 6

Is schizophrenia a single illness?

Answer 6

No, its now classified as a syndrome with multiple domains of dysfunction.

Question 7

Define epigenetics.

Answer 7

Gene and environment interactions

Question 8

In what percentage of patients with schizophrenia respond well to antipsychotic drugs, have some benefits, and little to no benefit?

Answer 8

Respond well - 28%
Some benefit - 38%
No benefit - 34%

Question 9

List 3 positive and 2 negative symptoms of schizophrenia.

Answer 9

Positive
Delusions (paranoia most common)
Hallucinations (voices)
Disordered thought

Negative
Social withdrawal
Flattened emotions

Question 10

Define positive and negative symptoms.

Answer 10

Positive
Psychotic behaviours not seen in normal people
Negative
Associated with disruptions to normal emotions and behaviours

Question 11

List 3 cognitive symptoms of schizophrenia.

Answer 11

Poor executive functioning
Trouble focusing or paying attention
Problems with working memory

Question 12

What is the mechanism behind schizophrenia?

What has it been linked to?

Answer 12

Uncertain - linked to a functional excess of dopaminergic activity

Question 13

List three pharmacological evidences to the dopamine hypothesis of schizophrenia.

Answer 13

Agents enhancing catecholamine release can induce schizophrenia-like symptoms
Dopamine depletion controls positive symptoms
Many useful antipsychotics are antagonists to dopamine D2 receptors

Question 14

Name the four dopamine pathways in the brain.

Answer 14

Tubero-hypophyseal pathway
Mesocortical pathway
Nigrostriatal pathway
Mesolimbic pathway

Question 15

Name two hypotheses related to the cause of schizophrenia (aside from the dopamine hypothesis) and provide a piece of pharmacological evidence if applicable (3).

Answer 15

5-HT - LSD (an antagonist at CNS 5-HT receptors) induces schizophrenia-like symptoms
-Antipsychotic drugs are effective at blocking 5-HT receptors.

Glutamate - several glutamate receptor antagonists have been shown to induce schizophrenia-like symptoms.

Question 16

Are useful antipsychotics effective at blocking one or many receptors?

Answer 16

The useful ones tend to block more than one kind of receptor.

Question 17

Name two classical antipsychotic drugs.

What are they an agonist/antagonist to?

Answer 17

Chlorpromazine
Haloperidol
Both are an antagonist to dopamine D2 receptors.

Question 18

What is the typical onset of antipsychotic action? What is this suggestive of?

Answer 18

Takes several weeks

Suggestive of changes secondary to receptor blockades

Question 19

What are atypical antipsychotic drugs and how are they different to the classical drugs?
In what cases are these drugs useful?

Answer 19

Newer group of drugs that have a more diverse spectrum of activity compared to classicals.
They are useful when the classicals are not appropriate or have too many unwanted side effects.

Question 20

Give two examples of atypical antipsychotics.

Answer 20

Clozapine

Olanzapine

Question 21

Are atypicals more or less selective with their receptor targetting compared to classicals?

Answer 21

More selective receptor antagonism

Question 22

What are atypicals agonists or antagonists to?

Answer 22

Dopamine D2 receptors

Question 23

What is a feature of atypicals?

Answer 23

Blockade of the 5-HT2Δ receptors

Question 24

Between atypicals and classicals, which is more useful in tackling the negative symptoms of schizophrenia?

Answer 24

Atypicals

Question 25

Do antipsychotic drugs have few or many unwanted effects?

Answer 25

Many

Question 26

Name 2 extrapyrimidal motor disturbance effects antipsychotics can have, briefly describe the symptoms of each, and whether they more or less severe with therapy duration, including whether or not they are reversible. Which of these two is less severe with atypicals?

Answer 26

Parkinson's-like syndrome - due to D2 antagonism in other parts of the brain - less severe with time and reversible with withdrawal Tardive dyskinesia - involuntary movements - face and tongue - develops slowly, often irreversible - less severe with atypicals

Question 27

Describe why antipsychotics can cause endocrine disturbance - name the hormone affected and three consequences of this.

Answer 27

Dopamine is involved in the inhibition of prolactin release. Drugs therefore enhance prolactin release, causing breast swelling, pain, and lactation. This occurs in both men and women.

Question 28

Aside from motor and endocrine disturbances, name 4 side effects of antipsychotics and a reason why if applicable (2).

Answer 28

Sedation Atropine-like effects Postural hypotension (a-adrenoceptor antagonism) Weight gain (5-HT2 antagonism)

Question 29

Describe three symptoms of atropine-like effects.

Answer 29

Blurred vision Dry mouth Constipation