Drug-induced phospholipidosis

[btdt]

http://www.sciencedirect.com/science/article/pii/S0014579306010325

 

"Drug-induced phospholipidosis is characterized by intracellular accumulation of phospholipids with lamellar bodies, most likely from an impaired phospholipid metabolism of the lysosome. Organs affected by phospholipidosis exhibit inflammatory reactions and histopathological changes. Despite significant advances in the understanding of drug-altered lipid metabolism, the relationship between impaired phospholipid metabolism and drug-induced toxicity remains enigmatic. Here we review molecular features of inheritable lysosomal storage disorders as a molecular mimicry of drug-induced phospholipidosis for an improved understanding of adverse drug reaction."

 

". Essentially, drug-induced phospholipidosis is characterized by phospholipid accumulation in affected tissue of which lung, liver, brain, kidney, cornea and others have been reported [3].

So far, more than 50 novel chemical entities have been identified to induce phospholipidosis. These include antibiotics, antidepressants, antipsychotics, antimalarial and antiarrythmic drugs. Many of these are cationic amphiphilic drugs (CADs) and share particular physical properties resulting from a chemical structure containing a hydrophilic ring and hydrophobic regions. Several of these drugs display severe adverse effects, such as acute pneumonitis or hepatitis as observed under amiodarone treatment [4]. However, the relationship between drug-induced phospholipidosis and adverse drug effects remains unexplained. Specifically, the onset of phospholipidosis may or may not be associated with clinical symptoms, including inflammatory reactions and histopathological changes, such as macrophagic infiltration or fibrosis. Clinically relevant phospholipidosis has been observed under administration of amiodarone, fluoxetine, gentamicin, perhexiline and 4.4′-dieethylaminoethoxyhexestrol [5].

The term drug-induced phospholipidosis ascribes to a condition that has been defined by the appearance of intracellular accumulation of phospholipids and lamellar bodies. Beyond this definition, each CAD induces its own specific phospholipid composition and selectively targets organs. There are species differences in drug-induced phospholipidosis and the presence of lamellar bodies may not always signify drug-induced phospholipidosis [6]. Animal models and cell culture systems have been used to study induction of lamellar bodies in response to several cationic amphiphilic drugs [7]. Essentially, the lysosome seems to be the primary target for drug-induced phospholipidosis and may serve as a storage organelle for phospholipid accumulation as well. Inhibition of lysosomal enzymes by CADs decreases phospholipid degradation thereby rendering lipid-drug particles indigestible [5]. As of today, drug-induced phospholipidosis remains an unresolved issue due to unclear molecular causes, and its sporadic relationship with adverse drug reactions. Indeed, the biological consequences of phospholipid accumulation in targeted organs such as liver or kidney remain, at least in part, speculative. Here we focus on drug-induced phospholipidosis, the origin of the lamellar bodies and its relationship to organ toxicity. Notably, some basic understanding on the various causes of phospholipidosis have been reviewed elsewhere [7] and [8]."

 

Sounds like a maybe I wonder if anyone has done more recent research??? 

only posted a bit as I know there are rules... about too much. 

 

Calling all smart people and those with smart friends... 

ideas.. 

 

[btdt]

http://google2.fda.gov/search?q=cache:l2grEUu9focJ:www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/advisorycommitteeforpharmaceuticalscienceandclinicalpharmacology/ucm210798.pdf++During+Recovery+from+Amiodarone&client=FDAgov&site=FDAgov&lr=&proxystylesheet=FDAgov&output=xml_no_dtd&ie=UTF-8&access=p&oe=UTF-8

 

 

FDA archived page really hard to read give list of other drugs... known to cause issues in humans others know to cause it in animals but human incidents still unknown.

 

really hard to read