chlorpromazine (Thorazine, Ormazine, Propaphenin, Sonazine, Chloractil)
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Introduction
Tradenames: Thorazine, Ormazine.
Indications
- management of psychotic disorders
- relief of restlessness & apprehension prior to surgery
- treatment of nausea/vomiting
- treatment of intractable hiccups: 25-50 mg PO/IM TID-QID PRN
- adjunctive management of tetanus
- Tourette's syndrome
- episodic dyscontrol syndrome[7]
Contraindications
(relative)
- narrow-angle glaucoma
- bone marrow depression
- severe liver or cardiac disease
Dosage
Tabs: 10, 25, 50, 100, 200 mg.
Suppository: 25, 100 mg.
Concentrate: 30 mg/mL (120 mL)
Syrup: 10 mg/5 mL.
Injection: 25 mg/mL (1 & 2 mL)
May be given IV when diluted at max rate of 1 mg/min.
Caution:
- monitor for hypotension
- avoid contact with skin; may cause contact dermatitis
Pharmacokinetics
- variable absorption
- highly bound to plasma proteins
- widely distributed to tissues including CNS
- metabolized by liver by cyt P450 2D6
- 1/2 of the dose excreted by liver, the other 1/2 through the enterohepatic circulation
elimination via liver
elimination via kidney
1/2life = 30 hours
protein binding = 95-98 %
elimination by hemodialysis = -
elimination by peritoneal dialysis = -
Adverse effects
- common (> 10%)
- extrapyramidal effects
- tardive dyskinesia
- 10-20% of patients on long term therapy
- generally irreversible
- pseudoparkinsonism
- dystonia
- akathisia
- tardive dyskinesia
- constipation
- high postural hypotension potential
- decreased sweating
- dizziness
- nasal congestion
- extrapyramidal effects
- less common (1-10%)
- difficulty urinating, sunburn, skin rash, changes in menstrual cycle, male sexual dysfunction, breast pain, weight gain, nausea/vomiting, stomach pain, tremor
- uncommon (< 1%)
- agranulocytosis, cholestatic jaundice (vanishing bile duct syndrome), neuroleptic malignant syndrome (rare), priapism, blue-gray discoloration of skin, impaired temperature regulation, galactorrhea, leukopenia, hepatotoxicity, changes in the lens & cornea
- other
- moderate anticholinergic effects
- highly sedating
- QT prolongation
- direct myocardial depression
- increased serum transaminases
- lowers seizure threshold
- drug-induced lupus
- drug adverse effects of antipsychotic agents
- drug adverse effects of psychotropic agents
- drug adverse effects of dopaminergic receptor antagonists
- drug adverse effects of antihypertensive agents
Drug interactions
- chlorpramazine increases plasma concentrations of:
- increased QT interval when used concurrently with:
- anticholinergic agents decrease pharmacologic effects of chlorpromazine
- meperidine (Demerol) increases sedative & hypotensive effects of chlorpromazine
- concurrent administration of propranolol increases plasma levels of both drugs
- chlorpromazine directly antagonizes effects of anti-Parkinson agents
- additive effects with other CNS depressants, hypotensive & anticholinergic agents
- terfenadine & astemizole should be avoided
- concurrent use of TCA increases risk of neuroleptic malignant syndrome
- lithium may increase absorption of chlorpromazine
- pharmaceutical agents that inhibit cyt P450 2D6 may increase levels of chlorpromazine
- drug interaction(s) of lithium carbonate with phenothiazine
- drug interaction(s) of antipsychotics & dopamine receptor agonists
- drug interaction(s) of antipsycotics with benzodiazepines
- drug interaction(s) of beta-adrenergic receptor antagonists with phenothiazines
- drug interaction(s) of NSAIDs & antihypertensives
Laboratory
- specimen:
- serum, plasma (EDTA)
- collect at trough concentration
- store at -70 degrees C
- methods: GLC-ECD, GC-MS, HPLC, RIA
- interferences: diazepam interferes with analysis by GLC-ECD
Mechanism of action
- low potency antipsychotic
- low potency dopamine D2 receptor antagonist
- also binds variably to:
More general terms
Additional terms
- cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)
- Gilles de la Tourette's syndrome
- hiccups (singultus)
- mania (manic state)
- nausea
- psychosis
- vanishing bile duct syndrome (idiopathic ductopenia)
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1147.
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
- ↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
- ↑ 7.0 7.1 7.2 Deprecated Reference