Poisons and Treatments

Overview (Poisons and Treatments)

Treatment	Poison(s)	Notes
Deferoxamine	Iron	Used for aluminum poisoning in renal failure Used in repeat transfusions that can cause iron overload (thalassemia) Used in iron overdose
Deferasirox
Prussian blue	Cesium Thallium	Used in the case of a radioactive incident
Penicillamine	Copper (Wilson’s disease)	Water-soluble form of penicillin Avoid in patients who have penicillin allergy Weak association with improve outcomes in scleroderma
EDTA	Lead	Can chelate and deplete calcium ions Only needed in moderate to severe lead poisoning
Dimercaprol (BAL)	Arsenic Lead Mercury	Used in conjunction with EDTA for lead poisoning
Succimer	Arsenic Lead Mercury	Chelation therapy more commonly used in children
N-acetylcysteine	Acetaminophen	Best if given with 8-10 hours Also a mucolytic Best next step in management if you suspect acetaminophen intoxication yet have no lab results (it is a benign treatment)
Sodium bicarbonate	Salicylates  Tricyclic antidepressants (TCA)	First sign of OD is hyperventilation and respiratory alkalosis Do not give with physostigmine First do an EKG, if wide QRS (in TCA overdose) then try sodium bicarbonate Deprotonation of drugs causes improved urinary excretion
Potassium iodide	Radioactive iodine (I-131)	Given to prevent the uptake of I-131 Can also be used in thyroid storm as iodine initially decreases thyroid hormone production
Ammonium chloride (NH4Cl, acidic)	Amphetamines (basic)	Eliminates amphetamines by acidifying urine which results in a charged amphetamine molecule which is excreted
Atropine	Anticholinesterases Organophosphates Sarin (nerve gas)	Atropine blocks Ach receptors decreasing the effect of these drugs. Hyoscyamine is second line if atropine is not available Pralidoxime, if given in a timely manner, regenerates acetylcholinesterase reversing the initial pathology
Pralidoxime
Hyoscyamine
Physostigmine	Antimuscarinic Anticholinergic agents	Do not give if patient may have TCA OD as it may lead to heart block or asystole Tertiary amine that can cross the BBB and reverse CNS symptoms of atropine
Naloxone/naltrexone	Opioids	Precipitates withdrawal symptoms in chronic opioid users Not indicated in neonates who may be withdrawing Indicated particularly in adult patients who have respiratory depression Naltrexone decreases alcohol cravings
Flumazenil	Benzodiazepines	May cause seizures in addicted benzodiazepine users Not routinely used, better to let the patient “sleep off” their benzodiazepine overdose Ensure patient maintains respiratory effort and airway
Ethanol IV infusion	Antifreeze (ethylene glycol) Methanol	Think antifreeze when ingested substance is said to be sweet and individual appears “drunk without the typical smell of alcohol”
Fomepizole
Glucagon	β-blockers	IM glucagon is best initial therapy
β-blockers (propranolol, esmolol)	Theophylline	OD symptoms are due to β2 activation: hypotension, tachycardia, hypokalemia, hyperglycemia
Digitalis antibody, lidocaine, Mg2+	Digitalis	GI disturbance and visual halos classic in overdose
Amyl and sodium nitrite	Cyanide	Cyanide found in rodenticides “gopher goitter”, released in burning of plastics and wool, and plants such as cassava Cyanide binds Fe3+ of cytochrome c in the electron transport chain and blocks cellular respiration Nitrites generate methemoglobin, which can save the ETC by binding up the cyanide
Sodium thiosulfate
Hydroxycobalamin
Methylene blue	Methemoglobin	Iron in the heme molecule is Fe3+ which cannot bind oxygen until it is reduced to Fe2+ by treatment
Vitamin C
100% O2 (consider hyperbaric O2)	Carbon monoxide (CO)	CO binds with much greater affinity than O2
Aminocaproic acid	tPA Streptokinase	–
Vitamin K	Warfarin	Bridge with heparin If patient suddenly has increase in PT/PTT look for other medications that are P450 inhibitors
Plasma infusion
Protamine	Heparin	Protamine is a highly positively charged peptide which strongly binds to the negatively charged heparin
Antivenin	Rattlesnake bite

Iron Poisoning

• Most deaths due to iron poisoning (ingestion of iron tablets) occur in children between 12 – 24 months of age
• Symptoms occur within 30 min to several hours
  • abdominal pain, diarrhea, vomiting
  • cyanosis, drowsiness, hyperventilation resulting from acidosis
• Death can result in six hours, but an apparent recovery may happen from 6 – 12 hours with death ensuing in the next 12 hours
• If not treated early, damage to the stomach can lead to pyloric stenosis or gastric scarring
• Early treatment with deferoxamine can reduce mortality significantly from 45% to 1%
• Mechanism of action of iron related damage
  • iron overdose results in the peroxidation of membrane lipids leading to cell death
• the Fenton reaction produces dangerous free radicals

Methanol and Ethylene Glycol Toxicity

• Each are competitive substrates for alcohol dehydrogenase (ADH) 
• Methanol 
  • metabolized by ADH to formaldehyde followed by aldehyde dehydrogenase to form formic acid which is toxic to the optic nerve
    • early toxicity of formic acid is metabolic acidosis by formic acid itself
    • formic acid also binds to cytochrome oxidase blocking oxidative phosphorylation
    • resulting in lactic acidosis which is the latter and leading cause of the metabolic acidosis
  • signs and symptoms appear within 12 – 24 hours after ingestion
    • CNS depression
      • methanol acts similarly as ethanol as a CNS depressant
    • metabolic acidosis
    • visual changes
      • blindness occurs with as little as 30 mL and death at 100 mL ingestion
• Ethylene glycol 
  • colorless, odorless, sweet-tasting liquid
  • toxicity derives from the hepatic oxidation of ethylene glycol to oxalic acid
    • degraded by same pathway as methanol
      • the glycolic acid produced by aldehyde dehydrogenase is converted in oxalic acid
    • oxalic acid binds calcium and forms calcium oxalate crystals that damage the heart, brain, lungs, kidneys
  • signs and symptoms develop in stages after ingestion
    • first stage: 0.5 – 12 hours
      • stronger inebriant than methanol and ethanol causing mild depression of CNS resulting in seizures and coma
      • patients appear “drunk without smelling like alcohol”
      • within 4 – 12 hours, calcium oxalate crystals deposit in the brain causing CNS toxicity, cerebral edema, meningismus (nuchal rigidity, photophobia, headache without infection or inflammation)
      • hypocalcemia occurs due to binding of calcium by oxalic acid and can cause prolonged QT, arrhythmias, myocardial depression
    • second stage: 12 – 24 hours
      • tachypnea occurs to offset the metabolic acidosis due to the toxic metabolites produced
      • multiorgan failure (CHF, lung injury, myositis) due to widespread crystal deposition
      • NOTE: most deaths occur in the second stage
    • third stage: 24 – 72 hours
      • acute anuric renal failure from crystal deposition but full recovery occurs within weeks to months
• Treatment
  • IV ethanol: competitive substrate for ADH and has greater affinity for ADH than methanol and ethylene glycol
  • fomepizole: inhibits ADH preventing production of toxic metabolites

Ingested seafood toxins

• Tetrodotoxin
  • Highly potent toxin that binds to fast voltage-gated Na+ channels, preventing depolarization
  • Presents with nausea, diarrhea, paresthesias, weakness, dizziness, and loss of reflexes

Poisons and Treatments

Poisonings and their treatments are important topics covered in the USMLE (United States Medical Licensing Examination). Here’s an overview of some common poisonings and their treatments, which are frequently tested on the USMLE:

1. Acetaminophen (Paracetamol) Poisoning:
   • Acetaminophen overdose can cause liver toxicity.
   • Treatment includes administration of N-acetylcysteine (NAC), which is the antidote for acetaminophen toxicity. NAC replenishes glutathione stores and helps prevent liver damage.
2. Benzodiazepine Poisoning:
   • Benzodiazepine overdose can lead to central nervous system depression and respiratory depression.
   • Treatment includes supportive measures such as airway management, respiratory support, and the administration of flumazenil, which is a benzodiazepine receptor antagonist.
3. Opioid Poisoning:
   • Opioid overdose can cause respiratory depression, pinpoint pupils, and CNS depression.
   • Treatment includes supportive measures such as airway management, naloxone administration (opioid receptor antagonist), and monitoring of vital signs.
4. Iron Poisoning:
   • Iron overdose can lead to severe gastrointestinal symptoms and multi-organ failure.
   • Treatment includes immediate administration of deferoxamine, an iron chelator, to prevent further iron absorption and facilitate iron excretion.
5. Carbon Monoxide Poisoning:
   • Carbon monoxide (CO) poisoning can occur due to inhalation of CO gas, which binds to hemoglobin and reduces oxygen-carrying capacity.
   • Treatment includes removal from the CO source, administration of 100% oxygen, and hyperbaric oxygen therapy in severe cases.
6. Cyanide Poisoning:
   • Cyanide poisoning can result from exposure to cyanide-containing compounds, which inhibit cellular respiration.
   • Treatment includes administration of antidotes such as hydroxocobalamin, sodium nitrite, or sodium thiosulfate, along with supportive measures and rapid decontamination.
7. Lead Poisoning:
   • Lead poisoning occurs due to ingestion or inhalation of lead-containing substances, leading to systemic toxicity.
   • Treatment includes removing the source of lead exposure, chelation therapy (e.g., with succimer or dimercaprol), and management of associated symptoms.

These are just a few examples of poisonings and their treatments. It’s essential to have a comprehensive understanding of various toxic substances, their clinical presentations, and the specific antidotes or treatments associated with each poisoning. Familiarizing yourself with poisonings and their management is important for success in the USMLE exams and for the practice of medicine.

Check out Ultimate USMLE Step 1 Study Notes.