Intoxicant / Dynamics/Symptoms / Kinetics / Antidote
Methanol / - Formic acid is toxic to the retina & ↓ respiration
- Depletes NAD+, necessitating Pyruvate à Lactate
ð Results in anion gap metabolic acidosis /
1. Metabolized to formic acid via acohol dehydrogenase (fast)
2. Metabolized to Formate via folate-dependent pathway (slow) / - Ethanol
- Fomepizole
o Hella expen$ive
Ethylene glycol / - Calcium oxalate damages kidneys (stones):
Acute tubular necrosis
- Depletes NAD+, necessitating Pyruvate à Lactate
ð Results in anion gap metabolic acidosis
Key to differentiation: lack of eye symptoms / 1. Metabolized to aldehydes + calcium oxalate
Heavy Metals
Elemental Mercury (vapor) / - Binds to SH groups in proteins irreversibly
o SH is often in the active site of enzymes
Symptoms:
- Renal damage
- Giogivostmatitis: infection of gums
- CNS effects: visual, muscle tremor, mental / - Not absorbed through skin, but can be via lungs à CNS toxicity / Chelating agents
- Compete for binding of the metal via polydentate (multiple atoms binding a central metal) as in heme
1. EDTA
- Need IV injection b/c charged
- Side effects: Zn deficiency, renal damage
i. Antidote-antidote: Calcium salt
Inorganic Mercury / - Mostly peripheral damage
o Can’t get into CNS (charged)
Organic Mercury (methylmercury) / - CAN get into CNS. See worse central symptoms
Lead / Symptoms:
- Blood: Anemia (due to ↓ heme synth), ↑ membrane fragility, basophilic stippling
- Nerve: wrist drop, encephalopathy / -
Arsenic / - As5+ + As3+ bind ATP à histiotoxic hypoxia
- As3+ also binds to SH groups (more toxic) / - / Dimercaprol (BAL - British antilewisite)
- Needs to be solublized in in peanut oil and injected IM (painful)
- Two SH groups bind to arsenic
Succimer (Water soluble dimercaprol, less side efx)
Iron / - Fe3+ à Fe2+ à OH radicals à damage
- Vitamin C facilitates this / - / Deferoxamine (IV, IM), excreted in urine
- Does not remove Iron from cytochrome
Prussian Blue (Also cesium, thalium – dirty bombs)
Copper / - Geneitic: Wilson’s Disease / - / Penicilamine
Carbon Poisons
Carbon monoxide / - Forms CarboxyHb / - 50% COHb @ 1000ppm, smoker: 6% / - 100% O2
Cyanide (ex nitroprusside) / - Binds Fe3+, inhibiting cytochrome oxidases / o / - Sodium nitrite (NaNO3) to methHb
- Sodium thiosolfate to thycyante (prophylactic
- Hydroxocobolamin to cyanocobolamin (B12) (cobalt)
Bioaccumulation: Intake > metabolism + excretion Biomagnification: When concentration of a contaminant increases as it moves up the food chain.