Atypical antipsychotics

Question 1

Olanzapine

Answer 1

First line drug- similar to clozapine: blocks D2, D4, 5-HT2a, anti-ach effects, improves both positive and negative
Oral, long lasting- liver metabolism
No agranulocytosis (less toxicity), high ant-ach (low extrapyramidal) side effects: wt gain, increased hyperglycemia/T2DM
tx: schizophrenia, bipolar

Question 2

Risperidone

Answer 2

First line drug for psychosis- both neg and pos. sx
Used in combo with SSRI
Inhibits D2 and esp. 5-HT2a, a1
Enhances DA in basal ganglia- low extrapyramidal effects
tardive dyskinesia unlikely
Oral
side effects: a-block (postural hypotension), HA, N, wt gain, most likely to lengthen QT, increase prolactin, extrapyramidal at high doses only
tx: depression, autism, schizophrenia used previous in AD, but no antipsychotic should be used in elderly, esp. dementia, delusions and psychosis in PD
- paliperidone is an active metabolite of risperidone

Question 3

Ziprasidone

Answer 3

similar to risperidone- blocks D2/5HT2a, antidepressant
oral or IM
CYP3A4 - drug interactions prolong QT sedation hyperprolactinemia, avoid in pts with cardiac conduction defects or recent MI or TCA, and use caution in pts. with seizures
tx: tourettes, acute mania
delusions and psychosis in PD

Question 4

Clozapine

Answer 4

MOA: Binds to D4 and 5HT2a with greater affinity than D2 receptors. also blocks a1 and histamine
seizures likely
use is reserved for pts who do not respond to conventional drugs or when use limited by tardive dyskinesia.
very expensive
Oral- individualized, metabolized in liver
Less affinity for D2 receptors,- less extrapyramidal effects
inhibits M/H/a1- unlikely to cause tardive dyskinesia,
side effects: agranulocytosis- life threatening, monitor blood counts, wt. gain, dec. seizure threshold, hypotension (a1), tachycardia (a1), increased salivation (no anticholinergic), sedation (histamine blocker)
tx: schizophrenia, tx delusions and hallucinations in pts with PD

Question 4

Iloperidone

Answer 4

D2/5HT2a, a-block

similar to other antipsychotics, slight QT poss

Question 5

Quetiapine

Answer 5

First line drug, improves pos. and neg.
metabolite: norquetiapine
very similar to clozapine, Also blocks 5HT2C - inc release of NE from locus coeruleus
No agranulocytosis, few extrapyramidal, no prolactin release
side effects: wt gain, dizzy, constipation
TX: depression adjunct, sleep with depression, bipolar disorder

Question 6

Lurasidone

Answer 6

D2/5HT2a, partial at 5-HT1a, NO a/H block

some agranulocytosis, neutropenia (monitor blood count)

Question 7

Paliperodone

Answer 7

Antipsychotic- atypical

Question 9

Asenapine

Answer 9

Blocks multiple 5-HT: 5-HT2a, and 5-HT2c, D3, and histamine
PTSD off- label 
metabolic effects, other than drugs 
Small QT increase 
PTSD label

Question 10

Aripiprazole (abilify)

Answer 10

MOA: partial agonist at D2 and 5HT1a, Antagonist at 5HT2a, a1 blocker, histamine blocker
- dopamine receptors are activated when dopaminergic tone is low, and blocked is dopaminergic tone is high
- metabolized by CYP3A4 and CYP2D6
- NO prolactin or QT interval effect
side effects: orthostatic hypotension, sedation, elevated blood glucose, dec. motility of esophagus, dec. ability to regulate temp in hypothalamus, low incidence of extrapyramidal effects

Question 11

Drugs that cause hyperglycemia

Answer 11

Olanzapine
risperidone
quetiapine
phenothiazides

Question 12

Drugs that cause sedation

Answer 12

Phenothiazides
Quetiapine
Aripriprazole

Question 13

Drug interactions with Antipsychotics

Answer 13

• sedative hypnotics = inc. sedation
• anticholinergics= inc. anti chol. side effects (dry mouth, urinary retention, etc.)
• carbamazepine and smoking induces liver enzymes- dec antipsychotic concentration
• interactions with hypertensives unpredictable due to a1 blockade