Flashcards in Pharm chelation therapy Deck (46)
what is the mechanism of heavy metal toxicity?
-binds 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
effects of acute heavy metal exposure on the cardiovascular system
tachycardia and in some cases dysrhthmias and cardiomyopathy
effects of acute heavy metal exposure on the CNS
altered mental status and peripheral neuropathy
effects of acute heavy metal exposure on the GI system
nausea, vomiting and diarrhea
effects of acute heavy metal exposure on the renal system
proteinuria, aminoaciduria and acute tubular necrosis
effects of chronic heavy metal exposure
more subtle findings - increased effects at organ sites that may be less accessible acutely (esp CNS and PNS, hematologic, renal, skin/skeleton/CT abnormalities, neoplasm)
how is heavy metals diagnosis made?
-question occupation and hobbies
-labs: CBC with peripheral smear, renal function, liver function, u/a, acid-base balance and radiograph anaylsis
-serum metal levels, whole blood metal levels, urine metal levels, hair analysis
what are the 4 most common heavy metal exposures?
lead, arsenic, mercury, thallium
what is done for acute toxicity of heavy metal toxicity?
-GI decontamination (activated charcoal, whole bowel irrigation)
what is done for chronic toxicity of heavy metals?
-removal from source!!
how does chelation work? (mechanism)
-chelating agent forms complexes with heavy metals and prevents or reverses the binding of metallic cations to reactive groups (ligands)
what are characteristics of ideal chelators?
-VD of the chelator greater than VD of chelate
-high water solubility
-ability to reach the site of where the metal is stored
-capacity to form nontoxic complexes
-stable at physiologic pH
-low affinity for trace elements
british anti-lewisite (BAL) class and mechanism
dithiol: forms stable chelate via electron pair donation and coordination with metal ion
mixed with peanut oil (peanut allergies)
arsenic, lead, inorganic mercury poisoning
BAL side effects
renal toxicity (unless urine is alkalinized), pain at injection site (IM), nausea, vomiting, increases in BP and HR
what is done to prevent metal-induced renal toxicity? why must this be done?
urinary alkalinization because dissociation of BAL-metal chelate in acidic urine happens
2,3-dimercaptosuccin acid (DMSA) class and mechanism
dithiol: coordinate bonding to sulfur (arsenic and mercury) or sulfur and oxygen (lead and cadmium)
arsenic, lead, mercury, cadmium poisoning
DMSA side effects
mild ALT/AST elevation - otherwise well tolerated
when is DMSA most used?
lead poisoning in children
how is DMSA administered
orally - can be given outpatient
edetate calcium disodium (EDTA) mechanism
displacement of calcium by lead
which version of EDTA used? which should not be used? why?
CaNa2EDTA - NOT Na2EDTA because it causes severe hypocalcemia
EDTA side effects
malaise, fever - renal toxicity
how is EDTA administered? when?
IV at hospital - esp given when there is encephalopathy due to lead poisoning
prussian blue mechanism
stays in gut and not absorbed until it grabs metal - goes into gut and is excreted that way
prussian blue therapeutics
thallium and radioactive cesium poisoning