Olanzapine

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Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Olanzapine.jpg

[edit] MECHANISM OF ACTION

Olanzapine, is an antipsychotic drug belonging to the class of atypical antipsychotics (Second generation antipsychotics). Other atypical antipsychotic drugs include Risperidone, Paliperidone, Quetiapine, Aripiprazole, Clozapine, Ziprasidone and Amisulpride.

Olanzapine binds to α1, dopamine D2, histamine H1, muscarinic, and serotonin 5-HT2 receptors.

Its efficacy in Schizophrenia is mediated through a combination of antagonism at dopamine D2 receptors in the mesolimbic pathway and serotonin 5HT2A receptors in the frontal cortex. Antagonism at D2 receptors relieves positive symptoms while antagonism at 5HT2A receptors relieves negative symptoms of schizophrenia.

Antagonism of dopamine receptors is also associated with extrapyramidal effects such as tardive dyskinesia

Olanzapine by binding to the D2 receptor, elevate serum prolactin

Olanzapine is a potent antagonist of the muscarinic M3 receptor which may underlie its diabetes side-effects.

Olanzapine’s antagonism of muscarinic receptors may explain its anticholinergic-like effects

Antagonizing H1 histamine receptors causes sedation and may cause weight gain, although antagonistic actions at serotonin 5-HT2C and dopamine D2 receptors have also been associated with weight gain and appetite stimulation

Antagonism of adrenergic α1 receptors may explain the orthostatic hypotension observed with this drug.

[edit] INDICATIONS

Oraly:

  • Treatment of schizophrenia. Schizophrenia is a mental illness that has a number of symptoms, including disorganised thinking and speech, hallucinations (hearing or seeing things that are not there), suspiciousness and delusions (mistaken beliefs)
  • Acute treatment of manic (extremely high mood) or mixed episodes associated with bipolar I disorder and maintenance treatment of bipolar I disorder alone or as an adjunct to valproate or lithium carbonate
  • Olanzapine/Fluoxetine Combination: Treatment Resistant Depression (Major Depressive Disorder in adults who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode)
  • Olanzapine/Fluoxetine Combination: Depressive Episodes Associated with Bipolar I Disorder in adults


Intramuscular:

  • Treatment of acute agitation associated with schizophrenia and bipolar I mania.

[edit] DOSAGE

  • Schizophrenia in adults: Starting dose: 5-10 mg once daily; Target dose: 10 mg/day within several days
  • Bipolar I Disorder (manic or mixed episodes) in adults: The starting dose is 15 mg as a single daily dose in monotherapy or 10 mg daily in combination therapy
  • Agitation associated with Schizophrenia and Bipolar I Mania in adults: IM: 10 mg (5 mg or 7.5 mg when clinically warranted) Assess for orthostatic hypotension prior to subsequent dosing (max. 3 doses daily, 2-4 hrs apart)

[edit] CONTRAINDICATIONS

  • Hypersensitivity to Olanzapine

[edit] WARNINGS AND PRECAUTIONS

  • Elderly Patients with Dementia-Related Psychosis: Olanzapine is not approved for the treatment of dementia-related psychosis and/or behavioural disturbances and is not recommended for use in this particular group of patients because of an increase in mortality and the risk of cerebrovascular adverse events (e.g., stroke, transient ischemic attack).
  • Suicide: The possibility of a suicide attempt is inherent in schizophrenia and in bipolar I disorder, and close supervision of high-risk patients should accompany drug therapy
  • Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. NMS is a potentially life-threatening condition associated with antipsychotic medicinal products. Rare cases reported as NMS have also been received in association with olanzapine. Clinical manifestations of NMS are hyperpyrexia (extreme elevation of body temperature), muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all antipsychotic medicines, including olanzapine must be discontinued.
  • Hyperglycemia: In some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients taking olanzapine. Patients taking olanzapine should be monitored for symptoms of hyperglycemia and undergo fasting blood glucose testing at the beginning of, and periodically during, treatment.
  • Hyperlipidemia: Undesirable alterations in lipids have been observed. Appropriate clinical monitoring is recommended, including fasting blood lipid testing at the beginning of, and periodically during, treatment.
  • Weight Gain: Potential consequences of weight gain should be considered. Patients should receive regular monitoring of weight.
  • Tardive Dyskinesia (involuntary movements, especially of the lower face): Discontinue if clinically appropriate.
  • Orthostatic Hypotension: Orthostatic hypotension associated with dizziness, tachycardia, bradycardia and, in some patients, syncope, may occur especially during initial dose titration. Use caution in patients with cardiovascular disease, cerebrovascular disease, and those conditions that could affect hemodynamic responses.

[edit] INTERACTIONS

  • Diazepam: May potentiate orthostatic hypotension.
  • Alcohol: May potentiate orthostatic hypotension.
  • Carbamazepine: Carbamazepine, an inducer of CYP1A2, causes an approximately 50% increase in the clearance of olanzapine
  • Fluvoxamine: : Fluvoxamine, a CYP1A2 inhibitor, may increase olanzapine levels.
  • CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs and alcohol.
  • Antihypertensive Agents: because of its potential for inducing hypotension, Olanzapine may enhance the effects of certain antihypertensive agents
  • Levodopa and Dopamine agonists: Olanzapine may antagonize the effects of levodopa and dopamine agonists.

[edit] PREGNANCY AND LACTATION

Pregnancy Category C (US). Olanzapine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: Olanzapine is excreted in breast milk. It is recommended that women receiving olanzapine should not breast-feed.

[edit] SIDE EFFECTS

most frequently (seen in ≥ 1% of patients) adverse reactions: orthostatic hypotension, dry mouth, constipation, weight gain, dizziness, sedation, fatigue, personality disorder, tremor , akathisia (motor restlessness), eosinophilia, elevated prolactin, cholesterol, glucose and triglyceride levels


For more serious adverse effects see WARNINGS AND PRECAUTIONS

[edit] RELATED LINKS

Antipsychotics (Typical and Atypical): pharmacology, indications and adverse effects

[edit] BIBLIOGRAPHY

[edit] REFERENCES