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phopholipidosis and antidepressants‏


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I found this old file today thought I would share it not of sound enough mind to deal with it myself will let you folks take a look.
 
 
Prog Neurobiol. 2000 Apr ;60 (6):501-12 10739086 (P,S,E,B) [Recommend] [Discuss] [My paper][Not mine] [Favorite][unfavor] [select][unselect] [Hide][unhide] Antidepressant-induced lipidosis with special reference to tricyclic compounds.

 

[My paper] Z Xia, G Ying, A L Hansson, H Karlsson, Y Xie, A Bergstrand, J W DePierre, L Nässberger 

Department of Biochemistry, Stockholm University, Sweden.

Cationic amphiphilic drugs, in general, induce phospholipid disturbances. Tricyclic, as well as other antidepressants belong to this group. In experimental animals, antidepressants induce lipid storage disorders in cells of most organs, a so-called generalized phospholipidosis. This disorder is conveniently detected by electron microscopic examination revealing myelin figures. Myelin figures or myeloid bodies are subcellular organelles containing unicentric lamellar layers. The lipidotic induction potency during in vivo is related to the apolarity of the compound. Metabolism of phospholipids takes place within the cell continuously. Several underlying mechanisms may be responsible for the induction of the phospholipid disturbance. For instance, it has been suggested that the compounds bind to phospholipids and such binding may alter the phospholipid's suitability as a substrate for phospholipases. Free TCA or metabolites thereof may also inhibit phospholipases directly, as has been demonstrated for sphingomyelinase in glioma and neuroblastoma cells. Both these mechanisms might result in phospholipidosis. Interaction between drug and phospholipid bilayer has been investigated by nuclear magnetic resonance technique. There seems to be large differences in the sensitivities amongst different organs. Steroid-producing cells of the adrenal cortex, testis and ovaries are in particular susceptible to drug-induced lipidosis. The so-called foam cells are lung macrophages located in the interstitium which become densely packed with myelin figures during TCA exposure. It requires about 3-6 weeks of treatment to develop this converted cell. In cell cultures however, phospholipidosis is demonstrated already after 24 h only. It appears that the cells that undergo TCA-induced lipidosis may recover after withdrawal of the drug. The time required to achieve complete recovery ranges from 3-4 weeks to several months, depending on the organ affected. Little is known about the functional significance of lipidosis. Even if TCA and other antidepressants show other effects, it has not been possible to exclusively relate it to phospholipidosis. However, few attempts have been made to correlate the physiological effects of TCAs in experimental animals to the morphological changes associated with phospholipidosis. There is an increasing evidence however, that cationic amphiphilic drugs may have effects on immune function, signal transduction and receptor-mediated events, effects that to some extent might be related to disturbances in phospholipid metabolism. 

Mesh-terms: Animals; Antidepressive Agents :: adverse effects; Antidepressive Agents, Tricyclic :: adverse effects; Human; Lipoidosis :: chemically induced; Lipoidosis :: metabolism; Lipoidosis :: pathology; Phospholipids :: metabolism; Support, Non-U.S. Gov't; 

Other papers by authors:

Toxicol Pathol. ;25 (1):53-60 9061852 (P,S,E,B) [Recommend] [Discuss] [My paper][Not mine] [Favorite][unfavor] [select][unselect] [Hide][unhide] Cationic amphiphilic drug-induced phospholipidosis.

 

[My paper] W H Halliwell 

Schering-Plough Research Institute, Lafayette, New Jersey 07848, USA.

Phospholipidosis, a phospholipid storage disorder, defines an excessive accumulation of intracellular phospholipids. Phospholipids are structural components of mammalian cytoskeleton and cell membranes. The metabolism of this essential cell component is regulated by the individual cell and may be altered by drugs that interact with phospholipids or the enzymes that affect their metabolism. Xenobiotics or their metabolites that induce phospholipidosis include a wide variety of pharmacologic agents, including antibacterials, antipsychotics, antidepressants, antiarrhythmics, antianginals, antimalarials, anorexic agents, cholesterol-lowering agents, and others. Each of these drugs shares several common physiochemical properties: hydrophobic ring structure on the molecule and a hydrophilic side chain with a charged cationic amine group, hence the class term cationic amphiphilic drugs (CADs). This paper reviews the phospholipid metabolism, physiochemical characteristics of CADs, specificity of phospholipidosis in animals and humans, functional effects of phospholipidosis, interaction of CADs with biologic membranes and lysosome metabolism, influence of CADs on phospholipases and phospholipid synthesis, and a proposed mechanism for induction of phospholipidosis in the lung. In human risk assessment, investigators should consider the many factors in evaluating a drug that induces phospholipidosis in animals. These include: the therapeutic class of drug, presence of active metabolites, tissue or organ selectivity in animals and humans, influence of concurrently administered drugs, reversibility of effect, and other factors that increase or decrease the induction of phospholipidosis. Generalities regarding the etiology, incidence, and effect of the drug on a specific host may not be made. Each drug must be evaluated separately to identify the risk when administered for therapeutic effect in humans. 

Mesh-terms: Animals; Cations; Human; Lipoidosis :: chemically induced; Phospholipids :: metabolism; Surface-Active Agents :: metabolism; Surface-Active Agents :: toxicity; 

Other papers by authors:

Ok I know I am pushing it with this one but am adding it becasue I had a blood test that said mitochondrial disorder.

 

Int J Neurosci. 2007 Oct ;117 (10):1465-80 17729157 (P,S,E,B) [Recommend] [Discuss] [My paper][Not mine] [Favorite][unfavor] [select][unselect] [Hide][unhide] Medroxyprogesterone acetate induces c6 glioma chemosensitization via antidepressant-like lysosomal phospholipidosis/myelinosis in vitro.

 

[My paper] Meric A Altinoz, Gunduz Gedikoglu, Aydin Sav, Emin Ozcan, Kursat Ozdilli, Ayhan Bilir, Rolando F Del Maestro 

The authors have previously shown that medroxyprogesterone acetate (MPA) inhibits growth and increases drug sensitivity in C6 glioma with myeloid bodies. Myeloid bodies can occur in cells either due to robust toxicity with mitochondrial membrane disruption or due to milder events such as seen in lysosomal-phospholipidosis. Exact patterns of myelinosis accompanying to MPA chemo-sensitization is important, because uncoupling of nuclear versus mitochondrial toxicity of anti-neoplastics by MPA would lead to safer employment of glioma chemotherapy with reduced neurotoxicity. By monitoring and comparing cell kinetics with fine structural features of cell death, the authors estimated subcellular effects accompanying growth-inhibitory drug actions in C6 glioma. The analysis revealed that MPA induced mainly lysosomal phospholipidosis, while inhibiting clonogenicity alone and augmenting procarbazine efficacy. It induced apoptosis in combination with cisplatin. It reduced mitochondrial-damage-based early cytotoxicity of methotrexate, yet it did not hinder its anti-clonogenic efficacy. Progesterone analogues - similar to antidepressants - inhibit cholesterol esterification, and this efficacy relates with their P-glycoprotein inhibition. Reducing esterification and plasma-membrane localization of cholesterol may lead MPA induction of lysosomal phospholipidosis, growth indolency, and drug sensitization in glioma. 

Other papers by authors:

__________________

You can't fool all of the people all of the time.

 

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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  • 1 year later...
phopholipidosis is an autoummune disease just to join the dots 
 
 
Best Pract Res Clin Rheumatol. 2004 Oct;18(5):677-88.
Drug-induced autoimmunity.
Abstract

Drug induced autoimmune syndromes have been recognized for many years. The classical presentation is that of drug-induced lupus, a generally milder version of the idiopathic disorder that is associated with production of antihistone antibodies. This pattern is now changing, in part due to the many new drugs that have been introduced into clinical practice for treatment of autoimmune diseases, including both conventional pharmaceuticals and biologicals. The number and complexity of drug-induced autoimmune syndromes has increased, and many are now associated with autoantibodies that have been classically defined as limited to idiopathic disease states. Furthermore, some of these drug-induced syndromes have life-threatening complications, so that recognition of drug-induced disease has become more difficult at a time when it is more urgent to establish a correct diagnosis. Many reports are limited to case descriptions, and few controlled investigations have been carried out. Nevertheless, it is possible to derive an approach to considering possible mechanisms by which these processes may take place. This chapter will consider these proposed mechanisms, using some of the implicated drugs to illustrate possible pathogenetic pathways.

PMID:   15454126   [PubMed - indexed for MEDLINE]

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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Curr Opin Rheumatol. 2009 Sep;21(5):547-51. doi: 10.1097/BOR.0b013e32832f13db.
Drug-induced autoimmunity.
Abstract
PURPOSE OF REVIEW:

This review aims to draw attention to the increased spectrum of the features of drug-induced autoimmunity (DIA), including both clinical and autoantibody profiles in addition to the potential chronicity of the syndrome.

RECENT FINDINGS:

In recent years, not only has the number of medications causing DIA increased but the spectrum of the features has broadened as well. With the use of newer medications, especially biologics, mostly directed towards immune system manipulation, the range of signs and symptoms of DIA as well as the patterns of autoantibody profiles have widened. Rashes and visceral involvement have started to be reported more often, especially with tumor necrosis factor antagonists. In addition, autoantibodies such as antidouble-stranded DNA, which are usually seen with idiopathic systemic lupus erythematosus, are appearing in place of the antihistone antibodies, typically found in drug-induced lupus. Finally, some medications have been implicated in causing the very same entity, which they may be used to treat. It is clear that progress in the field of pharmacogenetics and pharmacogenomics will help further our understanding of these and other adverse effects of medications.

SUMMARY:

Even though DIA has been known for many years, the underlying mechanisms remain unclear. However, with recently described new and unexpected features, novel hypotheses have been proposed, thus opening doors to further research in understanding these mechanisms.

J Autoimmun. 2014 Feb-Mar;48-49:66-72. doi: 10.1016/j.jaut.2014.01.005. Epub 2014 Jan 21.
Diagnosis and classification of drug-induced autoimmunity (DIA).
Abstract

Since sulfadiazine associated lupus-like symptoms were first described in 1945, certain drugs have been reported to interfere with the immune system and induce a series of autoimmune diseases (named drug-induced autoimmunity, DIA), exemplified by systemic lupus erythematosus (SLE). Among the drugs, procainamide and hydralazine are considered to be associated with the highest risk for developing lupus, while quinidine has a moderate risk, and all other drugs have low or very low risk. More recently, drug-induced lupus has been associated with the use of newer biological modulators, such as tumor necrosis factor (TNF)-alpha inhibitors and cytokines. In addition to lupus, other major autoimmune diseases, including vasculitis and arthritis, have also been associated with drugs. Because resolution of symptoms generally occurs after cessation of the offending drugs, early diagnosis is crucial for treatment strategy and improvement of prognosis. Unfortunately, it is difficult to establish standardized criteria for DIA diagnosis. Diagnosis of DIA requires identification of a temporal relationship between drug administration and the onset of symptoms, but the relative risk with respect to dose and duration for each drug has rarely been determined. DIA is affected by multiple genetic and environmental factors, leading to difficulties in establishing a list of global clinical features that are characteristic of most or all DIA patients. Moreover, the distinction between authentic DIA and unmasking of a latent autoimmune disease also poses challenges. In this review, we summarize the highly variable clinical features and laboratory findings of DIA, with an emphasis on the diagnostic criteria.

Copyright © 2014 Elsevier Ltd. All rights reserved.

KEYWORDS:

Anti-histone antibodies; Anti-nuclear antibodies; Anti-phospholipid syndrome; Drug induced lupus; Procainamide; Systemic lupus erythematosus

PMID:   24456934   [PubMed - indexed for MEDLINE]
PMID:   19593142   [PubMed - indexed for MEDLINE]    

WARNING THIS WILL BE LONG
Had a car accident in 85
Codeine was the pain med when I was release from hosp continuous use till 89
Given PROZAC by a specialist to help with nerve pain in my leg 89-90 not sure which year
Was not told a thing about it being a psych med thought it was a pain killer no info about psych side effects I went nuts had hallucinations. As I had a head injury and was diagnosed with a concussion in 85 I was sent to a head injury clinic in 1990 five years after the accident. I don't think they knew I had been on prozac I did not think it a big deal and never did finish the bottle of pills. I had tests of course lots of them. Was put into a pain clinic and given amitriptyline which stopped the withdrawal but had many side effects. But I could sleep something I had not done in a very long time the pain lessened. My mother got cancer in 94 they switched my meds to Zoloft to help deal with this pressure as I was her main care giver she died in 96. I stopped zoloft in 96 had withdrawal was put on paxil went nutty quit it ct put on resperidol quit it ct had withdrawal was put on Effexor... 2years later celexa was added 20mg then increased to 40mg huge personality change went wild. Did too fast taper off Celexa 05 as I felt unwell for a long time prior... quit Effexor 150mg ct 07 found ****** 8 months into withdrawal learned some things was banned from there in 08 have kept learning since. there is really not enough room here to put my history but I have a lot of opinions about a lot of things especially any of the drugs mentioned above.
One thing I would like to add here is this tidbit ALL OPIATES INCREASE SEROTONIN it is not a huge jump to being in chronic pain to being put on an ssri/snri and opiates will affect your antidepressants and your thinking.

As I do not update much I will put my quit date Nov. 17 2007 I quit Effexor cold turkey. 

http://survivingantidepressants.org/index.php?/topic/1096-introducing-myself-btdt/

There is a crack in everything ..That's how the light gets in :)

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