Chelation Therapy Flashcards
mechanism of toxicity for heavy metals
bind to sulfhydryl groups in various organ systems and enzymatic processes throughout the body. affinity for organ system toxicity is a result of the characteristics of the heavy metal and its distribution sites
chelating agent
forms complexes with heavy metals. prevents or reverses the binding of metallic cations to reactive groups.
chelate
complex formed with the metal and chelator. heterocyclic ring, 5 and 6 membered rings are the most stable
efficacy of chelating agents
relative affinity of the chelator for the heavy metal. distribution of the chelator compared with the distribution of the metal.
ideal chelator qualities
Vd of the chelator > Vd of the chelate. high water solubility. resistant to biotransformation. ability to reach the site of where the metal is stored. capacity to form nontoxic complexes. stable at physiological pH. low affinity for trace elements.
ideal chelate qualities
more stable than the endogenous chelate. stable at body pH. resistant to biotransformation. water soluble. readily excreted. nontoxic.
british anti-lewisite (BAL)
dimercaprol. mixed with peanut oil. Intramuscular dosing, not IV. useful in arsenic poisoning, lead poisoning (encephalopathy), inorganic mercury poisoning.
adverse effects of BAL
dose dependent. pain at injection site, nausea, vomiting, increases in BP and HR. Need to keep urine alkaline so BAL-metal dissociation doesn’t occur.
2,3-dimercaptosuccinic acid
Succimer. Useful in lead, arsenic, mercury, cadmium. Well tolerated. Nausea, vomiting, flatus, diarrhea, mild elevations in AST and ALT.
CaNaEDTA (edetate calcium disodium)
mainly used in lead poisoning. can be mistaken for NaEDTA.
CaNaEDTA adverse events
principal toxicity due to the metal chelate. Renal toxicity, malaise, fever, increased ALT and AST.
Prussian blue
useful in thallium and cesium poisoning. adverse events: not absorbed after oral dosing and well tolerated.
clinical effects of lead
lower levels associated with IQ changes. colic, abdominal pain. altered mental status. footdrop and wrist drop. anemia (microcytic). nephrotox. HTN (most common symptom in adults)
workup for lead poisoning
capillary/venous blood. hair and urine are not helpful. CBC, BMP, LFTs, erythrocyte protoporphyrin. abdominal radiograph.
lead poisoning treatment
removal from source. whole bowel irrigation if lead in bowel. succimer. if encephalopathic, CaNaEDTA plus BAL
iron pharmacokinetics
peak serum concentrations occur 2-6 hours after ingestion. massive amounts of iron absorption overwhelm transferrin and there is an increase in circulating free iron
toxicologic mechanism of iron
direct corrosive effect to GI mucosa. leads to volume depletion. high anion gap metabolic acidosis. Direct negative inotropic effect (hypotension). Vasodilator (hypotension)
clinical effects of iron
early: local tissue effects of GI tract. N/V.
intermediate: N/V decrease and increase in metabolic acidosis and sequelae.
Intermediate II: severe local and systemic effects which may result in death.
Late: hepatotoxicity, ARDS, renal
Fifth stage: gastric outlet obstruction
deferoxamine
chelates ferric iron and is excreted in the urine as ferrioxamine which imparts a reddish brown color change to the urine. reaches intracytoplasmic and intramitochondrial free iron. chelates free iron ONLY!
adverse events with deferoxamine
rate-related hypotension, anaphylactoid reactions, yersinia enterocolitis, acute lung injury (in patients treated over 24 hours)
