Chlorpromazine

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Adverse-effects 7 Drug-interactions 8 Laboratory 9 Mechanism-of-action 10 More General Terms 11 Additional Terms 12 Internet Database 13 References

Introduction

• Tradenames: Thorazine, Ormazine.

Indications

• management of psychotic disorders

• acute mania:

• 25 mg IM
• 25-50 mg IM 1 hour later
• increase dose gradually over several days to max of 400 mg every 4-6 hours
• substitute oral dose when patient is calm

• 500 mg/day is generally sufficient
• doses of up to 2 g/day may be necessary

• chronic psychosis:

• 25 mg PO TID
• increase gradually until effective dose reached, generally 400 mg/day

• relief of restlessness & apprehension prior to surgery

• 25-50 mg PO 2-3 hours prior to surgery
• 12.5-25 mg IM 1-2 hours 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

Contraindications

• (relative)
• narrow-angle glaucoma
• bone marrow depression
• severe liver or cardiac disease
  

• pregnancy category = c
• safety in lactation = ?

Dosage

• 10-50 mg PO/ IM BID/ TID/ QID

• 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

• constipation
• high postural hypotension potential
• decreased sweating
• dizziness
• nasal congestion

• 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 adverse effects of antipsychotic agents

Drug-interactions

• chlorpramazine increases plasma concentrations of:

• valproic acid
• tricyclic antidepressants ( TCAs)

• increased QT interval when used concurrently with:

• pimozide
• cisapride

• 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 antipsycotics with benzodiazepines
• drug interaction(s) of beta-adrenergic receptor antagonists with phenothiazines

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

• mesolimbic system
• frontal cortex
• chemoreceptor trigger zone ( CTZ)

• also binds variably to:

• cholinergic receptors
• alpha-1 adrenergic receptors
• histamine receptors

More General Terms

• phenothiazine
• antipsychotic agent
• dopaminergic receptor antagonist

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)

Internet Database

PubChem: 2726
PubChem: 6240

References

1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1147.
3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
5. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
6. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995

chlorpromazine (Thorazine, Ormazine, Propaphenin, Sonazine, Chloractil)