Flashcards in Pharm chelation therapy Deck (46):
1
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
2
effects of acute heavy metal exposure on the cardiovascular system
tachycardia and in some cases dysrhthmias and cardiomyopathy
3
effects of acute heavy metal exposure on the CNS
altered mental status and peripheral neuropathy
4
effects of acute heavy metal exposure on the GI system
nausea, vomiting and diarrhea
5
effects of acute heavy metal exposure on the renal system
proteinuria, aminoaciduria and acute tubular necrosis
6
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)
7
how is heavy metals diagnosis made?
-routine PE
-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
8
what are the 4 most common heavy metal exposures?
lead, arsenic, mercury, thallium
9
what is done for acute toxicity of heavy metal toxicity?
-ABCs
-GI decontamination (activated charcoal, whole bowel irrigation)
-chelation therapy
10
what is done for chronic toxicity of heavy metals?
-removal from source!!
-chelation therapy
11
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)
12
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
13
british anti-lewisite (BAL) class and mechanism
dithiol: forms stable chelate via electron pair donation and coordination with metal ion
14
BAL implication
mixed with peanut oil (peanut allergies)
15
BAL therapeutics
arsenic, lead, inorganic mercury poisoning
16
BAL side effects
renal toxicity (unless urine is alkalinized), pain at injection site (IM), nausea, vomiting, increases in BP and HR
17
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
18
2,3-dimercaptosuccin acid (DMSA) class and mechanism
dithiol: coordinate bonding to sulfur (arsenic and mercury) or sulfur and oxygen (lead and cadmium)
19
DMSA therapeutics
arsenic, lead, mercury, cadmium poisoning
20
DMSA side effects
mild ALT/AST elevation - otherwise well tolerated
21
when is DMSA most used?
lead poisoning in children
22
how is DMSA administered
orally - can be given outpatient
23
edetate calcium disodium (EDTA) mechanism
displacement of calcium by lead
24
EDTA therapeutics
lead poisoning
25
which version of EDTA used? which should not be used? why?
CaNa2EDTA - NOT Na2EDTA because it causes severe hypocalcemia
26
EDTA side effects
malaise, fever - renal toxicity
27
how is EDTA administered? when?
IV at hospital - esp given when there is encephalopathy due to lead poisoning
28
prussian blue mechanism
stays in gut and not absorbed until it grabs metal - goes into gut and is excreted that way
29
prussian blue therapeutics
thallium and radioactive cesium poisoning
30
prussian blue side effects
well tolerate - not absorbed after oral dosing into systemic circulation
31
normal role of iron
various intracellular processes (accepts and donates electrons), extracellular is bound to transferrin
32
when does iron toxicity occur?
free iron in circulation
33
what are the pharmacokinetics of iron?
peak serum concentrations occur 2-6 hours after ingestion (overwhelmed transferrin and increase in circulating free iron)
34
local toxicity of iron
direct corrosive effect to GI mucosa (leading to hematemesis, melena, periportal necrosis of liver and intetional ulceration and edema)
-resultant volume depletion
35
systemic toxicity of iron
-high anion gap metabolic acidosis
-uncoupler of oxidative phosphorylation!
-direct negative inotropic effect
-hypotension (vasodilator)
36
early clinical effects of iron toxicity
local tissue effects of GI tract (nausea and lots of vomiting) within 6 hours
37
intermediate clinical effects of iron toxicity
nausea and vomiting may temporarily decrease with an increase in development of metabolic acidosis and sequelae
38
late signs of iron toxicity
severe local and system effects - hepatotoxicity, ARDS, renal, gastric outlet obstruction
39
chelator for iron poisoning
deferoxamine
40
deferoxamine mechanism
chelates FREE iron and iron transported between transferrin and ferritin
41
deferoxamine side effects
rate-related hypotension, anaphylactoid reactions, yersinia enterocolitis (facilitates growth of unusual organisms), acute lung injury/ARDS
-can only treat for 24 hours before acute lung injury manifests
42
clinical pearls for lead poisoning in kids
colic, lower levels associated with IQ changes, think PICA
43
clinical pearls for lead poisoning in adults
hypertension, tolerate higher lead levels
44
clinical pearls for arsenic poisoning
rice-water diarrhea, prolonged QT, arsenical dermatitis, "rain drops on a dusty road"
45
clinical pearls for mercury poisoning
labile mood "mad as a hatter", intention tremor, mercury salts: caustic
46