Category Archives: Murder

Chicago Tylenol murders


Chicago Tylenol murders

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The Chicago Tylenol murders occurred when seven people died after taking pain-relief capsules that had been poisoned. The Tylenol poisonings, code-named TYMURS by the FBI, took place in the autumn of 1982 in the Chicago area of the United States. These poisonings involved Extra-Strength Tylenol medicine capsules which had been laced with potassium cyanide.[1] The incident led to reforms in the packaging of over-the-counter substances and to federal anti-tampering laws. The case remains unsolved and no suspects have been charged. A $100,000 reward, offered by Johnson & Johnson for the capture and conviction of the “Tylenol Killer,” has never been claimed.

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[edit] The incidents

Wednesday morning, September 29, 1982, 12-year-old Mary Kellerman of Elk Grove Village, Illinois, died after taking a capsule of Extra Strength Tylenol. Adam Janus of Arlington Heights, Illinois, died in the hospital shortly thereafter. Adam’s brother Stanley of Lisle, Illinois, and sister-in-law Theresa died after gathering to mourn his death, having taken pills from the same bottle. Soon afterward, Mary McFarland of Elmhurst, Paula Prince of Chicago, and Mary Reiner of Winfield, Illinois, also died in similar incidents.[2][3] Investigators soon discovered the Tylenol link. Urgent warnings were broadcast, and police drove through Chicago neighborhoods issuing warnings over loudspeakers.
As the tampered bottles came from different factories, and the seven deaths had all occurred in the Chicago area, the possibility of sabotage during production was ruled out. Instead, the culprit was believed to have entered various supermarkets and drug stores over a period of weeks, pilfered packages of Tylenol from the shelves, adulterated their contents with solid cyanide compound at another location, and then replaced the bottles. In addition to the five bottles which led to the victims’ deaths, three other tampered bottles were discovered.
Johnson & Johnson, the parent company of McNeil, distributed warnings to hospitals and distributors and halted Tylenol production and advertising. On October 5, 1982, it issued a nationwide recall of Tylenol products; an estimated 31 million bottles were in circulation, with a retail value of over US$100 million. The company also advertised in the national media for individuals not to consume any products that contained acetaminophen. When it was determined that only capsules were tampered with, they offered to exchange all Tylenol capsules already purchased by the public with solid tablets.

[edit] Suspects

During the initial investigations, a man named James W. Lewis sent a letter to Johnson & Johnson demanding $1 million to stop the cyanide-induced murders. Police were unable to link him with the crimes, as he and his wife were living in New York City at the time. He was convicted of extortion, served 13 years of a 20-year sentence, and was released in 1995 on parole. WCVB Channel 5 of Boston reported that court documents, released in early 2009, “show Department of Justice investigators concluded suspect James W. Lewis, who now lives in Cambridge, Massachusetts, was responsible for the poisonings, despite the fact that they did not have enough evidence to charge him.” Lewis continues to deny responsibility for the poisonings.[4][5]
A second man, Roger Arnold, was investigated and cleared of the killings; however, the media attention caused him to have a nervous breakdown, and he blamed a bar owner, Marty Sinclair, for the police investigation of him. In the summer of 1983, he shot and killed John Stanisha, whom he mistook for Sinclair, but who was, in fact, an innocent man who did not know Arnold.[6] Arnold was convicted in January 1984 and served 15 years of a 30-year sentence for second degree murder. He died in June 2008.
Laurie Dann, who poisoned and shot victims in a May 1988 rampage in and around Winnetka, Illinois, was briefly considered as a suspect, but no direct connection was found.[7]

[edit] Aftermath

The media gave Johnson & Johnson much positive coverage for its handling of the crisis; for example, an article in the Washington Post said, “Johnson & Johnson has effectively demonstrated how a major business ought to handle a disaster.” The article further stated that “this is no Three Mile Island accident in which the company’s response did more damage than the original incident,” and applauded the company for being honest with the public. In addition to issuing the recall, Johnson & Johnson established relations with the Chicago Police, the FBI, and the Food and Drug Administration. This way the company could have a part in searching for the person who laced the Tylenol capsules and they could help prevent further tamperings.[8]analgesic in the US. While at the time of the scare the market share of Tylenol collapsed from 35% to 8%, it rebounded in less than a year, a move credited to J&J’s prompt and aggressive reaction. In November, it reintroduced capsules but in a new, triple-sealed package, coupled with heavy price promotions and within several years, Tylenol had become the most popular over-the-counter
A number of copycat attacks involving Tylenol and other products (see Stella Nickell for information on the 1986 Excedrin tampering murders) ensued during the following years. One of these incidents occurred in the Chicago area; unlike Tylenol, it actually forced the end of the product affected by the hoax, Encaprin, from Procter & Gamble. However, the incident did inspire the pharmaceutical, food, and consumer product industries to develop tamper-resistant packaging, such as induction seals and improved quality control methods. Moreover, product tampering was made a federal crime.
Additionally, the tragedy prompted the pharmaceutical industry to move away from capsules, which were easy to contaminate as a foreign substance could be placed inside without obvious signs of tampering. Within the year, the Food and Drug Administration introduced more stringent regulations to avoid product tampering. This led to the eventual replacement of the capsule with the solid “caplet”, a tablet made in the shape of a capsule, as a drug delivery form and with the addition of tamper-evident safety-seals to bottles of many sorts.

[edit] Ongoing investigations

In early January 2009, Illinois authorities renewed the investigation. Federal agents searched the home of Lewis in Cambridge, Massachusetts, and seized a number of items.[9] In Chicago, an FBI spokesman declined to comment but said “we’ll have something to release later possibly.”[10] Law enforcement officials have received a number of tips related to the case coinciding with its anniversary. In a written statement,[11] the FBI explained,

This review was prompted, in part, by the recent 25th anniversary of this crime and the resulting publicity. Further, given the many recent advances in forensic technology, it was only natural that a second look be taken at the case and recovered evidence.

In January 2010, both Lewis and his wife submitted DNA samples and fingerprints to authorities.[5] Lewis stated “if the FBI plays it fair, I have nothing to worry about.”[5]

Seroquel


Quetiapine

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Quetiapine
Systematic (IUPAC) name
2-(2-(4-dibenzo[b,f][1,4]thiazepine- 11-yl- 1-piperazinyl)ethoxy)ethanol
Identifiers
CAS number 111974-69-7
ATC code N05AH04
PubChem CID 5002
IUPHAR ligand ID 50
DrugBank DB01224
ChemSpider 4827
Chemical data
Formula C21H25N3O2S 
Mol. mass 383.5099 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 9%
Metabolism Hepatic
Half-life 6 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat. C(US)
Legal status -only (US)
Routes Oral
 Yes(what is this?)  (verify)Y
Quetiapine (pronounced /kwɨˈtaɪ.əpiːn/ kwi-TYE-ə-peen), marketed by AstraZeneca as Seroquel and by Orion Pharma as Ketipinor, both as a quetiapine fumarate salt of the drug, is an atypical antipsychoticschizophrenia, bipolar I mania, bipolar II depression, bipolar I depression, and used off-label for a variety of other purposes, including insomnia and anxiety disorders. used in the treatment of
Annual sales are approximately $4.7 billion worldwide, and $2.9 billion in the U.S.[1] The patent in the U.S., which was set to expire in 2011, received a pediatric exclusivity extension, which pushed its expiration to March 26, 2012.[2] The patent already expired in Canada. Several pharmaceutical companies are now making generic versions of quetiapine. Quepin is a generic version manufactured and marketed by Specifar ABEE, Athens, Greece.[3]
Controversy arose over AstraZeneca’s aggressive marketing of the Seroquel for off-label uses, including treatment of PTSD in veterans. Several American soldiers and veterans have died while taking Seroquel.[4]

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[edit] Uses

Quetiapine (Seroquel) 25 mg tablets, next to US one-cent coin for comparison.

Quetiapine is indicated for the treatment of schizophrenia, depressive episodes associated with bipolar disorder, acute manic episodes associated with bipolar I disorder (as either monotherapy or adjunct therapy to lithium or valproate), and maintenance treatment of bipolar I disorder (as adjunct therapy to lithium or divalproex). Quetiapine received its initial indication from the U.S. Food and Drug Administration for treatment of schizophrenia in 1997.[5] In 2004, it received its second indication for the treatment of mania-associated bipolar disorder.[6] It is sometimes used off-label, often as an augmentation agent, to treat conditions such as obsessive-compulsive disorder, post-traumatic stress disorder, restless legs syndrome, autism, alcoholism, depression,[7] Tourette syndrome,[8] and has been used by physicians as a sedative for those with sleep disorders or anxiety disorders.[9]
In 2005, the National Institute of Mental Health examined quetiapine and other antipsychotics to uncover the comparative efficacy of “second generation” anti-psychotics against older anti-psychotics (known as “first generation” or “typical anti-psychotics”). Such information could be important to the patients, as the newer drugs are far more expensive than their older counterparts. Published in the New England Journal of Medicine, the results of the CATIE (“clinical antipsychotic trials of interventional effectiveness”) trial were somewhat mixed. 74% of trial participants (of the 1,493 people who were in different treatment groups) discontinued before the trial ended. The majority of the participants discontinued treatment due to intolerable side effects or lack of efficacy. Olanzapine (Zyprexa) was considered the most effective in terms of the time it took patients to drop out of the study, although it was associated with greater weight gain and glucoseperphenazine.[10] The CATIE trial was supported by a grant (N01 MH90001) from the NIMH and by the Foundation of Hope of Raleigh, N.C. The individual pharmaceutical companies, whose drugs were used, donated all of the study medication. intolerability found in diabetes patients. The effects of all other treatments (such as Seroquel) were considered to be similar to the effects of the generic (and dramatically less expensive) drug,
A report in British Medical Journal in 2005 showed that quetiapine was ineffective in reducing agitation among Alzheimer’s patients, whose usage of the drug constituted 29% of sales. In fact, quetiapine was found to worsen cognitive functioning in elderly patients with dementia.[11]
Use of quetiapine to minimize the symptoms of opioid withdrawal has been studied.[12]

[edit] Investigations

In 2007 and 2008, studies were conducted on quetiapine’s efficacy in treating generalized anxiety disorder and major depression. In April 2009, the Psychopharmacologic Drugs Advisory Committee of the US Food and Drug Administration (FDA) held a public meeting to discuss whether study results supported the FDA’s approval for anxiety and depression, with risks of metabolic side effects and of tardive dyskinesia and sudden cardiac death.[13]

In 2010 AstraZeneca was ordered to pay $520 million in a settlement with State and Federal authorities. According to the settlement AstraZeneca promoted the sale and use of Seroquel for uses not approved by the FDA, and paid illegal kickbacks to doctors. As a result of their promotional activity, physicians prescribed Seroquel for children, adolescents and dementia patients in long term care facilities.[14]

[edit] Pharmacology

Quetiapine has the following pharmacological actions:[15][16][17][18]
This means Quetiapine is dopamine, serotonin and adrenergic antagonist, anticholinergic substance and antihistamine. Quetiapine binds strongly to serotonin receptors. Serial PET scans evaluating the D2 receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D2[19] Theoretically, this allows for normal physiological surges of dopamine to elicit normal effects in areas such as the nigrostriatal and tuberoinfundibular pathways, thus minimizing the risk of side effects such as pseudo-parkinsonism as well as elevations in prolactin.[citation needed] receptor.

Zyprexa (? + rex(king))


Olanzapine

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Olanzapine
Systematic (IUPAC) name
2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine
Identifiers
CAS number 132539-06-1
ATC code N05AH03
PubChem CID 4585
IUPHAR ligand ID 47
DrugBank DB00334
ChemSpider 10442212
Chemical data
Formula C17H20N4S 
Mol. mass 312.439
SMILES eMolecules & PubChem
Physical data
Melt. point 195 °C (383 °F)
Solubility in water Practically insoluble in water mg/mL (20 °C)
Pharmacokinetic data
Bioavailability 87% [1]
Metabolism Hepatic (direct glucuronidation and CYP mediated oxidation)
Half-life 21–54 hours
Excretion urine 57%, feces 30%
Therapeutic considerations
Pregnancy cat. C
Legal status Prescription only
Routes oral, intramuscular
 Yes(what is this?)  (verify)Y

Zyprexa 10 mg tablets (AU)

Olanzapine (trade names Zyprexa, Zalasta, Zolafren, Olzapin, Oferta, Zypadhera or in combination with fluoxetine Symbyax) is an atypical antipsychotic, approved by the FDA for the treatment of schizophrenia and bipolar disorder.[2] Olanzapine is structurally similar to clozapine, but is classified as a thienobenzodiazepine. The olanzapine formulations are manufactured and marketed by the pharmaceutical company Eli Lilly and Company, whose patent for olanzapine proper expires in 2011 (in October 2009 a Canadian judge ruled that the 1991 patent was invalid).[3] Sales of Zyprexa in 2008 were $2.2B in the US alone, and $4.7B in total.[4]

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[edit] Indications and Usage

  • oral formulation: acute and maintenance treatment of schizophrenia in adults, acute treatment of manic or mixed episodes associated with bipolar I disorder (monotherapy and in combination with lithium or valproate)
  • intramuscular formulation: acute agitation associated with schizophrenia and bipolar I mania in adults
  • oral formulation combined with fluoxetine: treatment of acute depressive episodes associated with bipolar I disorder in adults, or treatment of acute, resistant depression in adults [5]
Known FDA approvals are as follows:
  • approved for the treatment of the manifestations of psychotic disorders on September 6, 1996[6]
  • approved in combination with fluoxetine for the treatment of depressive episodes associated with Bipolar disorder on December 24, 2003[7]
  • approved for the long-term treatment of bipolar I disorder on January 14, 2004[8]
  • approved in combination with fluoxetine for treatment of resistant depression on March 19, 2009.[9]

[edit] Off-label uses

Case-reports, open-label, and small pilot studies suggest efficacy of olanzapine for the treatment of some anxiety spectrum disorders (e.g. generalized anxiety disorder,[10] panic disorder,[11] post-traumatic stress disorder);[12] 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 an adjunctive treatment for major depressive disorder without psychotic features. It has also been used for Tourette syndrome and stuttering.[13][14] Olanzapine is also used in many addiction clinics as a sleep aid (usually 2.5–5 mg) due to its low abuse profile and zero addictive properties.

[edit] Prevention of psychosis

Olanzapine has been considered as part of an early psychosis approach for schizophrenia. The Prevention through Risk Identification, Management, and Education (PRIME) study, funded by the National Institute of Mental Health and Eli Lilly, tested the hypothesis that olanzapine might prevent the onset of psychosis in people at very high risk for schizophrenia. The study examined 60 patients with prodromal schizophrenia, who were at an estimated risk of 36–54% of developing schizophrenia within a year, and treated half with olanzapine and half with placebo.[15] In this study, patients receiving olanzapine had a lower risk of progressing to psychosis, although the difference did not reach statistical significance. Olanzapine was effective for treating the prodromal symptoms, but was associated with significant weight gain.[16]

[edit] Use in elderly

Citing an increased risk of stroke, in 2004 the Committee on 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. In the U.S., olanzapine comes with a black box warning for increased risk of death in elderly patients. It is not approved for use in patients with dementia-related psychosis.[17][18]

However, a BBC investigation in June 2008 found that this advice was being widely ignored by British doctors.

Risperdal (psedoscience and the psychiatric equivalent to AIDS/HIV/H4)


Risperidone

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Risperidone
Systematic (IUPAC) name
4-[2-[4-(6-fluorobenzo[d]isoxazol-3-yl)-
1-piperidyl]ethyl]-3-methyl-
2,6-diazabicyclo[4.4.0]deca-1,3-dien-5-one
Identifiers
CAS number 106266-06-2
ATC code N05AX08
PubChem CID 5073
IUPHAR ligand ID 96
DrugBank DB00734
ChemSpider 4895
Chemical data
Formula C23H27FN4O2 
Mol. mass 410.485 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 70% (oral)
Metabolism Hepatic (CYP2D6-mediated)
Half-life 3–20 hours
Excretion Urinary
Therapeutic considerations
Pregnancy cat. C
Legal status Prescription only
Routes Oral and extended-release intramuscular injection
 Yes(what is this?)  (verify)Y
Risperidone (pronounced Ris-PEAR-rǐ-dōne) is an atypical antipsychotic used to treat schizophreniaschizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in children with autism. The drug was developed by Janssen-Cilag and first released in 1994[1]. It is sold under the trade name Risperdal in the Netherlands, United States, Canada, Australia, United Kingdom, Portugal, Spain, Turkey, New Zealand and several other countries, Risperdal or Ridal in New Zealand, Sizodon or Riscalin in India, Rispolept in Eastern Europe, and Russia, and Belivon, or Rispen elsewhere. (including adolescent schizophrenia),

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[edit] Indications and Uses

  • treatment of schizophrenia in adults
  • treatment of schizophrenia in adolescents aged 13-17 years
  • alone or in combination with lithium or valproate, for the short-term treatment of acute manic or mixed episodes associated with Bipolar I Disorder in adults
  • alone in the short-term treatment of acute manic or mixed episodes associated with Bipolar I Disorder in children and adolescents aged 10-17 years
  • treatment of irritability associated with autistic disorder in children and young adults
  • it has also been used as a control drug for people with tourette syndrome and other tic disorders.
  • treatment of major depression with psychotic features
  • cure persistent or intractable hiccups[2]
Risperidone was approved by the United States Food and Drug Administration (FDA) in 1993 for the treatment of schizophrenia.[3]
On August 22, 2007, risperidone was approved as the only drug agent available for treatment of schizophrenia in youth ages 13–17; it was also approved that same day for treatment of bipolar disorder in youth and children ages 10–17, joining lithium. Risperidone contains the functional groups of benzisoxazolepiperidine as part of its molecular structure. In 2003 the FDA approved risperidone for the short-term treatment of the mixed and manic states associated with bipolar disorder. In 2006 the FDA approved risperidone for the treatment of irritability in children and adolescents with autism.[4] The FDA’s decision was based in part on a study of autistic children with severe and enduring problems of violent meltdowns, aggression, and self-injury; risperidone is not recommended for autistic children with mild aggression and explosive behavior without an enduring pattern.[5] Like other atypical antipsychotics, risperidone has also been used off-label for the treatment of anxiety disorders, such as obsessive-compulsive disorder; severe, treatment-resistant depression with or without psychotic features; tourette syndrome; disruptive behavior disorders in children; and eating disorders, among others. In two small studies risperidone was reported to successfully treat the symptoms of phencyclidine (PCP) psychosis due to acute intoxication[6] and chronic use.[7] and
A 2009 Cochrane Library review found no evidence from randomized controlled trials that risperidone is effective for the treatment of attention-deficit hyperactivity disorder (ADHD) in people with intellectual disabilities.[8] A multi-year UK study by the Alzheimer’s Research Trust suggested that this and other neuroleptic anti-psychotic drugs commonly given to Alzheimer’s patients with mild behavioural problems often made their condition worse. The study concluded that:
For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status and by some measures improved functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this possibility must be weighed against the unwanted effects of therapy.[9]

[edit] Availability

Risperdal 4 mg tablets (UK)

Janssen’s patent on Risperdal expired on December 29, 2003, opening the market for cheaper generic versions of the drug from other companies, and Janssen’s exclusive marketing rights expired on June 29, 2004 (the result of a pediatric extension.)
Risperidone is available as a tablet in 0.25, 0.5, 1, 2, 3 and 4 mg sizes, as an oral solution (30ml, 1 mg/ml), and as a 12.5 mg, 25 mg, 37.5 mg and 50 mg ampoule Risperdal Consta, which is a depot injectionRisperdal M-Tabs and elsewhere as Risperdal Quicklets. administered once every two weeks. It is also available as a wafer known in the United States and Canada as
Risperidone became available as a generic drug in October 2008 from Teva Pharmaceuticals, Dr. Reddy’s Laboratories, Inc. and Patriot Pharmaceutics. The Patriot generic is Janssen Pharmaceutical’s “authorized generic pharmaceutical.”

[edit] Side effects

Risperidone has been associated with weight gain.[10] Other common side effects include akathisia, sedation, dysphoria, insomnia, sexual dysfunction, low blood pressure, high blood pressure, muscle stiffness, muscletremors, increased salivation, constipation, and stuffy nose. pain,
Many antipsychotics are known to cause hyperprolactinemia which may lead to hypogonadism-induced osteoporosis, galactorrhoea, gynaecomastia, irregular menstruation and sexual dysfunction. However, risperidone is known to increase prolactin to a greater extent than other atypical antipsychotics. Although lactation is possible in both sexes using other antipsychotic drugs, risperidone is the biggest offender.[11][12][13] It is thought that once risperidone raises prolactin, it may cause prolactinoma, a benign tumor of the pituitary gland. Tumors, in general, are not considered reversible. Medical therapy may help reduce tumor size and restore normal reproduction and pituitary function, however, dopamine agonists[14] There is a higher association between pituitary neoplasms with use of risperidone and amisulpride than with other antipsychotic agents. are not likely to be prescribed to antipsychotic users, thus, surgery or radiation treatment may be required. This condition may recur if the patient is switched to a different antipsychotic. Risperidone has been known to cause increased thoughts of suicide.
Risperidone can potentially cause tardive dyskinesia (TD),[15] extrapyramidal symptoms (EPS),[15] and neuroleptic malignant syndrome (NMS).[15] Risperidone may also trigger diabetes and more serious conditions of glucose metabolism, including ketoacidosis and hyperosmolar coma, according to an FDA Warning Letter issued to Janssen Pharmaceutica, Inc. on 19-Apr-04.[16]

[edit] Pharmacology

This drug belongs to a class of antipsychotic drugs known as atypical antipsychotics that have more pronounced serotonin antagonism than dopamine antagonism, but risperidone is unique in this class because it retains dopamine antagonism. It has high affinity for D2 dopaminergic receptors. It has actions at several 5-HT (serotonin) receptor subtypes. These are 5-HT2C, linked to weight gain, 5-HT2A,linked to its antipsychotic action and relief of some of the extrapyramidal side effects (EPS) experienced with the typical neuroleptics.
It reaches peak plasma levels quickly regardless of whether it is administered as a liquid or pill. Risperidone is metabolised fairly quickly, so the potential for nausea subsides usually in two to three hours. However, the active metabolite, 9-hydroxy-risperidone, which has similar pharmacodynamics to risperidone, remains in the body for much longer, and has been developed as an antipsychotic in its own right, called paliperidone.
An intramuscular preparation, marketed as Risperdal Consta, can be given once every two weeks. It is slowly released from the injection site. This method of administration may be used on sanctioned patients who are declining, or consenting patients who may have disorganized thinking and cannot remember to take their daily doses.[17] Doses range from 12.5 to 50 mg given as an intramuscular injection once every two weeks.

Lexapro (symbolc misrepresentation)[Lexis-vocabulary, pro-(for, skilled]


Lexapro [Lexis(vocabulary) + Pro]

Escitalopram

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Escitalopram
Systematic (IUPAC) name
(S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile
Identifiers
CAS number 128196-01-0
ATC code N06AB10
PubChem CID 146570
DrugBank APRD00683
ChemSpider 129277
UNII 4O4S742ANY
Chemical data
Formula C20H21FN2O 
Mol. mass 324.392 g/mol
(414.43 as oxalate)
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 80%
Protein binding ~56%
Metabolism Liver, specifically the enzymes CYP3A4 and CYP2C19
Half-life 27–32 hours
Therapeutic considerations
Pregnancy cat. C
Legal status Rx Only (U.S) POM (U.K)
Routes Oral
 Yes(what is this?)  (verify)Y

Lexapro tablets

Cipralex brand escitalopram package and tablet sheet

Escitalopram (trade names Lexapro, Cipralex, Seroplex, Lexamil) is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is approved by the U.S. Food and Drug Administration (FDA) for the treatment in adults with major depressive disorder, generalized anxiety disorder, social anxiety disorder , or panic disorder. Escitalopram is the S-stereoisomer (enantiomer) of the earlier Lundbeck drug citalopram, hence the name escitalopram. Escitalopram is noted for its high selectivity of serotonin reuptake inhibition and has side effects typical for the SSRI class.

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[edit] History

Escitalopram was developed in a close cooperation between Lundbeck and Forest Laboratories. Its development was initiated in the summer of 1997, and the resulting new drug application was submitted to the U.S. FDA in March 2001. The short time (3.5 years) it took to develop escitalopram can be attributed to the previous extensive experience of Lundbeck and Forest with citalopram, which has similar pharmacology.[1]evergreening[2] (also called “lifecycle management”[3])– the long-term strategy pharmaceutical companies use in order to extend the lifetime of a drug, in this case of the citalopram franchise. Escitalopram is an enantiopure compound of the racemic mixture citalopram, used for the same indication, and for that reason it required less investment and less time to develop. Two years after escitalopram’s launch, when the patent on citalopram expired, the escitalopram sales successfully made up for the loss. On May 23, 2006, the FDA approved a generic version of escitalopram by Teva.[4] On July 14 of that year, however, the U.S. District Court of Delaware decided in favor of Lundbeck regarding the patent infringement dispute and ruled the patent on escitalopram valid.[5] The FDA issued the approval of escitalopram for major depression in August 2002 and for generalized anxiety disorder in December 2003. Escitalopram can be considered an example of “
In 2006 Forest Laboratories was granted an 828 day (2 years and 3 months) extension on its US patent for escitalopram.[6] This pushed the patent expiry from December 7, 2009 to March 14, 2012.

Geodon [geo (earth) + don(dominic)]


LORD
Don, from Latin dominus, is an honorific in Spanish ([don]), Portuguese (Dom, [dõ]), and Italian ([dɔn]). The female equivalent is Doña (Spanish: [ˈdoɲa]), Dona (Portuguese: [ˈdonɐ]), and Donna (Italian: [ˈdɔnna]), abbreviated “Dª” or simply “D.”

Dominus is the Latin word for master or owner.

Ziprasidone

Ziprasidone
Systematic (IUPAC) name
5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-
6-chloro-1,3-dihydro-2H-indol-2-one
Identifiers
CAS number 146939-27-7
ATC code N05AE04
PubChem CID 60854
IUPHAR ligand ID 59
DrugBank DB00246
ChemSpider 54841
Chemical data
Formula C21H21ClN4OS 
Mol. mass 412.936
Pharmacokinetic data
Bioavailability 100% (intramuscular)
60% (orally)
Metabolism hepatic (aldehyde reductase)
Half-life 7 hours
Excretion Urine and feces
Therapeutic considerations
Licence data US FDA:link
Pregnancy cat. C(US)
Legal status Prescription only
Routes oral, intramuscular
 Yes(what is this?)  (verify)Y
Ziprasidone (marketed as Geodon, Zeldox by Pfizer) was the fifth atypical antipsychotic to gain FDA approval (February 2001). In the United States, Ziprasidone is Food and Drug Administration (FDA) approved for the treatment of schizophrenia, and the intramuscular injection form of ziprasidone is approved for acute agitation in schizophrenic patients. Ziprasidone has also received approval for acute treatment of mania and mixed states associated with bipolar disorder. The brand name Geodon has been suggested to bring to mind the phrase ‘down (don) to earth (geo)’ referring to the goals of the medication.
The oral form of ziprasidone is the hydrochloride salt, ziprasidone hydrochloride. The intramuscular form, on the other hand, is the mesylate salt, ziprasidone mesylate trihydrate, and is provided as a lyophilized powder.
Geodon was one of four drugs which Pfizer in 2009 pleaded guilty to misbranding “with the intent to defraud or mislead”. Pfizer agreed to pay $2.3 billion (£1.4 billion) in settlement, and entered a corporate integrity agreement. Pfizer was found to have illegally promoted four of its drugs for use in conditions that had not been approved by the FDA.[1]

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[edit] Pharmacology

Ziprasidone has a high affinity for dopamine, serotonin, and alpha-adrenergic receptors and a moderate affinity for histamine receptors, where it is believed to act as an antagonist.[2] Ziprasidone also displays some inhibition of synaptic reuptake of serotonin and norepinephrine[2][3], although the clinical significance of this is unknown. The mechanism of action of ziprasidone is unknown. However it has been theorized that its antipsychotic activity is mediated primarily by antagonism at dopamine receptors, specifically D2. Serotonin antagonism may also play a role in the effectiveness of ziprasidone, but the significance of 5-HT2A antagonism is debated among researchers.[4] Ziprasidone has perhaps the most selective affinity for 5-HT2A receptors relative to D2 and 5-HT2C receptors of any neuroleptic.[5][6] Antagonism at histaminic and alpha adrenergic receptors likely explains some of the side effects of ziprasidone, such as sedation and orthostasis.

[edit] Pharmacokinetics

The systemic bioavailability of ziprasidone administered intramuscularly is 100%, or 60%, administered orally with food. After a single dose intramuscular administration, the peak serum concentration typically occurs at about 60 minutes after the dose is administered, or earlier. Steady state plasma concentrations are achieved within one to three days. The mean half-life ranges from two to five hours. Exposure increases in a dose-related manner and following three days of intramuscular dosing, little accumulation is observed.
Ziprasidone absorption is not optimally achieved when administered without food. Without a meal preceding dose, the bioavailability of the drug is reduced by approximately 50%.[7][8]
Ziprasidone is hepatically metabolized by aldehyde oxidase; minor metabolism occurs via cytochrome P450 3A4 (CYP3A4).[9] Medications that induce (e.g. carbamazepine) or inhibit (e.g. ketoconazole) CYP3A4 have been shown to decrease and increase, respectively, blood levels of ziprasidone.[10][11]

[edit] Adverse effects

Ziprasidone received a black box warning due to increased mortality in elderly patients with dementia-related psychosis.[7] It also slightly increases the QTc interval in some patients and increases the risk of a potentially lethal type of heart arrhythmia known as torsades de pointes. Ziprasidone should be used cautiously in patients taking other medications likely to interact with ziprasidone or increase the QTc interval.[12]
Patients in general will experience loss of focus and motivation as well as blurry vision to the point that stronger doses may cause thoughts of suicide while the medicine is in the patients system. Thoughts of suicide may occur. Typically side effects will start about an hour after ingestion and peak about four to five hours after ingestion. Patient will most likely be unable to operate machinery or drive a vehicle while the medicine is effecting the patient as blurred vision can be quite severe.
Ziprasidone may cause cause dangerous—even fatal—heartbeat irregularities.
Geodon generally adheres to the mid section of the prefrontal cortex. It derives from the ideas and thoughts process in the prefrontal cortex in which determines a treatment diagnosis for psychosis. Those who experience the symptoms of psychosis will experience on-going symptoms such as: lack of sleep, insomnia, and uncontrollable desires and experiences. Geodone adheres and corrects the prefrontal cortex by delivering an enzyme called (enzyme-B). This enzyme corrects the basal ganglia function which coorelates with the B-cortex hemispheres. In other words the enzyme delivers a vital nutrient into the system which is release by the geodome once again, called enzyme-b. The process of Geodon is somewhat confusing as it affects both the basal ganglia and prefrontal cortex. By affecting the basal ganglia the prefrontal cortex does what is called: identity change. This is a process in which enzymes are switched from one section of the brain to another. The prefrontal cortex is mainly involved in spacial recognition which will be slightly alleviated by the geodon. Those who experience spacial recognition problems usually suffer from psychosis.
Ziprasidone is known to cause activation into mania in some bipolar patients.[13][14][15]
This medication can cause birth defects, according to animal studies, although this side effect has not been confirmed in humans.[7]
Adverse events reported for ziprasidone include severe chest pains, impaired erectile function and stimulation, sedation, insomnia, orthostasis, life-threatening neuroleptic malignant syndrome, akathisia, and the development of permanent neurological disorder tardive dyskinesia. Rarely, temporary speech disorders may result.
Recently, the FDA required the manufacturers of some atypical antipsychotics include a warning about the risk of hyperglycemia and Type II diabetes with atypical antipsychotics. Some evidence suggests that ziprasidone may not be as bad as some of the other atypical antipsychotics (namely, olanzapine (Zyprexa)) at causing insulin resistance and weight gain.[16][17][18][19] In fact, in a trial of long term therapy with ziprasidone, overweight patients (BMI > 27) actually had a mean weight loss overall.[7] Ziprasidone, though, is not a weight loss drug. The weight loss reflected in this study on ziprasidone was really reflective of patients who had gained weight on other antipsychotics who were now trending back toward their baseline.[citation needed]clozapine and olanzapine). According to the manufacturer insert, ziprasidone caused an average weight gain of 2.2 kg (4.8 lbs) (which is significantly lower than other atypicals–

[edit] Off-label uses

In addition to its antipsychotic use, ziprasidone is sometimes prescribed for the treatment of tic disorders. A small study[20] has supported the efficacy of this use.

Antipsychotics Pseuodoscience Death and Symbolic name fraud


Antipsychotics

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An antipsychotic (or neuroleptic) is a tranquilizing psychiatric medication primarily used to manage psychosis (including delusions or hallucinations, as well as disordered thought), particularly in schizophreniabipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s. Most of the drugs in the second generation, known as atypical antipsychotics, have been developed more recently, although the first atypical antipsychotic, clozapine, was discovered in the 1950s and introduced clinically in the 1970s. Both generations of medication tend to block receptors in the brain’s dopamine pathways, but antipsychotic drugs encompass a wide range of receptor targets. and
A number of harmful and undesired (adverse) effects have been observed, including lowered life expectancy, weight gain, enlarged breasts and milk discharge in men and women (hyperprolactinaemia), lowered white blood cell count (agranulocytosis), involuntary repetitive body movements (tardive dyskinesia), diabetes, an inability to sit still or remain motionless (tardive akathisia), sexual dysfunction, a return of psychosis requiring increasing the dosage due to cells producing more neurochemicals to compensate for the drugs (tardive psychosis), and a potential for permanent chemical dependence leading to psychosis much worse than before treatment began, if the drug dosage is ever lowered or stopped (tardive dysphrenia).
Temporary withdrawal symptoms including insomnia, agitation, psychosis, and motor disorders may occur during dosage reduction of antipsychotics, and can be mistaken for a return of the underlying condition.[1][2]

 History

The original antipsychotic drugs were happened upon largely by chance and then tested for their effectiveness. The first, chlorpromazine, was developed as a surgical anesthetic. It was first used on psychiatric patients because of its powerful calming effect; at the time it was regarded as a “chemical lobotomy“. Lobotomy at the time was used to treat many behavioral disorders, including psychosis, although its effect was to markedly reduce behavior and mental functioning of all types. However, chlorpromazine proved to reduce the effects of psychosis in a more effective and specific manner than the extreme lobotomy-like sedation it was known for. The underlying neurochemistry involved has since been studied in detail, and subsequent antipsychotic drugs have been discovered by an approach that incorporates this sort of information.

Drug action

All antipsychotic drugs tend to block D2 receptors in the dopamine pathways of the brain. This means that dopamine released in these pathways has less effect. Excess release of dopamine in the mesolimbic pathway has been linked to psychotic experiences. It is the blockade of dopamine receptors in this pathway that is thought to control psychotic experiences.
Typical antipsychotics are not particularly selective and also block dopamine receptors in the mesocortical pathway, tuberoinfundibular pathway, and the nigrostriatal pathway. Blocking D2 receptors in these other pathways is thought to produce some of the unwanted side effects that the typical antipsychotics can produce (see below). They were commonly classified on a spectrum of low potency to high potency, where potency referred to the ability of the drug to bind to dopamine receptors, and not to the effectiveness of the drug. High-potency antipsychotics such as haloperidol, in general, have doses of a few milligrams and cause less sleepiness and calming effects than low-potency antipsychotics such as chlorpromazine and thioridazine, which have dosages of several hundred milligrams. The latter have a greater degree of anticholinergic and antihistaminergic activity, which can counteract dopamine-related side effects.
Atypical antipsychotic drugs have a similar blocking effect on D2 receptors. Some also block or partially block serotonin receptors (particularly 5HT2A, C and 5HT1A receptors):ranging from risperidone, which acts overwhelmingly on serotonin receptors, to amisulpride, which has no serotonergic activity. The additional effects on serotonin receptors may be why some of them can benefit the “negative symptoms” of schizophrenia.[74]

Controversy

Use of this class of drugs has a history of criticism in residential care. As the drugs used can make patients calmer and more compliant, critics claim that the drugs can be overused. Outside doctors can feel under pressure from care home staff.[81] In an official review commissioned by UK government ministers it was reported that the needless use of anti-psychotic medication in dementia care was widespread and was linked to 1800 deaths per year.[82][83] In the US, the government has initiated legal action against the pharmaceutical company Johnson and Johnson for allegedly paying kickbacks to Omnicare to promote its antipsychotic Risperidone (Risperdal) in nursing homes.[84]
There is some controversy over maintenance therapy for schizophrenia.[2][85] A review of studies about maintenance therapy concluded that long-term antipsychotic treatment was superior to placebo in reducing relapse in individuals with schizophrenia, although some of the studies were small.[86] A review of major longitudinal studies in North America found that a moderate number of patients with schizophrenia were seen to recover over time from their symptoms, raising the possibility that some patients may not require maintenance medication.[85] It has also been argued that much of the research into long-term antipsychotic maintenance may be flawed due to failure to take into account the role of antipsychotic withdrawal effects on relapse rates.[2]
There has also been controversy about the role of pharmaceutical companies in marketing and promoting antipsychotics, including allegations of downplaying or covering up adverse effects, expanding the number of conditions or illegally promoting off-label usage; influencing drug trials (or their publication) to try to show that the expensive and profitable newer atypicals were superior to the older cheaper typicals that were out of patent. For example in the US, Eli Lilly recently pleaded guilty to violating US laws for over a decade in regard to Zyprexa (olanzapine), and was ordered to pay $1.42 billion to settle criminal and civil allegations, including the biggest criminal fine for an individual corporation ever imposed in US history; while Astrazeneca Seroquel (quetiapine), amidst federal investigations of its marketing practices.[87] By expanding the conditions for which they were indicated, Astrazeneca’s Seroquel and Eli Lilly’s Zyprexa had become the biggest selling antipsychotics in 2008 with global sales of $5.5 billion and $5.4 billion respectively.[11] is facing about 9,000 personal-injury lawsuits from more than 15,000 former users of
Some critics have also analyzed the use of alleged front organizations and conflicted patient “advocacy” groups funded by pharmaceutical companies that seek to set the mental health agenda, including the use of the law to force people to take antipsychotics against their will, often justified by claims about risk of violence.[88]