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Zyprexa



Zyprexa Drug
Olanzapine (sold as Zyprexa, Zydis, or in combination with fluoxetine, as Symbyax) was the second atypical antipsychotic to gain FDA approval and has become one of the most commonly used atypical antipsychotics. Olanzapine has been FDA approved for the treatment of schizophrenia, acute mania in bipolar disorder, agitation associated with schizophrenia and bipolar disorder, and as maintenance treatment in bipolar disorder. Olanzapine is manufactured and marketed by the pharmaceutical company Eli Lilly and Company. It is available as a pill that comes in the strengths of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg. It is also available as Zydis orally disintegrating tables in the strengths of 5 mg, 10 mg, 15 mg, and 20 mg.


Case-reports, open-label, and small pilot studies suggest efficacy of olanzapine for the treatment of some anxiety spectrum disorders (e.g. general anxiety disorder, panic disorder, post-traumatic stress disorder); however, olanzapine has not been rigorously evaluated in randomized, placebo-controlled trials for this use and is not FDA approved for these indications. Other common off-label uses of olanzapine include the treatment of eating disorders (e.g. anorexia nervosa)and as as adjunctive treatment for major depressive disorder with psychotic features.

Pharmacology
Olanzapine is structurally similar to clozapine, and is classified as a thienobenzodiazepine. Olanzapine has a high affinity for dopamine and serotonin receptors. Like most atypical antipsychotics compared to the older typical ones, Olanzapine has a lower affinity for histamine, cholinergic muscarinic and alpha adrenergic receptors. The mechanism of action of olanzapine is unknown, however it is theorized that olanzapine's antipsychotic activity is mediated primarily by antagonism at dopamine receptors, specifically D2. Serotonin antagonism may also play a role in the effectiveness of olanzapine, but the significance of 5-HT2A antagonism is debated among researchers. Antagonism at muscarinic, histaminic and alpha adrenergic receptors likely explains some of the side effects of olanzapine, such as anticholinergic effects, weight gain, sedation and orthostatic hypotension.

Pharmacokinetics
Olanzapine displays linear kinetics. Its elimination half-life ranges from 21 to 54 hours. Steady state plasma concentrations are achieved in about a week. Olanzapine undergoes extensive first pass metabolism and bioavailability is not affected by food.

Metabolism
Olanzapine is metabolized by the Cytochrome P450 system isoenzymes 1A2 and 2D6 (minor pathway). Drug metabolism may be increased or decreased by agents that induce (e.g. cigarette smoke) or inhibit (e.g. fluvoxamine or ciprofloxacin) CYP1A2 activity respectively.

Adverse events
Some drug users have reported extreme tiredness and weakness generated by this drug. A recent drug user who took this drug for over 4 months complained of dramatic shift in sleep patterns from the normal 8-9 hours a day on average to 12 hours a day on average at the start of the treatment and ending at 16 hours a day at the end of the 4 months. The drug user also complained of slipping into a period of suicidal depression for the last month of the treatment and 3 months that followed the treatment during which complaints were made of extreme physical tiredness and horrific emotional pain. The drug user emphatically claimed " I have never suffered such emotional horror or had suicidal ideation before I took this drug or since. Neither have I ever sleep for more than 8-9 hours on average before I took this drug or since. This drug was clearly and unambiguously to blame for the emotional horror I suffered for a period of four months.The recent reports of the botched London drug trials remind me of those horrors." The drug user adds that the severe emotional depression eased of after 4 months and was completely gone after 6 months. Adverse events reported in the package insert for olanzapine include dry mouth, dizziness, sedation, insomnia, orthostatic hypotension, akathisia, and weight gain. Olanzapine is reported to cause extrapyramidal symptoms, tardive dyskinesia and neuroleptic malignant syndrome, although at a much reduced rate when compared to the classical anti-psychotics.

Recently the FDA required the manufacturers of all atypical antipsychotics to include a warning about the risk of hyperglycemia and diabetes with atypical antipsychotics. Additionally there are some case reports of olanzapine-induced diabetic ketoacidosis. There is data showing that olanzapine can decrease insulin sensitivity. In addition, increased triglyceride levels may also be an issue with olanzapine. Impaired glucose metabolism, high triglycerides, and obesity have been shown to be constituents of the metabolic syndrome and may increase the risk of cardiovascular disease. The data suggests that olanzapine may be more likely to cause adverse metabolic effects than some of the other atypical antipsychotics.

Citing an increased risk of stroke, in 2004 the Committee for the Safety of Medicines (CSM) in the UK issued a warning that olanzapine and risperidone, both atypical antipsychotic medications, should not be given to elderly patients with dementia.

The results of a large, random-design study funded by NIH's National Institute of Mental Health (NIMH) were published in September 2005. The 18-month study, which involved 1,400 participants at 57 sites around the country, found that "patients on olanzapine also experienced substantially more weight gain and metabolic changes associated with an increased risk of diabetes than those participants taking the other drugs."

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