Antipsychotics Flashcards
Chlorpromazine
1st Gen Low Potency Antipsychotic
Corneal Deposits
TX: Manic Phase of Bipolar Disorder
Thioridazine
1st Gen Low Potency Antipsychotic
Retinal Deposits
Haloperidol
1st Gen HIGH Potency Antipsychotic
TX: Tourette’s
Fluphenazine
1st Gen HIGH Potency Antipsychotic
Clozapine
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
Olanzapine
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
Quetiapine
2nd Gen Antipsychotic - Seroquel
Preferred AP
Sedation
Dizziness, Dry mouth, Cataracts, Orthostatic hypotension
TX: Depression
Risperidone
2nd Gen Antipsychotic
Selectivity for limbic sites - D3
Often used in Autism, OCD, Tourette’s
SE: Hyperprolactinemia, amenorrhea, galactorrhea, gynecomastia
Ziprasidone
2nd Gen Antipsychotic
Better antidepressant action - low potential for impairing cognitive abilities.
Lowest risk of Metabolic effects
Consider in Alzheimer’s related psychosis
Iloperidone
2nd Gen Antipsychotic
Less Weight Gain
Increase Hypotension and Somnolence
Sandy Hook shooting
Aripiprazole
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
Off-Label Uses for Antipsychotics
OCD PTSD Behavioral symptoms of dementia - cardiac risks Olanzapine in eating disorders - yikes Huntington's Nausea/Vomiting
Serotonin-Dopamine Antagonism Theory
Normal:
- Serotonin regulates Mesocortical Dopamine release
- Mesocortical DA pathway inhibits Mesolimbic DA pathway
Schizophrenia:
- Increased Serotonin in PFC inhibits Mesocortical Pathway = Hypofunction (Negative Symptoms)
- Loss of inhibition on the Mesolimbic Pathway = Hyperfunction. Excess Dopamine at the Nucleus Accumbens (Positive Symptoms)
NT’s altered in Schizophrenia
Dopamine - responsible for positive symptoms. Site of 1st Gen Antipsychotics - treat positive symptoms
Serotonin - Site of 2nd Gen Antipsychotics
Disruption of NMDA receptor (glutamate)
1st Gen MOA
D2 Antagonism - long time to dissociation
Antagonist: H1, Alpha-1, 5-HT2A receptors
Reduce Positive Symptoms
2nd Gen MOA
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.
Extrapyramidal Side Effects
Dystonia Akathesia Iatrogenic Parkinsonism Neuroleptic Malignant Syndrome Perioral Tremor Tardive Dyskinesia
Acute Dystonia
Risk 1-5 days
TX: Antiparkinsonia Drugs (L-Dopa)
Benztropine = Cogentin (anti-M1 activity and DAT inhibitor)
Akathisia
Motor restlessness, need to move constantly
Risk 5-60 days
TX: Switch drug, Antiparkinsonian, Benzo’s or Propanolol may help
Iatrogenic Parkinsonism
Risk 5-30 days
TX: Antiparkinsonian drugs
Neuroleptic Malignant Syndrome
Risk: Weeks Catatonia, Stupor, Fever, Unstable BP Myoglobinemia HYPERREFLEXIA, Clonus Can persist for days after discontinuing neuroleptics
TX: Dantrolene, Bromocriptine (D2 agonist)
Perioral Tremor
“Rabbit Syndrome”
Risk months-years
TX: Antiparkinsonian drugs
Tardive Dyskinesia
Risk: 15-25% after 1 year of treatment
Oral-Facial dyskinesia, widespread choreathetosis or dystonia
TX: Prevention is crucial, Reserpine for severe cases
2nd Gen Side Effects
Metabolic Syndrome
Hyperprolactinemia
Sedation/Hypersomnia
Dry Mouth, Constipation
Depression Treatment w/ Antipsychotics
Quetiapine - first agent
Aripiprazole - Adjunct
Olanzapine - Treatment resistant
CYP Metabolism
CYP inhibitors (ex: Cipro or Fluoxetine) will decrease the metabolism of AP Drugs Increased risk for NMS or other side effects
Interactions with Benzo’s
Can cause respiratory and cardiac arrest
Microsomal Drug-Metabolizers
i.e. Pherobarbital, Phenytoin
Can increase the metabolism of AP drugs
Treatment Response to AP’s
Positive Symptoms (dopamine) respond more completely than negative or cognitive symptoms
Poor Compliance - use extended release
Timecourse of EPS
ADAPT
Hours to Days: Acute Dystonia
Days to Months: Akathisia, Parkinsonism
Months to Years: Tardive dyskinesia
TX: Benztropine (AD, TD)
Benzodiazepenes, Beta-Blockers (Akithisia)
