Quetiapine

Chemical

Dibenzothiazepine derivative →second generation antipsychotic

Use

  1. ICU delirium
  2. Bipolar mania
  3. Schizophrenia

Presentation

Tablets

Dose

Starting at 12.5mg →up to 750mg/day (divided doses)

Route

PO

Onset

Peak levels 2hrs →SS 2 days

MoA (mechanism)

  • Unclear mechanism
  • ↓Dopaminergic transmission in mesolimbic pathway
  • 5HT2A & D2 antagonism →antipsychotic effects
  • 5HT1A partial agonism →antidepressant effects
  • α1 & H1 antagonism
    • α1 = hypotension
    • H1 = sedation + weight gain

PD

CNS

  • Antipsychotic
  • Fatigue

CVS

Hypotension

PK

A

OBA 100%

Peaks 2hrs

D

80% PPB

VD 10L/kg!

M

Hepatic sulfoxidation

CYP3A4

*DRUG INTERACTIONS*

E

Metabolites in urine

Adverse Effects

Neuroleptic Malignant Syndrome

NB: attributed to dopamine receptor blockade

  • Blocking D2 = mass GLUTAMATE release
  • Catatonia, neurotoxicity, myotoxicity
  • Blocking some serotonergic receptors activates 5HT receptors = ↓GABA & ↑glutamate release

→High fever, confusion, rigid muscles, labile BP, sweating, ↑HR

→Rhabdo, ↑K, AKI, seizures

→Due to use of antipsychotics, rapid withdrawal of LevoDopa

→Treat with Dantrolene, BZD, cooling

 

CYP3A4 inhibitors

CYP3A4 inducer

↓clearance

Erythromycin

↑clearance

Carbamazepine

Phenytoin

Common:

  • Dry mouth
  • Dizziness
  • Headache
  • Drowsiness
  • Weight gain
  • LFT derangement