Aluminium
- Increased levels of Al in brain tissues of patients with encephalopathy, having been exposed to Al accumulation through dialysis
- Mech: pro-oxidant activity which results in oxidative stress, free radical attack and oxidation of cellular proteins and lipids
- Effects
- Encephalopathy, osteodystrophy in renal dialysis patients
- Treatment
- Desferrioxamine
Arsenic
- Pyruvate dehydrogenase complex
- Mitochondrial enzyme complex linking glycolysis and TCA cycle. Differentially regulated in fed (active)/fasting (inactive) states.
- Reaction: pyruvate + NAD⁺ + CoA → acetyl-CoA + CO₂ + NADH.
- Contains 3 enzymes requiring 5 cofactors:
- Thiamine pyrophosphate (B₁)
- Lipoic acid
- CoA (B₅, pantothenic acid)
- FAD (B₂, riboflavin)
- NAD⁺ (B₃, niacin)
- Activated by: ↑ NAD⁺/NADH ratio, ↑ ADP, ↑ Ca²⁺
- The complex is similar to the α-ketoglutarate dehydrogenase complex (same cofactors, similar substrate and action), which converts α-ketoglutarate → succinyl-CoA (TCA cycle).
- The lovely coenzymes for nerds.
- Arsenic inhibits lipoic acid.
- Clinical findings: imagine a vampire (pigmentary skin changes, skin cancer), vomiting and having diarrhea, running away from a cutie (QT prolongation) with garlic breath.
- Effects
- Diarrhea, polyneuropathy, gastrointestinal pain, vomiting, shock, coma, renal failure
- Treatment
- Dimercaprol, Penicillamine
Cyanide vs carbon monoxide
- Both inhibit aerobic metabolism via inhibition of complex IV of ETC (cytochrome c oxidase) → hypoxia that does not fully correct with supplemental O₂ and ↑ anaerobic metabolism.
ㅤ | Cyanide | Carbon monoxide |
Exposure | Synthetic product combustion, amygdalin ingestion (found in apricot seeds), cyanide ingestion (e.g. in suicide attempts), fire victims. | Motor exhaust, gas heaters, fire victims. |
Presentation | - Headache, dyspnea, drowsiness, seizure, coma. - Skin may appear flushed (“cherry red”). - Venules in retina appear bright red. - Breath may have bitter almond odor. | - Headache, vomiting, confusion, visual disturbances, coma. - May have cherry-red skin with bullous skin lesions. - Multiple victims may be involved (e.g. family due to faulty furnace). |
Labs | Normal PaO₂. Elevated lactate → anion gap metabolic acidosis. | Normal PaO₂. Elevated carboxyhemoglobin on co-oximetry. Classically associated with bilateral globus pallidus lesions on MRI, although can rarely be seen with cyanide toxicity. |
Effect on oxygen-hemoglobin curve | Curve normal. Oxygen saturation may appear normal initially. Despite ample O₂ supply, it cannot be used due to ineffective oxidative phosphorylation. | Left shift in ODC → ↑ affinity for O₂ → decreased O₂ unloading in tissues. Binds competitively to Hb with >200x greater affinity than O₂ to form carboxyhemoglobin → decreased %O₂ saturation of Hb. |
Effects | Rapid symptom onset—seconds to minutes for inhalation/hours for oral exposure. Classical: rapid onset coma, seizures, shock, profound lactic acidosis. | Confusion, headache at carboxyhemoglobin levels of 20% to coma, posturing, and seizures at levels of 50–60%. Characteristic: delayed neurological deterioration occured 1–3 weeks after initial event—usually as extrapyramidal disorder (Parkinsonian gait, bradykinesia). |
Treatment | - Decontamination (e.g. remove clothing). - Hydroxocobalamin (binds cyanide → cyanocobalamin → renal excretion). - Nitrites (oxidize Hb → methemoglobin → binds cyanide → cyanomethemoglobin → decreased toxicity). - Sodium thiosulfate (↑ cyanide conversion to thiocyanate → renal excretion). - Resuscitation - Dicobalt edetate | - 100% O₂. - Hyperbaric oxygen if severe. |
- Images
Ergot
- Ergot poisoning is caused by the ingestion of ergot alkaloids, which are produced by the fungus Claviceps purpurea.
- Mechanism
- Direct smooth muscle stimulation
- Ergotamine decreases the vasodilation of cranial arteries, especially the branches of the external carotid artery that cause migraine headache.
- Ergotamine may also stimulate serotonin receptors, which causes vasoconstriction
- Central sympatholytic activity,
- Peripheral alpha-adrenergic blockade
- Symptoms
- Gangrenous (causing tissue damage and limb loss)
- Convulsive (causing neurological symptoms).
- Chronic ergot toxicity can lead to lower extremity ischemia.
- Effects
- Potent vasoconstricting agent from rye fungus (Claviceps purpurea). Ergotism is convulsive (diarrhea, paresthesias, headache) or gangrenous (dry gangrene due to vasoconstriction in fingers/toes).
- Treatment
- Discontinue the use of ergot-containing medications, caffeine, and cigarettes.
- For acute toxicity, there is no uniformly recommended treatment, but various therapies have been suggested.
- Anti-platelets
Lead
- Symptoms
- Headaches
- Cramps
- Demyelination andaxonal degeneration (peripheral neuropathy)
- Hyperactivity
- Severe abdominal pain (lead colic)
- Obstinate constipation
- Mental and physical development issues (in children)
- Mechanism of action
- Heavy metal that can build up in the body over time, even from small exposures.
- Lead can replace calcium in bones and teeth, leading to weaker structures.
- Can also disrupt the production of Hb (via inhibition of Ferrochelatase and ALA dehydratase enzyme)
- Effects
- Ataxia and tremor in children exposed to relatively low levels. Chronic exposure impairs psychomotor development; may cause substantial retardation in young children. Acute toxicity in children: brain edema, may be lethal even with efforts to relieve intracranial pressure. In adults: painless bilateral neuropathy targeting radial nerve → wrist drop, abdominal pain, constipation, anemia, basophilic stippling of erythrocyte precursors, and linear discoloration along gingival margin (lead lines).
- Treatment
- Chelation therapy
- Edetate disodium calcium (CaNa2EDTA),
- Dimercaprol (BAL),
- Succimer,
- D-penicillamine.
Manganese
- Symptoms (Top 3 most common): like Parkinson’s
- Loss of balance
- Dystonia
- Bradykinesia
- Polyneuropathy
- Mechanism of action
- Uncertain
- But there are clues pointing at the interaction of manganese with iron, zinc, aluminum, and copper.
- Disturbed iron metabolism could underlie the neurotoxic action of manganese.
- Treatment
- Levodopa
- Replenishes the deficit of dopamine and initially improves extrapyramidal symptoms, but the response to treatment goes down after 2 or 3 years.
- Chelation therapy
- EDTA (ethylenediaminetetraacetic acid)
- Enhances excretion of manganese and brings its blood levels down, but symptoms remain largely unchanged.
Mercury
- Symptoms
- Muscle weakness
- Poor coordination
- Numbness in the hands and feet
- Mechanism of action
- Source: elemental mercury, inorganic salts, and organic compounds.
- Methylmercury
- Most deadly form of mercury
- Which can bioaccumulate in the food chain, particularly in fish.
- Easily absorbed through the gut, and it is deposited in most tissue
- But does not cross the blood-brain barrier as efficiently as elemental mercury.
- Can cause damage to the nervous system, kidneys, and other organs.
- Oxidized mercury binds strongly to SH groups; this reaction can inactivate enzymes, lead to tissue damage and interfere with various metabolic processes
- Effects
- Depends on route (vapor, ingestion, skin). Vapor toxicity: fatigue, weakness, abdominal cramp, headache, fever. Chronic toxicity: tremors, gingivitis, erethism (behavior change). Other features: peripheral neuropathy, ataxia, visual disturbance.
- Treatment
- Acute poisoning
- Chelation
- Dimercaptosuccinic acid (DMSA)
- Dimercaptopropane sulfonate (DMPS)
- Decontamination may involve placing the patient on an IV or providing oxygen.
Organophosphates
- Anticholinesterase poisoning
- Often due to organophosphates (e.g., parathion) that irreversibly inhibit AChE. Organophosphates commonly used as insecticides; poisoning usually seen in farmers.
Effect Type | Features | Management |
Muscarinic effects | Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Emesis, Lacrimation, Sweating, Salivation (Smnemonic). | DUMBBELSS Reversed by atropine (competitive inhibitor). Atropine crosses BBB to relieve CNS symptoms. |
Nicotinic effects | Neuromuscular blockade (mechanism similar to succinylcholine). | Reversed by pralidoxime, regenerates AChE via dephosphorylation (if given early). Must coadminister with atropine to prevent transient worsening of symptoms. Pralidoxime does not cross BBB easily. |
CNS effects | Respiratory depression, lethargy, seizures, coma. | ㅤ |
- Effects
- Severe abdominal cramps, blurred vision, twitching, and loss of consciousness, bronchospasm, diaphragmatic paralysis
- Treatment
- Atropine (muscarinic features), Oximes (nicotinic features). May require intubation and ventilation.
Thallium
- A heavy metal
- Can be ingested, inhaled
- Mechanism
- Thallium is structurally similar to potassium and is treated as such at the cellular level.
- Tissues with high potassium concentrations also accumulate large concentrations of thallium.
- This causes early stimulation, followed by inhibition of potassium-dependent processes.
- Inhibiting pyruvate kinase and succinate dehydrogenase leads to disruption of the Kreb’s cycle and glucose metabolism, with a result of
- Decreased ATP production → impairment of the sodium-potassium ATPase → swelling and vacuolization of cells
- Riboflavin sequestration due to thallium and inhibition of flavin adenine dinucleotide disrupts the electron transport chain and decreases ATP production.
- Thallium’s high ability for disulfide bonds disrupts cysteine residue cross-linking, causing a reduction in keratin formation.
- Ribosomes are damaged by thallium’s effects on protein synthesis, especially the 60S ribosome.
- Lastly, thallium causes degeneration of myelin in the central and peripheral nervous systems, though the mechanism remains unknown.
- Clinical features
- Stomach pain, nausea, vomiting, and diarrhea within hours of exposure
- Peripheral neuropathy, muscle weakness, tremors, convulsions, and altered mental status within days of exposure
- Hair loss and alopecia within weeks of exposure
- Treatment
- Hemodialysis and hemoperfusion to remove thallium from the blood stream.
- Use of additional potassium to mobilize thallium from the tissue.
- Stomach pumping, use of activated charcoal, or bowel irrigation depending on the prognosis.
- Inducing vomiting within 4 to 6 hours of thallium ingestion.
- Administering multiple doses of activated carbon followed by saline purgatives to help eliminate thallium from the body.
Summary
Toxin | Treatment |
Acetaminophen | N-acetylcysteine (replenishes glutathione) |
AChE inhibitors, organophosphates | Atropine > pralidoxime |
Antimuscarinic, anticholinergic agents | Physostigmine (crosses BBB), control hyperthermia |
Arsenic | Dimercaprol, succimer |
Benzodiazepines | Flumazenil |
β-blockers | Atropine, glucagon, saline |
Carbon monoxide | 100% O₂, hyperbaric O₂ |
Copper | "Penny"cillamine (penicillamine), trientine (3 copper pennies) |
Cyanide | Hydroxocobalamin, nitrites + sodium thiosulfate |
Dabigatran | Idarucizumab |
Digoxin | Digoxin-specific antibody fragments |
Direct factor Xa inhibitors (eg, apixaban) | Andexanet alfa |
Heparin | Protamine sulfate |
Iron (Fe) | Deferoxamine, deferasirox, deferiprone |
Lead | Penicillamine, calcium disodium EDTA, dimercaprol, succimer, (correct lead poisoning in PEDS patients) |
Mercury | Dimercaprol, succimer |
Methanol, ethylene glycol (antifreeze) | Fomepizole > ethanol, dialysis |
Methemoglobin | Methylene blue, vitamin C (reducing agent) |
Methotrexate | Leucovorin |
Opioids | Naloxone |
Salicylates | NaHCO₃ (alkalinize urine), dialysis |
TCAs | NaHCO₃ (stabilizes cardiac cell membrane) |
Warfarin | Vitamin K (delayed effect), PCC (prothrombin complex concentrate)/FFP (immediate effect) |
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