Is thiamine needed to keep flagyl safe?

[Guest guest]

Sharon,

You had mentioned to me recently that an elevation of clostridia markers

was making your doctor want to consider a round a flagyl and you had

expressed some concerns about this since your child had seemed to lose some

muscle tone or strength the last time he used this drug.

I found something interesting today, and that is that the lesions in the

brain that can be caused by the class of drugs to which flagyl belongs look

like the lesions in thiamine deficiency and flagyl may be an anti-vitamin

of thiamine. It may be that taking thiamine before, during, or after the

flagyl might be a good strategy, as flagyl apparently can do damage to

thiamine-dependent processes which produces oxidative stress. I don't

know if this depletion of thiamine is part of its activity against

pathogens, however, and I don't see an article that has addressed that.

One article below looked at concurrent use of thiamine. It might be even

better to start thiamine long enough before flagyl that it has gotten to

all the right places that thiamine should go. About 30% of those with

neurological illness that end up hospitalized are thiamine-deficient

according to several articles, and the average population has about half

that number.

Also, thiamine deficiency seems to be part of the catabolic condition,

probably because the process of catabolizing tissues uses up a lot of

thiamine. The families of alcoholics may have predispositions to thiamine

deficiency issues, so they may be more likely to have toxic issues with flagyl.

Free Radic Biol Med. 1995 Feb;18(2):311-9. Related Articles, Links

[Click here to read]

Early metabolic changes during m-Dinitrobenzene neurotoxicity and the

possible role of oxidative stress.

Romero IA, Lister T, s HK, Seville MP, Wylie SP, Ray DE.

Physiology Group, Biomedical Sciences, King's College, Strand, London, UK.

m-Dinitrobenzene (m-DNB) is an industrial chemical causing

gliovascular lesions in the brain stem similar to those produced by

nitroimidazoles and by thiamine deficiency. To identify early

preneuropathic indices of toxicity we examined the action of m-DNB on

glycolysis and on measures of oxidative stress in the brain both in vivo

and in vitro. Significant increases in local cerebral glucose utilization

were seen in 14 of 30 brain regions prior to development of lesions. Rat

brain astrocyte cultures also showed increases in both glucose consumption

and lactic acid formation in the first 24 h following exposure to 0.5 mM

m-DNB and prior to the development of cytotoxicity. The concentration of

reduced glutathione in these cultures was decreased to about half of

control values over a 2-h incubation period, indicating an early

disturbance of redox balance. The rate of reduction of nitroblue

tetrazolium increased eightfold during a 1-h incubation period, suggesting

a free radical-mediated process. Superoxide dismutase partially prevented

this increase, although other protective agents failed to do so possibly

due to lack of cellular penetration. These observations show that m-DNB

neurotoxicity involves early metabolic stimulation and redox disruption

that may be causally associated with the production of free radicals.

PMID: 7744316 [PubMed - indexed for MEDLINE]

Arch Neurol. 2003 Dec;60(12):1796-800. Related Articles, Links

[Click here to read]

Metronidazole-induced encephalopathy and inferior olivary hypertrophy:

lesion analysis with diffusion-weighted imaging and apparent diffusion

coefficient maps.

Seok JI, Yi H, Song YM, Lee WY.

Movement Disorder Division, Department of Neurology, Samsung Medical

Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

BACKGROUND: Although several cases of metronidazole-induced

encephalopathy have been reported, to our knowledge, there is no previous

report of brain changes in anterior commissure, basal ganglia, cerebellar

white matter, and inferior olivary nuclei on magnetic resonance images. The

precise mechanisms of action of metronidazole-induced encephalopathy have

not been determined. OBJECTIVES: To report a unique case of

metronidazole-induced encephalopathy extensively involving multiple lesions

and to determine the precise mechanism of action of metronidazole-induced

encephalopathy. SETTING: University hospital.Patient A 74-year-old woman

hospitalized with complaints of progressive dysarthria, dysphagia, and gait

disturbance 3 months after the initiation of metronidazole

therapy.Intervention Brain magnetic resonance imaging and discontinuation

of metronidazole therapy.Main Outcome Measure We observed changes of

multiple lesions found on magnetic resonance imaging and analyzed apparent

diffusion coefficient map values. RESULTS: Initial fluid-attenuated

inversion recovery brain magnetic resonance images showed high signal

intensities in diffuse subcortical white matter, anterior commissure,

splenium, basal ganglia, midbrain, cerebellar white matter, and bilateral

inferior olivary nuclei. These lesions were resolved after discontinuation

of metronidazole therapy. However, the lesions in the inferior olivary

nuclei were not resolved; rather they became hypertrophic. Apparent

diffusion coefficient map values in the symptom period decreased and were

normalized after discontinuation of metronidazole therapy. CONCLUSIONS: We

describe a patient with metronidazole-induced encephalopathy involving

reversible lesions in the anterior commissure, basal ganglia, and

cerebellar white matter, which have not been reported previously. We

observed inferior olivary hypertrophy, believed to be the result of lesions

in the midbrain and cerebellar white matter rather than the result of

lesions induced by metronidazole therapy. By using diffusion-weighted

imaging and apparent diffusion coefficient maps, we found that

metronidazole-induced encephalopathy might be caused by cytotoxic edema.

Publication Types:

* Case Reports

PMID: 14676060 [PubMed - indexed for MEDLINE]

Arch Biochem Biophys. 1987 Sep;257(2):357-62. Related Articles, Links

Enzymatic conversion of the antibiotic metronidazole to an analog of

thiamine.

Alston TA, Abeles RH.

Graduate Department of Biochemistry, Brandeis University, Waltham,

Massachusetts 02254.

We propose that adverse effects of the antibiotic metronidazole may be

due, wholly or in part, to its conversion to a thiamine analog and

consequent vitamin B1 antagonism. Consistent with this hypothesis, the drug

is accepted as a substrate for the thiaminase (EC 2.5.1.2) elaborated as an

exoenzyme by the human gut flora constituent Bacillus thiaminolyticus and

is also a substrate for the intracellular thiaminase of the mollusk Venus

mercenaria. The product, identified as the

1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-hydroxyethyl)-2-methyl-4 -

nitroimidazolium cation, is a close structural analog of thiamine and is an

effective inhibitor of thiamine pyrophosphokinase in vitro. Due to its

susceptibility to nucleophilic attack, the analog is unstable, releasing

inorganic nitrite under mild conditions. Enzymatic alkylation reactions

such as that effected by thiaminase may have general pharmacological

significance as a route of increasing the electrophilicity and/or reduction

potential of drugs which are heterocyclic weak bases.

PMID: 2821910 [PubMed - indexed for MEDLINE]

Fortschr Neurol Psychiatr. 1987 Apr;55(4):130-9. Related Articles, Links

[Diabetic coma and Wernicke-Korsakoff syndrome. On the clinical

significance of acquired thiamine deficiency]

[Article in German]

Vieregge P, Stuhlmann W.

Following consideration of the nosological role of hyperglycemic

states in psychiatry the case report of a fifty-five year-old patient is

presented suffering from fatty cell degeneration of the liver and a

relapsing pancreatitis due to chronic alcoholism. After a long period of

abstinence without previously known diabetes mellitus a sudden ketoacidotic

coma developed with maximum serum glucose level of 2020 mg%. Having emerged

during coma treatment Wernicke's encephalopathy passed into Korsakoff's

syndrome the main features of which remained unchanged for more than one

year. In this case thiamine deficiency of different pathogenetical origin

is discussed: defective exogeneous availability due to malabsorption;

depletion of endogeneous thiamine stores due to enlarged requirements for

glucose oxidation during coma therapy; antimetabolic effects to thiamine by

nitroimidazole-derivatives administered parenterally.

Publication Types:

* Case Reports

PMID: 3596452 [PubMed - indexed for MEDLINE]

Toxicol Lett. 1983 Jun;17(1-2):181-5. Related Articles, Links

Protection against misonidazole-induced neuropathy in rats: a

biochemical assessment.

Rose GP, Dewar AJ, Stratford IJ.

A biochemical method for assessing the chemically induced

neurotoxicity of misonidazole (MISO) in the rat has been used to assess

whether the concurrent administration of thiamine, thiamine pyrophosphate

(TPP) or vitamin E (Vit.E) could afford protection against the neurotoxic

side effects of the drug. The tissues analysed were distal sections of the

sciatic/posterior tibial nerve (SPTN), trigeminal ganglia and cerebellum.

MISO was administered i.p. to Wistar rats at a dose of 400 mg/kg per day

for 7 consecutive days to produce the maximal measurable enzyme changes

after 4 weeks. The concurrent i.p. and i.m. dosing of thiamine (0.1-100

mg/kg) for 15 consecutive days did not abate the subsequent PNS and CNS

enzyme changes. However, with concurrent i.m. dosing of 1.0 mg/kg TPP or

p.o. dosing of vitamin E (30 mg/kg) afforded some protection against both

the PNS and CNS MISO-induced neurotoxic side effects as measured biochemically.

Vet Clin North Am Equine Pract. 2000 Dec;16(3):471-85. Related Articles, Links

Clostridial enterocolitis.

RL.

Department of Microbiology, College of Veterinary Medicine and

Biomedical Sciences, Colorado State University, Fort , Colorado,

USA. rjones@...

Equine clostridial enterocolitis is being recognized with increasing

frequency. It has been identified in foals with diarrhea,

antibiotic-associated enterocolitis, or nosocomial enterocolitis. The

sporadic occurrence of clostridial enterocolitis, the variety of types of

clostridia involved, and the difficulty of experimentally reproducing the

disease suggest that it is a poorly defined multifactorial syndrome. The

risk factors associated with susceptibility to colonization and progressive

infection are largely based on anecdotal observations and extrapolation

from human studies. Quantitative studies are needed to decipher the complex

interactions between host and indigenous microflora that provide for and

maintain a healthy colonization resistance environment. It seems that such

studies might be more beneficial in furthering our understanding of the

pathogenesis of clostridial enterocolitis than attempting to implicate

another agent or toxin as the sole cause of the disease in equids.

Treatment protocols that interrupt the pathogenesis of the disease need to

be devised and critically evaluated to complement the present protocols

emphasizing supportive care. Perhaps it is time to consider clostridial

enterocolitis as yet another consequence of the use of antimicrobials

analogous to the selective pressures that result in the emergence of

multiple drug-resistant pathogens.

Publication Types:

* Review

* Review, Tutorial

PMID: 11219344 [PubMed - indexed for MEDLINE]