Lecture 79: Antipsychotics

Question 1

Typical antipsychotics are pure..

Answer 1

Dopamine antagonists

Question 2

Atypical antipsychotics are both…

Answer 2

Dopamine antagonists and 5HT2A antagonists

Question 3

Antipsychotics are also called

Answer 3

Neuroleptics

Question 4

All DA receptors are…

Answer 4

G-protein coupled

Question 5

Neuroleptics act on…which is coupled to? This causes

Answer 5

D2; Gi; less DA neurotransmission

Question 6

Low potency antipyschotic

Answer 6

Clorpromazine

Question 7

Mid potency antipyschotic

Answer 7

Perphenazine

Question 8

High potency antipyschotics (2)

Answer 8

Fluphenazine, haloperidol

Question 9

Anitpsychotic “potency” is based on…Why is this important?

Answer 9

D2 Blockade; higher potent = less dirty

Question 10

Describe “dirty” SEs of antipsychotics via receptors

Answer 10

ACh, H1, alpha1 blockade

Question 11

Therapeutic use of antipsychotics (5)

Answer 11

Primary and secondary psychotic disorder, mood disorders (bipolar and MDD w/ psychotic features), severe agitation, delirium, Tourette’s

Question 12

What drugs are available once-a-month dosing?

Answer 12

F

Question 13

DA-related effects of antipsychotics and pathway

Answer 13

1. Parkinsonian-like (nigrostriatal); 2. Relief of psychosis (mesolimbic); 3. Increased negative symptoms (mesocortical); 4. Elevated prolactin –> breast enlargement/lactation (tuberoinfundibular pathway)

Question 14

Neurological adverse effects (3). Which drugs convey highest risk?

Answer 14

1. Extrapyramindal symptoms (EPS; Parkinsonism, acute dystonia, akathisia); 2. Tardive dyskineasia; 3. Neuroleptic malignant syndrome; high potency drugs

Question 15

How many patients get neuroleptic-induced Parkisonism (%)? When do they occur? What is treatment? Why?

Answer 15

15%; within several months; anticholinergics –> typically balance b/t DA and ACh, if you block DA, you should block ACh to re-achieve balance

Question 16

Describe acute dystonic reaction: symptoms, when it occurs, treatment

Answer 16

Spastic contractions in face and body; occurs quickly (within days); anticholinergic

Question 17

Describe akathisia: symptoms

Answer 17

Subjective feeling of inner restlessness w/ objective increased motor activity

Question 18

Describe tardive dyskinesia: symptoms, onset (%), treatment

Answer 18

Writhing movements of mostly face; 5%/year (long-term use); not reversible –> stopping/switching antipsychotic

Question 19

Describe neuroleptic malignant syndrome: symptoms, onset time, mortality (%)

Answer 19

Autonomic symptoms (fever, sweating), motor & behavior symptoms (rigidity, dystonia, agitation, confusion); can occur ANY TIME; 20-30% if untreated

Question 20

Other antipsychotic SEs by 3 receptors and 1 other important SE

Answer 20

M1, H1, alpha1 receptor blockade; cardiac (QT prolongation)

Question 21

Atypical antipsychotics

Answer 21

Clozapine, risperidone, olazapine, ziprasidone, quetiapine, aripiprazole

Question 22

What makes an antipsychotic atypical (2)

Answer 22

1. D2 AND 5HT2A antagonists; 2. Rapid dissociation from D2 receptor

Question 23

Why does 5HT2A antagonism work? How does it work in real patients?

Answer 23

Turns off GABA interneuron –> more DA release (tempering DA blockade); complicated net actions on DA activity, varies per patient

Question 24

Theoretical benefits of atypicals and which are true/not true (4)

Answer 24

Reduced EPS (true), reduced hyperprolactinemia (true), cognitive enhancement (not true), improved adherence (not true)

Question 25

How to choose an antipsychotic? Example.

Answer 25

Look at receptor binding profile (i.e. olazapine blocks H1 more than risperidone, so it is more sedating, good for agitated people)

Question 26

Therapeutic use of antipsychotics (3)

Answer 26

1. Psychotic disorders; 2. Mood disorders w/ psychotic features; 3. Treatment resistant MDD; 4. Aggression/irritability in children with autism (Risperidone)

Question 27

T/F: Atypicals are associated with off-label uses

Answer 27

True! Multiple

Question 28

How is Aripiprazole different?

Answer 28

"Third generation" --> partial agonist at DA D2 receptor and 5-HT1A; antagonist at 5-HT2A

Question 29

What is the most effective AND drug of choice for treatment resistant schizophrenia? What's interesting about this drug and why is it not always first line?

Answer 29

Clozapine; low potency as D2-receptor antagonist; potentially irreversible risk of agranulocytosis

Question 30

Risperidone has similar SEs to...why?

Answer 30

Typicals because it is a strong blocker of D2

Question 31

Adverse effect of atypical antipsychotics

Answer 31

Metabolic syndrome: visceral obesity, low insulin resistance, high triglycerides, hypertension low HDL-cholesterol

Question 32

Mortality with atypical antipsychotics

Answer 32

2-3x increased mortality from all causes

Question 33

What are the "worst" atypicals for metabolic syndrome. Best?

Answer 33

Clozapine and olanzapine; aripiprazole

Question 34

Other adverse effects of antipsychotics

Answer 34

Cardiac, sedation, EPS (risperidone), seizures...

Question 35

Rare serious SEs of clozapine

Answer 35

Agranulocytosis and myocarditis

Question 36

What is a common off label use of antipsychotics? Good data? Why is this concerning?

Answer 36

Treat behavioral disturbances in ELDERLY; NO; can cause over sedation/falls (orthostatic hypotension), increases ALL CAUSES of mortality

Question 37

The only two antispychotics shown to increase cognition/social life. But these are...Why?

Answer 37

Clozapine and olanzapine; 2nd line; more likely to induce metabolic syndrome (and scary SEs)

Question 38

Why do we use atypical antipsychotics first line?

Answer 38

You CAN treat metabolic syndrome but NOT tardive dyskinesia