Antipsychotics 2

Question 1

What are the two typical antipsychotics?

Answer 1

Chlorpromazine

Haloperidol

Question 2

What is the mechanism of action for the typical antipsychotics?

Answer 2

Blocking dopamine recepotrs (particularly D2) in the mesocortical and mesolimbic pathways

Question 3

True/False

Clinical potencies of antipsychotic drugs correlate well with their affinities for D1 dopamine receptors

Answer 3

FALSE (D2)

Question 4

In addition to D2 antagonism, most antipsychotics drugs also have affinities for which other receptors?

Answer 4

(HAMS)

Histamine (H!)
alpha-1 Adrenergic
Muscarinic cholinergic
Serotonin (5-HT)

Question 5

What are the common problems with the typical antipsychotic drugs? (3)

Answer 5

a. Persistent symptoms in about 30% of patients (treatment refractory)
b. Only modest improvement of negative and cognitive symptoms
c. Side Effects

Question 6

What are the main side effects of the typical antipsychotic drugs? (2)

Answer 6

1. Extrapyramidal symptoms (EPS)- due to D2 receptor blockade in the nigrostriatal pathway
2. Hyperprolactinemia- due to D2 blockade in the tuberoinfundibular system

Question 7

How is parkinsonism different than Dru-induced parkinsonism aka antipsychotic drug use?

Answer 7

In antipsychotic dugs, the have the normal amount of dopamine available but they block the D2 receptor.
In parkinson’s, there is a dopamine deficiency

Question 8

What are the 4 different dopamine pathways? and what are their functions?

Answer 8

Mesolimbic- Arousal, memoriy, stimulus processing, motivation
Mesocortical- Cognition, communication, social function, response to stress
Nigrostriatal- Extrapyramidal motor control
Tubero-Infundibular- Inhibits prolactin release

Question 9

How are the Atypical antipsychotics classified?

Answer 9

1. Reduced tendency to cause EPS (and hyperprolactinemia)
2. a) Relatively weak D2 dopamine receptor blocking activity
   b) Serotonin 2A (5-HT2A) receptor antagonism
3. Each atypical agent has a unique receptor blocking profile
4. For unknown reasons, metabolic syndrome (weight gain, hyperlipidemia, hyperglycemia) is more common with atypical antipsychotics)

Question 10

Why aren’t antipsychotic effects affected by 5-HT2A antagonism?

Answer 10

Because inhibition of dopamine release by serotnin is NOT prominent in mescortical/mesolimbic pathways

Question 11

What are the atypical antipsychotic drugs

Answer 11

Clozapine
Risperidone
Olanzapine
Ziprasidone
Ariprizole

Question 12

What are the differences in Typical and Atypical antipsychotics in terms of efficacy? in terms of side effects? in terms of pharmacology?

Answer 12

Efficacy- Clozapine is more effective in reducing negative symptoms
Side Effects- The atypical drugs are less likely to cause EPS or Hyperprolactinemia
Pharmacology- The atypicals are less potent D2 antagonists and much stronger 5-HT2A antagonists

Question 13

How do you typically select the type of antipsychotic to be used?

Answer 13

Based more on anticipated side effects and less on the therapeutic expectancy

Question 14

What is the time course of the use of antipsychotics?

Answer 14

From 48hrs to several weeks

Question 15

What other uses are antipsychotics indicated for?

Answer 15

Schizoaffective Disorder
Manic phase in Bipolar disorder
Tourette's syndrome
Huntington's Disease
Autistic Disorders

Question 16

In which antipsychotic is sedation is a big problem?

Answer 16

Chlorpromazine

Question 17

In which antipsychotic(s) is weight gain a big problem?

Answer 17

Clozapine and Olanzapine

Question 18

What are the main side effects of EPS?

Answer 18

Parkinsonism
Tardive Dyskinesia
Neuroleptic malignant syndrome

Question 19

How are the side effects of the EPS treated?

Answer 19

Parkinsonism- with anti-muscarinic drugs (benztopine) but NEVER L-DOPA

Tardive Dyskinesia- Can be irreversible in adults is is the biggest problem when using antipsychotics for >1yr. There is no adequate tx

Neuroleptic malignant syndrome- immediate discontinuation of antipsychotics. Dopamine receptor agonist (bromocriptine) and muscle relaxant (diazepam or dantrolene)

Question 20

Chlorpromazine

Answer 20

Neuoleptic, inexpensive
Many side effects- especially autonomic
High muscarinic and alpha1 adrenergic receptor blocking activity
Highly SEDATIVE

Question 21

Haloperidol

Answer 21

Inexpensive, potent, few autonomic effects
Severe EPS and hyperprolactinemia
STRONG D2 receptor antagonist

Question 22

Clozapine

Answer 22

Less likely to cause EPS
MOST efficacious antipsychotic drug
May develop AGRANULOCYTOSIS- life threatening
Only used for patients resistant to typical antipsychotics
STRICT blood monitoring is mandatory

Question 23

Olanzapine

Answer 23

2nd most effective atypical antipsychotic
MOST WIDELY USED
Relatively strong histamine receptor (H1) antagonist
Side effects= sedation, METABOLIC SYNDROME, low seizure threshold (so contraindicated in someone who normally gets seizures)

Question 24

Risperidone

Answer 24

MOST potent D2 receptor blocker
Associated with EPS and hyperprolactinemia at higher dose
Less potent anti muscarinic so get better compliance w/ this drug

Question 25

Ziprasidone

Answer 25

Low affinity for muscarinic, alpha1, and H1 receptors (so less sedation, less postural hypotension, less weight gain) PROLONGS QT INTERVAL (contraindicated in pts with heart problems)

Question 26

Aripiprazole

Answer 26

PARTIAL AGONIST FOR D2 (high affinity for D2 receptor but only has ~30% of intrinsic activity of dopamine)- so less EPS 5-HT2A receptor antagonist Minimally sedating (newer drug so less pt data on it)