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| __NOTOC__
| | #REDIRECT [[Isosorbide mononitrate#Overdosage]] |
| {{Isosorbide mononitrate
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| {{CMG}}; {{AE}} {{PB}}
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| ===Hemodynamic Effects===
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| The ill effects of ISMN overdose are generally the results of ISMN’s capacity to induce [[vasodilatation]], venous pooling, reduced cardiac output, and [[hypotension]]. These hemodynamic changes may have protean manifestations, including increased intracranial pressure, with any or all of persistent throbbing [[headache]], [[confusion]], and moderate [[fever]]; [[vertigo]]; [[palpitations]]; visual disturbances; [[nausea]] and [[vomiting]] (possibly with colic and even bloody diarrhea); [[syncope]] (especially in the upright posture); air hunger and dyspnea, later followed by reduced ventilatory effort; diaphoresis, with the skin either flushed or cold and clammy; [[heart block]]and [[bradycardia]]; [[paralysis]]; [[coma]]; [[seizure]]s and death.
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| Laboratory determinations of serum levels of ISMN and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of ISMN overdose.
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| There are no data suggesting what dose of ISMN is likely to be life threatening in humans. In rats and mice, there is significant lethality at doses of 2000 mg/kg and 3000 mg/kg, respectively.
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| No data are available to suggest physiological maneuvers (e.g. maneuvers to change the pH of the urine) that might accelerate elimination of ISMN. In particular, dialysis is known to be ineffective in removing ISMN from the body.
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| No specific antagonist to the vasodilator effects of ISMN is known, and no intervention has been subject to controlled study as a therapy of ISMN overdose. Because the [[hypotension]] associated with ISMN overdose is the result of venodilatation and arterial [[hypovolemia]], prudent therapy in this situation should be directed toward an increase in central fluid volume. Passive elevation of the patient’s legs may be sufficient, but intravenous infusion of normal saline or similar fluid may also be necessary.
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| The use of [[epinephrine]] or other arterial [[vasoconstrictor]]s in this setting is likely to do more harm than good.
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| In patients with renal disease or [[congestive heart failure]], therapy resulting in central volume expansion is not without hazard. Treatment of ISMN overdose in these patients may be subtle and difficult, and invasive monitoring may be required.
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| ===Methemoglobinemia===
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| [[Methemoglobinemia]] has been reported in patients receiving other organic nitrates, and it probably could also occur as a side effect of ISMN. Certainly nitrate ions liberated during metabolism of ISMN can oxidize hemoglobin into [[methemoglobin]]. Even in patients totally without [[cytochrome b5]] reductase activity, however, and even assuming that the nitrate moiety of ISMN is quantitatively applied to oxidation of hemoglobin, about 2 mg/kg of ISMN should be required before any of these patients manifest clinically significant (≥ 10%) [[methemoglobinemia]]. In patients with normal reductase function, significant production of [[methemoglobin]] should require even larger doses of ISMN. In one study in which 36 patients received 2 to 4 weeks of continuous nitroglycerin therapy at 3.1 to 4.4 mg/hr (equivalent, in total administered dose of nitrate ions, to 7.8-11.1 mg of ISMN per hour), the average [[methemoglobin]] level measured was 0.2%; this was comparable to that observed in parallel patients who received placebo.
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| Not withstanding these observations, there are case reports of significant [[methemoglobinemia]] in association with moderate overdoses of organic [[nitrate]]s. None of the affected patients had been thought to be unusually susceptible.
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| [[Methemoglobin]] levels are available from most clinical laboratories. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial pO2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air.
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| When [[methemoglobinemia]] is diagnosed, the treatment of choice is methylene blue, 1 to 2 mg/kg intravenously.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = ISOSORBIDE MONONITRATE TABLET [ZYDUS PHARMACEUTICALS (USA) INC.] | url =http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=897a0327-25d4-4769-bd6a-0e674264017f | publisher = | date = | accessdate = 30 January 2014 }}</ref>
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| ==References==
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| {{Reflist|2}}
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| [[Category:Drugs]]
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