Antipsychotics Flashcards
Define psychosis and appreciate schizophrenia as one common form of psychosis
Psychosis: means delusions and/or psychotic hallucinations
List the major positive and negative symptoms of schizophrenia
+auditory hallucinations
+delusions
+disorganized speech
+disorganized behavior
- flat effect
- social withdrawal
- lack of motivation
- lack of speech/thought
Briefly describe the dopamine hypothesis of psychosis
All current antipsychotic drugs block DA neurotransmission
Drugs that release DA from terminals and DA agonists can cause psychotic symptoms
Compare/contrast first and second generation antipsychotics regarding their affinity for D2 and 5-HT2A receptors
1st generation =
D2 antagonists
2nd generation =
D2 + 5HT2A antagonists
(Some efficacy against negative symptoms)
Describe MOA and clinical use of:
Haloperidol
D2 antagonist
Indication: clearly effective for positive symptoms
Describe MOA and clinical use of:
Trifluperazine
D2 antagonist
Indication: clearly effective for positive symptoms
Describe MOA and clinical use of:
Fluphenazine
D2 antagonist
Indication: clearly effective for positive symptoms
Describe MOA and clinical use of:
Chlorpromazine
D2 antagonist
Indication: clearly effective for positive symptoms
(Low potency 1st gen.)
Describe MOA and clinical use of:
Thioridazine
D2 antagonist
Indication: clearly effective for positive symptoms
(Low potency 1st gen)
Describe MOA and clinical use of:
Clozapine
D2 antagonist
5HT2A antagonist
Describe MOA and clinical use of:
Quetiapine
D2 antagonist
5HT2A antagonist
Describe MOA and clinical use of:
Olanzapine
D2 antagonist
5HT2A antagonist
Describe MOA and clinical use of:
Aripriprazole
PARTIAL D2 agonist
5HT2A antagonist
Describe MOA and clinical use of:
Risperidone
D2 antagonist
5HT2A antagonist
Describe MOA and clinical use of:
Ziprasidone
D2 antagonist
5HT2A antagonist
Describe major AEs of:
Haloperidol
EPS (acute and chronic)
Describe major AEs of:
Trifluperazine
EPS (acute and chronic)
Describe major AEs of:
Fluphenazine
EPS (acute and chronic)
Describe major AEs of:
Chlorpromazine
EPS (acute and chronic)
Describe major AEs of:
Thioridazine
EPS (acute and chronic)
Describe major AEs of:
Clozapine
Agranulocytosis
(No neutrophils)
Seizures
Salivation
Describe major AEs of:
Quetiapine
Less AE than other 2nd generation antipsychotics
Describe major AEs of:
Olanzapine
Most problematic for weight gain and metabolic changes
Describe major AEs of:
Aripiprazole
Less AE than other 2nd generation antipsychotics
Describe major AEs of:
Risperidone
WORSE than other 2nd generation antipsychotics in terms of increasing prolactin secretion and causing EPS
Describe major AEs of:
Ziprasidone
Causes QT prolongation
What are the first generation (aka typical) antipsychotics?
Haloperidol
Trifluperazine
Fluphenazine
Chlorpromazine
Thioridazine
What are second generation (aka atypical) antipsychotics?
Clozapine
Quetiapine
Olanzapine
Aripiprazole
Risperidone
Ziprasidone
Compare and contrast positive/negative symptoms regarding their responsiveness to antipsychotic drugs
Most treat positive
Clozapine works against negative symptoms
Define one major location of 5-HT2A R’s and correlate drugs with an affinity for these receptors with the incidence of extrapyramidal side effects
Nigrostriatal pathway
2nd generation antipsychotics will help decrease EPS
Briefly define bipolar disease
Symptoms of major depression and mania/hypomania
Bipolar I = more mania
+extreme mood swings, very euphoric then very depressed
Bipolar II = recurrent depressive episodes + hypomanic episodes
+less extreme on positive side, still very sad
List three classes of drugs (inc. examples) used for tx of bipolar disease
Lithium = 1st line
Antiseizure drugs
+valproic acid
+carbamazepine
+lamotrigine
2nd gen antipsychotics \+ziprasidone \+olanzapine \+risperidone \+aripiprazole \+quetiapine
For lithium, describe clinical uses and major side effects and contraindications
Indications:
bipolar disease
AEs = “L..M..N..O..P”
- movement problems - tremor
- nephrogenic DI
- hypOthyroidism
- Pregnancy NO!
- N/V
- kidney dysfunction
CI
- pregnancy
- renal disease
- thyroid dysfunction
What are AEs of 1st generation antipsychotics?
From D2 receptor blockade
Extrapyramidal Sx's (EPS) Acute = -dystonia -akathisia -Parkinsonian syndrome
Late EPS = tardive dyskinesia
Neuroleptic malignant syndrome (rare)
Hyperprolactinemia
How do you treat acute extrapyramidal symptoms from 1st generation antipsychotics?
Dec. dose
Change to a 2nd gen.
Administer muscarinic receptor antagonist = trihexyphenidyl
Change to a lower potency antipsychotic
What are differences amongst 1st generation antipsychotics and their potencies?
Low potency = more blockade of H1, M, alpha1
High potency = more extrapyramidal effects
What are AEs of 1st generation antipsychotics?
Due to M, alpha1 and H1 blockade
M blockade =
Anticholinergic: dry mouth, blurred vision, urinary retention, constipation
alpha1 blockade = orthostatic hypotension
H1 blockade = sedation, inc. weight and appetite
What is the MOA of second generation antipsychotics?
D2 receptor blockade
5HT2A receptor blockade
What are indications for 2nd generation antipsychotics?
Schizophrenia - more effective against negative symptoms compared to 1st gen. Antipsychotics
What are AEs of 2nd generation antipsychotics?
Dec. risk of EPS
Can cause metabolic syndrome
What are the high potency first generation antipsychotics?
“Try to Fly High”
Trifluperazine
Fluphenazine
Haloperidol
