Antipsychotics

Question 1

Chlorpromazine

Answer 1

1st Gen Low Potency Antipsychotic
Corneal Deposits

TX: Manic Phase of Bipolar Disorder

Question 2

Thioridazine

Answer 2

1st Gen Low Potency Antipsychotic

Retinal Deposits

Question 3

Haloperidol

Answer 3

1st Gen HIGH Potency Antipsychotic

TX: Tourette’s

Question 4

Fluphenazine

Answer 4

1st Gen HIGH Potency Antipsychotic

Question 5

Clozapine

Answer 5

2nd Gen Antipsychotic
TX: Treatment resistant schizophrenia or suicidal schizophrenia

AGRANULOCYTOSIS
Highly sedating - patients will be in a stupor
Strongest affinity for muscarinic receptors - side effects
Seizure, Metabolic syndrome, Hepatic Injury

Question 6

Olanzapine

Answer 6

2nd Gen Antipsychotic
D2 antagonist + Inverse agonist* at 5-HT2A
(vs. the others which are plain old antagonists)

TX: Treatment-resistant Depression, off-label for eating disorders

SE: Metabolic Syndrome - the worst of all of them

Question 7

Quetiapine

Answer 7

2nd Gen Antipsychotic - Seroquel
Preferred AP
Sedation
Dizziness, Dry mouth, Cataracts, Orthostatic hypotension

TX: Depression

Question 8

Risperidone

Answer 8

2nd Gen Antipsychotic
Selectivity for limbic sites - D3
Often used in Autism, OCD, Tourette’s

SE: Hyperprolactinemia, amenorrhea, galactorrhea, gynecomastia

Question 9

Ziprasidone

Answer 9

2nd Gen Antipsychotic
Better antidepressant action - low potential for impairing cognitive abilities.

Lowest risk of Metabolic effects
Consider in Alzheimer’s related psychosis

Question 10

Iloperidone

Answer 10

2nd Gen Antipsychotic

Less Weight Gain
Increase Hypotension and Somnolence

Sandy Hook shooting

Question 11

Aripiprazole

Answer 11

2nd Gen Antipsychotic - Abilify
Preferred AP
Targets both 5-HT2A and D2 receptors (like the rest)

Partial D2 and 5-HT1A receptor AGONIST with less potency
Pops on and off D2 receptor, so there is less risk of EPS

TX: Useful for Schizophrenia, Bipolar Disorder, Adjunct for MDD

Question 12

Off-Label Uses for Antipsychotics

Answer 12

OCD
PTSD
Behavioral symptoms of dementia - cardiac risks
Olanzapine in eating disorders - yikes
Huntington's
Nausea/Vomiting

Question 13

Serotonin-Dopamine Antagonism Theory

Answer 13

Normal:

1. Serotonin regulates Mesocortical Dopamine release
2. Mesocortical DA pathway inhibits Mesolimbic DA pathway

Schizophrenia:

1. Increased Serotonin in PFC inhibits Mesocortical Pathway = Hypofunction (Negative Symptoms)
2. Loss of inhibition on the Mesolimbic Pathway = Hyperfunction. Excess Dopamine at the Nucleus Accumbens (Positive Symptoms)

Question 14

NT’s altered in Schizophrenia

Answer 14

Dopamine - responsible for positive symptoms. Site of 1st Gen Antipsychotics - treat positive symptoms

Serotonin - Site of 2nd Gen Antipsychotics
Disruption of NMDA receptor (glutamate)

Question 15

1st Gen MOA

Answer 15

D2 Antagonism - long time to dissociation
Antagonist: H1, Alpha-1, 5-HT2A receptors

Reduce Positive Symptoms

Question 16

2nd Gen MOA

Answer 16

D2 Antagonists
Antagonists/Inverse Agonists 5HT2A Receptor

Inverse antagonist = Binds to an agonist site, but causes the opposite response. Kind of a double hit to Serotonin with these 2nd Gen drugs.

Question 17

Extrapyramidal Side Effects

Answer 17

Dystonia
Akathesia
Iatrogenic Parkinsonism
Neuroleptic Malignant Syndrome
Perioral Tremor
Tardive Dyskinesia

Question 18

Acute Dystonia

Answer 18

Risk 1-5 days

TX: Antiparkinsonia Drugs (L-Dopa)
Benztropine = Cogentin (anti-M1 activity and DAT inhibitor)

Question 19

Akathisia

Answer 19

Motor restlessness, need to move constantly
Risk 5-60 days

TX: Switch drug, Antiparkinsonian, Benzo’s or Propanolol may help

Question 20

Iatrogenic Parkinsonism

Answer 20

Risk 5-30 days

TX: Antiparkinsonian drugs

Question 21

Neuroleptic Malignant Syndrome

Answer 21

Risk: Weeks
Catatonia, Stupor, Fever, Unstable BP
Myoglobinemia
HYPERREFLEXIA, Clonus
Can persist for days after discontinuing neuroleptics

TX: Dantrolene, Bromocriptine (D2 agonist)

Question 22

Perioral Tremor

Answer 22

“Rabbit Syndrome”
Risk months-years

TX: Antiparkinsonian drugs

Question 23

Tardive Dyskinesia

Answer 23

Risk: 15-25% after 1 year of treatment
Oral-Facial dyskinesia, widespread choreathetosis or dystonia

TX: Prevention is crucial, Reserpine for severe cases

Question 24

2nd Gen Side Effects

Answer 24

Metabolic Syndrome
Hyperprolactinemia
Sedation/Hypersomnia
Dry Mouth, Constipation

Question 25

Depression Treatment w/ Antipsychotics

Answer 25

Quetiapine - first agent
Aripiprazole - Adjunct
Olanzapine - Treatment resistant

Question 26

CYP Metabolism

Answer 26

CYP inhibitors (ex: Cipro or Fluoxetine) will decrease the metabolism of AP Drugs
Increased risk for NMS or other side effects

Question 27

Interactions with Benzo’s

Answer 27

Can cause respiratory and cardiac arrest

Question 28

Microsomal Drug-Metabolizers

Answer 28

i.e. Pherobarbital, Phenytoin

Can increase the metabolism of AP drugs

Question 29

Treatment Response to AP’s

Answer 29

Positive Symptoms (dopamine) respond more completely than negative or cognitive symptoms

Poor Compliance - use extended release

Question 30

Timecourse of EPS

Answer 30

ADAPT
Hours to Days: Acute Dystonia
Days to Months: Akathisia, Parkinsonism
Months to Years: Tardive dyskinesia

TX: Benztropine (AD, TD)
Benzodiazepenes, Beta-Blockers (Akithisia)