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Medical uses of Methylene Blue
(wikipedia 8/2012)
Methylene blue is a monoamine oxidase inhibitor (MAOI),[6] and if infused
intravenously at doses exceeding 5 mg/kg, may precipitate serious serotonin
toxicity, serotonin syndrome, if combined with any selective serotonin reuptake
inhibitors (SSRIs) or other serotonin reuptake inhibitor (e.g., duloxetine,
sibutramine, venlafaxine, clomipramine, imipramine).[7]
Methylene blue is also structurally similar to chlorpromazine and the typical
antipsychotics. It is the basic compound from which chlorpromazine and many
other antipsychotics are made.[8]
Methylene blue is a component of a frequently prescribed urinary
analgesic/anti-infective/anti-spasmodic known as "Prosed", a combination of
drugs which also contains phenyl salicylate, benzoic acid, hyoscyamine sulfate,
and methenamine (aka hexamethylenetetramine and not to be confused with
'methanamine').[9]
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Malaria
Methylene blue was identified by Paul Ehrlich about 1891 as a successful
treatment for malaria. It disappeared as an anti-malarial during the Pacific War in
the tropics, since American and Allied soldiers disliked its two prominent, but
reversible side effects: turning the urine green, and the sclera (the whites of the
eyes) blue. Interest in its use as an anti-malarial has recently been revived,[10]
especially due to its low price. Several clinical trials are in progress, trying to find
a suitable drug combination. Initial attempts to combine methylene blue with
chloroquine were disappointing;[11] however, more recent attempts have
appeared more promising.
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Cancer
Recent research suggests that methylene blue, toluidine blue, and other
3,7-diaminophenothiazinium-based redox cyclers induce selective cancer cell
apoptosis by NAD(P)H:quinone oxidoreductase (NQO1)-dependent bioreductive
generation of cellular oxidative stress.[12] Combined with plant auxin
(indole-3-acetic acid), methylene blue is being investigated for the photodynamic
treatment of cancer.[13]
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Combined with light
Methylene blue combined with light has been used to treat resistant plaque
psoriasis,[14] AIDS-related Kaposi's sarcoma,[15] West Nile virus,[16] and to
inactivate staphylococcus aureus,[17] HIV-1,[18] Duck hepatitis B,[19] adenovirus
vectors,[20] and hepatitis C.[21] Phenothiazine dyes and light have been known to
have virucidal properties for over 80 years.[22] In some circumstances, the
combination can cause DNA damage that may lead to cancer.[23][24]
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Methemoglobinemia
While many texts indicate that methylene blue has oxidizing agent properties, its
effects as an oxidizing agent occurs only at very high doses. At pharmacologic
doses it has reducing agent properties. It is owing to this reason that methylene
blue is employed as a medication for the treatment of methemoglobinemia. This
can arise from ingestion of certain pharmaceuticals, toxins, or broad
beans.[citation needed]. Normally, through the NADH or NADPH dependent
methemoglobin reductase enzymes, methemoglobin is reduced back to
hemoglobin. When large amounts of methemoglobin occur secondary to toxins,
methemoglbin reductases are overwhelmed. Methylene blue, when injected
intravenously as an antidote, is itself first reduced to leucomethylene blue, which
then reduces the heme group from methemoglobin to hemoglobin. Methylene
blue can reduce the half life of methemoglobin from hours to minutes. [25] At high
doses, however, methylene blue actually induces methemoglobinemia, reversing
this pathway.[25]
Methylene blue also blocks accumulation of cyclic guanosine monophosphate
(cGMP) by inhibiting the enzyme guanylate cyclase: this action results in reduced
responsiveness of vessels to cGMP-dependent vasodilators like nitric oxide and
carbon monoxide. Cardiac surgical teams have found this very useful in the
treatment of extremely low blood pressure (hypotension)which may occur during
heart surgery requiring cardiac bypass.[26] Similar use is noted in the treatment
of hypotension associated with overwhelming infections (sepsis).[27]
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Cyanide poisoning
Since its reduction potential is similar to that of oxygen and can be reduced by
components of the electron transport chain, large doses of methylene blue are
sometimes used as an antidote to potassium cyanide poisoning, a method first
successfully tested in 1933 by Dr. Matilda Moldenhauer Brooks in San
Francisco.[28]
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Carbon monoxide poisoning
Methylene blue was also used in the mid-twentieth century in the treatment of
carbon monoxide poisoning.[28]
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Dye/Stain
Methylene blue is used in endoscopic polypectomy as an adjunct to saline or
epinephrine, and is used for injection into the submucosa around the polyp to be
removed. This allows the submucosal tissue plane to be identified after the polyp
is removed, which is useful in determining if more tissue needs to be removed, or
if there has been a high risk for perforation. Methylene blue is also used as a dye
in chromoendoscopy, and is sprayed onto the mucosa of the gastrointestinal tract
in order to identify dysplasia, or pre-cancerous lesions. Intravenously injected
methylene blue is readily released into the urine and thus can be used to test the
urinary tract for leaks or fistulas.
In surgeries such as sentinel lymph node dissections, methylene blue can be
used to visually trace the lymphatic drainage of pertinent tissues. Similarly,
methylene blue is added to bone cement in orthopedic operations to provide
easy discrimination between native bone and cement. Additionally, methylene
blue accelerates the hardening of bone cement, increasing the speed at which
bone cement can be effectively applied.
It can also be used to stain lymph nodes.
When methylene blue is "polychromed" (Oxidized in solution or "ripened" by
fungal metabolism,[29] as originally noted in the thesis of Dr D L Romanowsky in
1890's), it gets serially demethylated and forms all the tri, di, mono and non
methyl intermediates - which are Azure B, Azure A, Azure C and thionine
respectively.[30] This is the basis of the basophilic part of the spectrum of
Romanowski-Giemsa effect. If only synthetic Azure B and Eosin Y is used, it may
serve as a standardized Giemsa stain; but, without methylene blue, the normal
neutrophilic granules tend to overstain and look like toxic granules. On the other
hand, if methylene blue is used it might help to give the normal look of neutrophil
granules and may additionally also enhances the staining of nucleoli and
polychromatophilic RBCs (reticulocytes).[31]
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