Quetiapine
Chemical
Dibenzothiazepine derivative →second generation antipsychotic
Use
- ICU delirium
- Bipolar mania
- 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