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19 terms

Toxicology

STUDY
PLAY
Ethanol toxicity
-Parent compound is toxicant
Methanol toxicity
-Metabolized to toxic formic acid by alcohol dehydrogenase complex (generates NADH)
-Slow natural detox to CO2 and H2O by a folate-dependent pathway
-Antidote is ethanol or orphan drug fomepizole
-Generates acidosis because need for NAD+ to oxidize methanol to formaldehyde drives formation of lactate from pyruvate
Ethylene Glycol toxicity
-Metabolized to nephrotoxic calcium oxalate by alcohol dehydrogenase complex
-Antidote is ethanol or orphan drug fomepizole
Paraquat toxicity
-Free radicals formed are toxic
Doxorubicin toxicity
-Superoxide from causes lung and heart damage
Fomepazole toxicity
-Antidote to methanol or ethylene glycol intoxication
Mercury toxicity
-antidote is succimer, dimercaprol
-Toxic forms include mercury vapor (high exposure through dental amalgams), inorganic mercury salts (found in food and cannot pass through the BBB, therefore only causes kidney damage) and methylmercury (BIOACCUMULATES in the foodchain and causes kidney damage and CNS effects [minamata disease])
-Elemental Hg absorbs through lungs via vapor, but not skin
-Irreversibly complexes with 2 cysteine SH residues found in protein, so must give antidote ASAP
-Sx: renal damage, giogivostomatitis, visual disturbances, muscle tremor, mental deterioration
Lead toxicity
-Antidote is EDTA, succimer, dimercaprol
-Absorbed via respiratory and GI routes
-Sx: anemia (inhibits heme synthesis, which causes basophilic stippling, and increases membrane fragility, which decreases halflife of RBCs), wrist drop, and encephalopathy
Arsenic toxicity
-Antidote is succimer, dimercaprol
-Trivalent form inactivates proteins via complexing with cys-SH; pentavalent form inactivates ATP; both forms are freely exchangeable in the body
Iron toxicity
-Typically due to OD of medications
-Ferrous produces toxic OH radicals, and vitamin C in multivitamins will reduce ferric to ferrous to complete the cycle
Carbon monoxide toxicity
-Forms carboxyhemoglobin releasing oxygen
-Antidote is 100% oxygen
Cyanide anion toxicity
-Binds to ferric, inhibiting cytochrome oxidase
-Comes from Nitroprusside poisoning or burning plastic
-antidote is a combination of 3 things:
1) Sodium nitrite produces cyanide scavenging methemoglobin
2) sodium thiosulfate accelerates the conversion of cyanide to thiocyanate
3)Hydroxycobalamin is convereted to B12
Detox with sodium nitrite (converts to mehemoglobin), sodium thiosulfate (converts to thiocyanate), and hydroxocobolamin (coverts to B12)
Copper toxicity
-Occurs with wilson's disease and antidote is Penicillamine
EDTA-Ca
-Chelating agent for any divalent cations, especially LEAD
-IV or IM
-Must be bound to Ca when injected so it doesn't chelate Ca necessary for cardiac SM contractivity
-More effective in prevention than reactivation
Dimercaprol
-Rx: for lead, mercury, and arsenic poisoning
-IM dissolved in peanut oil
-AE: HTN, tachycardia, pain in injection site
Succimer
-Rx for Pb (chronic and acute), Arsinic (acute), and inorganic elemental Hg
-Water soluble analog of dimercaprol
-Orally effective
-Fewer side effects
Deferoxamine
-Competes with loosely bound Fe but not heme Fe or Fe in cytochromes
-Fe comblex is excreted in urine
-administer IV or IM
Penicilamine
-Antidote for wilson's disease
Ferric Hexacyanoferrate (prussian blue)
-Oral treatment of radioactive Cs (found in dirty bombs) and thallium intoxication