Antipsychotics

Question 1

What is the major dopaminergic tract that is the source of psychosis?

Answer 1

Mesolimbic tract

Question 2

One theory says that too much dopamine can cause….

Answer 2

Schizophrenia

Question 3

How does the binding affinity of the antipsychotic drug affect its dosing?

Answer 3

The greater the binding affinity for DA receptors, the smaller dose is needed for the antipsychotic effect

Question 4

List the Low Potency FGAs

Answer 4

Chlorpromazine

Thioridazine
Perphenazine
Thiothixene

Question 5

What % of DA receptors need to be blocked to produce a therapeutic effect? What about side effects in the nigrostriatal and tuberoinfundibular tracts?

Answer 5

Therapeutic: block 60-65% of D2 receptors in the mesolimbic tract

Side effects in nigrostriatal and tuberinfundibular tracts: above 80% D2 receptor blockage

Question 6

Chlorpromazine

Adverse Effects

Answer 6

Dopamine - EPS or Tardive dyskinisia; increased prolactin

Muscarinic- blurred vision, urinary retention, dry mouth, constipation

Alpha 1 adrenergic – orthostasis

H1 - sedation; weight gain

Question 7

List the High Potency FGAs

Answer 7

Haloperidol

Fluphenazine
Trifluoperazine

Question 8

High Potency FGAs

Adverse effects

Answer 8

Dopamine- EPS and TD; hyperprolactinemia (galactorrhea, gynecomastia)

No H1, musc, alpha1 side effects!

Question 9

Excess dopamine blockage in the Nigrostriatal pathway tends to cause…

Answer 9

ExtraPyramidal Symptoms

Tardive dyskinisia

Question 10

Excess dopamine blockage in the Tuberoinfundibular pathway tends to cause…

Answer 10

Hyperprolactinemia

Gynecomastia, Galactorrhea
Low GnRH
Osteopenia (increased fractures)

Question 11

List some SGAs

Answer 11

Clozapine

Risperidone
Quetiapine
Aripiprazole
Olanzapine
Asenapine
Ziprasidone
Iloperidone
Paliperidone
Luraisdone

Question 12

SGAs

MOA

Answer 12

Dual antagonism of both the presynaptic 5HT-2A and postsynaptic D2 receptors

Blocking the 5HT-2A receptors causes a disinhibition of DA release, thus causing excess DA in the synapse, so SGA DA blockade is not as long lasting

Question 13

Which SGA is a partial agonist of the DA receptor? Describes its pharmacodynamics

Answer 13

Aripiprazole

Has agonist effects in a low dopamine environment. Has antagonist effects in a high dopamine environment

Question 14

Positive Results of using Clozapine (a SGA)

Answer 14

Has efficacy in treating negative symptoms of schizophrenia

Helps with TD

Decrease risk of suicide or violence

Helps with treatment resistant schizophrenia

Question 15

Clozapine is the 3rd line choice for antipsychotics (after 2 others failed). This is due to its adverse effects, including…

Answer 15

Common: Sedating, Weight Gain
Metabolic Syndrome
Anticholinergic

Rare:
AGRANULOCYTOSIS
Myocarditis
Decreased Seizure threshold

Question 16

All antipsychotics have the potential side effect of NMS. What is that?

Answer 16

NMS = Neuroleptic Malignant Syndrome

Caused by excess dopamine blockade

Dopamine system goes haywire, causing mental status changes, rigidity, tremor, fever, inc HR, low BP, inc RR

Question 17

What is the recommendation for treating elderly patients with antipsychotics?

Answer 17

Treat with low doses for minimal time

FGAs and SGAs can cause sudden death in elderly patients with dementia

Question 18

Which SGA has the longest half life?

Answer 18

Aripiprazole (3 days)

Question 19

Describe the protein binding of Antipsychotics

Answer 19

90% protein bound, unbound portion passes through the BBB

Question 20

Avg half life for antipsychotics

Answer 20

About 30 hours (so you reach steady state between 4-7 days)

Question 21

What is the only treatment for Tardive Dyskinisia?

Answer 21

Clozapine

Question 22

Aripiprazole

Adverse Effects

Answer 22

Dopamine- akathesia

Low risk of weight gain

Musc, Adrenergic, H1– none

Question 23

What is the relationship between Risperidone and Palliperidone?

Answer 23

Risperidone is metabolized to Palliperidone

Question 24

Palliperidone

Excretion

Answer 24

Mostly renally excreted, so used in pts with liver disease

Question 25

What is special about the administration of Ziprasidone and Lurasidone?

Answer 25

MUST be taken with food (improves absorption by 50%)