iron (click on this)

1. Formulations (in order of elemental iron content): Fumarate /Sulfate/ Gluconate /childrens Flintstones vitamins/carbonyl iron.
2. Elemental iron is different in each formulation: F(0.3) /S (0.2)/ G (0.1); Flintstones and carbonyl do not have enough bioavailable in OD to cause problems, but childrens vitamins have sorbitol sweetener, which causes diarrhea, dehydration
3. Severe iron toxicity occurs when ingestion is greater than 60 mg/kg; Vomiting with 30 mg/kg.
4. Mechanisms: iron is a potent oxidant and interferes with many enzyme systems (mitochondria, coagulation factors); usually bound to proteins (transferring and ferritin) which controls toxic effects but these storage systems are overwhelmed in toxicity and free iron wreaks havoc on multiple organ systems, esp liver and cardiovascular.
5. MUST KNOW-- the 4 stages of iron toxicity:

                                               i.     Local irritation w/ vomiting (hemorrhagic) and diarrhea—looks like AGE

                                             ii.     “Quiescent” stage—GI symptoms stop but tachycardia may persist—DO NOT DISCHARGE PATIENT

                                            iii.     Systemic toxicity: vasomotor collapse, myocardial depression, lethargy, cerebral edema, liver failure (periportal necrosis), coagulopathy, ARDS, renal failure

                                            iv.     Late complications—GI strictures, gastric outlet obstruction

6. Diagnosis: KUB for tablets; serum iron levels 4-6 hrs after ingestion (> 350-500 is toxic; > 700 fatal). TIBC, serum ferritin and transferrin are not useful; surrogate markers such as glucose and WBC reflect stress response and are generally nonspecific.
7. Treatment:

                                               i.     IVFs (aggressive volume repletion may be limited by ARDS). Cannot dialyze or use charcoal for iron!

                                             ii.     Deferoxamine (fungal molecule from Streptomyces pilosus) is an iron chelator, but not a great antidote. 100 mg DFO will bind only 8.5 mg of iron! (Example: a potentially fatal ingestion of 50 mg/kg in a 50 kg adult will be a dose of 2500 mg; this will take 25 GRAMS of DFO). DFO can only be given at 15-30 mg/kg/hr because higher doses result in hypotension.  Thus it would take 16 HOURS to infuse all the DFO in a critically ill patient.

                                            iii.     Yersinia enterolitica sepsis is associated with DFO used in iron toxicity; possible reason is that this organism grows well in iron-rich environments when a siderophore (iron carrier ) is available.