Friday, March 11, 2011

See few articles below about drug metabolism
and mitochondria.

Clearly, prevention is paramount, secondly, look at other options of dealing with health issues, and thirdly, be responsible for your own health issues. Read up on the pharmacological content of prescribed meds, validity, the science, effective?, side effects and adverse reactions. Read about what other patients themselves experienced, over a period of time. Most who suffer ill health do not make the association with off the counter meds and/or prescribed meds. It takes longer than a few weeks or months, sometimes years for inflammation to progress.

Nuclear Receptors and the Regulation of Drug-Metabolizing Enzymes and Drug Transporters: Implications for Interindividual Variability in Response to Drugs

1. Bradley L. Urquhart, PhD
2. Rommel G. Tirona, PhD
3. Richard B. Kim, MD

From the Division of Clinical Pharmacology, Department of Medicine (Dr Urquhart, Dr Tirona, Dr Kim), and the Department of Physiology & Pharmacology (Dr Tirona), University of Western Ontario, London, Ontario, Canada.

1. Address for correspondence: Richard B. Kim, MD, Division of Clinical Pharmacology, London Health Sciences Centre—University Hospital, Room ALL-152, 339 Windermere Road, London, Ontario N6A 5A5, Canada; e-mail:


Erratic or unpredictable response to drugs remains a challenge of modern drug therapy. An important determinant of such interindividual differences in drug response is variability in the expression of drug-metabolizing enzymes and/or transporters at sites of absorption and/or tissue distribution. Variable drug-metabolizing enzyme and transporter expression can result in unpredictable exposure and tissue distribution of drugs and may manifest as adverse effects or therapeutic failure. In the past decade, important new insights have been made relating to the regulatory mechanisms governing the expression of drug-metabolizing enzymes and transporters by ligand-activated nuclear receptors. Specifically, there is compelling evidence to demonstrate that PXR, CAR, FXR, LXR, VDR, HNF4α, and AhR form a battery of nuclear receptors that regulate the expression of many important drug-metabolizing enzyme and transporters. In this review, the authors focus on clinically important drug-metabolizing enzymes such as CYP3A4, CYP2B6, CYP2C9, CYP2C19, UGT1A1, SULT2A1, and glutathione S-transferases and their regulation by nuclear receptors. They also review the nuclear receptor-mediated regulation of drug transporters such as MDR1, MRP2, MRP4, BSEP, BCRP, NTCP, OATP1B3, and OATP1A2. Finally, they outline how the drug development process has been affected by the current understanding of the involvement of nuclear receptors in the regulation of drug disposition genes.

I was curious about comparative study for ADRs between Fqs and other antibiotics. Those who are suffering from ADRs, (NOT allergic reactions), from other antibiotics, take note. So yes, many of us, have/had ADRs from non FQs pre/post floxing!! Figures seem to vary, one other study show cephalosporins to be between 19-40%...

Abstract and Introduction

Extensive pharmacologic and clinical development of quinolone antimicrobial agents has resulted in improved antimicrobial activity, pharmacokinetic features, toxicity, and drug-drug interaction profiles. Nalidixic acid and other early quinolones had limited use due to poor pharmacokinetics, relatively narrow antimicrobial spectrum of activity, and frequent adverse effects. Beginning with the development of fluoroquinolones, such as norfloxacin and ciprofloxacin, in the 1980s, the agents assumed a greatly expanded clinical role because of their broad antimicrobial spectrum of action, improved pharmacokinetic properties, and more acceptable safety profile. Although the pharmacokinetics and efficacy of the drugs have improved significantly, a major area of continued emphasis is to further reduce the frequency and severity of adverse events and drug-drug interactions. Older agents such as ciprofloxacin and ofloxacin are still extensively prescribed, but the focus of this article is on the newer fluoroquinolones (levofloxacin and other drugs that have been approved or have been under investigation since approximately 1997).

For those who are still keen on taking antibiotics, read about the mitochondria cytoxicity, which means essentially, DNA damage. There are several articles posted on the forum about damage to mitochondria, worse offenders are: antibiotics (Fqs, macrolides, tetracyclines, clyndamicin, Rifamopin), anti-depressants and NSAIDs... This study is well designed and discusses glycation, cell death, lactic acidosis etc.

For those of us who are having problems with foods, vits & supps, and metabolozing drugs, read on...

It appears that minute dosage of anything is not being metabolized (for some of us), and reaches a level of toxicity. This can apply to some compounds in some type of foods. This partly explains the inability to metabolize, the aforementioned including environmental pollutants.

"Enzymes that metabolize xenobiotics have historically
been called drug-metabolizing enzymes, although they are
involved in the metabolism of many foreign chemicals to
which humans are exposed. Dietary differences among
species during the course of evolution could account for
the marked species variation in the complexity of the
drug-metabolizing enzymes.

Today, most xenobiotics to which humans are exposed
come from sources that include environmental pollution,
food additives, cosmetic products, agrochemicals, processed
foods, and drugs. In general, these are lipophilic
chemicals, that in the absence of metabolism would not be
efficiently eliminated, and thus would accumulate in the
body, resulting in toxicity. With very few exceptions, all
xenobiotics are subjected to one or multiple pathways that
constitute the phase 1 and phase 2 enzymatic systems. As
a general paradigm, metabolism serves to convert these
hydrophobic chemicals into derivatives that can easily be
eliminated through the urine or the bile."

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List of some Fluoroquinolones Antibiotics

List of some fluoroquinolones antibiotics- for list of symptoms go to:

Generic & Brand Name of most common Fluoroquinolones

Brand Name: Trovan - Zithromax
Generic Name: Trovafloxacin and Azithromycin

Brand Name: Factive
Generic Name: Gemifloxacin Mesylate

Brand Name: Zagam
Generic Name: Sparfloxacin

Brand Name: Vigamox
Generic Name: Moxifloxacin

Brand Name: Vigamox
Generic Name: Moxifloxacin

Brand Name: Cinobac
Generic Name: Cinoxacin

Brand Name: Penetrex
Generic Name: Enoxacin

Brand Name: Tequin
Generic Name: Gatifloxacin (Removed from US Market - May 2006)

Brand Name: Levaquin
Generic Name: Levofloxacin

Brand Name: Floxin
Generic Name: Ofloxacin

Brand Name: Synercid
Generic Name: Quinupristin and Dalfopristin

Brand Name: Trovan - Zithromax

Brand Name: Zymar
Generic Name: Gatifloxacin Ophthalmic Solution

Brand Name: Avelox
Generic Name: Moxifloxacin HCL

Brand Name: Floxin Otic Singles

Brand Name: Ciprodex
Generic Name: Ciprofloxacin and Dexamethasone

Brand Name: Raxar
Generic Name: Grepafloxacin

Brand Name: Ocuflox
Generic Name: Ofloxacin Ophthalmic

Brand Name: Quixin
Generic Name: Levofloxacin

Brand Name: Cipro
Generic Name: Ciprofloxacin

Brand Name: Proquin XR
Generic Name: Ciprofloxacin Hcl

Brand Name: Requip XL
Generic Name: Ropinirole Extended Release Tablets

Brand Name: Zanaflex
Generic Name: Tizanidine

Brand Name: Noroxin
Generic Name: Norfloxacin

Brand Name: Maxaquin
Generic Name: Lomefloxacin Hcl

Brand Name: Ciloxan Ophthalmic Solution
Generic Name: Ciprofloxacin HCL Ophthalmic Solution

Brand Name: Cipro XR
Generic Name: Ciprofloxacin Extended-Release

Generic Name Norloaxin Brand Name: Noroxin

Generic Name Temafloxacin Brand name Omniflox